Simple and non-invasive screening method for diabetes based on myoinositol levels in urine samples collected at home.

OBJECTIVE: To establish a simple screening method for diabetes based on myoinositol (MI) in urine samples collected at home. RESEARCH DESIGN AND METHODS: Initially, 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. RESULTS: Differing 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. CONCLUSIONS: MI measurement in urine samples collected at home before and after the meal would be a simple, non-invasive and valuable screening method for diabetes.

Clinical Significance of Peripheral Endothelial Function for Left Atrial Blood Stagnation in Nonvalvular Atrial Fibrillation Patients With Low-to-Intermediate Stroke Risk.

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 <1.62, the sensitivity and specificity for the identification of patients with SEC were 58% and 89%, respectively. CONCLUSIONS: Impaired endothelial function assessed by RH-PAT might help to predict the presence of SEC in patients with low-to-intermediate risk of stroke. (Circ J 2016; 80: 2117-2123).

Clinical Utility of Atrial Electromechanical Conduction Time Measured with Speckle Tracking Echocardiography after Catheter Ablation in Patients with Atrial Fibrillation: A Validation Study with Electroanatomical Mapping.

PURPOSE: Our recent report demonstrated that atrial electromechanical conduction time (EMT-ε) measured with speckle tracking echocardiography could predict cardiac events in patients with pathological left ventricular hypertrophy. This study aimed to validate EMT-ε by comparison with electroanatomical mapping and to investigate the clinical utility of EMT-ε in patients with atrial fibrillation (AF) undergoing catheter ablation. METHODS: Forty-six patients with preserved LV ejection fraction (LVEF ≥ 50%) undergoing pulmonary vein isolation (PVI) for AF were studied. Atrial electrical conduction delay was determined by measuring atrial electrical activation time (EAT) using three-dimensional electroanatomical mapping just after PVI. Echocardiographic parameters were acquired within 24 hours and at 6 months after PVI. The study also included 10 control subjects. RESULTS: AF patients had a larger left atrial (LA) volume index (LAVI) and more prolonged EMT-ε compared with control subjects. According to the validation study, EAT was closely related to EMT-ε and a', and this association was independent of LAVI and the presence of persistent AF (EMT-ε: R(2) = 0.342, P < 0.0001, a': R(2) = 0.337, P < 0.0001). At 6 months after PVI, LAVI and EMT-ε were significantly improved. During continued follow-up beyond 6 months (total follow-up, 26 ± 12 months), the EMT-ε shortening at 6 months after PVI was significantly greater in AF-free patients than patients with AF recurrence. CONCLUSIONS: This study suggested that the EMT-ε could be a useful echocardiographic marker of LA electromechanical abnormalities in patients with AF.

Qualitative and quantitative assessment of adenosine triphosphate stress whole-heart dynamic myocardial perfusion imaging using 256-slice computed tomography.

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.

Impact of septal curvature on regional strain in patients with hypertrophic cardiomyopathy.

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: ß=-0.421, P<0.001; septal thickness: ß=0.401, P=0.002). In addition, global longitudinal strain and E/e' were worse in the lower septal curvature index group compared with the higher group. CONCLUSIONS: Septal longitudinal strain is associated with the degree of septal curvature. This indicates a possible link between LV wall configuration and regional myocardial function.

Impact of type 2 diabetes on serial changes in tissue characteristics of coronary plaques: an integrated backscatter intravascular ultrasound analysis.

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 mm(3), P = 0.02) and total lipid volume (TLV; 67 ± 26 vs. 55 ± 30 mm(3), 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 <6.5%. CONCLUSION: Accelerated plaque progression with an increase in the lipid-rich component of non-culprit plaques was observed in T2DM, despite the use of standard medical treatment. Better glycaemic control ameliorated the worsening of plaque characteristics in T2DM.

Direct measurement of radial strain in the inner-half layer of the left ventricular wall in hypertensive patients.

