Impact of the distribution of epicardial and visceral adipose tissue on left ventricular diastolic function.

Although epicardial adipose tissue (EAT) and abdominal visceral adipose tissue (VAT) can contribute to left ventricular diastolic dysfunction (LVDD), the impact of these distribution has not been fully understood. A total of 235 patients who underwent cardiac computed tomography angiography and Doppler echocardiography was included in this study. We evaluated the association of indexed EAT volume and VAT area with septal and lateral early diastolic mitral annular velocity (e'). The VAT area index was significantly associated with septal and lateral e' velocity after adjusted for conventional cardiovascular risk factors and obstructive coronary artery disease (ß-estimate; - 0.015 and - 0.019, both p = 0.01). The natural logarithmic EAT volume index (ln EAT volume index) also showed a significant association with septal and lateral e' (ß-estimate; - 1.72 and - 0.99, both p < 0.01). The significant association of ln EAT volume index with septal and lateral e' was observed even after adjusting for VAT area index (ß-estimate; - 0.79 and - 1.52, both p < 0.03). In the subgroup analysis, there were significant association of ln EAT volume index with both septal and lateral e' in the lower VAT group (ß-estimate; - 1.40 and - 1.53, both p < 0.03) and with lateral e' in the higher VAT group (ß-estimate - 1.64, p = 0.006). In contrast, ln EAT volume index was not associated with septal e' in the higher VAT group (p = 0.98). EAT accumulation was significantly associated with LVDD independently of obstructive coronary artery disease and abdominal VAT. The impact of EAT on LVDD may vary depending on the amount of abdominal VAT.

Nurse-Led Collaborative Management Using Telemonitoring Improves Quality of Life and Prevention of Rehospitalization in Patients with Heart Failure.

The effects of disease management using telemonitoring for patients with heart failure (HF) remain controversial. Hence, we embedded care coordination and enhanced collaborative self-management through interactive communication via a telemonitoring system (collaborative management; CM). This study evaluated whether CM improved psychosocial status and prevented rehospitalization in patients with HF in comparison with self-management education (SM), and usual care (UC).We randomly allocated 59 patients into 3 groups; UC (n = 19), SM (n = 20), and CM (n = 20). The UC group received one patient education session, and the SM and CM groups participated in disease management programs for 12 months. The CM group received telemonitoring concurrently. All groups were followed up for another 12 months. Data were collected at baseline and at 6, 12, 18, and 24 months.The primary endpoint was quality of life (QOL). Secondary endpoints included self-efficacy, self-care, and incidence of rehospitalization. The QOL score improved in CM compared to UC at 18 and 24 months (P < 0.05). There were no significant differences among the 3 groups in self-efficacy and self-care. However, compared within each group, only the CM had significant changes in self-efficacy and in self-care (P < 0.01). Rehospitalization rates were high in the UC (11/19; 57.9%) compared with the SM (5/20; 27.8%) and CM groups (4/20; 20.0%). The readmission-free survival rate differed significantly between the CM and UC groups (P = 0.020).We conclude that CM has the potential to improve psychosocial status in patients with HF and prevent rehospitalization due to HF.

Coronary Artery Calcium Is Associated with Left Ventricular Diastolic Function Independent of Myocardial Ischemia.

It has been shown in several studies that coronary artery calcium (CAC) burden or CAC progression is associated with heart failure. We tested the hypothesis that the extent of CAC is associated with left ventricular (LV) diastolic parameters derived from gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with no evidence of myocardial ischemia.157 patients undergoing coronary computed tomography (CT), gated SPECT, and transthoracic echocardiography (TTE) were enrolled in this study. The CAC score was calculated according to the Agatston method. The peak filling rate (PFR) and the one-third mean filling rate (1/3MFR) were obtained as LV diastolic parameters.There were 139 patients with CAC and 18 patients without. The CAC score ranged from 0 to 4,976. There were no significant differences in the LV end-diastolic volume (LVEDV) (61 ± 21 mL versus 62 ± 22 mL, P = 0.79) and LV ejection fraction (LVEF) (66 ± 9% versus 68 ± 9%, P = 0.43). Patients with CAC had lower PFR than those without (2.2 ± 0.5 EDV/s versus 2.6 ± 0.7 EDV/s, P = 0.03). Multivariate linear regression analysis showed that ln (CAC score + 1) was significantly associated with PFR (ß = -0.20, P = 0.01) and 1/3MFR (ß = -0.18, P = 0.049).Our data suggest that the extent of CAC is inversely associated with LV diastolic parameters derived from gated SPECT independent of myocardial ischemia.

