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Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. At 3 years, Kaplan–Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%–2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%–3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79–1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28–0.78; P < 0.05). Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia. ClinicalTrials.gov, NCT02285166.

Objectives The purpose of this study was to clarify the prognostic significance of diagnosing whether the failing heart is functioning on the descending limb of the Starling curve by using echocardiography with passive leg lifting (PLL). Background Patients with advanced heart failure can shift to the descending limb of the Starling curve, in which pre-load does not lead to an expected increase in forward left ventricular stroke volume (LVSV). Methods Thirty-five consecutive patients with left ventricular (LV) ejection fraction of Results Despite PLL, a paradoxical decrease in forward LVSV was observed in 15 (43%) patients. Changes in forward LVSV inversely correlated with those in functional mitral regurgitation (r = −0.56). The primary endpoint of cardiac death or hospitalization due to worsening heart failure occurred in 15 (43%) patients during follow-up (2.8 ± 2.2 years). There were a number of significant predictors of the primary endpoint in the univariate Cox analysis: baseline E/A ratio (p = 0.0002), paradoxical decrease in LVSV despite PLL (hazard ratio: 4.44; 95% confidence interval: 1.41 to 14.0; p = 0.011), baseline LV end-systolic volume (p = 0.023), and baseline LV ejection fraction (p = 0.034). In the bivariate Cox analysis, an addition of the paradoxical decrease in LVSV significantly enhanced the predictive power of all other univariate predictors. Conclusions Heart failure patients with LV systolic dysfunction on the descending limb of the Starling curve can be recognized by the paradoxical decrease in LVSV despite PLL, and the prognostic predicting power is additive to the other traditional echocardiographic predictors. Also, our results suggest that functional mitral regurgitation is an important reason for the descending limb of the Starling curve, which is clinically recognized as the pre-load–induced decrease in forward LVSV.

Background We have previously reported the usefulness of our newly developed visual aortic stenosis (AS) score in screening for AS using pocket-sized echocardiography. The objective of this study was to investigate whether the visual AS score and/or conventional aortic valve calcification score derived from pocket-sized echocardiography can be used to predict AS-related events. Methods One hundred and nine patients with systolic ejection murmur (SEM) or known AS (64 males, age 75 ± 9 years) were enrolled and a visual AS score and an aortic valve calcification score were assessed using pocket-sized echocardiography. The primary endpoint was defined as AS-related events, including cardiac death and aortic valve replacement, during the follow-up period. Results In a multivariate Cox proportional hazards analysis, AS-related events were independently predicted by an aortic valve calcification score ≥3 (HR, 3.5; 95% CI, 1.1–11; p = 0.033) and a visual AS score ≥3 (HR, 15; 95% CI, 1.8–125; p = 0.013). During 18 ± 9 months of follow-up, the event-free survival rate was 98% in patients with both a visual AS score

Background Pocket-sized echocardiography may serve as an initial tool to screen for aortic stenosis (AS). The purpose of this study was to evaluate the usefulness of a novel and simple method using pocket-sized echocardiography to screen for AS. Methods Subjects ( n = 130) with systolic ejection murmur or known AS were studied. After physical examination, each aortic cusp's opening was visually scored using pocket-sized echocardiography as follows: 0 = not restricted, 1 = restricted, or 2 = severely restricted. The sum of the scores was defined as the visual AS score. On the basis of high-end echocardiography, an aortic valve area index 2 /m 2 and an aortic valve area index of 0.60 to 0.85 cm 2 /m 2 were considered to indicate severe and moderate AS, respectively. Results For diagnosing severe AS ( n = 27), a visual AS score ≥4 had sensitivity of 85% and specificity of 89%. For diagnosing moderate to severe AS ( n = 57), a visual AS score ≥3 had sensitivity of 84% and specificity of 90%. The areas under the receiver operating characteristic curves for diagnosing severe and moderate to severe AS with a visual AS score (0.946 and 0.936, respectively) were slightly larger than those for a skilled physical examination (0.917 and 0.898, respectively) ( P = NS for both) but were significantly larger than for an aortic valve calcification score also obtained using pocket-sized echocardiography (areas under the curve, 0.816 [ P = .0015] and 0.827 [ P = .0001], respectively). Conclusions A novel and simple method using pocket-sized echocardiography is useful for rapid grading of AS in subjects with systolic ejection murmur.

