Development of 60 MHz integrated backscatter intravascular ultrasound and tissue characterization of attenuated signal coronary plaques that cause myocardial injury after percutaneous coronary intervention.

The purpose of the present study was to develop a 60 MHz integrated backscatter intravascular ultrasound (IB-IVUS) and to evaluate its usefulness for the detection of lipid area with backward attenuation of ultrasound signal (AT) that for the prediction of post-procedural myocardial injury (PMI) after percutaneous coronary intervention (PCI). In a pathological study, images were acquired from 221 cross-sections of 18 coronary arteries from 13 cadavers obtained at autopsy. In the clinical training study, we compared non-targeted plaques in 38 patients by a previous IB-IVUS system (38 MHz) and a new IB-IVUS system (60 MHz). In the clinical testing study, we included 70 consecutive patients who underwent PCI. Serum troponin-I was measured just before and 24 h after PCI to evaluate PMI. As the % microcalcification + % cholesterol cleft area increased, the attenuation of IB values increased (r = 0.56, p < 0.001). The slopes of regression lines of the area of each tissue component between 38 and 60 MHz IB-IVUS were excellent. The lipid pool area with AT tended to be more useful than that of the conventional lipid pool area for the prediction of PMI (p = 0.11). We developed a 60 MHz IB-IVUS imaging system for tissue characterization of coronary plaques. Cutoff value of purple color was the most reliable value for the prediction of PMI.

Elevated plasma GLP-1 levels and enhanced expression of cardiac GLP-1 receptors as markers of left ventricular systolic dysfunction: a cross-sectional study.

OBJECTIVE: We aimed to elucidate usefulness of plasma glucagon-like peptide-1 (GLP-1) levels for the assessment of left ventricular (LV) dysfunction by examining the relationship among plasma GLP-1 levels, expression of cardiac GLP-1 receptors and LV function in patients with impaired and preserved LV function. DESIGN: Prospective study. SETTING: Number of participating center: 1, Gifu, Japan. PARTICIPANTS: Number of patients enrolled: 102 patients who underwent elective cardiac catheterisation for coronary artery disease, cardiomyopathy and valvular heart disease, and 6 patients who underwent cardiac biopsy. RESULTS: The plasma GLP-1 level was significantly increased in patients with impaired LV function (5.7±1.9 pmol/L) as compared with those with preserved LV function (2.7±1.6 pmol/L). Plasma GLP-1 and plasma brain natriuretic peptide (BNP) levels were inversely correlated with the LV ejection fraction(EF), respectively. Plasma GLP-1 level positively correlated with plasma BNP level. Multivariate logistic regression analysis revealed that plasma GLP-1 level was an independent determinant of the impaired LV function, whereas plasma BNP level was not. Intensity of immunostaining for GLP-1 receptor protein was significantly enhanced in patients with impaired LV function compared with those with preserved LV function. CONCLUSIONS: The plasma GLP-1 level was increased in patients with impaired systolic LV function and inversely correlated with the LVEF. The expressions of GLP-1 receptors were enhanced in hearts with impaired LV function. These may suggest that endogenous GLP-1-GLP-1 receptor system serves as a compensatory mechanism for systolic LV dysfunction. TRIAL REGISTRATION: UMIN-CTR, ID=UMIN000009361, registration number: R000011000.

Comparison between integrated backscatter intravascular ultrasound and 64-slice multi-detector row computed tomography for tissue characterization and volumetric assessment of coronary plaques.

