Upper-Arm SBP Decline Associated with Repeated Cuff-Oscillometric Inflation Significantly Correlated with the Arterial Stiffness Index.

We evaluated the clinical significance of the new non-invasive vascular indices to explore their potential utility using repeated cuff-oscillometric inflation. In 250 consecutive outpatients, we performed a cross-sectional, retrospective, single-center, observational study to investigate sequential differences in arterial stiffness using blood pressure, arterial velocity pulse index (AVI), and arterial pressure volume index (API) with repeated measurements. Males accounted for 62.7% of the patients, and the mean age was 68.1 ± 12.1 years. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the first reading in repeated measurements were 133.07 ± 21.20 mmHg and 73.94 ± 13.56 mmHg, respectively. The mean AVI and API were 23.83 ± 8.30 and 31.12 ± 7.86, respectively. In each measurement of these parameters, although DBP and AVI did not show significant changes throughout repeated measurements, SBP and API decreased significantly according to the measurement orders. Furthermore, changes in SBP and API were significantly correlated in several of the models. In this study, it was concluded that upper-arm SBP decline associated with repeated cuff-oscillometric inflation was significantly correlated with the arterial stiffness index. The findings of this study will allow clinicians to easily recognize the progression of atherosclerosis through regular, routine practice. In conclusion, this study suggests that changes in repeated SBP measurements may be predictive of arterial stiffness and atherosclerosis.

Rationale and Design of the Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study): Implications of Biologics against Rheumatoid Arthritis and the Vascular Complications, Subclinical Atherosclerosis.

To explore the biological and immunological basis of human rheumatoid arthritis and human atherosclerosis, we planned and reported a detailed design and rationale for Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study) using highly sensitive, high-throughput, human autoantibody measurement methods with cell-free protein synthesis technologies. Our previous study revealed that subjects with atherosclerosis had various autoantibodies in their sera, and the titers of anti-Th2 cytokine antibodies were correlated with the severity of atherosclerosis. Because rheumatoid arthritis is a representative autoimmune disease, we hypothesized that both rheumatoid arthritis and atherosclerosis are commonly developed by autoantibody-mediated autoimmune processes, leading to incessant inflammatory changes in both articular joint tissues and vessel walls. We planned a detailed examination involving carotid artery ultrasonography, measurements of adhesion molecules, such as ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) for the evaluation of atherosclerosis progression, and high-throughput, high-sensitivity, autoantibody analyses using cell-free technologies, with detailed examinations of the disease activity of rheumatoid arthritis. Analyses of correlations and associations between biological markers and degrees of carotid atherosclerosis over time under consistent conditions may enable us to understand the biological and humoral immunity background of human atherosclerosis and autoimmune diseases.

The Types and Proportions of Commensal Microbiota Have a Predictive Value in Coronary Heart Disease.

Previous clinical studies have suggested that commensal microbiota play an important role in atherosclerotic cardiovascular disease; however, a synthetic analysis of coronary heart disease (CHD) has yet to be performed. Therefore, we aimed to investigate the specific types of commensal microbiota associated with CHD by performing a systematic review of prospective observational studies that have assessed associations between commensal microbiota and CHD. Of the 544 published articles identified in the initial search, 16 publications with data from 16 cohort studies (2210 patients) were included in the analysis. The combined data showed that Bacteroides and Prevotella were commonly identified among nine articles (n = 13) in the fecal samples of patients with CHD, while seven articles commonly identified Firmicutes. Moreover, several types of commensal microbiota were common to atherosclerotic plaque and blood or gut samples in 16 cohort studies. For example, Veillonella, Proteobacteria, and Streptococcus were identified among the plaque and fecal samples, whereas Clostridium was commonly identified among blood and fecal samples of patients with CHD. Collectively, our findings suggest that several types of commensal microbiota are associated with CHD, and their presence may correlate with disease markers of CHD.

Gut microbiota and atherosclerosis: role of B cell for atherosclerosis focusing on the gut-immune-B2 cell axis.

