Satoshi Ichimiya

Impact of a Single Intravenous Administration of Nicorandil Before Reperfusion in Patients With ST-Segment–Elevation Myocardial Infarction

Background—Intravenous nicorandil, a hybrid compound of ATP-sensitive potassium channel opener and nitric oxide donor, has been reported to ameliorate early functional and clinical problems in patients with acute myocardial infarction. However, its effects on the late phase remain unclear. Methods and Results—This follow-up study to 5 years of a randomized, double-blinded trial was conducted among 368 patients with first ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). They were randomly assigned to receive 12 mg of nicorandil or a placebo intravenously just before reperfusion. We analyzed incidence of cardiovascular death or rehospitalization for congestive heart failure after PCI as well as various aspects of epicardial flow and microvascular function. Mean follow-up was 2.4 years (SD, 1.4). A total of 12 (6.5%) patients receiving nicorandil and 30 (16.4%) receiving placebo had cardiovascular death or hospital admission for congestive heart failure (hazard ratio, 0.39; 95% CI, 0.20 to 0.76; P=0.0058). Postprocedural TIMI 3 flow was obtained in 89.7% of the nicorandil group and in 81.4% of the placebo (hazard ratio, 1.99; 95% CI, 1.09 to 3.65; P=0.025). Corrected TIMI frame count was furthermore lower in the nicorandil group (21.0±9.1 versus 25.1±14.1; P=0.0009). ST-segment resolution >50% was observed in 79.5% and 61.2% of the nicorandil and placebo groups, respectively (hazard ratio, 2.45; 95% CI, 1.54 to 3.90; P=0.0002). Conclusions—The addition of intravenous nicorandil to PCI leads to beneficial clinical outcomes and prevents cardiovascular events of long duration and death in patients with ST-segment–elevation myocardial infarction.

Comparison Between Valsartan and Amlodipine Regarding Cardiovascular Morbidity and Mortality in Hypertensive Patients With Glucose Intolerance: NAGOYA HEART Study

It has not been fully examined whether angiotensin II receptor blocker is superior to calcium channel blocker to reduce cardiovascular events in hypertensive patients with glucose intolerance. A prospective, open-labeled, randomized, controlled trial was conducted for Japanese hypertensive patients with type 2 diabetes mellitus or impaired glucose tolerance. A total of 1150 patients (women: 34%; mean age: 63 years; diabetes mellitus: 82%) were randomly assigned to receive either valsartan- or amlodipine-based antihypertensive treatment. Primary outcome was a composite of acute myocardial infarction, stroke, coronary revascularization, admission attributed to heart failure, or sudden cardiac death. Blood pressure was 145/82 and 144/81 mm Hg, and glycosylated hemoglobin was 7.0% and 6.9% at baseline in the valsartan group and the amlodipine group, respectively. Both of them were equally controlled between the 2 groups during the study. The median follow-up period was 3.2 years, and primary outcome had occurred in 54 patients in the valsartan group and 56 in the amlodipine group (hazard ratio: 0.97 [95% CI: 0.66–1.40]; P=0.85). Patients in the valsartan group had a significantly lower incidence of heart failure than in the amlodipine group (hazard ratio: 0.20 [95% CI: 0.06–0.69]; P=0.01). Other components and all-cause mortality were not significantly different between the 2 groups. Composite cardiovascular outcomes were comparable between the valsartan- and amlodipine-based treatments in Japanese hypertensive patients with glucose intolerance. Admission because of heart failure was significantly less in the valsartan group.

Correlation between circulating adiponectin levels and coronary plaque regression during aggressive lipid-lowering therapy in patients with acute coronary syndrome: Subgroup analysis of JAPAN-ACS study

OBJECTIVE The Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering therapy with a statin resulted in a significant regression of coronary atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived protein with anti-atherogenic properties. Here, we investigated the association between adiponectin levels and the change in the plaque volume in ACS patients. METHODS Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and 12 months after the PCI. The percent change in the plaque volume (%PV) in a non-culprit coronary artery segment was evaluated. The serum adiponectin and lipid parameters were measured both at baseline and at the follow-up. RESULTS At baseline, adiponectin was correlated positively with HDL-cholesterol and negatively correlated with triglyceride, but no correlation was observed with the PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in adiponectin was also associated with an increase of HDL-cholesterol and decrease of triglyceride, however, no significant correlation was observed with the %PV. A significantly higher incidence of major adverse cardiac events (MACE) was observed in patients with hypo-adiponectinemia at baseline. A multiple logistic regression analysis identified adiponectin as a significant independent predictor of MACE. CONCLUSION Adiponectin levels measured after PCI could serve as a marker of MACE in patients with ACS.