BACKGROUND: The purpose of this study was to determine the cut-off values of Hounsfield units (HU) for the discrimination of plaque components and to evaluate the feasibility of measurement of the volume of plaque components using multi-detector row computed tomography (MDCT). METHODS: Coronary lesions (125 lesions in 125 patients) were visualized by both integrated backscatter intravascular ultrasound (IB-IVUS) and 64-slice MDCT at the same site. The IB values were used as a gold standard to determine the cut off values of HU for the discrimination of plaque components. RESULTS: Plaques were classified as lipid pool (n =50), fibrosis (n =65) or calcification (n =35) by IB-IVUS. The HU of lipid pool, fibrosis and calcification were 18 ± 18 HU (-19 to 58 HU), 95 ± 24 HU (46 to 154 HU) and 378 ± 99 HU (188 to 605 HU), respectively. Using receiver operating characteristic curve analysis, a threshold of 50 HU was the optimal cutoff values to discriminate lipid pool from fibrosis. Lipid volume measured by MDCT was correlated with that measured by IB-IVUS (r =0.66, p <0.001), whereas fibrous volume was not (r =0.21, p =0.059). CONCLUSION: Lipid volume measured by MDCT was moderately correlated with that measured by IB-IVUS. MDCT may be useful for volumetric assessment of the lipid volume of coronary plaques, whereas the assessment of fibrosis volume was unstable.

Relationship among coronary plaque compliance, coronary risk factors and tissue characteristics evaluated by integrated backscatter intravascular ultrasound.

BACKGROUND: The purpose of the present study was to evaluate the mechanical properties of coronary plaques and plaque behavior, and to elucidate the relationship among tissue characteristics of coronary plaques, mechanical properties and coronary risk factors using integrated backscatter intravascular ultrasound (IB-IVUS). METHODS: Non-targeted plaques with moderate stenosis (plaque burden at the minimal lumen site: 50-70%) located proximal to the site of the percutaneous coronary intervention target lesions were evaluated by IB-IVUS. Thirty-six plaques (less calcified group: an arc of calcification ≤10°) in 36 patients and 22 plaques (moderately calcified group: 10° < an arc of calcification ≤60°) in 22 patients were evaluated. External elastic membrane volume (EEMV) compliance, lumen volume (LV) compliance, plaque volume (PV) response (difference between PV in systole and diastole), EEM area stiffness index were measured at the minimal lumen site. Relative lipid volume (lipid volume/internal elastic membrane volume) was calculated by IB-IVUS. RESULTS: In the less calcified group, there was a significant correlation between EEMV compliance and the relative lipid volume (r = 0.456, p = 0.005). There was a significant inverse correlation between EEM area stiffness index and the relative lipid volume (p = 0.032, r = -0.358). The LV compliance and EEM area stiffness index were significantly different in the diabetes mellitus (DM) group than in the non-DM group (1.32 ± 1.49 vs. 2.47 ± 1.79%/10 mmHg, p =0.014 and 28.3 ± 26.0 vs. 15.7 ± 17.2, p =0.020). The EEMV compliance and EEM area stiffness index were significantly different in the hypertension (HTN) group than in the non-HTN group (0.77 ± 0.68 vs. 1.57 ± 0.95%/10 mmHg, p =0.012 and 26.5 ± 24.3 vs. 13.0 ± 16.7, p =0.020). These relationships were not seen in the moderately calcified group. CONCLUSION: The present study provided new findings that there was a significant correlation between mechanical properties and tissue characteristics of coronary arteries. In addition, our results suggested that the EEMV compliance and the LV compliance were independent and the compliance was significantly impaired in the patients with DM and/or HTN. Assessment of coronary mechanical properties during PCI may provide us with useful information regarding the risk stratification of patients with coronary heart disease.

In-hospital monitoring of T-wave alternans in a case of amiodarone-induced torsade de pointes: clinical and methodologic insights.

We report a case of macroscopic T-wave alternans occurring 30 min before the onset of amiodarone-induced torsade de pointes, illustrating a means to monitor for proarrhythmia.

Sudden reversible pacemaker failure in a patient with cardiac sarcoidosis: an unfortunate case of ventricular septal pacing.

We report a case of sudden marked deterioration of ventricular stimulation threshold resulting in pacemaker failure 16 months after a ventricular septal lead implantation for atrioventricular block. Echocardiography revealed septal wall thinning at the electrode-tissue interface, which was not detected pre-operatively. Endomyocardial biopsy confirmed cardiac sarcoidosis. The increased threshold was reversible with prednisolone.

