Yasuyuki Mochida

New electrocardiographic criteria for predicting the site of coronary artery occlusion in inferior wall acute myocardial infarction

In patients with inferior wall acute myocardial infarction (AMI), the site of the culprit lesion is an important determinant of outcome. Patients with right ventricular infarction have a poor prognosis, whereas those with occlusion of the left circumflex coronary artery (LCx) have a good prognosis. Therefore, we assessed whether standard 12-lead electrocardiograms obtained on admission could identify the site of coronary artery occlusion, (i.e., a site proximal to the origin of the right ventricular branch of the right coronary artery [RCA], a site distal to the origin of the right ventricular branch of the RCA, or a site in the LCx). The ratio of ST depression in lead V3 to ST elevation in lead III (V3/III ratio) was evaluated immediately before coronary angiography in 152 patients with a first inferior wall AMI confirmed by coronary angiography within 12 hours after the onset of symptoms. For occlusion of the proximal RCA, distal RCA, and LCx, V3/III ratio was 0.2+/-0.3, 0.8+/-0.5, and 2.5+/-2.5 (p = 0.0001), respectively. The V3/III ratio <0.5 identified proximal RCA occlusion, 0.5 <V3/III ratio < or = 1.2 identified distal RCA occlusion, and 1.2 <V3/III ratio identified LCx occlusion with sensitivities of 91%, 84%, and 84%, and specificities of 91%, 93%, and 95%, respectively. We conclude that the V3/III ratio is useful in predicting the site of coronary artery occlusion in patients with inferior wall AMI.

Angiotensin-Converting Enzyme Gene Polymorphism Adds Risk for the Severity of Coronary Atherosclerosis in Smokers

To investigate the relation between the angiotensin-converting enzyme (ACE) gene polymorphism and acute coronary syndromes with respect to environmental factors, we analyzed the association of genotype with the coronary angiographic findings of patients with acute myocardial infarction or unstable angina pectoris, and we examined the linkage of each genotype with established risk factors for coronary artery disease. We determined the ACE genotype in 152 Japanese patients with acute coronary syndromes and 399 healthy individuals. The genotype distributions were not different between the two groups (P=.74, chi2 test). In the former group, coronary angiograms were evaluated by criteria based on the number of diseased vessels, the number of stenotic lesions (> or = 50%), and the relative abnormal arterial portion (extent index). Although the number of stenotic lesions was higher in patients with the DD genotype than in those with the ID or II genotype (P=.006), there were no differences in the number of diseased vessels or the extent index. When only smokers were analyzed, the number of diseased vessels (P=.032), number of stenotic lesions (P=.003), and extent index (P=.019) were all higher in patients with the DD genotype than in those with the ID or II genotype. In contrast, these differences in the respective parameters did not exist in nonsmokers. The results indicate smoking-associated effects of the ACE genotype on the severity of coronary atherosclerosis.

A case of giant coronary artery aneurysm and literature review

A 40-year-old man was referred to our hospital because of an abnormal shadow on the left cardiac border on the chest roentgenogram at the regular medical health examination without any symptoms. A giant coronary artery aneurysm of left anterior descending artery with a maximum diameter of approximately 50 mm was detected with computed tomography and coronary angiography. The patient was treated and followed up medically. Four years later, the size of the coronary artery aneurysm became larger. Then resection of the coronary artery aneurysm and coronary artery bypass grafting were successfully performed. Coronary artery aneurysms are rare in adults and are usually found in association with Kawasaki disease, coronary atherosclerosis, and so on. We also review the literature of giant coronary artery aneurysms exceeding 50 mm in diameter.

Sustained Inhibition of Oxidized Low-Density Lipoprotein Is Involved in the Long-Term Therapeutic Effects of Apheresis in Dialysis Patients

Objective—Low-density lipoprotein (LDL) apheresis is a potential therapy for conventional therapy–resistant peripheral artery disease. In the present study, we examined the chronic effects of LDL apheresis on clinical parameters in vivo and endothelial cell functions in vitro in hemodialysis patients who had the complication of peripheral artery disease. Methods and Results—Twenty-five patients were enrolled, and the responses of 19 patients to LDL apheresis were analyzed. Patients were classified into 2 groups according to change in ankle-brachial pressure index (ABI) after treatment: patients with improved ABI (responders, n=10) and patients with worsened ABI (nonresponders, n=9). In the responders, apheresis resulted in a long-term reduction of circulating levels of oxidized LDL, C-reactive protein, and fibrinogen. In human umbilical vein endothelial cells (HUVECs), the serum from the responders increased expression of activated endothelial nitric oxide synthase protein and proliferative activity. Furthermore, there was a significant correlation between ABI and activated endothelial nitric oxide synthase protein level in HUVECs treated with responder serum (R=0.427, P<0.05). Conclusion—These results demonstrate that LDL apheresis decreases oxidized LDL and inflammation and improves endothelial cell function in the responders. This may be one of the mechanisms involved in the long-term therapeutic effect of LDL apheresis on peripheral circulation in hemodialysis patients.

Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease

OBJECTIVE To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin. METHODS Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks. RESULTS Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks. CONCLUSION Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.