End-stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low-density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized-LDL (ox-LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox-LDL levels, plasma MPO levels, and serum high-sensitivity C-reactive protein (hs-CRP) levels during initial HD in patients with diabetic ESRD. Patients (n=28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox-LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme-linked immunosorbent assay kit. Plasma ox-LDL levels and MPO levels after a single HD session increased significantly (ox-LDL, P

AimsThe effects of inotropic agents on left ventricular (LV) synchrony in heart failure patients are still unknown. The purpose of this study was to investigate the effects of dobutamine on LV mechanical dyssynchrony and LV systolic performance in patients with dilated cardiomyopathy (DCM) and a narrow QRS using real-time three-dimensional echocardiography (RT3DE).Methods and resultsThirty-three patients with idiopathic DCM and a narrow QRS underwent low-dose dobutamine stress echocardiography (LDSE) with RT3DE. A time-global LV volume curve and time-regional LV volume curves were derived from RT3DE. Regional LV stroke volumes were summed in each stage, and the dobutamine-induced increase in the sum of regional LV stroke volumes was considered as the sum of regional contractile reserve. Systolic dyssynchrony index (SDI) was calculated as follows: (standard deviation of time to minimal volume for regional LV segments)×100/RR duration. Among the 33 patients, low-dose dobutamine increased global LV stroke volume (SV) in 28 (85%), but decreased global LVSV in the remainder (15%). The sum of regional contractile reserve was modestly correlated with the dobutamine-induced increase in global LVSV (R=0.57, p

Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with (123)I-labeled BMIPP (β-methyl iodophenyl-pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients.Prospective observational study.Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years).Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4).Cardiac-derived death, including cardiac and sudden death.HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors.Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P0.001). Three-year cardiac-derived death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009).Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed.Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death in this population.

Low high-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease (CAD) and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Recently, myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. This study investigated the relationship between plasma MPO and serum PON-1 levels in patients with stable (SAP) and unstable angina pectoris (UAP). Plasma MPO levels and serum PON-1 concentration/activity were measured in patients with SAP (n = 226), UAP (n = 151) and in control subjects (n = 99). Plasma MPO levels in UAP patients were significantly higher than those in SAP patients or in control subjects (UAP, 21.6[16.7-44.6]; SAP, 19.3[15.7-29.1]; control, 15.9[14.7-18.7] ng/mL; P < 0.0001). Serum PON-1 concentrations in UAP and SAP patients were significantly lower than those in control subjects (UAP, 55.6[45.9-69.7]; SAP, 55.0[46.9-64.9]; control, 62.5[51.1-78.8] μg/mL; P = 0.0002). Plasma MPO levels showed a weak inverse correlation with serum PON-1 concentrations in all subjects (R = -0.163, P < 0.0005). Moreover, in women, plasma MPO levels showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity in SAP (concentration: R = -0.537, P < 0.0001; arylesterase-activity: R = -0.469, P < 0.001) and UAP (concentration: R = -0.340, P < 0.05; arylesterase-activity: R = -0.350, P < 0.05) patients, but not in men. This study demonstrates that plasma MPO levels have a significant inverse correlation with PON-1 levels, especially in women, in SAP and UAP patients, and suggests that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression of coronary plaque instability

ObjectivesThis study sought to investigate the association between pathological characteristics of aspirated intracoronary thrombi and the incidence of angiographically visible distal embolization (AVDE) during primary percutaneous coronary intervention (p-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombus aspiration.BackgroundAVDE of atherosclerotic and thrombotic material has been shown to impair myocardial perfusion and contribute to poor clinical outcome in patients with STEMI. Recent studies have shown that thrombus composition and size are associated with the incidence of AVDE.MethodsAspirated thrombi from 164 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, erythrocytes, and inflammatory cells.ResultsThe angiographic results showed that AVDE during p-PCI occurred in 22 (13.4%) patients. Pathological analysis revealed that thrombi from patients with AVDE had a greater erythrocyte-positive area (60 ± 15% vs. 43 ± 21%, p < 0.0005) and more myeloperoxidase-positive cells (943 ± 324 cells/mm2 vs. 592 ± 419 cells/mm2, p < 0.0005) than those from patients without AVDE. Thrombus size, quantified as the thrombus surface area, was positively correlated with the erythrocyte component (r = 0.362, p < 0.0001). Moreover, multivariate logistic analysis demonstrated that erythrocyte-positive area in the thrombi, glucose levels on admission, larger vessel diameter (≥3.5 mm), and pre-balloon dilation were independent predictors of the incidence of AVDE.ConclusionsThis study demonstrated that the erythrocyte-rich component of aspirated thrombi may be associated with the incidence of AVDE during p-PCI in patients with STEMI.