Both stimulation of GLP-1 receptors and inhibition of glycogenolysis additively contribute to a protective effect of oral miglitol against ischaemia-reperfusion injury in rabbits.

BACKGROUND AND PURPOSE: We previously reported that pre-ischaemic i.v. miglitol reduces myocardial infarct size through the inhibition of glycogenolysis during ischaemia. Oral administration of miglitol has been reported to produce glucagon-like peptide 1 (GLP-1). We hypothesized that p.o. administration of miglitol, an absorbable antidiabetic drug, reduces myocardial infarct size by stimulating GLP-1 receptors and inhibiting glycogenolysis in the myocardium. EXPERIMENTAL APPROACH: The effects of p.o. and i.v. administration of miglitol on myocardial infarct size were compared in a rabbit model of ischaemia induced by 30 min of coronary occlusion and 48 h of reperfusion. The levels of phospho(p)-PI3kinase and p-Akt were measured in cardiac tissue by use of Western blot analysis. RESULTS: Both p.o. and i.v. administration of miglitol reduced the infarct size, and this effect was greater after p.o. than after i.v. administration under similar plasma miglitol concentrations. The reduction in infarct size induced by p.o. miglitol but not that induced by i.v. miglitol was partially inhibited by treatment with exendin(9-39), a GLP-1 receptor blocker. Both p.o. and i.v. miglitol improved ejection fraction and ±dP/dt after myocardial infarction. Miglitol administered p.o. but not i.v. up-regulated the myocardial expression of phospho(p)-PI3kinase and p-Akt following myocardial infarction; an effect that was inhibited by exendin(9-39). CONCLUSIONS AND IMPLICATIONS: Administration of miglitol p.o. reduces myocardial infarct size through stimulation of GLP-1 receptors and activation of PI3kinase-Akt pathway in addition to the inhibition of glycogenolysis. These findings may have clinical implications for the p.o. administration of miglitol for the treatment of patients with diabetes mellitus combined with coronary artery disease.

Continuous T-wave alternans monitoring to predict impending life-threatening cardiac arrhythmias during emergent coronary reperfusion therapy in patients with acute coronary syndrome.

AIMS: T-wave alternans (TWA) can precede onset of ventricular tachyarrhythmia (VTA). We evaluated the usefulness of continuous TWA monitoring in ultra-short-term prediction of impending life-threatening VTA upon emergent reperfusion in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: Twenty consecutive ACS patients undergoing emergent reperfusion therapy were studied. Continuous ambulatory electrocardiograms (ECGs) (leads V1 and V5) were recorded during emergency room visit and therapy. Peak TWA was determined before and after reperfusion by the modified moving average method. Coronary balloon angioplasty/stenting was successfully performed in 19 patients and intracoronary vasodilator was administered in 1 patient with coronary spasm. Three (15.0%) patients developed VTA requiring cardioversion soon after reperfusion. Peak TWA before reperfusion was higher in patients with VTA than in those without (33.0 ± 4.4 vs. 15.8 ± 4.0 µV, P < 0.001). Two patients with arrhythmia exhibited an upsurge in TWA to 75 and 105 µV before onset of VTA. In the third patient, macroscopic TWA appeared in leads V1-V4 in a 12-lead ECG prior to VTA upon pharmacological resolution of vasospasm, although the ambulatory ECG field of view could not detect the upsurge. CONCLUSION: Acute coronary syndrome patients at risk of developing VTA soon after reperfusion exhibit premonitory episodes of increased TWA. Thus, TWA monitoring may be useful for ultra-short-term prediction of life-threatening cardiac arrhythmia risk upon emergent reperfusion in ACS patients. Continuous 12-lead ECGs may be required to optimize detection of TWA, which is regionally specific.

Tissue characterization of coronary plaques and assessment of thickness of fibrous cap using integrated backscatter intravascular ultrasound. Comparison with histology and optical coherence tomography.

