Hiroki Oe

Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in non- diabetic subjects: a preliminary report

BackgroundPostprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile.MethodsA randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test.ResultsAlogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 μg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from −4.2 ± 0.5% to −2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = −0.46, p = 0.03) and RLP-C (r = −0.45, p = 0.04).ConclusionAlogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.

Prevalence and Clinical Course of the Juveniles with Brugada‐Type ECG in Japanese Population

Background: Although many studies on Brugada syndrome have been done, with many reports of genetic findings and clinical features, little evidence exists to support the role of this syndrome in sudden cardiac death in a juvenile population. We sought to determine the prevalence and clinical course in children exhibiting Brugada‐type ECG in a community‐based population.

Diagnostic Accuracy and Cost‐Effectiveness of a Pocket‐Sized Transthoracic Echocardiographic Imaging Device

The recently introduced pocket‐sized portable transthoracic echocardiography (pTTE) is accurate for measurement of cardiac chamber size and function as well as for assessment of valvular regurgitation. This study aimed to compare the diagnostic accuracy of the pocket‐sized pTTE with the standard TTE (sTTE) and assess its cost‐effectiveness.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. Objective: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). Methods: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. Results: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months’ supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). Conclusion: Three months’ supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Clinical utility of new real time three-dimensional transthoracic echocardiography in assessment of mitral valve prolapse.

Background: Noninvasive and accurate assessment of mitral valve anatomy has become integral in the presurgical evaluation of patients with mitral valve prolapse (MVP). Recently developed real time three‐dimensional (RT3D) ultrasound allows online acquisition, rendering, and can provide accurate information on cardiac structures. We sought to evaluate the feasibility of RT3D for the assessment of MVP segments when compared with transesophageal echocardiography (TEE) and intraoperative findings. Methods: We examined 42 patients with MVP using RT3D, two‐dimensional (2D) transthoracic echocardiography (TTE) and TEE. For RT3D analysis, cropping planes were used to slice the 3D volume on line to visualize the prolapsed segments of the mitral valve leaflets. The mitral valve was divided into six segments based on the American Society of Echocardiographys recommendations. Two experienced cardiologists evaluated echocardiographic images. Results: Adequate RT3D images of the mitral valve were acquired in 40 out of 42 patients. The sensitivity and specificity of RT3D for defining prolapsed segments when compared with TEE were 95% and 99%, respectively (anterior leaflet: 96% and 99%, posterior leaflets: 93% and 100%, respectively). The sensitivity and specificity of TTE were 93% and 97%, respectively (anterior leaflet: 96% and 98%, posterior leaflets: 90% and 97%, respectively). Interobserver agreement for RT3D (Kappa 0.95, 95% confidence interval [CI] 0.91–1.00) was significantly greater than for TTE (Kappa 0.85, 95% CI 0.78–0.93) (P < 0.05). The elapsed time for completion of RT3D (14.4 ± 2.8 min) was shorter than for TEE (26.4 ± 4.7 min, P < 0.0001) and TTE (19.0 ± 3.1 min, P< 0.0001). Conclusions: RT3D is fast, accurate, and highly reproducible for assessing MVP.

Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals – a randomized cross-over trial

BACKGROUND Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. METHODS Healthy volunteers [10] were given supplementation at 4g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. RESULTS Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4h=-0.5±1.2 vs. -2.0±1.6%, P=0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2-4h, and returned to baseline at 8h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve=220±209 vs. 374±216mg/h/dL, P=0.04) and remnant lipoprotein-cholesterol (incremental area under the curve=21.7±13.8 vs. 13.3±12.9mg/h/dL, P=0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4h after the cookie test. CONCLUSION Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state.

Cardiac dysfunction and prolonged hemodynamic deterioration after implantable cardioverter-defibrillator shock in patients with systolic heart failure