Atherosclerosis is the leading cause of cardiovascular mortality and morbidity worldwide and is described as a complex disease involving several different cell types and their molecular products. Recent studies have revealed that atherosclerosis arises from a systemic inflammatory process, including the accumulation and activities of various immune cells. However, the immune system is a complicated network made up of many cell types, hundreds of bioactive cytokines, and millions of different antigens, making it challenging to readily define the associated mechanism of atherosclerosis. Nevertheless, we previously reported a potential persistent inflammatory process underlying atherosclerosis development, centered on a pathological humoral immune response between commensal microbes and activated subpopulations of substantial B cells in the vicinity of the arterial adventitia. Accumulating evidence has indicated the importance of gut microbiota in atherosclerosis development. Commensal microbiota are considered important regulators of immunity and metabolism and also to be possible antigenic sources for atherosclerosis development. However, the interplay between gut microbiota and metabolism with regard to the modulation of atherosclerosis-associated immune responses remains poorly understood. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis, with particular focus on humoral immunity and B cells, especially the gut-immune-B2 cell axis. Graphical abstract Under high-fat and high-calorie conditions, signals driven by the intestinal microbiota via the TLR signaling pathway cause B2 cells in the spleen to become functionally active and activated B2 cells then modify responses such as antibody production (generation of active antibodies IgG and IgG3), thereby contributing to the development of atherosclerosis. On the other hand, intestinal microbiota also resulted in recruitment and ectopic activation of B2 cells via the TLR signaling pathway in perivascular adipose tissue (PVAT), and, subsequently, an increase in circulating IgG and IgG3 led to the enhanced disease development. This is a potential link between microbiota alterations and B cells in the context of atherosclerosis.

Lubiprostone as a potential therapeutic agent to improve intestinal permeability and prevent the development of atherosclerosis in apolipoprotein E-deficient mice.

The interaction between atherosclerosis and commensal microbes through leaky gut syndrome (LGS), which is characterized by impaired intestinal permeability and the introduction of undesired pathogens into the body, has not been fully elucidated. Our aim was to investigate the potential role of a ClC-2 chloride channel activator, lubiprostone, which is reported to have beneficial effects on LGS, in the development of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. After a 15-week feeding period of a Western diet (WD), ApoE-/- mice were treated with a Western-type diet (WD) alone or WD with oral supplementation of lubiprostone for 10 weeks. This feeding protocol was followed by experimental evaluation of LGS and atherosclerotic lesions in the aorta. In mice with lubiprostone, in vivo translocation of orally administered 4-kDa FITC-dextran was significantly improved, and RNA expression of the epithelial tight junction proteins, Zo-1 and occludin, was significantly up-regulated in the ileum, compared to the WD alone group, suggesting a possible reversal of WD-induced intestinal barrier dysfunction. As a result, WD-induced exacerbation of atherosclerotic lesion formation was reduced by 69% in longitudinally opened aortas and 26% in aortic root regions. In addition, there was a significant decrease in circulating immunoglobulin level, followed by an attenuation of inflammatory responses in the perivascular adipose tissue, as evidenced by reduced expression of pro-inflammatory cytokines and chemokines. Lubiprostone attenuates atherosclerosis by ameliorating LGS-induced inflammation through the restoration of the intestinal barrier. These findings raise the possibility of targeting LGS for the treatment of atherosclerosis.

Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study.

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1ß, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

Takotsubo Cardiomyopathy in a Patient with Previously Undiagnosed Hypertrophic Cardiomyopathy with Latent Obstruction.

A 62-year-old woman with takotsubo cardiomyopathy (TCM) accompanied by cardiogenic shock due to the obstruction of left ventricular outflow tract (LVOT) and massive mitral regurgitation (MR) was admitted to the emergency department. After successful treatment with intensive care, dobutamine stress-echocardiography was performed, which reproduced a dynamic LVOT gradient, severe MR and cardiogenic shock. A histological examination obtained from the right ventricular septum demonstrated hypertrophied and bizarre myocytes, with myocyte disarray. Besides TCM, a diagnosis of preexisting hypertrophic cardiomyopathy with latent obstruction was made. She was discharged with medical therapy including a beta-blocker, which would not be routinely employed in the treatment of a patient with TCM.

New non-invasive indexes of arterial stiffness are significantly correlated with severity and complexity of coronary atherosclerosis.

