Differential association of docosahexaenoic and eicosapentaenoic acids with carotid intima-media thickness.

BACKGROUND AND PURPOSE: Recent studies reported the differential effect of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA). We examined the differential association of DHA and EPA with carotid intima-media thickness (IMT) in Japanese individuals in Japan and in U.S. white individuals and explored whether DHA or EPA contributes to the difference in IMT between the two groups. METHODS: A population-based cross-sectional study in 608 Japanese and U.S. white men aged 40 to 49 was conducted to assess IMT, serum DHA, EPA, and other cardiovascular risk factors. RESULTS: Japanese compared to U.S. whites had significantly lower IMT (mean±SD, 618±81 and 672±94 µm for Japanese and whites, respectively; P<0.001) and had >2-fold higher levels of DHA and EPA. DHA, but not EPA, had an inverse association with IMT in both Japanese and U.S. whites. The inverse association remained only in Japanese men after adjusting for risk and other factors. The significant difference in multivariable-adjusted IMT became nonsignificant after further adjusting for DHA (mean difference, 17 µm; 95% CI, -8 to 43; P=0.177) but not EPA. In this multivariable-adjusted model, DHA but not EPA was a significant predictor of IMT (P=-0.032 versus 0.863, respectively). CONCLUSIONS: These data suggest that DHA may have a more potent antiatherogenic effect than EPA, especially in levels observed in the Japanese, independent of risk factors.

Association between brachial-ankle pulse wave velocity and endothelium-dependent and -independent coronary vasomotor function.

1. Coronary endothelial function and brachial-ankle pulse wave velocity (baPWV) are independent predictors of cardiovascular events. Thus, in the present study we examined the relationship between baPWV and endothelium-dependent and -independent coronary vasodilatory functions. 2. Sixty-five patients (12 diabetic and 53 non-diabetic) with no significant stenosis of the coronary artery were studied and baPWV determined. After cardiac catheterization, graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 µg/min), nitroglycerin (NTG; 250 µg) and papaverine (Pa; 12 mg) were administered into the left anterior descending coronary artery. Coronary blood flow (CBF) was measured using a Doppler flow wire. 3. In the 65 patients, an inverse correlation was found between baPWV and the percentage change in epicardial coronary artery diameter (Δ%CoD), as well as the percentage change in CBF (Δ%CBF), following administration of BK (endothelium-dependent vasodilator). Moreover, inverse correlations were found between baPWV and Δ%CoD following administration of NTG (endothelium-independent vasodilator) and Δ%CBF following administration of Pa (endothelium-independent vasodilator). 4. Multivariate analysis revealed diabetes to be independently and significantly associated with baPWV, BK-induced Δ%CBF and Δ%CoD and Pa-induced Δ%CBF. 5. In conclusion, the results of the present study suggest that increased baPWV is associated with endothelium-dependent and -independent coronary vasodilatory dysfunction. Non-invasive and straightforward baPWV measurement may be useful for the assessment of coronary risk factors, particularly in diabetic patients.

Clinical features of myocardial triglyceride in different types of cardiomyopathy assessed by proton magnetic resonance spectroscopy: comparison with myocardial creatine.

BACKGROUND: Myocardial lipid overstorage may produce cardiomyopathy, leading to dysfunction, but advanced heart failure may cause lipolysis via sympathetic nerve activation. In the failing heart, the creatine kinase system may also be impaired. The aims of this study were to assess myocardial triglyceride (TG) and creatine (CR) in different types of cardiomyopathy and to investigate whether they are related to the severity of cardiac dysfunction. METHODS AND RESULTS: In patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 12) or ischemic cardiomyopathy (ICM, n = 10), and normal subjects (NML, n = 22), myocardial TG and CR were evaluated using proton magnetic resonance spectroscopy. To assess cardiac sympathetic nerve activity, myocardial MIBG (a radioactive guanethidine analog) uptake was measured in DCM. Myocardial TG was significantly lower in hypertrophic cardiomyopathy (HCM) (1.92 ± 0.99 µmol/g), but higher in ICM (7.59 ± 4.36 µmol/g) than in NML hearts (4.05 ± 1.94 µmol/g). There was no significant difference in TG between DCM (4.84 ± 6.45 µmol/g) and NML. Myocardial CR in HCM (20.4 ± 8.4 µmol/g), DCM (14.8 ± 4.8 µmol/g), and ICM (19.4 ± 6.3 µmol/g) was significantly lower than that in NML hearts (27.1 ± 4.3 µmol/g). Overall, myocardial CR correlated positively with the severity of heart failure estimated by ejection fraction or myocardial BMIPP (a radioactive fatty acid analog) uptake, but TG did not. In DCM, myocardial TG correlated with body mass index, but not with MIBG uptake. CONCLUSIONS: Myocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. In contrast, myocardial CR reflects the severity of heart failure despite different pathoetiologic mechanisms of dysfunction. In DCM, myocardial TG may be affected by an overweight state rather than cardiac sympathetic nerve dysfunction. Thus, myocardial CR has a closer relationship to heart failure severity than does myocardial TG.

