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Aims Hypertension is a strong risk factor for heart failure with preserved ejection fraction. Curcumin has p300-specific histone acetyltransferase inhibitory activity, suppresses cardiomyocyte hypertrophy and fibrosis, and significantly reduces myocardial brain natriuretic peptide (BNP) expression without altering blood pressure in a rat model of hypertensive heart disease. This double-blind, placebo-controlled, randomized study, for the first time, aimed to examine the efficacy of a high-absorption curcumin for the prevention of hypertensive heart disease in humans. Methods and results Patients exhibiting initial signs of hypertensive heart disease with left ventricular ejection fraction ≥60% and stable blood pressure Conclusions A high-absorption curcumin agent did not affect the E/E′ ratio, rather it significantly inhibited the increase in plasma BNP levels in patients with initial signs of hypertensive heart disease.

Background: Frailty is a complex clinical syndrome associated with ageing and chronic illness, and is common in heart failure (HF). Vascular endothelial dysfunction including maladaptive angiogenesis and lymphangiogenesis is involved in the pathogenesis of HF, and is also considered to be the causes of frailty. We investigated the association of vascular endothelial growth factor (VEGF) families, central regulators of angiogenesis and lymphangiogenesis, with frailty, and prognostic role of these cytokines in frail HF patients. Methods: We performed a multicenter prospective cohort study to determine the predictive value of VEGF families for prognosis among patients with HF. A total of 1,024 patients (mean age, 75.5 years, 58.7% male) were included in the analyses. Serum levels of VEGF, VEGF-C, VEGF-D, and soluble VEGF receptor-2 (sVEGFR-2) were measured. Frailty was assessed by Canadian Study of Health and Aging Clinical Frailty Scale (CFS). Results: A total of 256 (25.1%) patients had frailty (CFS≥5) at baseline. Frail patients were older, more likely female, and had lower body mass index, higher NYHA class, and higher rates of prior hospitalization for HF, HF with preserved ejection fraction, anemia, cerebrovascular disease, and dementia. N-terminal pro brain natriuretic peptide, high sensitivity troponin I, and high sensitivity C-reactive protein levels were higher in frail patients. During the 2-year follow-up, 211 all cause death occurred. In Kaplan-Maier analysis, frail patients showed significantly higher incidence of all-cause (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.14-5.42). Regarding VEGF families, frail patients had significantly lower levels of sVEGFR-2 and VEGF-C, and higher levels of VEGF-D. Multiple regression analysis revealed that VEGF-C had inverse correlation with CFS (P, 0.03). After adjusting for clinical confounders, a low VEGF-C level was independently associated with all-cause death in frail patients (HR, 0.74; 95%CI, 0.58-0.94 for 1-SD increase), but was not in non-frail patients (HR, 0.87; 95%CI, 0.64-1.14 for 1-SD increase) (P for interaction, 0.09). Conclusions: In HF patients, a low VEGF-C value was associated with frailty and was independent risk for all-cause death in frail patients.

Aims Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR‐2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR‐2 (sVEGFR‐2) levels is associated with poor prognosis in patients with chronic heart failure (HF). Methods and results We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR‐2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all‐cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR‐2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (

Background Metformin is the most widely used oral antihyperglycemic agent for patients with type 2 diabetes mellitus (T2DM). Despite the possible benefits of metformin on diabetes mellitus (DM) and heart failure (HF), acute or unstable HF remains a precaution for its use. Objective The aim of the present prospective randomized controlled trial was to assess whether metformin treatment has beneficial effects on patients with T2DM with hypertension without overt HF. Methods A total of 164 patients (92 males, 72 females; median age 66 years) were included in this study. Patients with T2DM with a history of hypertension were randomized 1:1 to treatment for 1 year with either metformin (metformin-treated group) or other hypoglycemic agents (control group). The primary endpoints were changes in brain natriuretic peptide (BNP) levels, left ventricular (LV) mass index, and indicators of LV diastolic function. We also evaluated changes in both clinical findings and blood laboratory examination data. Results We observed no significant changes between baseline and 1-year post-treatment in LV mass index, BNP levels, or E/e′ (early diastolic transmitral flow velocity/early diastolic mitral annular velocity; an indicator of LV diastolic function) in either the metformin-treated (n = 83) or the control (n = 81) groups. The metformin-treated group had a significant reduction of body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C), but the control group did not. We determined that renal function, including serum creatinine and estimated glomerular filtration rate, deteriorated significantly in the control group but not in the metformin-treated group. Conclusion LV mass and diastolic function were not affected after 1 year of metformin treatment in patients with T2DM. However, we observed benefits in terms of reductions in both BMI and LDL-C levels and preservation of renal function. Trial Registration UMIN000006504. Registered 7 October 2011.

Background: High circulating levels of galectin-3 are associated with all-cause mortality, cardiovascular (CV) mortality, and/or major adverse CV events (MACE) in patients with CV diseases such as heart failure and coronary artery disease (CAD). However, the impact of sex on the prognostic value of galectin-3 in patients with suspected or known CAD remains unclear. Methods: Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the impact of sex on the association between galectin-3 levels and the risks of all-cause death, CV death, and MACE defined as a composite of CV death, nonfetal myocardial infarction, and nonfetal stroke. Galectin-3 was measured in 1624 men and 794 women enrolled in the ANOX Study. Patients were followed up over 3 years. Results: The mean ages (standard deviations) were 69.8 (10.6) years in men and 72.2 (9.9) years in women ( P P =0.004). In the entire patient cohort, the galectin-3 level was significantly associated with all-cause death (hazard ratio per 1 standard deviation increase [HR], 1.28; 95% confidence interval [CI], 1.16-1.42), CV death (HR, 1.24; 95% CI, 1.04-1.46), and MACE (HR, 1.24; 95% CI, 1.09-1.41) after adjusting for potential clinical confounders. These associations were still significant in women (HR for all-cause death, 1.59; 95% CI, 1.26-1.98; HR for CV death, 1.53; 95% CI, 1.06-2.21; HR for MACE, 1.61; 95% CI, 1.21-2.09), whereas in men, galectin-3 was significantly associated with all-cause death (HR, 1.23; 95% CI, 1.08-1.39), but not with CV death (HR, 1.14; 95% CI, 0.93-1.40) or MACE (HR, 1.15; 95% CI, 0.99-1.35). Furthermore, galectin-3 provided incremental prognostic information for all-cause death, but not for CV death or MACE, to the model with potential clinical confounders and the established CV biomarkers in the entire cohort and in women, but not in men. Conclusions: We identified a significantly stronger prognostic value of galectin-3 in women than in men among patients with suspected or known CAD.