BACKGROUND: The purpose of this study was to develop a new online integrated backscatter intravascular ultrasound (IB-IVUS) system and to validate its ability to measure fibrous cap thickness by comparing IB-IVUS images with those from optical coherence tomography (OCT). METHODS AND RESULTS: Images were acquired from 125 segments of 26 coronary arteries obtained at autopsy from 11 cadavers. In the training study (n=30), 242 regions-of-interest on color-coded maps were compared with histology. In the validation study, 95 cross-sections were diagnosed by IB-IVUS and histology. In 24 patients with stable angina, 28 arterial cross-sections were imaged by IB-IVUS and OCT in vivo. In the training study, cutoff values of 39 decibels (dB) and 17dB were the optimal predictors of lipid pool/fibrosis and fibrosis/calcification, respectively, with 38-MHz mode; 42dB and 20dB, respectively, with 43-MHz mode. In the validation study, IB classified the fibrous, lipid-rich and fibrocalcific components with an accuracy of 92%, 91% and 95%, respectively. Agreement between the histological and IB-IVUS diagnoses was excellent (Cohen's κ=0.83). There was a correlation between the fibrous cap thickness measured by IB-IVUS and OCT (r=0.74, P<0.001). CONCLUSIONS: The IB-IVUS system with improved resolution provides high diagnostic accuracy for the analysis of the tissue characteristics of coronary plaques, and enables estimation of the thickness of the fibrous cap in the clinical setting.

Demonstration of intraluminal thrombus in the carotid artery by optical coherence tomography: technical case report.

OBJECTIVE: Intraluminal thrombus in the carotid artery is often misdiagnosed because clinical imaging, such as angiography and duplex ultrasonography, fails to accurately identify it. Recently, it was reported that optical coherence tomography (OCT), a new imaging modality, can visualize intravascular thrombus in the coronary artery. CLINICAL PRESENTATION: An 83-year old male was admitted due to newly developed motor weakness of the left hand. Diffusion weighted magnetic resonance imaging showed multiple high intensity spots in the territory of the right middle cerebral artery, and magnetic resonance angiography revealed significant stenosis at the origin of the right internal carotid artery. Because of an apparent change in plaque shape on the angiogram just before carotid artery stenting, further examinations such as intravascular ultrasonography (IVUS) and OCT were performed. EXAMINATION: After IVUS examination, both the common carotid and external carotid arteries were occluded by an occlusion balloon system prepared for carotid artery stenting. Then the stenotic site was imaged by OCT from the distal section at 1 mm/sec using a built-in pull-back system with continuous injection of saline through the guiding catheter to remove blood from the field of view. Since intraluminal thrombus was clearly demonstrated by an OCT, carotid endarterectomy was performed instead of stenting, and thrombus was confirmed by surgical specimen. CONCLUSION: OCT may provide useful information for diagnosis of an intraluminal thrombus in the carotid artery, which is important for the appropriate selection of therapeutic strategy.

Postconditioning effect of granulocyte colony-stimulating factor is mediated through activation of risk pathway and opening of the mitochondrial KATP channels.

Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac function after myocardial infarction. However, whether postinfarct acute effect of G-CSF is mediated through the same signaling pathways as those of ischemic postconditioning is still unclear. We examined the postinfarct acute effect of G-CSF on myocardial infarct size and its precise molecular mechanism. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Rabbits were intravenously injected 10 µg/kg of G-CSF (G-CSF group) or saline (control group) immediately after reperfusion. The wortmannin + G-CSF, PD-98059 + G-CSF, N(ω)-nitro-L-arginine methyl ester (l-NAME) + G-CSF, and 5-hydroxydecanoic acid sodium salt (5-HD) + G-CSF groups were respectively injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), L-NAME (10 mg/kg), and 5-HD (5 mg/kg) 5 min before G-CSF administration. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the signals such as protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK), eNOS, p70S6 kinase (p70S6K), and glycogen synthase kinase-3ß (GSK3ß) in the ischemic myocardium after 48 h of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7 ± 2.7%) than in the control group (42.3 ± 4.6%). The infarct size-reducing effect of G-CSF was completely blocked by wortmannin (44.7 ± 4.8%), PD-98059 (38.3 ± 3.9%), L-NAME (42.1 ± 4.2%), and 5-HD (42.5 ± 1.7%). Wortmannin, PD-98059, L-NAME, or 5-HD alone did not affect the infarct size. Western blotting showed higher myocardial expression of phospho-Akt, phospho-ERK, phosho-eNOS, phosho-p70S6K, and phosho-GSK3ß at 10 min and 48 h after reperfusion in the G-CSF group than in the control group. In conclusion, postreperfusion G-CSF administration reduces myocardial infarct size via activation of phosphatidylinositol 3-kinase-Akt and ERK prosurvival signaling pathways and their downstream targets eNOS, p70S6 kinase, GSK3ß, and mitochondrial ATP-dependent K(+) channel.

