Masakazu Ogawa

Homocysteine and hemostatic disorder as a risk factor for myocardial infarction at a young age

INTRODUCTION Hyperhomocysteinemia is a coronary risk factor, but its pathophysiologic mechanism remains unclear. MATERIALS AND METHODS The importance of hyperhomocysteinemia in the pathogenesis of early myocardial infarction, was determined in case-control study of 127 men with a first early myocardial infarction <or=45 years and 150 age-matched male controls. We measured plasma concentrations of homocysteine, fibrinogen, antithrombin, tissue factor, tissue factor pathway inhibitor, tissue plasminogen activator, plasminogen activator inhibitor-I, plasminogen, alpha(2)-antiplasmin, lipoprotein(a), protein C, protein S, factor VII, and activated factor VII. RESULTS Homocysteine concentrations were higher in patients with early myocardial infarction than in controls (11.2+/-5.3 and 8.3+/-5.0 micromol/l, respectively, P<0.001). Hyperhomocysteinemia was associated with early myocardial infarction (odds ratio=2.22, P<0.001) by multivariate logistic regression analysis. Tissue factor, antithrombin, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor-I, lipoprotein(a), diabetes, and smoking also had associations. In a stepwise logistic regression analysis, hyperhomocysteinemia was the strongest predictor of early myocardial infarction (R(2)=0.19, P<0.001). Hyperhomocysteinemia also had positive correlations with tissue factor (rho=0.26, P=0.009), tissue factor pathway inhibitor (rho=0.23, P=0.020), and tissue plasminogen activator (rho=0.25, P=0.011) in patients with early myocardial infarction, but not in controls. CONCLUSIONS Hyperhomocysteinemia is an independent risk factor for early myocardial infarction, and is associated with a hypercoagulable state mediated by the extrinsic coagulation cascade.

Effect of Right Ventricular Apex Pacing on the Tei Index and Brain Natriuretic Peptide in Patients with a Dual‐Chamber Pacemaker

Background: Asynchronous electrical activation induced by right ventricular apex (RVA) pacing can cause various abnormalities in left ventricular (LV) function, particularly in the context of severe LV dysfunction or structural heart disease. However, the effect of RVA pacing in patients with normal LV and right ventricular (RV) function has not been fully elucidated. The aim of this study was to characterize the effects of RVA pacing on LV and RV function by assessing isovolumic contraction time and isovolumic relaxation time divided by ejection time (Tei index) and by assessing changes in plasma brain natriuretic peptide (BNP).

Time-course of Toll-like receptor 2 expression, as a predictor of recurrence in patients with bacterial infectious diseases

The clinical course of bacterial infectious diseases is often variable, especially in elderly patients. Thus, new biological markers have been sought to predict the disease outcome. Recent studies have revealed that Toll‐like receptor (TLR) 2 and/or TLR4 on circulating monocytes are significantly up‐regulated in bacterial infections. However, the lack of reliable quantification methods hampers extensive study on the modulation of these molecules in response to the patients clinical condition. In this study, we developed a new quantitative flow cytometric analysis system for TLR2. We then carried out a longitudinal study on TLR2 expression levels on monocytes from patients suffering from bacterial infectious diseases during and after antibiotic treatment. The clinical outcome divided 37 patients into ‘cure’ (n = 24) and ‘recurrence’ (n = 13) groups. A significant difference between the two groups was recognized in the TLR2 levels just after antibiotic treatment (antibody‐binding sites/cell, 4395 ± 784 versus 5794 ± 1484, P < 0·001). The risk of recurrence was associated significantly with TLR2 (P < 0·001), but not C‐reactive protein (P = 0·351) levels assayed during the first remission. Furthermore, antibiotic effectiveness was associated inversely with TLR2 levels during antibiotic administration (P < 0·001). Taken together, TLR2 expression levels on monocytes provide critical information for planning treatment against bacterial infectious diseases.