Background—We investigated the acute effects of implantable cardioverter-defibrillator shock on myocardium, cardiac function, and hemodynamics in relation to left ventricular systolic function. Methods and Results—We studied 50 patients who underwent implantable cardioverter-defibrillator implantation and defibrillation threshold (DFT) testing: 25 patients with left ventricular ejection fraction (LVEF) ≥45% and 25 patients with LVEF <45%. We measured cardiac biomarkers (creatine kinase, creatine kinase-MB, myoglobin, cardiac troponin T and I, and N-terminal probrain natriuretic peptide). Left ventricular relaxation was assessed by global longitudinal strain rate during the isovolumetric relaxation period using speckle-tracking echocardiography. Blood sampling and echocardiography were performed before, immediately after, and 5 minutes and 4 hours after DFT testing. Mean arterial pressure was measured directly during DFT testing. Cardiac biomarkers showed no significant changes in either group. LVEF was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in the group with reduced LVEF (P<0.001), whereas LVEF reduction was not observed in the group with preserved LVEF (P=0.637). Global isovolumetric relaxation period was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in both groups (preserved LVEF: 0.39±0.14 versus 0.23±0.13* versus 0.23±0.13* versus 0.40±0.13 s−1, *P<0.001 versus baseline; reduced LVEF: 0.15±0.05 versus 0.08±0.04† versus 0.09±0.04† versus 0.15±0.05 s−1, †P<0.001 versus baseline, repeated-measures ANOVA). Time to recovery of mean arterial pressure to the baseline was prolonged in the group with reduced LVEF (P<0.001). Conclusions—Implantable cardioverter-defibrillator shock transiently impairs cardiac function and hemodynamics especially in patients with systolic dysfunction, although significant tissue injury is not observed.

Usefulness of three-dimensional automated quantification of left ventricular mass, volume, and function by 64-slice computed tomography.

OBJECTIVES Quantification of left ventricular (LV) mass has important prognostic implications. However, accurate measurement of LV mass has been difficult, in part because of the oblique angle at which the heart lies within the chest and the continuous movement of the heart itself. Multislice computed tomography (MSCT) allows assessment not only of coronary stenosis but LV volume, function, and mass. A novel three-dimensional (3D) region-growing-based semi-automated segmentation algorithm for measurements of LV mass, volume, and function was recently developed. This study evaluated this new 3D automated method for measurement of LV mass, by comparison with a well-established 2D manual contour-drawing algorithm. METHODS AND RESULTS The study population consisted of 50 consecutive patients who underwent ECG-gated MSCT for evaluation of coronary arteries. The 3D algorithm for reliable segmentation was unsuccessful in two patients. In the remaining 48 patients, however, LV segmentation using this algorithm was performed and delivered visually reliable segmentation results. The 3D algorithm for analysis of LV function and mass is feasible based on volumetric data, and exhibits good correlation and agreement with the results obtained with the conventional 2D algorithm. The time required for the new automated algorithm was significantly shorter than that for the manual contour-drawing algorithm (P<0.0001) (automated algorithm: 468.0±205.1 s, manual algorithm: 1362.4±410.5 s, mean ±S.D.). CONCLUSIONS The 3D semi-automated region-growing segmentation algorithm for analysis of LV function and mass is feasible based on volumetric data, and exhibits good correlations and agreement with the results of the conventional 2D manual contour-drawing algorithm.

Beta-Blockers and Oxidative Stress in Patients with Heart Failure

Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca2+ overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca2+ overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

Morphological But Not Functional Changes of the Carotid Artery Are Associated With the Extent of Coronary Artery Disease in Patients With Preserved Left Ventricular Function

Background and Purpose— The atherosclerotic process is associated with both morphological and functional changes in the carotid artery. We evaluated the relationship between these parameters of the carotid artery and the extent of coronary artery disease (CAD) in patients with preserved left ventricular function. Methods— The study population consisted of 104 stable patients with CAD who had preserved left ventricular function (left ventricular ejection fraction ≥45%). All patients underwent carotid ultrasound for evaluation of carotid artery plaque score defined by the sum of plaque thickness, maximum percent area stenosis, and carotid arterial stiffness index β calculated by a combination of changes in carotid arterial diameter and blood pressure. Results— Plaque score and percent area stenosis correlated with the extent of CAD defined as the number of diseased coronary vessels (P<0.001 and 0.002, respectively), but arterial stiffness β did not (P=0.39). Using logistic regression analyses adjusting for confounding coronary risk factors and arterial stiffness β, plaque score and percent area stenosis were independently correlated with multivessel CAD (P=0.001 and 0.004, respectively). Conclusions— Carotid artery plaque burden, but not arterial stiffness, is associated with the extent of CAD, suggesting morphological rather than functional changes in the carotid artery may be a more accurate predictor of the extent of CAD and multivessel CAD independent of left ventricular function.