Clinical significance of diastolic function as an indicator of myocardial ischemia assessed by 16-frame gated myocardial perfusion SPECT.

OBJECTIVE: Studies have suggested that ischemia-induced diastolic dysfunction persists longer than systolic dysfunction. We examined whether global left ventricular (LV) diastolic function during stress testing assessed by 16-frame gated myocardial perfusion single-photon emission computed tomography (SPECT) is useful as an indicator of myocardial ischemia. METHODS: Thirty-nine patients underwent 16-frame technetium-99m (Tc-99m) quantitative gated SPECT (QGS), including treadmill exercise testing for suspected ischemic heart disease. Diastolic parameters of the first-third filling fraction (1/3FF), and the peak filling rate (PFR) were calculated by a time-volume curve from the QGS data. RESULTS: The patients were divided into four groups, namely, IS, NL, DN, and DD, on the basis of tracer accumulation and the LV ejection fraction (LVEF) at rest. In the IS group (reversible tracer uptake reduction suggesting ischemia; n=11), LVEF, 1/3FF, and PFR after stress were significantly lower than those at rest, whereas in the NL group (normal perfusion; n=10) and DN group (fixed tracer uptake reduction with normal systolic function; EF>or=60% at rest; n=10), LVEF, 1/3FF, and PFR after stress did not differ from those at rest. However, in the DD group (fixed tracer uptake reduction with cardiac dysfunction; EF<60%, average 47.1%; n=8), LVEF, 1/3FF, and PFR were significantly altered after stress. CONCLUSIONS: Altered global LV diastolic function during stress assessed by 16-frame gated myocardial perfusion SPECT is useful for the detection of myocardial ischemia. However, similar findings are observed in patients with cardiac dysfunction but without detectable ischemia. Our findings do suggest that tests should be performed with caution to determine whether ischemia exists on the basis of altered global LV function after stress in patients with cardiac dysfunction.

Assessment of cardiac function in patients with heart disease by quantitative gated myocardial perfusion SPECT.

OBJECTIVE: We examined the cardiac function of patients who underwent Tc-99m sestamibi quantitative gated myocardial single photon emission computed tomography with 16-framing data acquisition between January 1, 2004 and March 31, 2006 for an evaluation of suspected or known heart disease in our hospital. METHODS: In 192 patients aged >or=40 years, the left ventricular (LV) systolic function [parameter: ejection fraction (EF)] and diastolic function [first third filling fraction (1/3FF), peak filling rate (PFR), and time-to-peak filling (TPF)] were estimated by volume curve analysis. In 51 (age >or=60 years) of 192 patients, brachial-ankle pulse wave velocity (baPWV) was also measured. RESULTS: The correlation between diastolic parameters PFR and 1/3FF was mild (r = 0.28, P < 0.001). On the basis of EF and PFR, 192 patients were divided into four groups: P (preserved LV function), Q (isolated systolic dysfunction, EF < 50%), R (isolated diastolic dysfunction, PFR < 1.8 EDV/s), and S (both dysfunctions). The numbers of patients in P, Q, R, and S groups were 94 (49.0%), 7 (3.6%), 31 (16.1%), and 60 (31.3%), respectively. The 1/3FF correlated weakly but significantly with age (r = -0.16, P < 0.05). The TPF also correlated weakly with age (r = 0.25, P < 0.01), but EF did not. The baPWV, an indicator of cardiovascular stiffness, correlated inversely with 1/3FF (r = -0.59, P < 0.001) or correlated positively with TPF (r = 0.45, P < 0.001), but not with EF. CONCLUSIONS: Our study suggests that cardiovascular stiffness associated with increased baPWV may contribute to the occurrence of diastolic dysfunction in elderly patients.