Impact of pitavastatin on high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome: The PREMIUM Study

BACKGROUND Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted. PURPOSE To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial. METHODS This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks. RESULTS In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009). CONCLUSION Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.

Relation Between Estimated Glomerular Filtration Rate and Composition of Coronary Arterial Atherosclerotic Plaques

It is well known that chronic kidney disease is a risk factor for atherosclerosis. The present study was conducted to identify any relation between the estimated glomerular filtration rate (eGFR) and coronary plaque characteristics using integrated backscatter intravascular ultrasound (IB-IVUS), which can detect coronary plaque composition. We performed IB-IVUS for 201 consecutive patients undergoing percutaneous coronary intervention, and they were divided into 3 groups according to the eGFR values (group 1 [n = 20], ≥90 ml/min/1.73 m(2); group 2 [n = 123], 60 to 90 ml/min/1.73 m(2); and group 3 [n = 58], <60 ml/min/1.73 m(2)). Coronary plaques in nonculprit lesions on 3-dimensional analysis were evaluated using IB-IVUS. The baseline characteristics were similar, except for older age and a greater prevalence of men in group 3. IB-IVUS showed a percentage of lipid volume of 44.7 ± 5.0% in group 1, 53.6 ± 6.2% in group 2, and 63.5 ± 6.2% in group 3 (p <0.01), with a corresponding percentage of fibrous volume of 53.9 ± 4.9%, 45.1 ± 6.0%, and 35.3 ± 6.1%, respectively (p <0.01). The eGFR correlated significantly with both parameters (r = -0.68, p <0.001 and r = 0.68, p <0.001, respectively). In conclusion, lower eGFR levels were associated with greater lipid and lower fibrous contents, contributing to coronary plaque vulnerability.

Apex and subxiphoid approaches to Ebstein's anomaly using cross-sectional echocardiography

Abstract Apex and subxiphoid cross-sectional echocardiography was performed with an electronic sector scan on 11 patients having Ebsteins anomaly, isolated or associated with other cardiac diseases. For control study, 10 normal subjects and 10 ASD patients were similarly examined. In the apical four-chamber view, the displacement of the STL was measured in end-diastole using 8 mm. cinematography. It ranged from 1.4 to 3.2 cm., with an average of 2.1 ± 0.5 cm. in eight out of the 11 patients, whereas in control subjects, there was no displacement of the STL. From the apical three-chamber view of the right side of the heart, the downward displacement of the STL into the right ventricular cavity was also clearly visualized, as well as the tricuspid valve ring. Thus, the right-sided heart was seen to be divided into the functional and atrialized right ventricles and the right atrium by the displacement of the STL. In addition, the CT inserting into the ATL was observed in five cases from the three-chamber view and in four instances from the four-chamber view. The interpretable subxiphoid cross-sectional images were obtained in nine of the 11 patients. The right and left sides of the heart were widely visualized and the elongated ATL was fully observed from the tip to the thickened root. Moreover, the CT inserting into the ATL was visualized in six out of the nine patients.

Impact of Admission Anemia on Coronary Microcirculation and Clinical Outcomes in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Microvascular dysfunction after primary percutaneous coronary intervention (PCI) augments myocardial damage and prognosis in acute myocardial infarction. However, the relationship between baseline anemia and coronary microcirculation in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. We performed primary PCI in 337 consecutive patients with STEMI. Anemia was defined as a hemoglobin level < 13 g/dL in men and < 12 g/dL in women. Admission anemia was present in 17.5% of the patients enrolled. Data on epicardial coronary flow, STsegment resolution (STR) on electrocardiography, myocardial injury, and the incidence of adverse cardiac events defined as cardiac death or hospitalization for congestive heart failure were analyzed. The median follow-up period was 54.8 months. Despite comparable epicardial coronary flow, the rate of STR ≥ 50% was lower in anemic patients compared with non-anemic patients (55.9% versus 71.2%, P = 0.02). On multivariate logistic regression analysis, baseline anemia was an independent negative predictor of STR ≥ 50% (odds ratio, 0.53; 95% confidence interval: 0.31-0.92, P = 0.03). Moreover, anemic patients had higher maximum creatine kinase levels normalized for body surface area (2,215 ± 1,318 IU/L/m(2) versus 1,797 ± 1,199 IU/L/m(2), P = 0.047). Anemia remained an independent significant predictor of adverse events on multivariate Cox proportional hazard analysis (hazard ratio, 2.34; 95% confidence interval: 1.01-5.64, P = 0.048). In conclusion, admission anemia was related to microcirculatory dysfunction and poor prognosis in patients with STEMI. The decreased oxygen delivery might exacerbate microvascular function.