Background: Smoking is a risk factor for mortality in the general population and in patients with coronary artery disease (CAD). Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors. Recently, we demonstrated that circulating VEGF-D levels are associated with the risk of mortality in patients with suspected or known CAD. However, whether VEGF-D levels differ according to smoking status and whether smoking modifies the relationship between VEGF-D and mortality in those patients are unknown. Methods: Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the association between smoking status and VEGF-D and the impact of smoking status on the association between VEGF-D levels and the risk of all-cause death. VEGF-D was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study. Patients were followed up over 3 years. Results: The mean age (standard deviation [SD]) of the patients was 70.6 (10.4) years; 67.2% were men. Current smokers exhibited significantly higher levels of VEGF-D compared to former smokers and never smokers (median [interquartile range], 343 [214-556], 312 [201-500], 291 [182-485] pg/mL, respectively; P =0.006). Stepwise multiple linear regression analysis revealed that the log-transformed VEGF-D level was independently associated with current smoking ( P =0.002), but not with former smoking. After adjusting for potential clinical confounders, the VEGF-D level was significantly associated with all-cause death in never smokers (hazard ratio per 1-SD increase [HR], 1.31; 95% confidence interval [CI], 1.10-1.55) and in former smokers (HR, 1.22; 95% CI, 1.08-1.37), but not in current smokers (HR, 0.92; 95% CI, 0.65-1.22). Furthermore, VEGF-D provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in former smokers or in current smokers. Conclusions: Current smoking was independently associated with higher levels of VEGF-D. The prognostic value of VEGF-D on mortality was most pronounced in never smokers among patients with suspected or known CAD.

Introduction: Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) acts as an endogenous inhibitor of VEGF, a key regulator of angiogenesis and lymphoangiogenesis. However, little is known about the critical role of sVEGFR-2 in heart failure (HF). Methods: We performed a multicenter prospective cohort study (PREHOSP-CHF Study) to determine the predictive value of sVEGFR-2 for major adverse cardiovascular (CV) events (MACE) among patients with chronic HF (CHF). A total of 1,021 patients were included in the analyses. The mean age (SD) was 75.5 (12.6) years. 59.6% were male. The primary outcome was MACE defined as a composite of CV death or HF hospitalization. The secondary outcomes were all-cause death and CV death. Serum levels of sVEGFR-2 were determined employing specific enzyme-linked immunosorbent assays. Results: The patients with lower sVEGFR-2 concentrations were older, and had higher rates of female sex, atrial fibrillation and anemia. The baseline sVEGFR-2 level was inversely correlated with left ventricular ejection fraction, and was positively correlated with the body mass index. During the median follow-up of 730 days, a total of 210 (20.6%) all-cause deaths, 99 (9.7%) CV deaths and 308 (30.2%) HF hospitalizations occurred. Unadjusted Cox proportional hazard analyses revealed that the patients with the lowest quartile (Q1) of sVEGFR-2 did not show a significantly higher risk of MACE (p=0.7), but showed the greatest risks of CV death (p=0.003) and all-cause death (p=0.007). Even after adjusting for established risk factors and CV biomarkers (N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein), those with the Q1 of sVEGFR-2 exhibited the greatest risk of CV death (p=0.02; hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.17-3.66 [vs. Q2]; HR, 2.42; 95%CI, 1.30-4.68 [vs. Q3]; HR, 1.52; 95%CI, 0.80-2.99 [vs. Q4]), but not that of all-cause death. The sex-stratified analyses revealed that the association between sVEGFR-2 and CV death was still significant in men, but not in women (p for interaction, 0.07). Conclusions: A low sVEGFR-2 value was not associated with MACE, but was independently associated with CV mortality among patients with CHF.

Background: The impact of chronic kidney disease (CKD) on the association of cardiovascular (CV) and renal biomarkers with the presence and severity of coronary artery disease (CAD) in patients with suspected CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 2324 patients with suspected but no history of CAD undergoing elective coronary angiography, we assessed the impact of CKD on the association of CV and renal biomarkers with the presence and severity of CAD. Heparin-free fasting serum levels of soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), VEGF, placental growth factor (PlGF), N-terminal pro-brain natriuretic peptide (NT-proBNP), contemporary sensitive cardiac troponin-I (cTnI), high-sensitivity CRP (hs-CRP), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured in 887 CKD and 1437 non-CKD patients enrolled in the EXCEED-J study. The severity of CAD was quantified using the Gensini score. Results: The mean age (standard deviation) of the patients was 69.8 (10.8) years; 65.6% were men. Serum levels of all biomarkers except PlGF were significantly higher in CKD than in non-CKD patients. In the entire patient cohort, only natural log-transformed (Ln-) cTnI was significantly associated with CAD, multi-vessel or left main trunk disease (MVD/LMTD), and Ln-Gensini score after adjustment for potential confounders. These associations were still significant in non-CKD, but not in CKD: Ln-cTnI was significantly associated with MVD/LMTD and Ln-Gensini score, but not with CAD. Stepwise regression analyses including potential confounders and all biomarkers revealed that Ln-cTnI was independently associated with CAD, MVD/LMTD, and Ln-Gensini score in the entire cohort and in non-CKD, but not in CKD: Ln-cTnI was independently associated with MVD/LMTD and Ln-Gensini score, but not with CAD. No other biomarker exhibited an independent association with CAD, MVD/LMTD, or Ln-Gensini score in the entire cohort, in non-CKD, or in CKD. Conclusions: Among CV and renal biomarkers measured in this study, only Ln-cTnI was independently associated with the presence and severity of CAD in patients with suspected CAD. These associations were attenuated in patients with CKD.