Alcohol consumption and coronary artery calcium in middle-aged Japanese men.

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.

Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy.

OBJECTIVES: This study noninvasively examined total creatine (CR) of the myocardium in dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) using proton magnetic resonance spectroscopy ((1)H-MRS). BACKGROUND: Abnormalities in CR metabolism in failing hearts have been reported. A biochemical study suggested that myocardial metabolic changes are very similar in DCM and HCM despite the different heart failure (HF) mechanisms. METHODS: Using cardiac-gated (1)H-MRS with magnetic resonance image (MRI)-guided point-resolved spectroscopy (PRESS) localization, we quantitatively measured septal CR. Patients with either DCM (n = 11) or HCM (n = 7) and age-matched normal subjects (n = 14) were examined. RESULTS: Myocardial CR was significantly lower in DCM patients (16.1 +/- 4.5 micromol/g wet weight [range 10.2 to 22.9], p < 0.05) than that in subjects with normal hearts (27.6 +/- 4.1 micromol/g [range 21.4 to 36.2]). Myocardial CR in HCM patients (22.6 +/- 8.1 micromol/g [range 12.2 to 34.5]) was significantly lower than that in subjects with normal hearts (p < 0.05) but was significantly higher than that in DCM patients (p < 0.05). In 18 patients with either DCM or HCM, myocardial CR correlated positively with left ventricular ejection fraction (LVEF) (y = 0.22x + 9.8, r = 0.73, p = 0.0006) but correlated negatively with plasma B-type natriuretic peptide (BNP) levels (y = -0.012x + 22.4, r = -0.54, p = 0.022). CONCLUSIONS: This study showed that (1)H-MRS can noninvasively detect CR depletion associated with the severity of HF in cardiomyopathy.

Much lower prevalence of coronary calcium detected by electron-beam computed tomography among men aged 40-49 in Japan than in the US, despite a less favorable profile of major risk factors.

BACKGROUND: Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the US and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40-49 in the US and Japan. METHODS: We conducted a cross-sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography. RESULTS: Systolic blood pressure, total cholesterol, low density lipoprotein (LDL)-cholesterol, and smoking rates were higher among the Japanese (122.6 +/- 14.1 versus 113.7 +/- 9.6 mmHg, P < 0.01; 5.72 +/- 0.90 versus 4.99 +/- 0.81 mmol/l (220.9 +/- 34.6 versus 192.8 +/- 31.3 mg/dl), P < 0.01; 3.52 +/- 1.01 versus 3.10 +/- 0.78 mmol/l (136.0 +/- 39.0 versus 119.7 +/- 30.0 mg/dl), P < 0.01; and 48 versus 15%, P < 0.01, respectively). Triglycerides and fibrinogen were similar. High density lipoprotein (HDL)-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score >0 was strikingly lower among the Japanese than the Americans (13% versus 47%, P < 0.01). CONCLUSIONS: Much lower prevalence of coronary calcium despite a less favourable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance.

Left ventricular systolic/diastolic function evaluated by quantitative ECG-gated SPECT: comparison with echocardiography and plasma BNP analysis.