Association of N-Terminal Pro B-Type Natriuretic Peptide With Blood Pressure and Pulse Pressure in Elderly People　- A Cross-Sectional Population Study.

BACKGROUND: N-Terminal pro B-type natriuretic peptide (NT-proBNP) is widely used as a marker of ventricular dysfunction. However, data regarding the association of NT-proBNP with blood pressure (BP) and pulse pressure (PP) in the elderly population are limited.Methods and Results:The present cross-sectional study involved 6,529 participants, aged ≥70 years, without cardiovascular disease (CVD), who underwent general health examinations. Serum NT-proBNP concentrations were determined, with high NT-proBNP concentrations defined as those ≥125 pg/mL. Subjects were divided into five groups based on PP (<50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 mmHg). NT-proBNP was positively associated with systolic BP, whereas a U-shaped association was found between diastolic BP and NT-proBNP. The odds ratios for high NT-proBNP concentrations in the PP ≥80 and ≥70 to <80 mmHg groups (OR 1.83 [P<0.001] and 1.40 [P<0.005], respectively) were significantly higher than in the PP <50 mmHg group. All data were adjusted for age, sex, body mass index, hemoglobin concentration, serum creatinine, pulse rate, smoking, alcohol intake, and antihypertensive medication intake, and the presence of diabetes and dyslipidemia. CONCLUSIONS: The results suggest that NT-proBNP concentrations may be a marker of not only ventricular dysfunction, but also arterial stiffness in the elderly population without CVD.

Impact of the Coronary Artery Calcium Score on Mid- to Long-Term Cardiovascular Mortality and Morbidity Measured With Coronary Computed Tomography Angiography.

BACKGROUND: Although the coronary artery calcium score (CACS) is a prognostic measurement in asymptomatic individuals, it is measured in symptomatic patients using coronary computed tomography angiography (CCTA). We aimed to examine the predictive value of the CACS for mid- to long-term cardiovascular mortality and morbidity in patients who underwent CCTA. Methods and Results: We studied 736 patients with suspected coronary artery disease (CAD) who underwent CCTA. During a median follow-up period of 6.5 years, there were 39 primary outcomes (composite of cardiovascular disease death, non-fatal myocardial infarction, and non-fatal stroke). The estimated 10-year cumulative rates of the primary outcome were significantly increased across CACS classes (3.9%, 9.2%, 11.8%, and 18.2% in CACS of 0, 1-99, 100-399, and ≥400, respectively, P<0.001). These rates of cardiovascular disease death and stroke were also significantly increased across CACS classes. Multivariate Cox proportional hazard analysis showed that a CACS ≥100 was independently predictive for the primary outcome (hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.40-6.00, P=0.003), as well as the presence of ≥50% stenosis on CCTA (HR 2.27, 95% CI 1.13-4.46, P=0.022). CONCLUSIONS: An elevated CACS with the use of CCTA is an independent predictor of mid- to long-term cardiovascular mortality and morbidity in patients suspected of having CAD.

Association between histological features of epicardial adipose tissue and coronary plaque characteristics on computed tomography angiography.