Treatment with Lindera strychnifolia reduces blood pressure by decreasing sympathetic nerve activity in spontaneously hypertensive rats.

Lindera strychnifolia (Tendai-Uyaku), a medicinal plant, has long been used for the treatment of cardiac, renal and rheumatic diseases in Japan. We investigated the effect of Lindera strychnifolia on systolic blood pressure, cardiac function, and plasma noradrenaline levels in rats. Spontaneously hypertensive rats (SHR) were given free access to water or extract solution of Lindera strychnifolia, which was extracted with a ratio of 10 g Lindera strychnifolia roots/20 ml water. Systolic blood pressure was measured by using a tail-cuf sphygmomanometer twice a week from 10 to 30 weeks of age, and compared to the age-matched Wistar Kyoto rats (WKY) as a control group. At 30 weeks of age, heart function was measured by echocardiography and blood samples were taken for detection of plasma noradrenaline levels, and rats were then sacrificed. Systolic blood pressure gradually increased from 10 to 30 weeks of age in the SHR group, while it did not change in the WKY group. In the Lindera-treated SHR group, the increase in systolic blood pressure was significantly attenuated from 21 to 30 weeks of age. Echocardiography showed a significant increase in ejection fraction in the Lindera-treated SHR group (60.4 +/- 7.8%) as compared to the SHR group (39.7 +/- 23.4%). Plasma noradrenaline levels were significantly decreased in Lindera-treated SHR group compared to the SHR group. These results suggest that Lindera strychnifolia has an anti-hypertensive effect and improves cardiac function in spontaneous hypertensive rats. These effects may be related to the decrease in plasma noradrenaline levels by Lindera strychnifolia.

Effects of benidipine and some other calcium channel blockers on the prognosis of patients with vasospastic angina. Cohort study with evaluation of the ergonovine coronary spasm induction test.

BACKGROUND: It has been reported that the morbidity rate of vasospastic angina is higher in Japan compared to western countries, and its prognosis has already been reported. However, the prognosis of vasospastic angina in relation to coronary angiographic findings, prognostic risk factors and treatment has not yet been fully investigated. METHODS AND RESULTS: From January 2000 to October 2005, 1047 patients with vasospastic angina diagnosed by coronary angiography at Gifu University Hospital and related hospitals were registered in a cohort study (follow-up rate: 91.4%, median follow-up duration: 3.8 years). The presence of coronary artery stenosis, diabetes mellitus, total spasm, and age of more than 65 years had a negative prognostic impact on cardiovascular events. Patients were treated with calcium channel blockers such as diltiazem (CAS 33286-22-5, CAS 42399-41-7), amlodipine (CAS 111470-99-6), nifedipine (CAS 21829-25-4), and benidipine (CAS 91599-74-5). Among these calcium channel blockers, when patient background was matched by the propensity score in patients treated with calcium channel blockers only, the cardiovascular event rate was significantly lower in the benidipine group than in the diltiazem group. CONCLUSION: The study demonstrated for the first time that total spasm is a risk factor, independent of other factors, for cardiovascular events in patients with vasospastic angina. Treatment with benidipine showed a better prognosis than that with diltiazem.