OBJECTIVE: The aim of this study was to evaluate the left ventricular (LV) functional parameters calculated using quantitative electrocardiography (ECG)-gated myocardial perfusion single photon emission computed tomography (QGS). In addition to LV systolic parameters, diastolic parameters were compared with those by ultrasound echocardiography (UCG) and also with plasma B-type natriuretic peptide (BNP) concentrations. METHODS: We examined 46 patients with various forms of heart disease. By the QGS data with 16 framing data acquisition using technetium (Tc)-99m methoxyisobutylisonitrile (MIBI) perfusion, we calculated the following parameters: LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), peak filling rate (PFR), filling rate during the first third of the filling time (1/3FR) and first third filling fraction (1/3FF). By UCG, we measured mitral early to atrial (E/A) wave velocity ratio and pulmonary venous inflow systolic/diastolic (S/D) ratio as diastolic functional parameters. Plasma BNP concentrations were also measured. RESULTS: There was a significant correlation between LVEDV, ESV and EF measured by QGS and UCG (EDV, r = 0.71, p < 0.001; ESV, r = 0.82, p < 0.001; EF, r = 0.75, p < 0.001). The PFR, 1/3FR and 1/3FF obtained by QGS correlated positively with E/A ratio (PFR, r = 0.54, p < 0.001; 1/3FR, r = 0.61, p < 0.001; 1/3FF, r = 0.42, p < 0.01) and negatively with S/D ratio (PFR, r = -0.40, p < 0.01; 1/3FR, r = -0.38, p < 0.05; 1/3FF, r = -0.39, p < 0.01) obtained by UCG. Plasma BNP concentrations in EF < 50% patients were greater than those in EF > or = 50% patients (335.2 +/- 60.2 vs. 101.2 +/- 41.3 pg/ml, p < 0.01, both n = 17). Plasma BNP levels were also compared between higher and lower 1/3FF patients matched for LVEF. Plasma BNP concentrations in 1/3FF < 35% patients were significantly greater than those in 1/3FF > or = 35% patients (312.9 +/- 62.5 vs. 120.5 +/- 32.8 pg/ml, p < 0.05, both n = 14). CONCLUSIONS: The degree of LV systolic and diastolic dysfunctions evaluated by QGS correlated with that by UCG or BNP. The QGS functional parameters offer useful information regarding cardiac failure.

Stiffness and impaired blood flow in lower-leg arteries are associated with severity of coronary artery calcification among asymptomatic type 2 diabetic patients.

OBJECTIVE: To clarify whether stiffness and impaired blood flow in lower-leg arteries are associated with severity of coronary artery calcification among asymptomatic diabetic patients. RESEARCH DESIGN AND METHODS: We enrolled 102 asymptomatic type 2 diabetic patients with no history of cardiovascular complications consecutively admitted to our hospital. Agatston coronary artery calcium (CAC) score, as a marker of coronary artery calcification, was obtained using electron-beam computed tomography. Total flow volume and resistive index, as an index of vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Brachial-ankle pulse-wave velocity (PWV), as an index of distensibility in the lower-extremity arteries, was also measured using an automatic device. RESULTS: When the patients were grouped according to CAC scores of 0-10 (n = 54), 11-100 (n = 25), and > 100 (n = 23), those with the highest scores, which is considered to show possible coronary artery disease, showed the highest brachial-ankle PWV (P < 0.001) and resistive index (P < 0.001) and the lowest total flow volume (P < 0.001) among the groups. Simple linear regression analyses showed that both brachial-ankle PWV (r = 0.508, P < 0.001) and resistive index (r = 0.500, P < 0.001) were positively correlated and total flow volume (r = -0.528, P < 0.001) was negatively correlated with the log-transformed CAC score. Receiver operator characteristic curve analyses indicated that 1,800 cm/s for brachial-ankle PWV, 1.03 for resistive index, and 70 ml/min for total flow volume were diagnostic values for identifying patients with the highest scores. CONCLUSIONS: Quantitatively assessed stiffness and impaired blood flow in lower-leg arteries may help identify diabetic patients with possible coronary artery disease.

Detection of calf muscle alterations in patients with chronic heart failure by P magnetic resonance spectroscopy: Impaired adaptation to continuous exercise.

Previous studies suggested that alteration of systemic skeletal muscle metabolism is a major determinant of exercise tolerance in patients with chronic heart failure (CHF). The authors examined calf muscle metabolism during continuous exercise of the foot in patients with CHF compared with normal subjects using (31)P magnetic resonance spectroscopy. The subjects were patients with New York Heart Association class II CHF who had previously suffered New York Heart Association class IV heart failure. Plantarflexion of the foot was repeated for 8 min 40 s at a rate of one contraction per second against a 2 kg load inside the magnet. At rest, during exercise (divided into the first one-half [EX1] and the latter one-half [EX2]) and at recovery, (31)P magnetic resonance spectroscopy data sets were acquired every 4 min 20 s. At rest, the phosphocreatine to hexamethylphosphoric triamide (PCr:HMPT) and the inorganic phosphate (Pi) to PCr ratios in the CHF group were not different from those in the normal group. During EX1 in the normal group, PCr levels decreased and Pi levels increased. Although exercise continued, these changes improved during EX2, suggesting there was an adaptation to exercise. The degree of change in the PCr:HMPT ratio during EX1 in the CHF group was not significantly different from that during EX1 in the normal group; however, the improvement during EX2 in the CHF group was impaired. The Pi:PCr ratio of EX1 to EX2 in the CHF group was significantly greater than that in the normal group (0.74+/-0.22 versus 0.19+/-0.05, respectively, P<0.005). Thus, in CHF, adaptation to continuous exercise may be impaired by alteration of skeletal muscle metabolism and this alteration may worsen exercise capacity.

