Seiji Koga

Atorvastatin induces associated reductions in platelet P-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases

The development and progression of atherosclerosis comprises various processes, such as endothelial dysfunction, chronic inflammation, thrombus formation, and lipid profile modification. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that have pleiotropic effects in addition to cholesterol-lowering properties. However, the mechanisms of these effects are not completely understood. Here, we investigated whether atorvastatin affects the levels of malondialdehyde-modified low-density lipoprotein (MDALDL), an oxidized LDL, the proinflammatory cytokine interleukin-6 (IL-6), or platelet P-selectin, a marker of platelet activation, relative to that of LDL cholesterol (LDL-C). Forty-eight patients with coronary artery disease and hyperlipidemia were separated into two groups that were administered with (atorvastatin group) or without (control group) atorvastatin. The baseline MDA-LDL level in all participants significantly correlated with LDL-C (r = 0.71, P < 0.01) and apolipoprotein B levels (r = 0.66, P < 0.01). Atorvastatin (10 mg/day) significantly reduced the LDL-C level within 4 weeks and persisted for a further 8 weeks of administration. Atorvastatin also reduced the MDA-LDL level within 4 weeks and further reduced it over the next 8 weeks. Platelet P-selectin expression did not change until 4 weeks of administration and then significantly decreased at 12 weeks, whereas the IL-6 level was gradually, but not significantly, reduced at 12 weeks. In contrast, none of these parameters significantly changed in the control group within these time frames. The reduction (%) in IL-6 between 4 and 12 weeks after atorvastatin administration significantly correlated with that of MDALDL and of platelet P-selectin (r = 0.65, P < 0.05 and r = 0.70, P < 0.05, respectively). These results suggested that the positive effects of atorvastatin on the LDL-C oxidation, platelet activation and inflammation that are involved in atherosclerotic processes are exerted in concert after lowering LDL-C.

The echocardiographic Tei-index reflects early myocardial damage induced by anthracyclines in patients with hematological malignancies

Anthracyclines are antineoplastic agents that are effective against solid tumors and hematological malignancies. However, drug-induced cardiotoxicity imposes dose limitations. Myocardial damage due to anthracyclines has been assessed by measuring left ventricular ejection fraction (LVEF) or fraction shortening (FS) by echocardiography and criteria for discontinuing treatment have been established based on these indexes. However, cardiotoxicity is already irreversible when either LVEF or FS fulfills these criteria. The Tei-index has recently been established to assess combined systolic and diastolic myocardial function during echocardiography. It can also detect small changes in cardiac function. We therefore surmised that the Tei-index would reflect early myocardial damage induced by anthracyclines. We treated 23 patients with the anthracycline, doxorubicin (DXR), and examined them at least twice during the treatment. An additional dose of DXR significantly correlated with a change in the Tei-index (ΔTei-index). In contrast, a change in LVEF did not correlate with increased doses of DXR. The ΔTei-index did not correlate with either LVEF or the Tei-index before treatment. These results suggested that the ΔTei-index is a more sensitive indicator of early cardiotoxicity induced by anthracyclines than LVEF regardless of its value before treatment.

Elevated levels of systemic pentraxin 3 are associated with thin-cap fibroatheroma in coronary culprit lesions: assessment by optical coherence tomography and intravascular ultrasound.

OBJECTIVES This study sought to determine whether systemic levels of pentraxin 3 (PTX3), a novel inflammatory marker, are associated with thin-cap fibroatheroma (TCFA). BACKGROUND Biomarkers predicting the presence of TCFA in vivo have not been established. METHODS We evaluated 75 patients (stable angina pectoris, n = 47; acute coronary syndrome, n = 28) with de novo culprit lesions who were examined by optical coherence tomography and intravascular ultrasound. We defined TCFA as lipid-rich plaque with a fibrous cap <65 μm thick. Systemic levels of PTX3 were compared between patients with and without TCFA. RESULTS Thirty-eight and 37 patients with and without TCFA, respectively, were identified. Levels of PTX3 were significantly higher in patients with than in those without TCFA (p < 0.001) and correlated inversely with fibrous cap thickness (r = -0.71, p = 0.001) and positively with the remodeling index (r = 0.25, p = 0.037). Multivariate logistic regression analysis showed that a higher PTX3 level was the most powerful predictor of TCFA (odds ratio: 3.26, 95% confidence interval: 1.75 to 6.05, p < 0.001). Receiver-operating characteristic curve analysis showed that >3.24 ng/ml of PTX3 could predict TCFA with 84% sensitivity and 86% specificity. CONCLUSIONS Higher levels of systemic PTX3 are associated with TCFA. Systemic PTX3 levels comprise a useful inflammatory marker that reflects coronary plaque vulnerability.

Effect of Nasal Continuous Positive Airway Pressure in Men on Global Left Ventricular Myocardial Performance in Patients With Obstructive Sleep Apnea Syndrome

The influence of obstructive sleep apnea syndrome (OSAS) on left ventricular function remains controversial. We examined the influence of OSAS on global left ventricular function using the myocardial performance index (Tei index) and plasma brain natriuretic peptide (BNP) level and investigated the effect of nasal continuous positive airway pressure (nCPAP) on these parameters. We obtained echocardiographic indexes including the Tei index and BNP concentrations from 27 patients with OSAS whose mean apnea-hypopnea index was 42.2+/-21.5 events/hour and who were undergoing nCPAP and from 22 control subjects. We defined global left ventricular dysfunction (GLVD) as a Tei index >or=0.50 and high BNP as >or=20 pg/ml. Compared with controls, the Tei index of patients with OSAS was significantly increased (p <0.01) and prevalence of GLVD was high (19%, p<0.05). The correlation between the Tei index and apnea-hypopnea index was significant (r=0.447, p<0.05). Although BNP levels were higher in patients with OSAS than in controls, the difference did not reach significance. BNP level was high in 37% of patients with OSAS and in only 9% of controls (p<0.05). The Tei index of patients with OSAS was significantly decreased after 1 month and 3 months of nCPAP (p<0.01), and prevalence of GLVD significantly decreased from 19% to 4% (p<0.05). In contrast, BNP significantly decreased at 3 months after nCPAP (p<0.05). In conclusion, patients with moderate to severe OSAS frequently have impaired global left ventricular myocardial performance, which can be reversed at the early stage after starting nCPAP.