BACKGROUND: Endothelial dysfunction and increased arterial stiffness gradually develop before the manifestation of catastrophic cardiovascular events. Therefore, detection and assessment of vascular function are required to address pre-existing pathological conditions. However, the currently available diagnostic devices and methods are insufficient due to variability among investigators and the time-consuming nature of manual procedures. METHODS: Recently, novel devices were developed for the detection of both arterial stiffness and endothelial dysfunction in a single blood pressure measurement using a cuff-oscillometric technique (AVE-1500, Shisei Datum, Japan). API (arterial pressure volume index) is defined as the reciprocal of the slope of the tangent of the brachial artery pressure-volume curve, and AVI (arterial velocity pulse index) is defined as the ratio of the difference between the ejection and reflection waves. In the present study, we performed retrospective, cross-sectional analyses of subjects (n = 102; mean age = 70.5 ± 10.4 years) with detailed coronary angiographic examinations and clinical background parameters. RESULTS: After adjusting for various variables using multiple linear regression analyses, we found that API, but not AVI, was significantly correlated with coronary artery severity and complexity scores. CONCLUSIONS: We propose that API may be a new vascular index useful for monitoring and assessing the severity and complexity of atherosclerosis in subjects with coronary artery disease and for evaluating atherosclerotic diseases.

Impact of flow-mediated dilatation and coronary calcification in providing complementary information on the severity of coronary artery disease.

BACKGROUND AND AIMS: Endothelial dysfunction and coronary artery calcification (CAC) may represent two distinct and separate processes in the development of coronary atherosclerosis. However, the interaction between these factors in determining the development of coronary artery disease (CAD) is uncertain. METHODS: Brachial artery flow-mediated dilatation (FMD) was measured by high-resolution ultrasound before coronary angiography, in 156 patients undergoing coronary CT angiography on suspicion of CAD (M/F 100/56, age 67 ± 11yrs). CAC score was measured with the Agatston method. RESULTS: The discriminative performance of FMD and CAC score in predicting the presence of type C lesion, multivessel disease, and high SYNTAX score (>22) was determined by ROC curve analysis. The optimal cutoff values for type C lesion were FMD ≤3.70% (AUC 0.663, p = 0.037) and log(CACscore+1)≥ 6.452 (AUC 0.735, p = 0.006). The combination of these cutoff values identified the lesion with the highest predictive accuracy of 82%. In addition, the optimal cutoff values for multivessel disease were FMD ≤5.40% (AUC 0.689, p = 0.001) and log(CACscore+1)≥ 5.914 (AUC 0.731, p = 0.001), while those for high SYNTAX score were FMD ≤4.10% (AUC 0.664, p = 0.020) and log(CACscore+1) ≥6.693 (AUC 0.817, p = 0.001). The combined measurement of each cutoff value identified multivessel disease and high SYNTAX score with predictive accuracy of 77% and 83%, respectively, which were significantly higher than each parameter alone, with the exception of the predictive accuracy of log(CACscore+1) for high SYNTAX score (p = 0.083). CONCLUSIONS: Endothelial dysfunction and CAC may provide complementary information in predicting the extent and severity of coronary artery disease.

Pulmonary Thromboembolism Caused by Prolonged Compression at the Femoral Access Site and a Venous Aneurysm of the Ipsilateral Popliteal Vein.

A 51-year-old female with dilated cardiomyopathy underwent a cardiac catheterization via right common femoral vein and artery. Prolonged compression with a bandage and extension of supine bed rest were needed. Immediately after standing up, she lost consciousness and developed electromechanical dissociation. The echocardiogram revealed a huge thrombus filling the main pulmonary trunk and massive enlargement of right ventricle, which suggested acute pulmonary thromboembolism (PTE). Images of computed tomography taken 2 months later detected a huge venous aneurysm of the right popliteal vein. Prolonged compression at the groin area might enhance blood stasis of the ipsilateral popliteal venous aneurysm, followed by life-threatening PTE.