High-density lipoprotein particle concentration and subclinical atherosclerosis of the carotid arteries in Japanese men.

OBJECTIVE: The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations. METHODS: We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan. RESULTS: Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P < 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not. CONCLUSION: HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD.

Assessment of myocardial creatine concentration in dysfunctional human heart by proton magnetic resonance spectroscopy.

Creatine depletion in the non-viable infarcted human heart was previously demonstrated with proton magnetic resonance (MR) spectroscopy (1H MRS). In the present study, we assessed total creatine (CR) in human hearts with non-ischemic dysfunctions such as cardiomyopathy. Using cardiac-gated 1H MRS with MR image-guided PRESS localization, we measured septal CR in healthy and diseased human hearts. Fifteen patients with chronic heart failure (CHF, left ventricular ejection fraction < 45%) and 14 age-matched normal subjects were examined. Myocardial CR was significantly (p < 0.001) lower in failing hearts (15.1+/-SD 5.0 micromol/g wet weight, range 8.0-22.9) than in normal hearts (27.6+/-4.1 micromol/g wet weight, range 20.8-36.2). Myocardial CR concentrations in six heart failure patients with plasma B-type natriuretic peptide (BNP) levels of > 200 pg/ml (11.5+/-0.9 micromol/g wet weight, range 9.9-12.3) were significantly lower than those in four heart failure patients with plasma BNP levels of < 200 pg/ml (19.8+/-2.5 micromol/g wet weight, range 17.7-22.9, p < 0.001). Thus, our study showed that myocardial CR was decreased in non-ischemic dysfunctional hearts. Noninvasive measurements of myocardial CR by 1H MRS may be useful in the assessment of the severity of heart failure.

[Electron-beam computed tomography for identification of high-risk persons in primary prevention of coronary heart disease in the United States and its implication for Japan].

Coronary heart disease (CHD) is the leading cause of death in the United States (US). Approximately half of deaths from (CHD) occur out of hospital, most being sudden. The majority of sudden cardiac deaths occur in asymptomatic subjects. Recent lipid-lowering trials in asymptomatic subjects have demonstrated the potential for risk reduction for CHD events by primary prevention. It is, however, generally acknowledged that risk will be underestimated in asymptomatic subjects who fall into the category of intermediate risk by the traditional risk factors. Non-invasive measurements of subclinical atherosclerosis, which is the end result of risk-factor exposure, have the possibility of improving the risk stratification of asymptomatic subjects in intermediate-risk. Electron-beam computed tomography (EBCT) is a non-invasive and highly sensitive means to detect calcification within coronary arterial wall. Coronary artery calcification (CAC) is a recognized marker of atherosclerosis. Atherosclerotic burden of coronary arteries correlates strongly with the amount of CAC measured by EBCT. Studies examining the predictive value of CAC among asymptomatic subjects consistently reported that CAC is a risk for CHD. Two studies reported that unadjusted odds ratios of CAC for CHD were over 20. Incremental value of EBCT over the traditional risk assessment models, however, has not been established. Although CHD mortality in Japan remains uniquely low in industrialized countries, among men aged 30-49, risk factor profiles for CHD are similar between men in the US and Japan, except higher prevalence of cigarette smoking in Japan and higher prevalence of obesity in the US. It is reported that the declining trend in CHD mortality in Japan has recently slowed down in metropolitan areas, especially in men aged 30-49, and that the incidence has increased in middle-aged workers in a metropolitan area. A mortality validation study reported that the differences in CHD mortality between the US and Japan were not as large as suggested by vital statistics. It is, therefore, important to evaluate subclinical atherosclerosis measured by EBCT in men in recent birth cohorts in Japan and compare it to that in men in the US in order to predict future trend in CHD in Japan.