The means by which epicardial adipose tissue (EAT) could influence coronary plaque progression biologically remain unclear. We investigated the association between the histological findings of EAT and coronary plaque characteristics assessed by coronary computed tomography angiography (CCTA). We enrolled 34 patients in whom one or more coronary plaques containing non-calcified components were detected on CCTA before cardiac surgery [coronary artery bypass graft (CABG) or non-CABG]. We evaluated visceral adipose tissue (VAT) area, EAT volume, and coronary plaque characteristics including minimum computed tomography density (CTD) and vascular Remodeling Index (RI). Lower CTD and higher RI were considered as high-risk characteristics, and coronary plaque with both CTD < 39 Hounsfield units and RI > 1.05 was defined as two-characteristic plaque (2-CP). The numbers of CD68+ macrophages and CD31+ microvessels were assessed in six random high-power fields (400×) of EAT samples obtained during cardiac surgery. The entire cohort showed a wide range of EAT volume, which were similar between patients with 2-CP and those without. Patients with 2-CP had more amounts of EAT macrophages (85 ± 38 versus 45 ± 22, p = 0.0005) and vascularity (62 ± 33 versus 37 ± 19, p = 0.013) than those without. On multivariate analyses adjusted for age, sex, coronary risk factors, statin use, type of surgery, VAT area, EAT volume, and coronary calcium score, the presence of 2-CP showed significant correlation with increased EAT macrophages (ß = 0.65, p = 0.014) and vascularity (ß = 0.74, p = 0.0053). Our findings support the hypothesis that EAT biologic activities are associated with coronary plaque vulnerability.

Choice reaction time and grip strength as predictors of cardiovascular mortality in middle-aged and elderly Japanese: from the Radiation Effects Research Foundation Adult Health study.

BACKGROUND: Cognitive function and physical function are important predictors of mortality. AIM: To investigate whether or not reaction time (RT) as a cognitive function and grip strength (GS) as a physical function were associated, alone or in combination, with mortality from heart disease or stroke. METHODS: The subjects included 4901 Adult Health Study participants in Hiroshima who had undergone RT and GS measurements, were 35-74 years old at baseline (1970-1972) and were followed until the end of 2007. RESULTS: After adjustment for other potential risk factors, RT was positively and GS was negatively associated with mortality from both heart disease and stroke. These associations were persistent in the model when adjusting simultaneously for RT, GS and other factors, but hazard ratios were attenuated. When we evaluated the associations by baseline age and gender, we found the greater hazard ratios for RT in the younger cohort, but no clear modification by age for GS. The interaction between RT and GS was statistically significant (P = 0.012) for stroke mortality. In the stratified analyses divided using the age-specific median value of RT or GS, the estimated hazard ratio of stroke mortality for RT was significant in participants with weak or strong GS but greater in the former, and for GS, it was only significant in participants with slow RT. CONCLUSION: RT and GS, alone and in combination, predicted heart disease and stroke mortalities. Interventions for both cognitive function and physical function may be beneficial for the prevention of cardiovascular disease mortality.

Clinical features and predictive value of serum inflammatory markers of perivascular involvement in immunoglobulin G4-related disease.

Vascular and/or perivascular involvements of sclerotic inflammation (perivasculitis) are a complication of immunoglobulin G4-related disease (IgG4-RD). We sought to examine clinical manifestations of perivasculitis by computed tomography (CT) in patients with elevated serum IgG4 levels, and then to evaluate some potential predictors of perivasculitis in definite IgG4-RD patients. From a database of patients with serum IgG4 measurements, we selected 81 patients with elevated serum IgG4 levels (≥135 mg/dl). Perivasculitis was defined radiologically as thickened contrast-enhanced rind surrounding the aorta and its major artery on CT imaging. We found 15 patients with perivasculitis; 10 patients in the definite (n = 37), four in the possible (n = 18), and one in the excluded (n = 26) IgG4-RD groups. Clinical predictors of perivasculitis were investigated in 34 untreated patients with definite IgG4-RD. Patients with perivasculitis (n = 10) had significantly higher age at diagnosis (74.2 ± 8.8 vs 63.5 ± 9.9 years, P = 0.006), higher levels of serum IgG4 (754 vs 292 mg/dl, P = 0.007) and C-reactive protein (CRP, 0.52 mg/dl vs 0.10 mg/dl, P = 0.001) than patients without perivasculitis (n = 24). The sensitivity and specificity of serum CRP ≥0.25 mg/dl for identifying perivasculitis in the definite IgG4-RD group were 100 and 71%, respectively (area under the receiver operating characteristic curve 0.863). Our results indicate that IgG4-related perivasculitis was associated with elevated levels of serum CRP and older age, and that CRP may be a useful marker for detecting perivascular involvement in IgG4-RD.