The aim of this study was to assess the effects of angiotensin receptor blocker (ARB)-based therapy on cardiovascular events in high-risk hypertensive patients with coronary artery disease (CAD) and impaired renal function in post hoc analysis of HIJ-CREATE (Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease). Patients (n=2049) were randomly assigned to candesartan-based or non-ARB treatment arms; 1022 patients (age 70 ± 6 years, 28% female) with impaired renal function, defined as creatinine clearance

Previous studies have shown that oxidative stress and endothelial dysfunction are related to impaired myocardial microcirculation after reperfusion. Moreover, elevated myeloperoxidase (MPO) levels are associated with endothelial dysfunction. Plasma MPO levels were measured in patients with ST-segment elevation acute myocardial infarction (n = 160) who had undergone percutaneous coronary stenting within 12 hours of symptom onset. We investigated whether the plasma MPO level at admission was associated with impaired myocardial microcirculation, as indicated by ST-segment resolution and myocardial blush grade after reperfusion, and left ventricular ejection fraction and remodeling at 6 months. The patients were divided into 2 groups according to the median MPO value for the entire cohort (low-MPO group < or =50 ng/ml, n = 80; high-MPO group >50 ng/ml, n = 80). ST-segment resolution and the myocardial blush grade were significantly lower in the high-MPO than in the low-MPO group (48 +/- 27% vs 61 +/- 24%, p

Summary Objectives The purpose of this study was to explore the possibility of using our novel echocardiographic index of inefficient left ventricular (LV) contraction in patient selection for cardiac resynchronization therapy (CRT). Methods Forty consecutive patients with LV ejection fraction ≤35% were divided into 2 groups, 9 CRT candidates and 31 non-CRT candidates based on conventional criteria. A global LV time–area curve and regional LV time–area curves in 6 radial sectors were obtained using two-dimensional echocardiography in the short-axis view with speckle tracking. Fractional inefficient contraction (FIC, %) was calculated as follows: (1 − global LV area change/sum of regional LV area changes) × 100. LV dyssynergy and dyssynchrony were quantified as the standard deviations of minimal values of circumferential speckle-tracking strain and their timings in the 6 sectors, respectively. Results There was no significant difference in LV dyssynchrony between CRT candidates and non-CRT candidates (79 ± 61 ms vs. 58 ± 26 ms, respectively). In contrast, FIC was significantly larger in CRT candidates than in non-CRT candidates (15.7 ± 11.0% vs. 5.4 ± 3.5%, respectively, p = 0.0018), with less overlap between groups. FIC showed a positive correlation with dyssynchrony (r = 0.64) and a negative correlation with dyssynergy (r = −0.42). Conclusions Our novel echocardiographic index of inefficient LV contraction, which increases with more dyssynchrony or less dyssynergy, may prove more useful in patient selection for CRT than other indices that focus on LV temporal dyssynchrony alone.

Aims To test whether angiotensin II receptor blockers (ARBs) therapy can reduce the incidence of cardiovascular events compared with non-ARB-based standard pharmacotherapy in coronary artery disease (CAD) patients with hypertension. Methods and results Angiographically documented CAD patients with hypertension were randomly assigned to receive either candesartan-based ( n = 1024) or non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors ( n = 1025). The primary endpoint was the occurrence of a first major adverse cardiovascular event (MACE). There were 552 primary events during a median follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (hazard ratio, 0.89; 95% confidence interval, 0.76–1.06). No significant differences existed between groups in terms of cardiovascular death (2.7 vs. 2.4%, 1.14; 0.66–1.95), non-fatal myocardial infarction (2.8 vs. 2.5%, 1.12; 0.66–1.88), or heart failure (3.9 vs. 4.3%, 0.91; 0.59–1.40). New-onset diabetes was diagnosed significantly less frequently with candesartan than with non-ARBs (0.37; 0.16–0.89). Incidence of study drug discontinuation due to adverse events was lower with candesartan than with non-ARBs (5.7 vs. 12.2%, P < 0.001). Conclusion Although candesartan showed no significant differences in MACE compared with the non-ARB treatment group, the drug significantly reduced the incidence of new-onset diabetes and was better tolerated. This study is registered as International Standard Randomised Controlled Trial No. UMIN000000790.

Cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing hemodialysis. Such patients frequently develop complications such as asymptomatic coronary artery disease (CAD). Accordingly, CAD must ideally be diagnosed at an early stage to improve prognosis. Although myocardial perfusion single photon emission computed tomography (SPECT) is valuable for diagnosing CAD, the stress test is not always applicable to patients on hemodialysis. Thus, we proposed a multicenter, prospective cohort study called "B-SAFE" to investigate the applicability of resting (123)I-labeled beta-methyl-iodophenylpentadecanoic acid ((123)I-BMIPP)-SPECT will be used to diagnose cardiac disease and evaluate the prognosis of hemodialysis patients by imaging myocardial fatty acid metabolism. B-SAFE began enrolling patients from June 2006 at 48 facilities. We performed (123)I-BMIPP-SPECT on 702 hemodialysis patients with risk factors for CAD until 30 November 2007 and plan to follow up for three years. The primary endpoints will be cardiac death and sudden death. This study should end in 2010.

AIM Predictions of the onset of acute myocardial infarction (AMI) in high risk individuals are of great clinical importance. Among various risk factors, elevated levels of oxidized low density lipoprotein (ox-LDL) in plasma have been shown to reflect unstable coronary plaques. Coronary calcification is a common finding in the elderly, however, its clinical implications as a risk factor for plaque rupture are controversial. This study was designed to investigate the clinical implications of plasma ox-LDL levels and coronary calcification detected by electron-beam computed tomography (EBCT), by comparing patients with AMI with those with stable angina pectoris (SAP). METHODS We measured plasma ox-LDL levels in AMI (n=34) and SAP (n=49) patients. In addition, a coronary calcium score was quantified with the Agatston system. The total coronary calcium score (TCS) was defined as the sum of the scores for each lesion. RESULTS TCS and total calcium area were significantly smaller in patients with AMI than in those with SAP. On the other hand, plasma ox-LDL levels were significantly higher in AMI patients than in SAP patients (p

Background Data about the long-term mortality of acute myocardial infarction (AMI) patients with renal insufficiency who received sufficient early revascularization are scant, so the present study evaluated the impact of serum creatinine levels on the long-term mortality in patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). Methods and Results The Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry has 3,021 consecutive AMI patients. Primary PCI was attempted in 1,451 patients and successful revascularization was obtained in 1,359 patients (93.6%). An elevated serum creatinine level, defined as creatinine ≥1.2 mg/dl, was observed in 216 patients (15.8%). Univariate analyses showed statistical differences between normal and elevated serum creatinine groups in age, gender, hypertension, previous myocardial infarction, number of diseased vessels and Killip class. During a median follow-up period of 39 [32-49] months, the event-free survival rate was lower in elevated creatinine group than normal creatinine group. Multivariate Cox proportional hazards model showed that serum creatinine level was an independent predictor of long-term mortality (adjusted hazard ratio 1.43 [95% confidence interval 1.03-1.99]). Conclusion The serum creatinine level on admission in patients with AMI predicts long-term mortality, even in those with successful primary PCI. (Circ J 2007; 71: 1354 - 1359)

Previous studies have shown that recent activation of the inflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilisation. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages.To elucidate the role of neopterin in coronary plaque destabilisation by immunohistochemical study of the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n = 25) and UAP (n = 25). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils and neopterin.In 22/25 patients with UAP, abundant neopterin-positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from patients with SAP, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin-positive macrophage score was significantly higher (p0.001) in patients with UAP than in patients with SAP. Moreover, the neopterin-positive macrophage score showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.55, p0.001; T cells, r = 0.70, p0.001).Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Its exact role in the process needs to be investigated further.

Objective— Recently, elevated levels of plasma oxidized low-density lipoprotein (LDL) have been shown to relate to plaque instability in human atherosclerotic lesions. We investigated prospectively patients admitted with acute myocardial infarction (AMI) who underwent primary coronary stenting to evaluate whether the 6-month outcome could be predicted by measuring plasma oxidized LDL (ox-LDL) levels at the time of hospital discharge. Methods and Results— Plasma ox-LDL levels were measured in 102 patients with AMI undergoing primary coronary stenting using a highly sensitive ELISA method. Measurements were taken on admission and at discharge, and the findings related to the clinical outcome. At 6-month follow-up, angiographic stent restenosis occurred in 25 (25%) of the 102 AMI patients. Plasma ox-LDL levels at discharge were significantly ( P =0.0074) higher in the restenosis group than those in the no-restenosis group (1.03±0.65 versus 0.61±0.34 ng/5 μg LDL protein). Multiple regression analysis showed that only plasma ox-LDL levels at discharge were a statistically significant independent predictor for late lumen loss after stenting (β=0.645; P Conclusions— This prospective study demonstrates that persistence of an increased level of plasma ox-LDL at discharge is a strong independent predictor of stent restenosis at 6-month follow-up in AMI patients.