Clinical usefulness of a novel program "Heart Function View" for evaluating cardiac function from gated myocardial perfusion SPECT.

OBJECTIVE: To investigate clinical usefulness of a novel program "Heart Function View (HFV)" for evaluating left ventricular (LV) function from myocardial perfusion SPECT (MPS), we compared LV functional parameters (F(x)) calculated by HFV with those obtained by the other similar programs QGS and cardioGRAF or by ultrasound echocardiography (UCG) and examined their correlations with clinical markers of heart failure: plasma BNP concentrations (BNPs) and exercise capacity. METHODS: Studied patients (n = 60) underwent technetium-99m tetrofosmin quantitative gated MPS including treadmill exercise for examining heart disease. Myocardial stress images were acquired 30 min after the first tracer injection during maximal exercise. Three hours later, the second tracer was injected, and resting images were acquired. LV systolic F(x) [ejection fraction (EF), peak ejection rate (PER)] and diastolic F(x) [first third filling fraction (1/3FF), first third filling rate (1/3FR), peak filling rate (PFR), time to PFR (TPF)] were analyzed, and phase standard deviation (SD) and histogram bandwidth were obtained by phase analysis. RESULTS: LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF obtained from HFV were well correlated with those from QGS, cardioGRAF and UCG. A diastolic parameter Doppler E/e' from UCG was significantly with PFR from HFV. There were good correlations between LVEDV, LVESV, LVEF, PER, PFR, 1/3FR, TPF and 1/3FF from HFV and those from cardioGRAF. LVEF, PER, 1/3FR, and PFR were significantly correlated with plasma BNP concentrations. In patients with non-ischemic heart disease (n = 42), phase SD and histogram bandwidth were correlated negatively with exercise capacity or PFR. CONCLUSIONS: HFV-derived LVF(x) are correlated with LVF(x) from the other programs or UCG, or with the clinical markers of heart failure and are thus useful in the functional assessment for patients with heart disease.

Clinical significance of lung iodine-123 metaiodobenzylguanidine uptake assessment in Parkinson's and heart diseases.

OBJECTIVE: Decreased heart iodine-123 metaiodobenzylguanidine ((123)I-MIBG) uptake [heart-to-mediastinum count ratio (H/M)] is reported in heart disease (HD) or Lewy body disease (LBD). When LBD is merged, therefore, information regarding HD severity may be ambiguous. We aimed to examine whether lung (123)I-MIBG uptake [lung-to-mediastinum count ratio (L/M)] assessment might be useful for differentiating two clinical conditions of HD and LBD, and to investigate whether L/M could reflect the grade of left ventricular (LV) dysfunction. METHODS: Three groups were examined: LBD (patient group with Parkinson's disease or dementia with Lewy bodies, n = 33), PS (group with other Parkinsonian syndromes, n = 20) and HD (group with heart disease). HD consisted of 4 subgroups: HD(I) [H/M(<2.30)-matched group with LBD, n = 34), HD(II) [H/M(≥2.30)-matched group with PS, n = 33], HD(III) [group for functional analysis, LV ejection fraction, first-third and peak filling rates (1/3FR and PFR) and time to PFR were calculated using gated SPECT, n = 35] and HD(IV) (group for examining cardiac prognosis, follow-up period of 1283 ± 506 days, n = 54). Using Doppler echocardiography, a diastolic parameter E/e' and pulmonary artery pressure (ePAP) were estimated. RESULTS: H/Ms did not differ between HD(I) and LBD, or between PS and HD(II). However, L/Ms were increased in the order of LBD, PS, HD(II) and HD(I) groups. In combined LBD, PS, HD(I) and HD(II), L/Ms correlated positively with a diastolic parameter E/e'. L/Ms correlated with ePAP, while H/Ms did not. H/Ms correlated with a systolic parameter EF (r = 0.56) and diastolic parameters 1/3FR (r = 0.51) and PFR (r = 0.51), and L/Ms correlated with diastolic parameters 1/3FR (r = -0.36) and PFR (r = -0.36) but not with EF in HD(III). Kaplan-Meier analysis showed earlier cardiac death in patients with decreased H/Ms, but not in patients with increased L/Ms in HD(IV). CONCLUSIONS: Our study suggest that increased lung (123)I-MIBG uptake is useful as a reference marker for differentiating two clinical conditions of HD and LBD, and can reflect the degree of LV diastolic dysfunction. Elevated ePAP caused by LV diastolic dysfunction may be involved in the mechanism(s) of increased lung uptake.