Background: Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating growth differentiation factor 15 (GDF-15) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether GDF-15 levels differ according to the diabetic status and whether DM modifies the relationship between GDF-15 and mortality in patients with stable CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between diabetic status and GDF-15 and the impact of DM on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 797 DM and 663 non-DM patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with DM exhibited significantly higher levels of GDF-15 compared to those without DM (median [interquartile range], 1472 [1049-2258] vs. 1274 [868-1874] pg/mL, respectively; P P Conclusions: Higher levels of GDF-15 were independently associated with DM in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with DM.

Background: Growth differentiation factor 15 (GDF-15) is a stress responsive cytokine of the transforming growth factor superfamily. Circulating levels of GDF-15 are elevated in various conditions including anemia and stable coronary artery disease (CAD), and associated with the risk of mortality in patients with stable CAD. However, whether anemia modifies the relationship between GDF-15 and mortality in patients with stable CAD is unknown. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between anemic status and GDF-15 and the impact of anemia on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 564 anemic and 896 non-anemic patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with anemia exhibited significantly higher levels of GDF-15 compared to those without anemia (median [interquartile range], 1953 [1302-3110] vs. 1175 [838-1579] pg/mL, respectively; P P Conclusions: Higher levels of GDF-15 were independently associated with anemia in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with anemia.

Background Whether circulating growth differentiation factor 15 (GDF‐15) levels differ according to smoking status and whether smoking modifies the relationship between GDF‐15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF‐15 and the impact of smoking status on the association between GDF‐15 and all‐cause death. GDF‐15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF‐15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log‐transformed GDF‐15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF‐15 level was significantly associated with all‐cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF‐15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF‐15. The prognostic value of GDF‐15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

ObjectiveTo establish a simple screening method for diabetes based on myoinositol (MI) in urine samples collected at home.Research design and methodsInitially, we evaluated the stability of urinary MI (UMI) at room temperature (RT; 25°C) and 37°C in 10 outpatients with type 2 diabetes. We then enrolled 115 volunteers without a current or history of diabetes. In all subjects, glucose intolerance was diagnosed by 75 g oral glucose tolerance test (75gOGTT). To assess the association between UMI or urine glucose (UG) and plasma glucose (PG), urine samples were also collected at 0 and 2 hours during 75gOGTT. All the subjects collected urine samples at home before and 2 hours after consuming the commercially available test meal. UMI levels at wake-up time (UMIwake-up), before (UMIpremeal) and 2 hours after the test meal (UMI2h-postprandial) were measured using an enzymatic method. ΔUMI was defined as UMI2h-postprandial minus UMIpremeal.ResultsDiffering from UG, UMI was stable at RT and 37°C. UMI was increased linearly along with an increase in PG, and no threshold for UMI was observed. UMI was closely associated with blood glucose parameters obtained from a 75gOGTT and hemoglobin A1c (HbA1c) at hospital after adjustment for age, sex, body mass index and serum creatinine. UMIwake-up, UMIpremeal, UMI2h-postprandial and ΔUMI at home were higher in diabetic subjects than non-diabetic subjects even after the above adjustment. Receiver operating characteristics curve (ROC) analyses revealed that for the screening of diabetes, the area under the curve for ROC for UMI2h-postprandial and ΔUMI (0.83 and 0.82, respectively) were not inferior to that for HbA1c ≥48 mmol/mol, which is the American Diabetes Association (ADA) criteria for diabetes.ConclusionsMI measurement in urine samples collected at home before and after the meal would be a simple, non-invasive and valuable screening method for diabetes.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor‐C ( VEGF ‐C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF ‐C. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF ‐C levels were significantly and inversely associated with all‐cause death (hazard ratio for 1‐ SD increase, 0.69; 95% confidence interval, 0.60–0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53–0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72–1.01). Even after incorporation of N‐terminal pro‐brain natriuretic peptide, contemporary sensitive cardiac troponin‐I, and high‐sensitivity C‐reactive protein into a model with established risk factors, the addition of VEGF ‐C levels further improved the prediction of all‐cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF ‐C value may independently predict all‐cause mortality.

Postcardiac injury syndrome (PCIS) occurs following a pericardial or myocardial injury. On the other hand, PCIS following cardiac catheter intervention is rare and can be difficult to diagnose because of its delayed onset. A 24-year-old man underwent radiofrequency ablation (RFA) for paroxysmal atrial fibrillation and suffered from general fatigue and left-sided pleural effusion three months after the procedure. His symptoms and effusion were effectively treated within a month by administrating nonsteroidal anti-inflammatory drugs. However, seven months later, he developed left-sided chest pain and low-grade fever. Computed tomography showed a thickening of the parietal pleura and reccurence of the pleural effusion. Pleural biopsy by video-assisted thoracoscopy demonstrated chronic pleuritis with a non-necrotizing granulomatous reaction. Given the previous RFA, and in the absence of infection or malignant disease, he was diagnosed with PCIS and treated with colchicine.