Evaluation of end-tidal CO2 pressure at the anaerobic threshold for detecting and assessing pulmonary hypertension.

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO2) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple regression analysis showed that PETCO2 at the AT was independently associated with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO2 at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO2 at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH.

Use of the augmentation index from applanation tonometry of the radial artery for assessing the extent of coronary artery calcium as assessed by coronary computed tomography.

BACKGROUND: The augmentation index (AI) obtained from applanation tonometry of the radial artery is technically the easiest and quickest of available methods for assessing arterial stiffness. We tested the hypothesis that the radial AI is associated with the extent of coronary artery calcium (CAC) as assessed by coronary computed tomography (CCT). METHODS AND RESULTS: This study included 161 patients with known or suspected coronary artery disease undergoing central hemodynamic measurements and CCT. Radial AI was recorded and was corrected in accordance with heart rate (radial AI@75). Thirty-seven patients had no CAC (CAC score = 0), 85 had low-grade CAC (CAC score = 1-399), and 39 had high-grade CAC (CAC score ≥400). Coronary risk factors, except for age and serum creatinine, were similar among the three groups. There were significant differences in brachial systolic blood pressure (SBP) (p = 0.011) and radial AI@75 (%) (p = 0.006). Multivariate analysis showed that age (ß = 0.27, p = 0.001), serum creatinine (ß = 0.18, p = 0.03), and radial AI@75 (ß = 0.24, p = 0.005) were significantly associated with ln (CAC score + 1), whereas brachial SBP was not. Additionally, serum creatinine (odds ratio: 11.91, 95% confidence interval: 1.46-112.0, p = 0.02) and radial AI@75 (per 10%) (odds ratio: 1.76, 95% confidence interval: 1.22-2.64, p = 0.002) were independent factors associated with high-grade CAC. CONCLUSIONS: Our results suggest that the radial AI is better for estimating CAC than brachial SBP in patients with known or suspected coronary artery disease.

Prognostic Factors for Survival in Pulmonary Hypertension Due to Left Heart Disease.

BACKGROUND: The epidemiological data of pulmonary hypertension (PH) due to left heart disease (LHD) are limited. This study investigated hemodynamic and clinical factors associated with mortality in patients with PH due to LHD. METHODS AND RESULTS: We conducted a retrospective review in 243 patients with PH due to LHD, defined as mean pulmonary arterial pressure ≥25 mmHg and pulmonary wedge pressure >15 mmHg at rest in right heart catheterization. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Seventy-five patients died during an average follow-up of 52 months (range, 20-73 months). On multivariate analysis, only diastolic pulmonary vascular pressure gradient (DPG) ≥7 mmHg among hemodynamic measurements was a predictor of mortality. Elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), more severe New York Heart Association (NYHA) class, anemia, and renal dysfunction were more strongly associated with mortality. Mean right atrial pressure (RAP) and currently available markers of pulmonary vascular remodeling including transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) had no effect on survival. CONCLUSIONS: DPG is weakly associated with mortality in PH due to LHD. Clinical factors such as NT-pro BNP, NYHA class, anemia and renal dysfunction are superior predictors. The prognostic ability of hemodynamic factors such as mean RAP, TPG, PVR and DPG is limited.

Association of epicardial and abdominal visceral adipose tissue with coronary atherosclerosis in patients with a coronary artery calcium score of zero.