BACKGROUND: Two-dimensional speckle tracking echocardiography (2D-STE) is a novel technology that directly measures regional left ventricular (LV) wall contraction. This study aimed to directly measure inner-layer thickening (radial strain) of the LV using 2D-STE, and to examine the relationship between radial strain and the degree of hypertrophy. METHODS: The study enrolled 63 untreated hypertensive patients with normal geometry (N group, n=32) or concentric hypertrophy (CH group, n=31), classified according to LV mass index (LVMI) and relative wall thickness (RWT). Thirty normotensive subjects (C group, n=30) served as controls. Radial strain (ɛ) in the inner half (ɛi) and all layers of the LV wall (ɛa) were calculated from the LV short-axis view by 2D-STE. RESULTS: LV ejection fraction did not differ significantly among the groups. However, ɛi and ɛa were significantly lower in the CH group compared with the C and N groups (p<0.01). A ratio of ɛi to ɛa was significantly lower in the CH group compared with the C and N groups (p<0.01). A multivariate regression model that included midwall fractional shortening, E/e', LVMI, RWT, and LV ejection fraction showed that LVMI (p=0.002) and RWT (p=0.014) were independent predictors (R(2)=0.59) of ɛi. CONCLUSION: Radial strain in the inner half layer of the LV wall decreases in parallel with the degrees of LV concentricity and hypertrophy in hypertensive patients. Radial strain in the inner half layer may identify subtle systolic dysfunction even in hypertensive patients with preserved LV chamber function.

Right ventricular septal pacing preserves global left ventricular longitudinal function in comparison with apical pacing: analysis of speckle tracking echocardiography.

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 < 0.0001). The GLS in RVA were the lowest among the 3 groups (GLS: CONTROL: -18.22.4%, RVA: -14.33.1%, P < 0.001 vs. control, RVS: -16.82.7%, P<0.01 vs. RVA). CONCLUSIONS: RVA created heterogeneous LV contraction, which resulted in deteriorated LV longitudinal contraction. RVS could be a better pacing alternative in terms of less LV dyssynchrony and better longitudinal function compared to RVA.

Usefulness of the MOSAIC (measurement of stenosis by aliasing coronary flow) method using transthoracic color Doppler echocardiography in unstable angina patients.

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 ≥ 47.5 cm/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.

The differences in left ventricular torsional behavior between patients with hypertrophic cardiomyopathy and hypertensive heart disease.

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±15 years), 35 patients with HHD (mean age, 63±13 years) 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.

Myocardial fibrosis attenuates the effect of cibenzoline on left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

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.

Regulation of subcutaneous adipose tissue blood flow is related to measures of vascular and autonomic function.

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.

Influence of meal intake on pulse wave indices in type 2 diabetes.

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<0.001; baPWV, 1652+/-286-1586+/-240 cm s(-1), P=0.002; CAVI, 9.52+/-0.92-9.20+/-0.89, P=0.037). Delta(120) (value 120 min after meal intake-fasting value) AI correlated significantly with age, body weight, Delta(120) systolic blood pressure (SBP), Delta(120) diastolic blood pressure, Delta(120) pulse pressure, Delta(120) heart rate and fasting AI. Delta (postprandial value-fasting value) baPWV correlated significantly with fasting baPWV, Delta SBP, Delta pulse pressure and HbA1c. In contrast, Delta CAVI did not correlate with any clinical variables. In conclusion, postprandial decreases in AI, baPWV and CAVI can lead to underestimate arterial stiffness in patients with type 2 diabetes. Postprandial changes in AI and baPWV, but not CAVI, are associated with changes in hemodynamic variables after daily meal intake.

A case of pulmonary stenosis after a repair for tetralogy of Fallot treated with percutaneous pulmonary valvuloplasty using a triple-balloon technique.