BACKGROUND In patients who have atrial fibrillation (AF) with CHADS2score of 0-1 (categorized as low-to-intermediate risk), there is little information on stratifying the risk of stroke. This study aimed to determine whether impaired endothelial function assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT) predicted left atrial blood stagnation in these patients. METHODS AND RESULTS We enrolled 81 consecutive patients with nonvalvular AF. The reactive hyperemia index (RHI) was measured using RH-PAT. Transesophageal echocardiography was performed to determine spontaneous echo contrast (SEC) before direct-current cardioversion or radiofrequency catheter ablation. SEC was found in 49 patients (60%). The RHI was significantly lower in patients with than without SEC. Multivariate analysis demonstrated that RHI was one of the independent determinants of SEC (OR per 0.1, 1.26; 95% CI, 1.11-1.49; P=0.002) in all patients. In addition, RHI was a significant determinant of SEC (AUC, 0.73; 95% CI, 0.63-0.89; P=0.0017) in patients with low-to-intermediate risk. At an RHI cut-off

Aims Several studies have demonstrated that type 2 diabetes mellitus (T2DM) is associated with accelerated atherosclerosis, which results in an increased risk of coronary vascular events. However, serial changes in plaque characteristics have not been reported in vivo . We evaluated the progression of coronary atherosclerosis in patients with T2DM using an integrated backscatter intravascular ultrasound (IB-IVUS) examination. Methods and results Forty-two T2DM and 48 non-diabetic patients who underwent percutaneous coronary intervention were enrolled in the study. Non-culprit 20-mm length coronary lesions with mild-to-moderate stenosis were measured using a 40-MHz (motorized pullback of 0.5 mm/s) IVUS catheter. IVUS examinations were performed on one target lesion in each patient. Six months later, a follow-up IVUS examination was repeated in the same coronary segment imaged at the baseline examination. T2DM patients demonstrated a greater total plaque volume (TPV; 139 ± 53 vs. 114 ± 45 mm3, P = 0.02) and total lipid volume (TLV; 67 ± 26 vs. 55 ± 30 mm3, P = 0.039) at the baseline examination. The progression of TPV (8.6 ± 15.4 vs. −2.2 ± 16.0%, P < 0.01) and TLV (10.8 ± 28.8 vs. −2.5 ± 20.0%, P < 0.05) from the baseline was observed in T2DM patients, but not in non-diabetic patients. The increase in TLV was blunted in T2DM patients who achieved HbA1c levels of

Background The aim of this study was to investigate the differences in left ventricular (LV) twisting behavior between patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD). Methods Forty-four patients with HCM (mean age, 63±15years), 35 patients with HHD (mean age, 63±13years) and 20 age and sex-matched control subjects were evaluated. After a standard echocardiographic examination, LV twist and twisting velocity profiles from apical and basal short-axis images were analyzed using two-dimensional speckle tracking imaging. Results LV diastolic and systolic dimensions, and ejection fraction were not significantly different among the groups. LV mass index and early diastolic mitral annular velocity were not significantly different between the HCM and HHD groups. The peak torsion in the HCM and HHD groups was significantly greater than that in the control group. The peak untwisting velocity in the HCM group was comparable with that in the control group. However, when the peak untwisting velocity was corrected by peak torsion, this ratio was significantly decreased in the HCM group compared with the values in the HHD and control groups. The time to peak untwisting velocity in the HCM group was significantly longer than the values in the HHD and control groups. Conclusions These results suggest that enhanced peak torsion in HCM may improve untwisting behavior, but this mechanism fails to fully compensate for impaired untwisting behavior compared with HHD.

Background: Right ventricular (RV) pacing alters left ventricular (LV) mechanical activation, resulting in adverse impacts on LV function. This study was aimed to investigate the acute effect of RV apical (RVA) and septal pacing (RVS) on LV dyssynchrony and function using speckle tracking echocardiography. Methods and Results: The 103 patients (749 years) with symptomatic bradyarrhythmia and preserved LV ejection fraction, and 50 age-matched control subjects were studied. All patients received a permanent pacemaker and were randomly assigned into 2 groups (RVA: n=51, RVS: n=52). After insertion, patients underwent an echocardiographic study during RV pacing. LV dyssynchrony and global strain parameters were analyzed using speckle tracking echocardiography. The QRS width and dyssynchrony indices by longitudinal and radial strain were significantly greater in RVA than in both the control and RVS. The LV longitudinal dyssynchrony index was significantly related to global longitudinal strain (GLS) among 103 patients receiving RV pacing (R2=0.25, P

Augmentation index (AI), brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) are available for the assessment of arterial stiffness in clinical practices. However, influences of meal intake on these indices are still poorly understood. The aim of this study is to elucidate the effects of daily meal intake on pulse wave indices in patients with type 2 diabetes. We studied 17 patients with type 2 diabetes. AI was measured at fasting, 60 and 120 min after a commercial mixed meal (500 kcal) intake. The baPWV and CAVI were measured at fasting and 80-100 min after meal intake. All pulse indices decreased significantly after meal intake (AI, 89.3+/-9.7% to 77.9+/-9.4%, 82.0+/-8.4%, P

SummaryWe describe the case of a 59-year-old male. His first percutaneous coronary intervention (PCI) using a bare metal stent was performed for a 90% stenosis in the mid portion of the left anterior descending artery (LAD). However, we performed re-PCI because in-stent restenosis developed during a chronic stage. After the first dilatation of the restenotic lesion, using a cutting balloon, the stenosis at the ostium of the septal branch, which takes off from the stent strut, became exacerbated. Therefore, after selective guidewire insertion to the septal branch, we performed balloon inflation. Unfortunately, a coronary dissection and perforation developed in the septal branch and a coronary arteriovenous shunt was also formed. Additional inflation for in-stent restenosis with a perfusion balloon provided successful occlusion of the ostium of the septal branch and the shunt flow disappeared. After careful re-selection of a guide wire into the septal branch, the perforated portion was then dilated using a small-sized conventional balloon. Finally, reperfusion of the septal branch was accomplished without any angiographic sign of coronary dissection, perforation or shunt. We herein report a rare case of coronary arteriovenous shunt formation due to the dissection and perforation of a coronary artery.