Comparison of effect between nitrates and calcium channel antagonist on vascular function in patients with normal or mildly diseased coronary arteries

The comparative long-term antianginal efficacy of long-acting nitrates versus calcium channel antagonists remains unclear. The goal of the present study was to compare the coronary endothelial cell function and coronary artery vasoconstriction between patients with normal or mildly diseased coronary arteries treated with long-acting nitrates or calcium channel antagonists. Forty-two patients suspected to have angina pectoris and with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. All patients were suspected to have angina pectoris and were receiving either long-acting nitrates (n = 18; Nitrates group) or calcium channel antagonists (n = 24; Ca-antagonists group) for at least 1 year. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Segments that showed the greatest constrictive response to Ach were used for assessment of vasoconstriction. The percent increase in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach was significantly smaller in the Nitrates group than in the Ca-antagonists group (33% ± 74% vs 83% ± 77%, P < 0.05; −3% ± 16% vs 11% ± 12%, P < 0.01, respectively). The percent diameter reduction in the region of greatest constrictive response to Ach was significantly greater in the Nitrates group than in the Caantagonists group (44% ± 39% vs 15% ± 32%, P < 0.02). Long-term treatment with long-acting nitrates may produce less favorable effects on coronary endothelial function and the constrictive response to Ach when compared with long-acting calcium channel antagonists in patients with normal or mildly diseased coronary arteries.

Left atrium volume index and pathological features of left atrial appendage as a predictor of failure in postoperative sinus conversion

BACKGROUND Previous studies showed that some parameters, including left atrium diameter and left atrium volume index (LAVI), predicted the success of sinus conversion. However, no previous studies have investigated the association of sinus conversion with LAVI and histopathological findings. This study was designed to investigate the relationship among LAVI, pathological assessment, and failure in sinus conversion after surgery for valvular atrial fibrillation (AF). METHODS AND RESULTS A total of 78 patients with left atrium enlargement and valvular AF who underwent maze procedure concomitantly with various cardiac surgeries were classified into one of two groups: those who successfully underwent sinus conversion (Group 1; n=40) and those who did not achieve sinus conversion (Group 2; n=38). Histopathological assessment was performed in 9 cases using tissues derived from the left atrial appendage (LAA). The degree of histopathological change was classified into 1 of 4 grades. LAVI was significantly less in Group 1 than in Group 2 (81 + or - 22 ml/m(2) vs. 122 + or - 49 ml/m(2), p<0.001). Preoperative LAVI predicted 100% failure of sinus conversion after surgery with a cut-off value of 135 ml/m(2). Histopathological analyses clearly showed that the grades for intercellular fibrosis, fatty infiltration, endocardial thickening, and nuclear enlargement/abnormalities were significantly and positively correlated with LAVI (r=0.75, p<0.05; r=0.74, p<0.05; r=0.69, p<0.05; r=0.77, p<0.05, respectively). CONCLUSIONS LAVI associated with histopathological features of the resected LAA is a predictor of failure in sinus conversion following surgical intervention in patients with valvular AF.

Plasma Level of Triglyceride-rich Lipoprotein Remnants Is Closely Associated with the Activation of Coagulation Factor VII in Patients with Myocardial Infarction

Remnant-like particles, which have been recognized to be atherogenic derivatives of chylomicrons and very low density lipoproteins, can be measured using a new assay kit. The purpose of the present study was to investigate the association of remnant-like particles with the coagulation system that has an important role in the pathogenesis of myocardial infarction. We assayed blood levels of total cholesterol, triglyceride, HDL-cholesterol, apolipoproteins, remnant-like particles-cholesterol, remnant-like particles-triglyceride, fibrinogen, factor VII antigen, activated factor VII, and tissue factor in 111 patients with a history of myocardial infarction and 128 control subjects. In simple regression analysis, plasma levels of remnant-like particles-cholesterol and remnant-like particles-triglyceride showed a significant positive correlation with the levels of activated factor VII (r=0.319, p<0. 001, and r=0.286, p=0.002, respectively) and the activated factor VII/factor VII antigen ratio (r=0.241, p=0.011, and r=0.249, p=0.008, respectively) in patients with myocardial infarction. In contrast, there were no significant differences between remnant-like particles and activated factor VII in control subjects. In stepwise multivariate regression analysis, the significant determinants of activated factor VII were remnant-like particles-cholesterol (10.2%), apolipoproteins A-I (5.1%), and E (7.1%); for the activated factor VII/factor VII antigen ratio, remnant-like particles-triglyceride (6. 2%), age at blood sampling (5.1%), and apolipoprotein A-I (4.0%) in patients with myocardial infarction. However, the significant determinants of activated factor VII and the activated factor VII/factor VII antigen ratio were HDL-cholesterol (9.9% and 9.2%, respectively) in control subjects. It is concluded that remnant-like particles may be a risk factor for myocardial infarction by activating the extrinsic coagulation pathway.