BACKGROUND: We sought to examine whether epicardial and abdominal visceral adipose tissue distribution is associated with coronary atherosclerosis in patients with a coronary artery calcium (CAC) score of zero, assessed by coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We studied 352 patients with suspected coronary artery disease (mean age 61±11 years, 57% male) with a CAC score of zero who had undergone CCTA. Non-calcified coronary plaques (NCPs) were detected in 102 patients (29%); those causing ≥50% stenosis were found in 15 patients (4%). Patients were divided into 4 groups on the basis of CT-based epicardial adipose tissue (EAT) volume and abdominal visceral adipose tissue (VAT) area using the sex-specific median value. Multivariate analysis showed that the adjusted odds ratios for the presence of NCPs in the high VAT area/low EAT volume group, and the high VAT area/high EAT volume group were 2.80 (95% confidence interval [95% CI]: 1.25-6.35, P=0.01) and 2.68 (95% CI: 1.36-5.45, P=0.004), respectively. Interestingly, the low VAT area/high EAT volume group showed an equivalent adjusted odds ratio of 3.02 (95% CI: 1.33-6.90, P=0.008). CONCLUSIONS: EAT volume is eligible as a marker to be evaluated in addition to VAT area in patients with a CAC score of zero.

Risk Factors for Progression of Degenerative Aortic Valve Disease in the Japanese- The Japanese Aortic Stenosis Study (JASS) Prospective Analysis.

BACKGROUND: Because of ethnic difference in the risk of degenerative aortic valve disease (DAVD), risk factors should be clarified in each race to establish prophylactic strategies for severe aortic valve stenosis (AS). METHODS AND RESULTS: This study prospectively followed 359 Japanese subjects with DAVD and age ≥50 years for 3 years. As both patients with peak aortic transvalvular flow velocity ≥2 m/s and <2 m/s were enrolled, subgroup analysis was also conducted. Most patients were under treatment for their comorbidities. The use of warfarin, but none of the traditional risk factors for atherosclerosis, was related to greater reduction in aortic valve area indexed to body surface area (iAVA). In patients with peak aortic transvalvular flow velocity <2 m/s, the use of an angiotensin-receptor blocker (ARB) was associated with less decrease in iAVA. In patients with peak velocity ≥2 m/s, changes in iAVA were not related to any baseline characteristics, but peak velocity was less increased under treatment with an angiotensin-converting enzyme inhibitor (ACEI). CONCLUSIONS: In Japanese, the use of warfarin may exacerbate DAVD, and augmented management of atherosclerotic risk factors beyond the recommendations in the current guidelines is unlikely to exert additional benefit. The prescription of ARB for DAVD patients before the development of AS or ACEI after the development of AS may be useful.

Development of new risk score for pre-test probability of obstructive coronary artery disease based on coronary CT angiography.

Existing methods to calculate pre-test probability of obstructive coronary artery disease (CAD) have been established using selected high-risk patients who were referred to conventional coronary angiography. The purpose of this study is to develop and validate our new method for pre-test probability of obstructive CAD using patients who underwent coronary CT angiography (CTA), which could be applicable to a wider range of patient population. Using consecutive 4137 patients with suspected CAD who underwent coronary CTA at our institution, a multivariate logistic regression model including clinical factors as covariates calculated the pre-test probability (K-score) of obstructive CAD determined by coronary CTA. The K-score was compared with the Duke clinical score using the area under the curve (AUC) for the receiver-operating characteristic curve. External validation was performed by an independent sample of 319 patients. The final model included eight significant predictors: age, gender, coronary risk factor (hypertension, diabetes mellitus, dyslipidemia, smoking), history of cerebral infarction, and chest symptom. The AUC of the K-score was significantly greater than that of the Duke clinical score for both derivation (0.736 vs. 0.699) and validation (0.714 vs. 0.688) data sets. Among patients who underwent coronary CTA, newly developed K-score had better pre-test prediction ability of obstructive CAD compared to Duke clinical score in Japanese population.

Insulin resistance and subclinical abnormalities of global and regional left ventricular function in patients with aortic valve sclerosis.