The repair process at the site of injury after percutaneous coronary intervention (PCI) is dominated by neointimal formation composed mainly of smooth muscle cells (SMC). Endothelin-1 (ET-1) is a powerful vasoconstrictor and SMC mitogen. Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin processing. The effects of ET-1 are mediated by binding to endothelin type A (ETA) and endothelin type B (ETB) receptors. The ligand/receptor/ligand-producing system (ET system) could be involved in the pathogenesis of neointimal formation in humans.Fifteen post-PCI sites obtained at autopsy and eight atherectomy specimens obtained from restenotic sites were investigated using immunohistochemical single and double staining techniques. Frozen sections were stained with antibodies against ECE, ET-1, ETA and ETB receptors, SMC, macrophages and endothelial cells.At the early stage, less than 3 months after PCI, neointimal SMC were positive for ECE, ET-1, ETA and ETB receptors. The expression of ECE, ET-1, ETA and ETB receptors in these neointimal SMC decreased markedly from 6 months onwards. The ECE, ET-1, ETA and ETB receptor-positive cell areas were significantly (P0.005) greater in the first 3 months after PCI compared with 6 months or more after PCI. Atherectomy specimens also showed similar positivity.These observations strongly suggest that the expression of ECE, ET-1, ETA and ETB receptors is enhanced in neointimal SMC at early stages after PCI injury in human coronary arteries. The increased expression of the ET system may contribute to SMC proliferation/migration and vasoconstriction in human post-PCI coronary lesions.

Background Many clinicians have seen the reperfusion phenomenon, a paradoxical response that includes a transient increase of chest pain, additional ST-segment elevation or ventricular arrhythmias immediately after coronary reperfusion, in patients with acute myocardial infarction (AMI). The aim of the present study was to investigate the impact of this phenomenon during coronary reperfusion on left ventricular (LV) remodeling in patients with AMI. Methods and Results One hundred and thirty-eight consecutive patients with a first anterior-wall AMI, undergoing coronary reperfusion treatment within 24 h of onset were prospectively evaluated for reperfusion phenomenon and followed up with scheduled evaluations of LV function and morphology with left ventriculography for 1 year. Of the 138 enrolled patients, 77 underwent serial left ventriculography at the acute, subacute and 1-year phases. Of these 77 patients, 39 demonstrated the reperfusion phenomenon. The LV end-diastolic volume index significantly increased from the acute to subacute phase and to the 1-year phase, but was unchanged in the 38 patients without reperfusion phenomenon. In multivariate analysis, reperfusion phenomenon was the only determinant of LV dilatation after AMI. Conclusions Reperfusion phenomenon was a strong predictor of LV remodeling after reperfusion therapy for AMI. (Circ J 2005; 69: 884 - 889)

A 52-year-old woman, a hemodialysis patient, was admitted because of exertional dyspnea. Echocardiography showed left ventricular (LV) dilatation and reduced contraction. Coronary angiography showed no fixed stenosis. She had elevated levels of parathyroid hormone (PTH) as a result of secondary hyperparathyroidism with advanced renal failure. After parathyroidectomy, marked improvement of LV function following immediate decrease of blood levels of PTH was observed. It is suggested that PTH might have a significant role in the pathogenesis of LV dysfunction and that parathyroidectomy might be effective as a therapy for heart failure in some patients with secondary hyperparathyroidism and LV dysfunction.

We report the case of a 19-year-old man with verapamil-sensitive idiopathic left ventricular tachycardia (ILVT), who had paroxysmal palpitations for 3 years. Programmed right atrial and ventricular stimulation easily induced ventricular tachycardia (VT) with QRS duration of 125ms, right bundle branch block pattern, and right inferior axis, which are characteristics of ILVT. Left ventricular endocardial mapping accidentally produced a complete left bundle branch block and provoked prolongation of the QRS duration of VT, which was 143ms. However, no changes occurred in the cycle length, inducibility, or maintenance of VT. The VT was eliminated successfully by catheter ablation at the pre-Purkinje potential (PP) recording site. These findings suggest that the main trunk of the left bundle branch is not a critical component of the re-entry circuit of ILVT.