LOX-1 ligands containing apolipoprotein B and carotid intima-media thickness in middle-aged community-dwelling US Caucasian and Japanese men.

OBJECTIVE: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than LDL cholesterol (LDLC), total LDL particles and usual measurement of oxidized LDL. The association between LAB and intima-media thickness (IMT) of carotid artery was investigated by ultrasound in US and Japan men. METHODS: Participants were 297 US Caucasian and 310 Japanese men, aged 40-49 years without past history of cardiovascular disease. Serum LAB levels were measured by ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. RESULTS: Serum LAB levels [median (interquartile range), µg/L] were 1321 (936, 1730) in US Caucasians and 940 (688, 1259) in Japanese. For Caucasian men, average IMT was higher in higher LAB quartile, which was 0.653, 0.667, 0.688, and 0.702 mm, respectively (p for trend = 0.02). Linear regression analysis showed serum LAB was significantly associated with IMT after adjustment for LDLC or total LDL particles in addition to other traditional or novel risk factors for atherosclerosis such as C-reactive protein. However, there was no significant relationship between LAB and IMT in Japanese men. CONCLUSION: Serum LAB, a new candidate biomarker for residual risk, was associated with an increased carotid IMT in US Caucasian men independently of various risk factors; however, ethnic difference should be clarified in the future.

Agranulocytosis immediately after oral administration of cibenzoline and dabigatran in a patient with paroxysmal atrial fibrillation.

This case report describes agranulocytosis immediately after oral administration of cibenzoline and dabigatran in a 70-year-old woman with paroxysmal atrial fibrillation (AF). No blasts were found in peripheral blood and bone marrow, and the white blood cell count increased abruptly by intravenous administration of granulocyte colony-stimulation factor, suggesting an allergic response caused by cibenzoline or dabigatran, or both. Though antiarrhythmic drugs with anticoagulation therapy are commonly used to treat paroxysmal AF, caution has to be paid to drug-induced agranulocytosis.

Relationship between exercise capacity and cardiac diastolic function assessed by time-volume curve from 16-frame gated myocardial perfusion SPECT.

OBJECTIVE: Echocardiographic studies have suggested an association between diastolic dysfunction and exercise intolerance. The aim of this study was to examine the relationship between exercise capacity and left ventricular (LV) function during stress myocardial scintigraphy, and to investigate whether or not this relationship is caused by ischemia during exercise. METHODS: The studied patients underwent technetium-99m sestamibi quantitative gated SPECT, including treadmill exercise. Myocardial stress images were acquired 30 min after the first tracer injection (370 MBq) during maximal exercise. Three hours later, the second tracer (740 MBq) was injected, and resting images were acquired 30 min after this injection. The presence of ischemia was determined by tracer accumulation. From the same data source, LV diastolic parameters [first third filling fraction (1/3FF), first third filling rate (1/3FR), peak filling rate (PFR) and time to PFR (TPF)], and systolic parameters [ejection fraction (EF), peak ejection rate (PER), time to PER (TPE) and first third ejection fraction (1/3EF)] were analyzed. RESULTS: Subjects with exercise inability (<6 METs) were excluded. In 45 patients, diastolic parameters 1/3FF, 1/3FR, PFR and TPF correlated significantly with exercise duration (r = 0.32*, 0.37*, 0.37* and -0.40(#), respectively; *p < 0.05, (#) p < 0.01), but systolic parameters EF, PER, TPE and 1/3EF did not. At rest, 1/3FF, PFR and PER were significantly increased, suggesting functional deterioration during exercise. Even after 3 h, 1/3FR, PFR and TPF still correlated significantly with exercise duration (r = 0.29*, 0.36* and -0.30*, respectively; *p < 0.05). Such findings were observed even when the 10 patients who exhibited ischemia during exercise were excluded (1/3FR: r = 0.34*; PFR: r = 0.37*; TPF: r = -0.36*; *p < 0.05, n = 35). CONCLUSIONS: Our findings suggested that LV diastolic dysfunction, not systolic dysfunction, is associated with limited exercise capacity independent of the occurrence of ischemia.