Objective The study objective was to compare the left ventricular (LV) dyssynchrony and torsional behavior between right ventricular apical (RVA) and right ventricular septal (RVS) pacing. Methods Forty-six patients with symptomatic sick sinus syndrome and preserved LV function were assigned to 2 groups: RVA (n = 23) and RVS (n = 23). Echocardiographic study including two-dimensional speckle tracking imaging was performed in the AAI and DDD modes. Results Mean QRS width during DDD mode was significantly longer with RVA pacing than with RVS pacing. Dyssynchrony, torsion, and untwisting rate during DDD mode were significantly worse with RVA than with RVS pacing. In patients with RVA pacing, there was an increase in longitudinal dyssynchrony from AAI to DDD mode that significantly correlated with the deterioration of untwisting rate. Conclusion In bradyarrhythmic patients with preserved LV function, RVS pacing resulted in a reduced LV dyssynchrony and better torsional behavior than RVA pacing.

The aim of this study was to investigate the relationship between postprandial remnant-like particle (RLP) metabolism and insulin resistance (IR). The study group consisted of 52 randomly selected subjects. To evaluate postprandial hyperlipidemia, serum lipid and lipoprotein concentrations during fasting and 4h after the fat-loading test were measured in each subject. IR was assessed using the index of homeostasis model assessment (HOMA-R). The subjects were divided into two groups according to the value of HOMA-R: an IR group (n=17) with a HOMA-R value >/=1.73, and a normal (NR) group (n=35) with a HOMA-R value

Although beta-blockers can not be used for the treatment of vasospastic angina, the effect of beta-blockers with vasorelaxant property on coronary vasospasm remains uncertain. In this study, we evaluated the effect of betaxolol, a new beta-blocker with calcium antagonistic property, as an additional therapy on vasospastic angina (VSA) with anginal attacks on effort. We enrolled 12 patients with VSA and anginal attacks with ST segment depression during exercise stress test. All patients received 1.25-5 mg of betaxolol for 3 months. Treadmill exercise stress test and adenosine triphosphate stress thallium-201 myocardial scintigraphy were performed before and 3 months after the onset of the betaxolol treatment. The other drugs including calcium antagonists, nitrates and nicorandil were continued. No patients experienced the exacerbation of angina during the betaxolol treatment. Exercise time to chest pain (317.5+/-72.1-454.2+/-75.5 s, P

We examined the effects of cilostazol on impaired coronary arterial responses in patients with vasospastic angina (VSA). Thirty patients who were diagnosed with VSA based on an acetylcholine provocation test and 10 subjects with normal coronary arteries were enrolled. The patients were divided into the following 3 groups: no antiplatelet agent treatment group, aspirin treatment, or cilostazol treatment groups. Coronary flow reserve (CFR), coronary flow volume at maximum hyperemia, and epicardial coronary artery diameter after administration of N(G)-monomethyl-L-arginine (L-NMMA) were examined using a Doppler flow wire before and 6 months after the start of this study. CFR, coronary flow volume at maximum hyperemia, and diameter changes by L-NMMA were significantly increased in the cilostazol treatment group compared with the other 2 groups. In conclusion, cilostazol increased CFR and flow-dependent coronary dilation; these changes were attributable to nitric oxide. Cilostazol may improve coronary vascular endothelial dysfunction and coronary hemodynamics in patients with VSA.

Purpose: HGF, one of endothelium-specific growth factors, might contribute to the repair process of vascular endothelial cell damage, suggesting that serum HGF concentration may be elevated in patients with arteriosclerosis. However, the cardiac metabolism of HGF has not been examined in patients with coronary artery disease (CAD). We examined the levels of hepatocyte growth factor (HGF) in the coronary circulation and its correlation with the severity of arteriosclerosis in patients with CAD. Methods: We measured serum HGF concentration obtained from the coronary sinus (CS) and ascending aorta (AA) in patients with atherosclerotic CAD (Group E, n = 33) or vasospastic angina (Group V, n = 26), or normal control subjects (Group N, n = 12). In Group E, the severity of coronary artery stenosis was evaluated using the Gensini's score. Results: Serum HGF concentrations (ng ml) in the CS were 0.112 ± 0.008 in Group E (p < 0.001 vs. Group V, p < 0.001 vs. Group N), 0.197 ± 0.012 in Group V (p = 0.031 vs. Group N), and 0.245 ± 0.021 in Group N. Serum HGF concentrations in the AA were 0.282 ± 0.014 in Group E (p = 0.045 vs. Group V, p = 0.021 vs. Group N), 0.246 ± 0.012 in Group V, and 0.237 ± 0.009 in Group N. Serum HGF extraction in the heart (HGF in the AA-HGF in the CS) in Group E (0.170 ± 0.018) was significantly higher compared with in Group V (0.049 ± 0.011) or Group N (0.008 ± 0.005). There was a significant negative correlation between the severity of coronary arteriosclerosis and serum HGF concentration in CS (r = −0.66, p < 0.001), and a significant positive correlation between the severity of coronary arteriosclerosis and HGF extraction in the heart (r = 0.75.p < 0.001). Conclusions: We conclude that the difference of HGF levels between CS and AA in patients with CAD are decreased, and extent of decreases in HGF levels correlates with the severity of coronary arteriosclerosis. The abnormality of HGF metabolism in the heart may contribute to the progression of coronary arteriosclerosis.