B-type natriuretic peptide as a predictor of ischemia/reperfusion injury immediately after myocardial reperfusion in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: In animal models of acute myocardial infarction (AMI), B-type natriuretic peptide (BNP) administered before and during coronary occlusion limits infarct size. However, the relation between plasma BNP levels and ischemia/reperfusion injury remains unclear. METHODS: 302 patients with ST-segment elevation AMI (STEMI) received emergency percutaneous coronary intervention within six hours from the onset. The patients were divided into two groups according to the plasma BNP level before angiography: group L (n=151), BNP ≤ 32.2 pg/ml; group H (n=151), BNP >32.2 pg/ml. The Selvester QRS-scoring system was used to estimate infarct size. RESULTS: The rate of ischemia/reperfusion injury immediately after reperfusion, defined as reperfusion ventricular arrhythmias (26% vs. 11%, p=0.001) and ST-segment re-elevation (44% vs. 22%, p=0.008), was higher in group L than in group H. Group L had a greater increase in the QRS score during percutaneous coronary intervention (3.55 ± 0.17 vs. 2.09 ± 0.17, p<0.001) and a higher QRS score 1 h after percutaneous coronary intervention (5.77 ± 0.28 vs. 4.51 ± 0.28, p=0.002). On multivariate analysis, plasma BNP levels in the lower 50th percentile were an independent predictor of reperfusion injury (odds ratio, 2.620; p<0.001). The odds ratios of reperfusion injury according to decreasing quartiles of BNP level, as compared with the highest quartile, were 1.536, 3.692 and 4.964, respectively (p trend=0.002). CONCLUSIONS: Plasma BNP level before percutaneous coronary intervention may be a predictor of ischemia/reperfusion injury and the resultant extent of myocardial damage. Our findings suggest that high plasma BNP levels might have a clinically important protective effect on ischemic myocardium in patients with STEMI who receive percutaneous coronary intervention.

Impact of n-3 polyunsaturated fatty acids in predicting ischemia/reperfusion injury and progression of myocardial damage after reperfusion in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: In animal models of acute myocardial infarction, n-3 polyunsaturated fatty acids (PUFAs) administered before coronary occlusion have been suggested to prevent induction of ventricular arrhythmia and limit infarct size. However, the relation between the serum levels of n-3 PUFAs and ischemia/reperfusion (I/R) injury remains unclear. METHODS: 211 patients with ST-segment elevation acute myocardial infarction received emergency percutaneous coronary intervention (PCI) within 6h from the onset. The patients were divided into two groups according to the sum of serum eicosapentaenoic acid (EPA) levels and docosahexaenoic acid (DHA) levels before PCI: group L (n=106), EPA+DHA <155µg/ml and group H (n=105), EPA+DHA ≥155µg/ml. The Selvester QRS-scoring system was used to estimate the serial change in infarct size. RESULTS: Time to reperfusion was similar between the 2 groups. The QRS score before PCI was higher in group L than in group H (2.42±2.00 vs 1.85±2.01, p=0.015). The proportion of patients with I/R injury immediately after reperfusion, defined as reperfusion ventricular arrhythmias (25% vs 11%, p=0.006) and ST-segment re-elevation (44% vs 22%, p<0.001), was also higher in group L than in group H, followed by a greater increment in the QRS score during PCI (3.51±2.51 vs 2.54±1.91, p=0.006) and higher peak levels of creatinine phosphokinase (3552±241U/L vs 2660±242U/L, p<0.01). On multivariate analysis, serum level of EPA+DHA was an independent predictor of reperfusion injury (odds ratio 0.985, p=0.032). CONCLUSION: Serum level of n-3 PUFAs before PCI may be a predictor of I/R injury and the resultant extent of myocardial damage. These findings suggest a protective effect of serum n-3 PUFAs on ischemic myocardium.

Refractory vasospasms of the coronary arteries due to multiple factors: an autopsy case.

A 41-year-old man was admitted with decompensated heart failure. Mechanical ventilation was maintained with a large dose of propofol. On day 4, significant ST elevation with complete atrioventricular block was noted, which subsequently induced cardiopulmonary arrest. Treatment with percutaneous cardiopulmonary support and therapeutic hypothermia was initiated. Emergent cardiac angiography showed simultaneous multivessel coronary spasms. Although nitroglycerin and nicorandil were ineffective, the intracoronary administration of fasudil, a Rho-kinase inhibitor, successfully resolved the vasospasms. However, during rewarming, the coronary vasospasms recurred, and the patient died of cardiogenic shock. In addition to hypertrophy, the autopsied heart demonstrated the accumulation of inflammatory cells in the pericardium and adventitia of the coronary arteries.

Longitudinal stent deformation elongating to left main trunk.