OBJECTIVE—Ischemic heart disease is a pivotal complication for diabetic patients. Electron-beam computed tomography (EBCT) represents the only noninvasive method that allows for accurate quantification of coronary artery calcification that reflects underlying atherosclerotic disease. Although coronary calcium score (CCS) cut points that predict the presence of angiographic stenosis have been established in nondiabetic individuals, it is not known whether coronary calcifications in diabetic patients are associated with the presence of significant coronary stenoses. In this study, we evaluated the relationship between coronary calcifications and angiographic stenosis in symptomatic patients with or without type 2 diabetes. RESEARCH DESIGN AND METHODS—In this study, 282 patients (204 men and 78 women) with chest pain, including 101 diabetic patients and 181 nondiabetic patients (mean age 63 ± 9.6 years), underwent coronary angiography and EBCT with determination of CCS using Agatston’s method. Luminal stenosis ≥ 50% was defined as significant coronary stenosis. RESULTS—Angiography identified 205 patients with significant stenoses (89 of 101 diabetic patients, 114 of 181 nondiabetic patients). The sensitivity and specificity of EBCT to detect significant coronary stenosis were not significantly different between diabetic and nondiabetic patients. In diabetic patients, a CCS ≥90 was associated with 75% sensitivity and 75% specificity, whereas a CCS ≥200 was associated with 64% sensitivity and 83% specificity. CONCLUSIONS—We demonstrated that calcification of the coronary arteries in symptomatic diabetic patients is well associated with severity of coronary stenosis, as in nondiabetic patients.

Background The Tranilast Restenosis Following Angioplasty Trial showed that oral administration of 600 mg/day of tranilast for 3 months markedly reduced the restenosis rate after percutaneous transluminal coronary angioplasty (PTCA) for de novo lesions. Methods We conducted the second multicenter, randomized, double-blinded placebo-controlled trial. A total of 297 patients with 329 lesions were randomly assigned to treatment with tranilast or a placebo for 3 months after successful PTCA for both de novo and restenotic lesions. Angiographic follow-up examination was done at 3 months, and angiograms were interpreted with a quantitative approach. Results Two hundred thirty-nine lesions (72.6%) in 216 of the patients (72.7%) met the criteria and were included in the assessment of restenosis. Lesion restenosis was defined as a loss of 50% or more of the initial gain, and the restenosis rates were 18.8% in the tranilast group (n = 112) and 44.1% in the placebo group (n = 127; P =.00005). The restenosis rate, defined as a percent stenosis of ≥50% at follow-up examination, was also significantly lower in the tranilast group (25.9% versus 41.9%; P =.012). The numbers of restenotic lesions were 38 (33.9% of 112) in the tranilast group and 30 (23.6% of 127) in the placebo group. In restenotic lesions, the lesion restenosis rate was significantly lower in the tranilast subgroup (18.4% versus 53.3% with the first restenosis criterion; P =.004). Conclusion The oral administration of tranilast for 3 months markedly reduced the restenosis rate after PTCA, even in restenotic lesions. (Am Heart J 2002;143:506-13.)

Oxidized low-density lipoprotein (ox-LDL) is considered to play a key role in the genesis of inflammatory processes in atherosclerotic lesions. It has also been shown that LDL isolated from patients with diabetes mellitus (DM) has an enhanced susceptibility to oxidation. Recently, a sandwich ELISA method for measurement of plasma ox-LDL levels has been developed. To elucidate the role of ox-LDL in plaque instability in coronary artery disease, we measured the plasma ox-LDL levels in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP), and moreover assessed whether a relationship is present between plasma ox-LDL levels and DM. We also measured the plasma ox-LDL level in a patient who died of AMI, thus enabling us to study the presence of ox-LDL and CD 36, which is one of the ox-LDL receptors, in the culprit lesion. Plasma ox-LDL levels were measured in 210 patients (AMI: 70, UAP: 70, SAP: 70), and in 55 control subjects. Plasma ox-LDL levels in AMI patients were significantly higher than in UAP patients (P