Impact of angiotensin II receptor blocker therapy (olmesartan or valsartan) on coronary atherosclerotic plaque volume measured by intravascular ultrasound in patients with stable angina pectoris.

Coronary plaques can be reduced by some medications. The aim of this study was to compare the effects of 2 angiotensin II receptor blockers (olmesartan at 20 mg/day or valsartan at 80 mg/day) on coronary plaque by coronary intravascular ultrasound. One hundred hypertensive patients with stable angina pectoris who underwent elective percutaneous coronary intervention were randomly selected to receive 1 of the 2 angiotensin II receptor blockers after coronary intervention. Nontarget coronary lesions with mild to moderate stenosis were measured by volumetric intravascular ultrasound at baseline and after 6 months. After 6 months, both the olmesartan and the valsartan groups showed significant reduction of the examined coronary plaque volume (46.2 ± 24.1 mm³ at baseline vs 41.6 ± 21.1 mm³ at 6 months: 4.7% decrease, p = 0.0002; and 47.2 ± 32.7 mm³ at baseline vs 42.5 ± 30.2 mm³ at 6 months: 4.8% decrease, p = 0.002, respectively). There was no statistically significant difference of plaque regression between the 2 groups (p = 0.96). In conclusion, there was a significant decrease from baseline in the coronary plaque volume in patients with stable angina pectoris who received olmesartan or valsartan for 6 months. In addition, there was no significant difference in the reduction of plaque volume achieved by these 2 medications.

Renal Dysfunction and Atherosclerosis of the Neointima following Bare Metal Stent Implantation

Background: Recently, neoatherosclerosis within the neointima after bare metal stent (BMS) implantation, which could cause late restenosis and very late stent thrombosis, has been a cause of concern. Renal dysfunction has been related to late cardiovascular events after coronary intervention. The present study was conducted focusing on the relationship between renal dysfunction and neointimal tissue characteristics with BMS restenosis using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: We prospectively performed IB-IVUS in 80 consecutive patients requiring target lesion revascularization after BMS implantation; the patients were divided into two groups according to the estimated glomerular filtration [eGFR: ≥60 (n = 49) and <60 ml/min/1.73 m2 (n = 31)]. Results: Patients with eGFR <60 ml/min/1.73 m2 had a significantly higher percentage of lipid tissue volume within the neointima and a lower percentage of fibrous tissue volume than those with eGFR ≥60 ml/min/1.73 m2 (23.2 ± 9.4 vs. 18.0 ± 7.0%, p = 0.005, and 75.3 ± 9.3 vs. 80.4 ± 7.0%, p = 0.007, respectively). Using logistic regression analysis, eGFR <60 ml/min/1.73 m2 and duration from stent implantation ≥48 months were independent predictors of increased lipid tissue volume within the neointima (odds ratio, 3.93; 95% confidence interval, 1.15-13.46, p = 0.03, and odds ratio, 7.56; 95% confidence interval, 2.02-28.30, p = 0.003, respectively). Conclusions: Lower eGFR levels were associated with greater lipid tissue volume within the neointima after BMS deployment, suggesting the development of atherosclerosis. Renal dysfunction may affect neointimal tissue characteristics and thus leading to an increased risk of late stent failure.

Impact of Plaque Burden in the Left Main Coronary Artery Determined by Intravascular Ultrasound on Cardiovascular Events in a Japanese Population Undergoing Percutaneous Coronary Intervention

The left main coronary artery (LMCA) is a particularly important target of atherosclerotic plaque accumulation. The aim of this study was to investigate the connection between subclinical plaque burden in the LMCA measured by intravascular ultrasound and future cardiovascular events. Two hundred eighteen consecutive patients underwent percutaneous coronary intervention for the left anterior descending coronary artery or the left circumflex coronary artery under intravascular ultrasound guidance. Plaque burden in the LMCA was analyzed for these patients, and major adverse cardiac events were also evaluated. Data were analyzed by grouping the patients into tertiles according to plaque burden values; tertile 1, <32% area stenosis; tertile 2, 32% to 45% area stenosis; and tertile 3, >45% area stenosis. During a 3-year follow-up period (average 16.1 months), 12% of tertile 1, 18% of tertile 2, and 40% of tertile 3 experienced major adverse cardiac events, mostly due to repeat revascularization (p <0.001). On Cox multivariate analysis, plaque burden in the LMCA (per percentage) detected by intravascular ultrasound remained an independent significant predictor of major adverse cardiac events (hazard ratio 1.04, 95% confidence interval 1.02 to 1.07) and future revascularization (hazard ratio 1.05, 95% confidence interval 1.02 to 1.07) (p <0.001). In conclusion, plaque burden in the LMCA is useful as an indicator of coronary atherosclerosis and may be a significant predictor of cardiovascular events, especially revascularization.