Clinical usefulness of ECG-gated18F-FDG PET combined with99mTc-MIBI gated SPECT for evaluating myocardial viability and function

ObjectivesThis study sought to evaluate an imaging approach using gated99mTc-MIBI (MIBI) SPECT and gated18F-FDG (FDG) PET for assessment of myocardial viability and cardiac function.MethodsForty-eight patients (38 men, mean age 68.1 ± 9.6 years) underwent ECG-gated FDG PET and MIBI SPECT within a week. The baseline diagnoses were coronary artery disease (31), mitral regurgitation (1), paroxysmal arrhythmia (10), and dilated cardiomyopathy (6). The gated FDG PET data were analyzed using pFAST software, and the gated MIBI SPECT data were analyzed using QGS software. Fifteen patients were diagnosed with myocardial infarction, and follow-up study was performed to assess the functional outcome four months later. An improvement in LVEF of >5% was defined as significant. The LV myocardium was divided into 17 segments, and regional defect scores were visually assessed using a 4-point scale for each segment (0 = normal, 1 = mildly reduced, 2 = moderately reduced, 3 = absent). A segment with a greater defect score on MIBI SPECT than on FDG PET was defined as a mismatch. The patients were divided into two groups: those with at least two mismatched segments (MM-group), and those with none or one (M-group).ResultsLVEF, EDV and ESV measured by gated FDG PET were highly correlated with those obtained by gated MIBI SPECT (r = 0.848, 0.855 and 0.911, p < 0.0001, respectively). The mean values of LVEF did not differ significantly, but EDV and ESV obtained by gated FDG PET were significantly grater than those obtained by gated MIBI SPECT (p < 0.0001). In 15 patients diagnosed with myocardial infarction, a significant association (p < 0.05) was found between the relative uptake of FDG PET and MIBI SPECT and the functional outcome 4 months later. Global LV function improved in 6 of the 8 patients showing mismatch but in only 1 of the 7 patients with matched defects, resulting in a sensitivity of 86% and specificity of 75%. The overall accuracy to predict global functional outcome was high (80%).ConclusionThis imaging approach allows accurate evaluation of myocardial viability. Furthermore, the high correlations of gated FDG PET and gated MIBI SPECT measurements hold promise for the assessment of left ventricular function using gated FDG PET.

Polymorphism of the type 6 adenylyl cyclase gene and cardiac hypertrophy.

Summary: We investigated whether polymorphism of the type 6 adenylyl cyclase gene influences the occurrence of left ventricular hypertrophy in a Japanese population. Type 6 adenylyl cyclase is a major cardiac adenylyl cyclase isoform and plays an important role in regulating cardiac function. We examined the type 6 adenylyl cyclase gene for single nucleotide polymorphism by heteroduplex analysis and found a mutation (T11215A) in intron 17. We genotyped the single nucleotide polymorphism (TT/TA/AA groups) by the mutagenically separated polymerase chain reaction method in 2068 subjects who underwent health screening for cardiovascular disease. Genetic variation was in the Hardy‐Weinberg equilibrium. We found no significant association between the frequency of left ventricular hypertrophy and any of the genotype groups. In the TT and the TA genotype group, however, left ventricular hypertrophy was associated with increased blood pressure, while no association with increased blood pressure was found in the AAgenotype group. It was concluded that the AA group may be at risk of developing left ventricular hypertrophy independent of increased blood pressure.

LONG-TERM EFFECT OF EZETIMIBE-STATIN COMBINATION THERAPY ON LOW-DENSITY LIPOPROTEIN CHOLESTEROL LOWERING IN PATIENTS WITH CORONARY ARTERY DISEASE; FOCUS ON CHOLESTEROL ABSORPTION AND SYNTHESIS

Authors: Kozo Okada, Kazuki Fukui, Hideo Himeno, Tutomu Endo, Makoto Shimizu, Shunichi Kobayashi, Tomohiko Shigemasa, Yukiko Morita, Atsushi Wada, Tomoaki Shimizu, Yasuyuki Mochida, Reimin Sawada, Tomoaki Ishigami, Kazuaki Uchino, Noriaki Iwahashi, Kazuo Kimura, Satoshi Umemura, Division of Cardiology, Yokohama City Univercity Medical Center, Yokohama , AL, Japan, Department of Cardiology, Yokohama City Univercity Hospital, Yokohama, AL, Japan

EFFECT OF EZETIMIBE PLUS LOW-DOSE ATORVASTATIN VERSUS DOUBLE-DOSE ATORVASTATIN ON INSULIN RESISTANCE AND LIPID METABOLISM IN CORONARY ARTERY DISEASE PATIENTS WITH OR WITHOUT METABOLIC SYNDROME

Background: Anti-hyperlipidemic treatment is one of the main treatment in the management of coronary artery disease (CAD). LDL-C goal of patients with CAD is defined <100mg/dl by Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. The effect of ezetimibe on insulin resistance and lipid profile in CAD patients with and without metabolic syndrome(METS) remains unclear. In this study we examined the effect of high-dose atorvastatin and low-dose atorvastatin plus ezetimibe therapy on insulin resistance and lipid metabolism in CAD patients with and without METS.