The patient was a 37-year-old female who had undergone a repair for tetralogy of Fallot (TOF) at the age of 4 years. Postoperative pulmonary stenosis remained, but she continued to be managed medically. Approximately 3 years ago, at the age of 34, she exhibited a worsening of fatigue and dyspnea during exertion (New York Heart Association III), and was therefore hospitalized for a detailed examination. In cardiac catheterization, a right ventricle to pulmonary artery peak-to-peak gradient of about 90 mmHg was observed. Since it appeared that medical treatment alone would not sufficiently control her heart failure, pulmonary valvuloplasty using a triple-balloon technique was performed for the pulmonary stenosis. The peak-to-peak gradient immediately after the procedure decreased to 13 mmHg. There were no indications of restenosis approximately 6 months after the procedure, and the symptoms of heart failure in her daily life improved thereafter.

Relationship between smaller calcifications and lipid-rich plaques on integrated backscatter-intravascular ultrasound.

We evaluated the relationship between coronary calcification and plaque characteristics using integrated backscatter-intravascular ultrasound (IB-IVUS), focusing on spotty calcification. Seventy-two patients with culprit plaques containing spotty calcification were evaluated. The average degree of all the spotty calcifications (averaged arc) negatively correlated with the % lipid volume (LV) on IB-IVUS. Multivariate analysis showed the averaged arc was an independent predictor of % LV. Our observations suggest that smaller plaque calcifications are associated with lipid-rich characteristics in patients with a spotty calcification pattern.

Dysfunctional central hemodynamic regulation after daily meal intake in metabolic syndrome.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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, P<0.02. Stepwise regression analysis revealed low-density-lipoprotein cholesterol (beta=0.333, P=0.001), high-density-lipoprotein cholesterol (beta=-0.209, P<0.05) and systolic blood pressure (beta=-0.377, P<0.001) as independent variables for determining delta rSBP2-120. CONCLUSION: 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.

The lurking potential of tangential forces: A case of an arteriovenous shunt developed by percutaneous coronary intervention for the septal branch.

We 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.

The close relationship between postprandial remnant metabolism and insulin resistance.

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 <1.73. Both fasting and postprandial RLP-cholesterol (RLP-C) concentrations were higher in the IR group than in the NR group (6.2+/-2.6 versus 4.1+/-1.7mg/dl fasting value, and 9.7+/-4.0 versus 5.8+/-2.9mg/dl postprandial value). The changes in RLP-C concentration during the fat-loading test were twice as high in the IR group compared with the NR group (3.5+/-2.4 versus 1.6+/-1.6mg/dl, P=0.0022). The HOMA-R correlated significantly with both fasting and postprandial triglyceride (r=0.41 and 0.43, respectively) and RLP-C (r=0.36 and 0.50, respectively) in all subjects. Multiple regression analysis indicate that postprandial RLP-C concentration was an independent predictor of HOMA-R regardless of age, BMI, and other lipid profiles. Thus, postprandial RLP metabolism is closely related to IR. Atherosclerotic proliferation in IR syndrome may be caused by the accumulation of postprandial remnant lipoproteins after the daily fat intake.

Beneficial effects of betaxolol, a selective antagonist of beta-1 adrenoceptors, on exercise-induced myocardial ischemia in patients with coronary vasospasm.

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<0.01) and maximal ST segment depression (1.67+/-0.67-1.16+/-0.46 mm, P<0.01) obtained by exercise stress test, the defect score (8.6+/-2.7-5.3+/-2.1, P<0.01), the extent score (14.8+/-5.8-8.8+/-4.6%, P<0.01), the severity score (17.5+/-7.3-11.3+/-5.2, P<0.01) and washout rate (31.4+/-5.6-37.6+/-5.0%, P<0.01) obtained by the scintigraphy were improved by betaxolol. Our results suggest that betaxolol increases regional myocardial blood flow and improves exercise capacity in patients with VSA. Betaxolol may become a drug for a new potential therapy for VSA.

Effect of cilostazol on vasomotor reactivity in patients with vasospastic angina pectoris.

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.