A 67-year-old woman was admitted with an acute coronary syndrome. Angiographic examination revealed diffuse severe stenosis of the left circumflex artery. A Pressure Wire Certus (St. Jude Medical, St. Paul, MN, USA) was passed to the second post-lateral (PL) branch. To prevent side-branch occlusion, a SION wire (Asahi Intecc Co., Aichi, Japan) was left in the first PL branch, and a SION blue wire (Asahi Intecc) was placed in the second obtuse marginal branch. We implanted an everolimus-eluting stent (PROMUS Element 2.5 × 24 mm, Boston Scientific, Natick, MA, USA) in the culprit lesion. After retrieving the protection wire in first PL branch with resistance, we performed post-dilatation. However, the intravascular ultrasound images showed that the proximal portion of the implanted stent had elongated approximately 2 mm to the left main trunk (LMT), although the position of the distal edge of the stent was unchanged. We decided to additionally place a stent from the ostium of the LMT to the proximal left anterior descending coronary artery, and a biolimus-eluting stent (NOBORI 3.0 × 18 mm, Terumo Co., Tokyo, Japan) was implanted successfully. Longitudinal stent elongation might be caused by the small number of links between the hoops of a stent, originally intended to improve deliverability.

Congenital aortopulmonary artery fistulas combined with bilateral coronary artery fistulas.

We describe an extremely rare case of "congenital aorto-pulmonary artery fistulas" combined with bilateral coronary artery fistulas associated with clinically significant left-to-right shunt. A multi-detector row computed tomographic scan revealed that tortuous anomalous vessels arising from the aortic arch, left anterior descending coronary artery, diagonal branch, and right coronary artery were connected to the main pulmonary trunk. After surgical intervention, the systemic-to-pulmonary flow ratio nearly normalized from 2.02 to 1.05. We describe the case and speculate as to the embryological pathogenesis of these unique fistulas.

Plaque Tissue Components Obtained from De Novo Lesions may Predict Restenosis after Directional Coronary Atherectomy.

BACKGROUND: A part of coronary stenotic lesions treated with directional coronary atherectomy (DCA) occur restenosis several months later. Specimens obtained by first DCA, present the histology of culplit lesions and may predict restenosis after PCI. METHODS: The study group comprised 76 patients (male/female 65/11, age 61 ± 11 years). Restenosis, defined as > 50% stenosis diameter by quantitative cineangiography, was present in 26 patients. The other 50 patients (< 50% stenosis) constitute the "no restenosis" group. Inflammatory cells and other atheroma components were planimetrically quantified as a percentage of total tissue area. RESULTS: As regards lymphocytes, neutrophils and smooth muscle cells, the grade of amount of cells did not differ between restenosis group and no restenosis group. The amount of obtained arterial media was similar, too. However, the area occupied by macrophages or calcified fragments was significantly larger in restenosis group than no restenosis group. And there was a tendency toward larger area occupied by cholesterol gruel, thrombus and myxomatous extracellular matrix (ECM) in restenosis group. CONCLUSION: Rich macrophages infiltration, calcified fragments, cholesterol rich gruel and myxomatous ECM from primary lesions can be predictors of restenosis after DCA, suggesting a possible role in restenotic process after PCI.

Significant association between neutrophil aggregation in aspirated thrombus and myocardial damage in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: This study was designed to clarify the relationship between myocardial damage and platelet-neutrophil aggregation in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 107 patients with ST-segment elevation AMI, in whom aspiration catheter was used during emergency percutaneous coronary intervention. Patients were divided into 2 groups according to the cellular density of neutrophils in the aspirated sample: group L (n=53), 100 neutrophils/0.025 mm(2) thrombus. Myocardial blush grade (MBG)

[Giant rheumatoid nodule causing simultaneous complete atrioventricular block and severe mitral regurgitation: a case report].

A 65-year-old female was first treated under a diagnosis of rheumatoid arthritis at the age of 62 years. Just after subcutaneous rheumatoid nodules appeared, she suddenly complained of shortness of breath and vomiting. The diagnosis was overt congestive heart failure with complete atrioventricular block and severe mitral regurgitation. She was treated with temporary pacing, and a permanent pacemaker was implanted 1 month later. She suffered recurrence of congestive heart failure and died 8 months later. Autopsy revealed a giant rheumatoid nodule located on the mitral valve and extending to the atrioventricular node. Presumedly this solitary giant nodule had induced complete atrioventricular block and severe mitral regurgitation.