Relationship between hyperglycemia and coronary vascular resistance in non-diabetic patients

BACKGROUND Hyperglycemia upon hospital admission in patients with acute myocardial infarction is associated with the no-reflow phenomenon after successful reperfusion, and increased mortality. However, the mechanism underlying this phenomenon remains unclear. Therefore, the aim of this study was to characterize coronary hemodynamics in a homogenous group of non-diabetic patients without coronary artery disease. METHODS AND RESULTS A total of 104 consecutive non-diabetic patients (mean age, 62+/-14 years) without coronary artery disease underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined by intra-coronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Coronary vascular resistance (CVR) was calculated as the mean arterial pressure divided by coronary blood flow (CBF). Baseline CVR was shown as CVR at control and minimal CVR was shown as CVR with papaverine administration. Fasting plasma glucose (FPG) level had a significant, positive correlation with baseline CVR and minimal CVR (r=0.24, p<0.02 and r=0.21, p<0.05, respectively). Hemoglobin A1c (HbA1c) also had a significant, positive correlation with baseline CVR and minimal CVR (r=0.31, p<0.01 and r=0.32, p<0.01, respectively). The percent change in CBF induced by Ach was inversely correlated with HbA1c but not with FPG (r=0.22, p<0.05 and r=0.06, p=0.57, respectively). By contrast, neither FPG nor HbA1c had significant correlation with coronary flow reserve to papaverine. CONCLUSION These data demonstrate that elevated glucose levels are associated with increases in baseline and minimal coronary vascular resistance. These changes may contribute to unfavorable coronary hemodynamics in non-diabetic patients without coronary heart disease.

Enjoying hobbies is related to desirable cardiovascular effects

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 ± 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% ± 77% vs 25% ± 37%, P < 0.05, 4% ± 13% vs −3% ± 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

A case of acute coronary syndrome caused by delayed coronary ischemia after transcatheter aortic valve implantation

An 84-year-old female patient suffered from dyspnea due to severe aortic stenosis. Several comorbidities and her advanced age made her acceptable for transcatheter aortic valve implantation (TAVI). The TAVI procedure was performed via a femoral access and a 26-mm CoreValve prosthesis (Medtronic, Minneapolis, MN, USA) was implanted. The prosthesis was deployed at a high position because of short distance between the annulus base and coronary arteries. Aortic angiography indicated normal contrast flow into both coronary arteries. Six months later she was readmitted to our hospital because of acute coronary syndrome. Although selective intubation of coronary arteries could not be achieved because of high valve position, both coronary arteries seemed to be well contrasted. As a consequence, the second coronary angiography was undertaken because of recurring chest pains. The aortic root angiogram showed a decreased contrast flow into both coronary arteries. During the examination she deteriorated rapidly, developed cardiopulmonary arrest, and a percutaneous cardiopulmonary support and an intra-aortic balloon pump needed to be inserted. She was then transferred to the operating room for aortic valve replacement. This is the first case of delayed coronary ischemia after TAVI, necessitating the removal of an implanted CoreValve and its replacement with a new prosthetic valve. <Learning objective: The higher position of the CoreValve implanted in the transcatheter aortic valve implantation (TAVI) procedure can rarely induce coronary obstruction, especially in patients with low lying coronary ostia and a small sinus of Valsalva. Percutaneous coronary intervention and coronary artery bypass graft are sometimes difficult in these patients, and replacement of the prosthetic valve may be an alternative. Patients with higher CoreValve position require close follow up to recognize any coronary perfusion defects at an early stage.>.