BACKGROUND: Insulin resistance, as a key mediator of metabolic syndrome, is thought to be associated with pathogenesis of calcific aortic valve disease and altered left ventricular (LV) function and structure. However, in patients with aortic valve sclerosis (AVS), the association between insulin resistance and subclinical impairment of LV function is not fully elucidated. METHODS: We studied 57 patients (mean age 70 ± 8 years, 22 women) with asymptomatic AVS but normal LV ejection fraction in echocardiography. LV longitudinal and circumferential strain and strain rate was analyzed using two-dimensional speckle tracking echocardiography. Patients with uncontrolled hypertension and diabetes mellitus, chronic kidney disease, and concomitant coronary artery disease were excluded. They were divided into the insulin-resistant group (AVS+IR; N = 28) and no insulin-resistant group (AVS-IR; N = 29) according to the median value of homeostatic model assessment index. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue (VAT) area. In addition, age- and sex- adjusted 28 control subjects were recruited for the comparison. RESULTS: There were no significant differences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score (median 94 versus 21, P = 0.022) and a larger VAT area (113 ± 42 cm2 versus 77 ± 38 cm2, P = 0.001) than the AVS-IR group. Notably, LV global longitudinal strain, strain rate (SR), and early diastolic SR were significantly lower in the AVS+IR group than in the AVS-IR group and in control subjects (strain: -16.2 ± 1.6% versus -17.2 ± 1.2% and -18.9 ± 0.8%; SR: -1.18 ± 0.26 s(-1) versus -1.32 ± 0.21 s(-1) and -1.52 ± 0.08 s(-1); early diastolic SR: -1.09 ± 0.23 s(-1) versus -1.23 ± 0.18 s(-1) and -1.35 ± 0.12 s(-1); P < 0.05 for all comparison), whereas circumferential function were not significantly different. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain (P = 0.017), SR (P = 0.047), and early diastolic SR (P = 0.049) regardless of LV mass index or VAT area. CONCLUSIONS: Insulin resistance is a powerful independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. Thus, it may be a novel therapeutic target to prevent subsequent heart failure in patients with AVS.

Association between serum levels of n-3 polyunsaturated fatty acids and coronary plaque detected by coronary computed tomography angiography in patients receiving statin therapy.

BACKGROUND: Intensive lipid-lowering therapy with statins reduces cardiovascular events, but residual cardiovascular risks remain. Intake of n-3 polyunsaturated fatty acids (PUFAs) has been associated with cardiovascular events. We examined the relationships between serum n-3 PUFAs and coronary atherosclerotic findings on computed tomography angiography (CTA) in patients undergoing statin treatment. METHODS AND RESULTS: We enrolled 172 subjects (mean age: 68.2 years; 64% men) prior to statin treatment for 6 months. Serum PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, were measured. When the patients were divided into 2 groups according to the median EPA level (61.3 µg/ml), the low-EPA group showed higher incidences of 3-vessel plaque involvement (62% vs. 43%, P=0.015), noncalcified plaques (NCPs) (74% vs. 52%, P=0.0016), extensive NCPs (≥ 2 segments) (56% vs. 34%, P=0.0036), and high-risk plaques (minimum CT density <39 HU and remodeling index >1.05) (43% vs. 22%, P=0.0034). Multivariate analyses revealed that low EPA levels were an independent factor for these coronary plaque findings. The DHA levels were not independently associated with these findings. CONCLUSIONS: Low serum EPA level, but not serum DHA, is associated with the presence and extent of NCPs and high-risk plaques detected by coronary CTA in patients undergoing lipid-lowering therapy with statins.

Pulmonary artery mapping for differential diagnosis of left-sided atrial tachycardia.

BACKGROUND: Distinguishing left-and right-sided atrial tachycardia (AT) is often challenging. The coronary sinus (CS) provides information only concerning the anterior left atrium (LA). Potentials recorded in the pulmonary artery (PA) have been substituted for those of the upper posterior LA because of their anatomical relationship. METHODS AND RESULTS: Three patterns were designed, using potentials in the PA, right atrium (RA) and CS, to predict the side of AT. Two patterns were for left-sided AT and 1 pattern was for right-sided AT. Ten left-sided and 11 right-sided ATs were investigated regardless of mechanism. Electrode catheters were inserted in the RA, His bundle region, and CS, and an ablation catheter was inserted into the left and/or right PA. The sequences from these catheters were analyzed before detailed electroanatomical mapping. Patterns were obtained for 20 of 21 ATs. The mechanism was focal in 16 ATs and macroreentry in 5. The method predicted left-sided AT with a sensitivity of 78%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 84%, and an accuracy of 90%. CONCLUSIONS: The use of potentials in PA combined with conventional RA and CS electrograms is useful for distinguishing left-sided AT from right-sided AT, regardless of mechanism.