Evidence is increasing for small vessel remodeling and disturbance of endothelium-dependent vasodilation in diabetic patients. Insulin increases vascular wall thickening and produces endothelial dysfunction. Troglitazone, a new insulin-sensitizer antidiabetic agent, is considered to reduce plasma insulin level and the present study assessed its effect on the coronary circulation of the patients with non-insulin-dependent diabetes mellitus (NIDDM). Analysis of the myocardial washout rate with adenosine triphosphate-stress thallium-201 scintigraphy was used to estimate coronary circulation, and for estimation of insulin sensitivity, the homeostasis model insulin resistance index (HOMA-R) was calculated. Patients were treated with monotherapy of either troglitazone (200 mg bid, n=12) or glibenclamide (2.5 mg daily, n=12) for 3 months. Age-, sex- and risk factors-matched subjects without NIDDM were employed as a control. Fasting plasma glucose and hemoglobin A1c were similarly decreased by troglitazone or glibenclamide. Plasma insulin level (pmol/L) decreased from 66.6±10.8 to 39.0±7.2 with troglitazone, but was unchanged by glibenclamide (58.8±7.2 to 66.0±10.8). The diabetic groups had a significantly lower washout rate than controls, which was improved by troglitazone, but not by glibenclamide. In addition, the increase in washout rate correlated significantly with the decrease in HOMA-R in the troglitazone group. In conclusion, troglitazone can restore coronary circulation by improving insulin resistance in patients with NIDDM. (Jpn Circ J 2001; 65: 487 - 490)

The present study examined the ability of dual-chamber (DDD) pacing to improve symptoms and exercise tolerance in patients with non-obstructive hypertrophic cardiomyopathy (HNCM). Seven patients with HNCM who had failed to benefit from pharmacotherapy participated in the study. The New York Heart Association (NHYA) functional class status and exercise tolerance, which was determined by the treadmill exercise test, were recorded and an echocardiographic observation was performed before, and 1 week, 3 months and 1 year after the implantation of a permanent DDD pacemaker. The atrioventricular delay (AVd) was determined by measuring the point of peak rapid filling velocity and maximum cardiac output (CO). Two patients were not implanted with a permanent pacemaker because their CO and blood pressure decreased or because palpitation occurred during temporary pacing. The ratio between early and late peaks of flow velocity (1.56, 1.21,0.95, and 0.86 before implantation and 1 week, 3 months and 1 year after implantation, respectively); deceleration time (ms: 263.2, 217.6, 204.6, 187.0); peak filling rate (ml/s: 146.2, 204.0, 233.2, 243.6); NYHA functional class status (2.0, 1.8, 1.6, 1.4); and exercise tolerance (s: 203, 264, 403, 480) were significantly improved after implantation. However, left ventricular dimension, percent fractional shortening, ejection fraction, acceleration time and the isovolumic relaxation time were not changed significantly. In conclusion, DDD pacing improved symptoms and the NYHA functional class status, which is associated with improvement of left ventricular diastolic function. It is proposed that DDD pacing would be useful in patients not only with obstructive but also non-obstructive hypertrophic cardiomyopathy refractory to medical treatment, depending on the careful selection of subjects.

In hypertensive patients, the relationships between glucose tolerance and left ventricular hypertrophy (LVH) and left ventricular diastolic function (LVDF) have been described in several reports.In this study, we examined the relationships between insulin resistance and LVH and LVDF in hypertensive patients from the therapeutic perspective.The study participants were essential hypertensive patients with impaired glucose tolerance (IGT-HT, n = 26), hypertensive patients with normal glucose tolerance (NGT-HT, n = 39), and normotensive control individuals (n = 18). Insulin resistance was evaluated by the insulin suppression test by use of the steady-state plasma glucose (SSPG) level. Left ventricular mass index (LVMI) and LVDF, which was determined by the E:A ratio, were estimated by echocardiography. Temocapril, an angiotensin-converting enzyme inhibitor, was administered in an open, non-randomized manner with a mean dose of 2.8+/-0.2 mg/ day, and the mean administration period was 18 weeks. The systolic and diastolic blood pressure, the LVMI, and the SSPG level were significantly higher in the hypertensive patients than in the control individuals. The mean systolic and diastolic blood pressures were significantly decreased by treatment with Temocapril. Before treatment, stepwise regression analysis showed that SSPG is an independent predictor for LVMI and LVDF. After treatment, the changes in LVMI (D-LVMI; %) (-15.1+/-1.5), the changes in LVDF (D-E:A; %) (-38.2+/-4.1), and the changes in insulin resistance (D-SSPG; %) (-13.7+/-1.7) were significantly higher in the IGT-HT group than in the NGT-HT group (-11.4+/-1.1, -18.1+/-1.7, -9.4+/-1.4, respectively), and the D-SSPG was an independent predictor for D-LVMI and D-E :A.The results of this study indicate that insulin resistance is an important factor affecting LVH and LVDF.