Background: The development of aortic valve stenosis (AS) involves multiple events, including inflammation and lipid deposition and oxidation. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. The aims of this study were to investigate the serum levels of sLOX-1 in patients with AS and also examine the expression of LOX-1 immunohistochemically in aortic valve specimens from these patients. Methods: Serum sLOX-1 levels were measured in patients with AS (n=128), stable angina pectoris (SAP, n=343) and in 53 control subjects using a sandwich ELISA method. Frozen aortic valve samples were also obtained surgically from a cohort of 20 AS patients. In addition, frozen aortic valve specimens were obtained at autopsy from individuals who died of non-cardiovascular causes (n = 11, mean age 68 yr) as a reference. Immunostaining of the samples was performed using antibodies against smooth muscle cells, macrophages, T-lymphocytes, neutrophils, microvessels, and LOX-1. Results: Serum sLOX-1 levels were significantly higher in AS patients compared with SAP patients ( P P Conclusions: This study demonstrates for the first time that serum sLOX-1 levels are elevated in patients with AS, and AS lesions contain a significantly higher percentage of LOX-1-positive macrophages. These findings suggest that LOX-1, a marker of oxidative stress, may play an important role in the development of aortic valve stenosis.

Background: We previously demonstrated that inflammatory biomarkers such as myeloperoxidase (MPO), a member of the heme peroxidase superfamily, and neopterin (produced by activated macrophages after interferon-γ stimulation by T-lymphocytes) are important in the pathogenesis of coronary plaque instability. Additional evidence supports high sensitivity C-reactive protein (hs-CRP) as an independent predictor of increased coronary risk. We assessed the prognostic significance of plasma MPO and neopterin levels, and serum hs-CRP levels in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). Methods: Plasma MPO, neopterin, and serum hs-CRP levels were measured in 219 SAP patients and 144 UAP patients at admission. Cardiovascular (CV) events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Over a mean follow-up of 27±14 months, 56 SAP patients (26%) had CV events. When SAP patients were stratified based on the median neopterin level (15.0 nmol/L), Kaplan-Meier analysis showed that the high-neopterin group (>15.0 nmol/L) had significantly worse outcomes (P=0.015) than the low-neopterin group. Multivariate analysis showed that elevated neopterin was the only independent factor associated with CV events (OR, 2.19; 95% CI, 1.18-4.09; P=0.014). In contrast, over a mean follow-up of 30±24 months, 33 UAP patients (23%) had CV events. When UAP patients were divided based on the median MPO level (16.0 ng/mL), Kaplan-Meier analysis showed that the high-MPO group (>16.0 ng/mL) had significantly worse outcomes (P=0.012) than the low-MPO group. Multivariate analysis showed that elevated MPO was the only independent factor associated with CV events (OR, 2.58; 95% CI, 1.07-6.23; P=0.035). With regard to hs-CRP levels, there were no significant differences in CV events between the two groups according to the median hs-CRP in both SAP and UAP patients. Conclusions: The clinical significance of elevated MPO and neopterin levels as independent predictors of CV events differs depending on the clinical condition of SAP and UAP patients, because of different production mechanisms of these biomarkers.

A 26-year-old female with idiopathic moyamoya disease developed chest pain with concomitant ST depression on electrocardiography. Coronary angiography detected no stenotic lesions in the epicardial coronary arteries. The clinical diagnosis was vasospastic angina pectoris. She was medicated with calcium antagonists, which reduced the frequency of chest pain episodes. Angina pectoris is a rare occurrence in young patients with moyamoya disease. Coronary artery disease and moyamoya disease may have common etiological factors.

3次救急施設として開設3年になる当院における心不全の臨床像と予後を明らかにすることを目的とした。開院1993年12月から1997年5月までに心不全と診断されて入院した連続312例(男性202例,年齢26～87歳)について,臨床像,治療,予後を調査した。基礎心疾患の内訳は冠動脈疾患38%,弁膜症21%,拡張型心筋症13%,高血圧性心疾患10%,その他18%であった。院内心臓死は6.4%,非心臓死は1.6%であった。心室内伝導障害は生存者に比べ,死亡者で高率であった。一方,年齢,性別,既往歴,基礎疾患,入院時血圧,脈拍数,心胸郭比,心房細動・心肥大・伝導障害の有無,左室径,左室容量,左室駆出率,静注薬使用の有無について多変量解析を行ったが院内予後に寄与する因子は見いだせなかった。退院後の1年生存率,3年生存率は91%,78%であった。他施設の既報告と比較して,院内死亡率に大きな差はなかったが,退院後の1年,3年生存率はやや良好であった。