Impact of Catheter Sheath Insertion into the Radial Artery on Vascular Endothelial Function Assessed by Reactive Hyperemia Peripheral Arterial Tonometry

The transradial approach has been used for coronary procedures, but this procedure carries a risk of injury to the endothelium of the radial artery. In this study, the vascular dysfunction caused by transradial catheterization was examined using reactive hyperemia peripheral arterial tonometry (RH-PAT), a recently developed technique for assessing endothelial function in digits, and the differences in injuries were compared according to the size of sheath.Forty-three patients undergoing transradial catheterization with 6-Fr sheaths (n = 17) or 4-Fr/5-Fr (non-6-Fr; n = 26) sheaths underwent RH-PAT using an Endo-PAT2000 before, the day after, and 6 months after catheterization. RH-PAT was assessed in the arm of sheath placement and in the other arm as a control.RH-PAT values decreased from 2.42 ± 0.67 before catheterization to 2.08 ± 0.41 the day after catheterization in the 6-Fr group (P = 0.031); this was more evident in patients with a longer procedure time (> 91 minutes). In contrast, the change in the non-6-Fr group was not significant. RH-PAT of the non-catheterized arm was unchanged in both groups. At 6 months after catheterization, RH-PAT values in the 6-Fr group had not completely returned to baseline.In conclusion, the insertion of a 6-Fr catheter sheath into the radial artery, especially with a longer procedure time, impaired vascular endothelial function assessed by RH-PAT the day after the procedure and was sustained for 6 months. Thus, the use of smaller size sheaths (< 6-Fr) with a shorter procedure should be considered when performing transradial catheterization.

iMap-Intravascular Ultrasound Radiofrequency Signal Analysis Reflects Plaque Components of Optical Coherence Tomography-Derived Thin-Cap Fibroatheroma

BACKGROUND The ability of iMap-intravascular ultrasound (IVUS) tissue characterization to detect thin-cap fibroatheroma (TCFA) identified on optical coherence tomography (OCT) has not yet been fully elucidated. METHODSANDRESULTS We evaluated 86 coronary lesions from 73 patients with stable angina pectoris using iMap-IVUS and OCT. We defined OCT-derived TCFA (OCT-TCFA) as lipid-rich plaque with a <65-μm-thick fibrous cap. The external elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden and remodeling index were measured on gray-scale IVUS. Plaque components categorized on iMap-IVUS as fibrotic, lipidic, necrotic or calcified are presented as absolute area and proportion (%) of total plaque area. OCT-TCFA (22 lesions) had significantly greater EEM CSA, P+M CSA, plaque burden and remodeling index than non-TCFA (64 lesions). Significantly larger %necrotic area, absolute lipidic and necrotic areas and smaller %fibrotic areas were found in OCT-TCFA than in non-TCFA. On multivariate analysis, absolute necrotic area was an independent predictor of OCT-TCFA. The area under the ROC curve for absolute necrotic area required to identify OCT-TCFA was 0.86. The sensitivity, specificity, positive and negative predictive values of absolute necrotic area ≥7.3 mm2 for identifying OCT-TCFA were 77%, 88%, 68% and 92%, respectively. CONCLUSIONS Coronary lesions with greater iMap-IVUS absolute necrotic area were closely associated with OCT-TCFA.

Longitudinal strain of right ventricular free wall by 2-dimensional speckle-tracking echocardiography is useful for detecting pulmonary hypertension

AIMS Echocardiography is widely used for screening pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH. MAIN METHODS Thirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG). KEY FINDINGS PSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r=0.633, p=0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP ≥ 35mmHg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567; p=0.042] and PVR ≥ 400dyn·s·cm(-5) (OR, 1.804; 95% CI 1.131-2.877; p=0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was -20.75%, based on receiver operating characteristic curve analysis. SIGNIFICANCE PSS of the RV free wall might serve as a useful non-invasive indicator of PH.

Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Reduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown.The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048).Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC.

Diverse Findings in Calcified Thrombus Between Histopathology and In Vivo Imaging Including Intravascular Ultrasound, Optical Coherence Tomography, and Angioscopy

A 46-year-old woman on hemodialysis due to end-stage renal disease was admitted for repeated thrombus formation in previously implanted drug-eluting stents in the right coronary artery. We could successfully aspirate this thrombus, and histopathology revealed a calcified thrombus comprising multiple microcalcifications and fibrinous materials. This is the first report showing how a calcified thrombus is visualized in vivo by intracoronary imaging modalities including intravascular ultrasound, optical coherence tomography, and angioscopy.

Chronic renal artery dissection with aneurysm formation treated by stent implantation with coil embolization with detailed intravascular ultrasound evaluation

Treatment options for chronic renal artery dissection, which is a rare cause of renal artery stenosis and renovascular hypertension, such as medical management, percutaneous intervention, and open surgical repair remain controversial. We describe a 55‐year‐old man with a chronic dissecting aneurysm of a renal artery complicated with renovascular hypertension that was initially diagnosed by computed tomography angiography, evaluated by intravascular ultrasound, and treated by stent implantation with coil embolization.© 2012 Wiley Periodicals, Inc.