The present study was conducted to assess the preventive effect of combined treatment with probucol, an antioxidant, and cilostazol, a phosphodiesterase inhibitor, against poststenting restenosis. Study patients were randomized to 4 modality groups 1 week before stenting: control, probucol (500 mg/day), cilostazol (200 mg/day), and probucol plus cilostazol. Treatment on these modalities was conducted from 5 prestent days until the poststenting follow-up evaluation (6 poststenting months). All patients received aspirin (81 mg/day). The efficacy of each modality against restenosis was evaluated in a total 126 patients with 165 coronary arterial lesions, using a quantitative method. The decrease in luminal diameter at the poststenting follow-up was 1.04 +/- 0.57 mm for controls, 0.88 +/- 0.82 mm for those taking probucol, 0.61 +/- 0.59 mm for those taking cilostazol (p

Recent studies have demonstrated that both insulin resistance (IR) and diabetes were the critical risk factors of heart failure (HF). Importantly, it is reported the high prevalence of previously unknown left ventricular dysfunction including the prevalence of HF preserved EF (HFPEF) in diabetic subjects. However, the underlying mechanism and a biomarker have not been well defined. To identify underlying mechanism and candidate biomarker of HF in subjects with type 2 diabetes (T2DM), we performed retrospective study of 143 T2DM and 181 non-diabetic subjects. We evaluated cardiac function by echocardiography measuring left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi) and the ratio of early transmitral flow velocity to tissue doppler early diastolic mitral annular velocity (E/e’). Here we demonstrate that plasma soluble insulin receptor (sIR), a novel biomarker of diabetes, was associated with left ventricular hypertrophy (LVH) and cardiac-dysfunction. Simple regression analysis revealed that circulating sIR was positively correlated with fasting glucose and negatively correlated with fasting insulin. Furthermore, sIR was positively correlated with LVMi and E/e’, and inversely correlated with LVEF ( R =0.25; p R =0.22, p =0.03, R =-0.19; p =0.02, respectively). Moreover, multivariable regression analysis revealed that sIR was associated with LVMi, E/e’ and LVEF after adjustment for age, gender, BMI, plasma fasting glucose, systolic blood pressure, and eGFR in subjects with T2DM ( β = 0.26; p β =0.25; p =0.02, β =-0.23; p

BACKGROUND: The aim of this study was to investigate the correlation of the qualitative transmural extent of hypoperfusion areas (HPA) using stress dynamic whole-heart computed tomography perfusion (CTP) imaging by 256-slice CT with CTP-derived myocardial blood flow (MBF) for the estimation of the severity of coronary artery stenosis. METHODS AND RESULTS: Eleven patients underwent adenosine triphosphate (0.16 mg/kg/min, 5 min) stress dynamic CTP by 256-slice CT (coverage: 8 cm, 0.27 s/rotation), and 9 of the 11 patients underwent coronary angiography (CAG). Stress dynamic CTP (whole-heart datasets over 30 consecutive heart beats in systole without spatial and temporal gaps) was acquired with prospective ECG gating (effective radiation dose: 10.4 mSv). The extent of HPAs was visually graded using a 3-point score (normal, subendocardial, transmural). MBF (ml/100g/min) was measured by deconvolution. Differences in MBF (mean ± standard error) according to HPA and CAG results were evaluated. In 27 regions (3 major coronary territories in 9 patients), 11 coronary stenoses (> 50% reduction in diameter) were observed. In 353 myocardial segments, HPA was significantly related to MBF (P < 0.05; normal 295 ± 94; subendocardial 186 ± 67; and transmural 80 ± 53). Coronary territory analysis revealed a significant relationship between coronary stenosis severity and MBF (P < 0.05; non-significant stenosis [< 50%], 284 ± 97; moderate stenosis [50-70%], 184 ± 74; and severe stenosis [> 70%], 119 ± 69). CONCLUSION: The qualitative transmural extent of HPA using stress whole-heart dynamic CTP imaging by 256-slice CT exhibits a good correlation with quantitative CTP-derived MBF and may aid in assessing the hemodynamic significance of coronary artery disease.

BACKGROUND The interventricular septum in hypertrophic cardiomyopathy (HC) has a unique shape, which is characterized by the convex curvature toward the left ventricle (LV). The aim of this study was to examine the relationship between curvature of the LV wall and regional myocardial strain. METHODS AND RESULTS Fifty-six patients with HC (mean age, 55±12 years) and 20 age- and sex-matched control subjects (mean age, 56±8 years) were enrolled. The curvature index (1/radius) was measured by drawing along the endocardial surface from the apical 4-chamber and short axis views. Peak systolic strain was calculated in the septal and lateral walls using 2-D speckle tracking echocardiography. The septal curvature index and septal longitudinal strain were significantly lower in the HC group than in the control group. A multivariate model using the HC patient data showed that the septal curvature index and septal thickness were the independent determinants of septal longitudinal strain (septal curvature index: β=-0.421, P

A case of renovascular hypertension with localized ischemia in the left kidney is described. The captopril test and renography showed a pattern typical of renin-dependent unilateral renovascular hypertension. However, renal arteriography did not show stenosis of the renal artery. Enhanced and dynamic computed tomography revealed ischemia in the dorsal portion of the left kidney and an aortic dissection with thrombosis, suggesting obstruction of the supplemental renal artery of double renal arteries. The localized renal ischemia was attributed to insufficient blood supply from the main renal artery to the obstructed area.(Hypertens Res 1993; 16: 221-224)

The aim of this study was to investigate the relationship between late gadolinium enhancement (LGE) and the effect of cibenzoline (CBZ) on left ventricular (LV) diastolic function in hypertrophic cardiomyopathy (HCM) patients. Echocardiography before and after intravenous CBZ (1.4 mg/kg over 5 minutes) and magnetic resonance imaging (MRI) were performed in 22 consecutive patients with HCM [mean age: 65 ± 14 years, obstructive HCM: 14, nonobstructive HCM (HNCM): 8]. The extent of LGE (%LGE = LGE volume/total LV volume) was obtained by contrast-enhanced MRI using custom software. LGE was observed in 19 patients (mean %LGE = 5.1% ± 3.9%). The propagation velocity of LV early filling flow (Vp) increased significantly in patients with obstructive HCM (26 ± 7 to 36 ± 14 cm/s, P = 0.001) and nonobstructive HCM (25 ± 9 to 36 ± 16 cm/s, P = 0.007). A significant negative correlation was observed between the change in Vp and %LGE in patients with HCM (r = 20.542, P = 0.009). Less extensive myocardial fibrosis, as demonstrated by LGE on contrast-enhanced MRI, may predict the ability of CBZ to improve LV diastolic function in HCM.