Feasibility of Simple Evaluation of Coronary Artery Calcium Using a Number of Chest Computed Tomography Slices: A Multicenter Study.

Objective: We aimed to evaluate the visual measurements of coronary artery calcium (CAC) on nonelectrocardiogram (ECG)-gated chest computed tomography (CT) using a simple scoring method that involves counting the number of CT slices containing CAC. Materials and Methods: We analyzed 163 participants who underwent both coronary and chest CT examinations at six centers within 3 months. Agatston scores were calculated on standard ECG-gated scans and classified as none (0), mild (1-99), moderate (100-400), or severe (>400). Next, chest CT images were reconstructed to standard 5.0 mm axial slices. Then, CAC on chest CT scans was measured using two methods: the Weston score (sum of the assigned score of each vessel, range: 0-12) and number of slices showing CAC (Ca-slice#). Results: When the Weston score and Ca-slice# were divided into four levels according to the optimal divisional levels corresponding to the Agatston score classes, good agreements with the 4-grade Agatston score were observed (kappa value=0.610 and 0.794, respectively). The sensitivity and specificity of Ca-slice# ≥9 to identify severe Agatston scores of >400 were 86% and 96%, respectively. Conclusion: The Ca-slice#, a simple scoring method using chest CT scans, was in good agreement with the ECG-gated Agatston score.

Association between plasma high-molecular-weight adiponectin and coronary plaque characteristics assessed by computed tomography angiography in conditions of visceral adipose accumulation.

BACKGROUND: Our group has previously reported that visceral adipose tissue (VAT) accumulation was associated with the extent and vulnerable characteristics of coronary plaques using coronary computed tomography angiography (CTA). An investigation of the associations between these coronary lesions with plasma adiponectin and leptin was performed. METHODS AND RESULTS: A total of 394 patients (220 men and 174 women) in the study were referred for CTA. Plain abdominal scanning was simultaneously performed to evaluate VAT areas. The median level of plasma high-molecular-weight (HMW) adiponectin in patients with CTA-based obstructive coronary artery disease was significantly lower than that in patients without (men: 1.45 vs. 1.88 µg/ml, P=0.002; women: 2.49 vs. 3.44 µg/ml, P<0.001). Multivariate analyses revealed that a lower HMW adiponectin concentration was significantly associated with the presence (men: P=0.019; women: P=0.018) and involved segment numbers (men: P=0.001; women: P=0.003) of coronary plaques. Furthermore, it was significantly related to coronary plaque with all 3 vulnerable characteristics of positive remodeling, low CT density (≤38 Hounsfield units), and adjacent spotty calcium (men: P=0.019; women: P=0.016). These associations were also observed with VAT areas, but not with plasma leptin concentrations, in both genders. CONCLUSIONS: Lower plasma HMW adiponectin is associated with the presence, extent, and vulnerable characteristics of coronary plaques assessed by CTA in both genders.

25-hydroxycholesterol-induced cell death via activation of ROCK/LIMK/cofilin axis in colorectal cancer cell spheroids.

25-Hydroxycholesterol (25OHC) induces anchorage-dependent programmed cell death, or anoikis, in colorectal cancer cells but the mechanism is not fully understood. Here, we found that 25OHC induced cofilin phosphorylation and promoted rearrangement of the actin cytoskeleton in spheroids of the colorectal cancer cell lines, DLD1 and HT29/WiDr. Cell death induced by 25OHC was inhibited by the actin polymerization inhibitor, cytochalasin D, and BMS-3, an inhibitor of LIMK, which phosphorylates and inactivates cofilin. In addition, we showed that cofilin phosphorylation induced by 25OHC was associated with caspase-3 activation, which can activate ROCK. Rho GTPase was directly activated by 25OHC. These results indicate that 25OHC affects actin dynamics through activation of the Rho/ROCK/LIMK/cofilin axis, eventuating in the cell death of colorectal cancer cell spheroids.