Appropriate blood vessel function is important to cardiovascular health. Adipose tissue plays an important role in metabolic homoeostasis, and subcutaneous abdominal ATBF (adipose tissue blood flow) is responsive to nutritional stimuli. This response is impaired in obesity, suggesting parallels with endothelial function. In the present study, we assessed whether regulation of ATBF is related to the regulation of endothelial function, assessed by FMD (flow-mediated vasodilatation) of the brachial artery. Impaired FMD is a marker of atherosclerotic risk, so we also assessed relationships between ATBF and a marker of atherosclerosis, common carotid artery IMT (intima-media thickness). As ATBF is responsive to sympatho-adrenal stimuli, we also investigated relationships with HRV (heart rate variability). A total of 79 healthy volunteers (44 female) were studied after fasting and after ingestion of 75 g of glucose. FMD, fasting ATBF and the responsiveness of ATBF to glucose were all negatively related to BMI (body mass index), confirming the adverse cardiovascular effects of adiposity. FMD was related to fasting ATBF (rs=0.32, P=0.008) and, at least in males, this relationship was independent of BMI (P=0.02). Common carotid artery IMT, measured in a subset of participants, was negatively related to fasting ATBF [rs=−0.51, P=0.02 (n=20)]. On the other hand, ATBF responsiveness to glucose had no relationship with either FMD or IMT. In multiple regression models, both fasting and stimulated ATBF had relationships with HRV. In conclusion, our results show that the regulation of ATBF has features in common with endothelial function, but also relationships with autonomic cardiovascular control as reflected in HRV.

Background The aim of this study was to investigate the significance of the MOSAIC (measurement of stenosis by aliasing coronary flow) method for the detection of proximal left coronary stenosis in patients with unstable angina (UA) using transthoracic Doppler echocardiography (TTDE). Methods Patients ( n = 107) with UA were evaluated. Proximal left coronary flow was sought in the short axis (SAX) at the aortic root level using color Doppler guidance. When detected coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared. Then, the color baseline was shifted until the color flow showed "isovelocity". Results Proximal coronary flow was detected in 86 (80.4%) of 107 patients. In these 86 patients, an optimal cutoff value of isovelocity≥47.5cm/s predicted significant coronary stenosis (percent diameter stenosis≥70%) of the proximal left anterior descending (AHA segment 6) or left main coronary artery with a sensitivity of 88%, specificity of 97%, positive predictive value of 98%, and negative predictive value of 86%. In all 107 patients, the same cutoff value predicted significant coronary stenosis with a sensitivity of 78%, specificity of 98%, positive predictive value of 98%, and negative predictive value of 81%. Conclusions The MOSAIC method may play a complementary role in expeditious risk stratification and decision making in patients with UA.

Metabolic substrate utilization of the human failing heart is an area of controversy. The purpose of this study is to directly quantify myocardial substrate utilization in moderately severe heart failure, type 2 diabetes and healthy controls using simultaneous coronary sinus and arterial blood sampling. Patients with heart failure (n = 9, mean NYHA 2.7+/-0.5), with type 2 diabetes (n = 5) and with normal heart function (n = 10) were studied after an overnight fast in connection with electrophysiological investigations/treatments.A systemic infusion of [(2)H(2)]palmitate allowed for the calculation of absolute palmitate extraction across the heart. Blood samples were analysed for non-esterified fatty acids, triacylglycerol, glycerol, glucose, pyruvate, lactate, 3-hydroxybutyrate, and blood gases after simultaneous sampling of arterial and coronary sinus blood. Arterio-coronary sinus metabolite concentration differences and fractional extractions for all substrates were similar between the groups. The absolute NEFA uptakes assessed by [(2)H(2)]palmitate extraction were also similar between the groups. Using direct measurements of metabolic substrate uptake by arterio-venous difference technique, the compensated human failing heart does not appear to have reduced myocardial fatty acid uptake.

Postprandial hyperlipidemia and insulin resistance play roles in the development of atherosclerosis in metabolic syndrome (MetS); however, the clinical significance of postprandial hemodynamic variables in this condition is still in question. The aim of this study was to investigate hemodynamic and metabolic indicators related to MetS after a mixed meal (Calorie mate, 500 kcal).Of 107 participants undergoing this investigation, 24 fulfilled ATPIII criteria for MetS. The remaining 83 subjects were controls. Both the augmentation index (AI) and late systolic blood pressure in the radial artery (rSBP2) as an index of central blood pressure were monitored using HEM-9000AI (Omron Healthcare, Kyoto, Japan) until 240 min after meal intake.Both AI and rSBP2 showed significant decreases after meal intake in both groups. Changes in postprandial AI showed a similar trend in the groups. rSBP2 reduction 60 min after meal ingestion was also comparable, -7.5+/-2.3 mmHg in MetS; -7.8+/-0.9 mmHg in control; however, delta rSBP2-120, the degree of rSBP2 reduction 120 min after meal ingestion comparing the fasting level, showed a significant difference between 2 groups, -0.5+/-2.0 mmHg in MetS; -5.3+/-0.9 mmHg in control, P0.02. Stepwise regression analysis revealed low-density-lipoprotein cholesterol (beta=0.333, P=0.001), high-density-lipoprotein cholesterol (beta=-0.209, P0.05) and systolic blood pressure (beta=-0.377, P0.001) as independent variables for determining delta rSBP2-120.Subjects with MetS exhibit signs of blunted rSBP2 (=central blood pressure) regulation after food intake. Dysfunctional postprandial hemodynamic regulation is another feature of MetS that may contribute to the progression of cardiovascular disease.