Ischemic heart disease has become more important in regard to mortality in hemodialysis (HD) patients. We examined the therapeutic outcome of initial percutaneous transluminal angioplasty (PTCA) in maintenance HD patients with angina pectoris. They consisted of 8 men and 4 women with a mean age of 56.3 ± 8.6 years and a mean duration of HD of 4.3 ± 4.0 years. Thirty-six non-HD patients treated with initial PTCA were matched for age, sex and coronary risk factors, and used as a control. Angiographic lesion success was confirmed by angiography in 21 (84%) of the 25 stenotic sites attempted and clinical success was obtained in 9 (75%) of the 12 HD patients, while there were 40 (78%) lesions successfully removed out of the 51 stenotic sites and there were 26 (72%) clinically successful cases out of the 36 non-HD patients, respectively. Angina recurred in 4 (44%) of 9 HD patients, and in 10 (38%) of 26 non-HD patients after successful PTCA, where the follow-up periods were 23 ± 20 and 28 ± 25 months, respectively. There was no significant difference in cumulative lesion survival curve between the two groups. In conclusion, PTCA for chronic HD patients is as effective as that for non-HD patients, at least regarding initial PTCA.

A rare case of peliosis hepatis associated with idiopathic restrictive cardiomyopathy is reported. A 75-year-old man was admitted for evaluation of marked edema and jaundice. Serum total bilirubin was elevated above 20 mg/dl. The liver biopsy under laparoscopy revealed marked sinusoidal dilatation and retention of red blood cells, which was consistent with a diagnosis of peliosis hepatis. Cardiac catheterization revealed right ventricular filling disturbance without specific findings on endomyocardial biopsy, suggesting idiopathic restrictive cardiomyopathy. The level of serum total bilirubin decreased in association with improvement of edema after drip infusion of furosemide therapy.

Reperfusion therapy for patients with acute myocardial infarction (AMI) is aimed at reopening the occluded infarct-related coronary artery and restoring antegrade flow. This results in the reduction of infarct size and improvement in outcomes. Intracoronary injection of fibrinolytic agents used to be the strategy used for reperfusion therapy. However, intravenous thrombolysis is now considered the treatment of choice for the initial management of patients with AMI in Western countries based on numerous megatrials which showed thrombolysis reduced mortality. The most commonly used fibrinolytic agent is tissue-plasminogen activator (t-PA) which has a higher affinity to fibrin than formerly used agents.Thrombolytic therapy has failed to achieve at Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 in over 50% of the cases. Percutaneous transluminal coronary angioplasty (PTCA) was introduced to obtain prompt and secure restoration of antegrade coronary flow. Several clinical trials have shown it to be more effective than thrombolysis. PTCA was used as a reperfusion tool in Japan in over 50% of the cases in 1994 and 70% in 1997.New pharmacological and mechanical interventions have been developed recently to achieve earlier and more successful perfusion. Pilot trials have shown a higher complete reperfusion rate (TIMI flow grade 3) with bioengineered second generation t-PA. Pilot studies of intracoronary stent deployment have shown higher success rates and a lower incidence of restenosis. However, large scale randomized trials will be required to confirm the clinical efficacy and safety of these new interventions.

Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyte-rich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.

End-stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low-density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized-LDL (ox-LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox-LDL levels, plasma MPO levels, and serum high-sensitivity C-reactive protein (hs-CRP) levels during initial HD in patients with diabetic ESRD. Patients (n=28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox-LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme-linked immunosorbent assay kit. Plasma ox-LDL levels and MPO levels after a single HD session increased significantly (ox-LDL, P0.005; MPO, P0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre-HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox-LDL levels during HD (R=0.62, P=0.0029). No significant change was observed in serum hs-CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox-LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox-LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.

We have performed lipid analyses by using a table-top ultracentrifuge based on the Hatch and Lees' method in 77 subjects (60 men, 17 women; mean age, 63 years) to clarify lipoprotein disorders in coronary artery disease. Sixty-four subjects had coronary artery disease and 13 normal subjects were controls. They were divided into the groups with stable angina pectoris and with unstable angina pectoris or acute myocardial infarction (acute coronary syndromes). In patients with coronary artery disease, there were no significant differences from control in age, body mass index, total cholesterol, however, HDL cholesterol was significantly lower than those in the controls. LDL cholesterol:LDL apoB ratio, which is thought to reflect the size of LDL in coronary artery disease, was significantly smaller than that in the controls; mean values were 1.2 in coronary artery disease and 1.4 in controls. There were no significant differences in those lipoprotein disorders between the patients with stable angina and those with acute coronary syndromes. Though these lipoprotein abnormalities would not play a trigger role in acute coronary syndromes, they are characteristic of the lipid profile of patients with coronary artery disease.

To evaluate the effect of intracoronary diltiazem on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA), 38 patients were randomly assigned to receive inactive placebo (n = 19; group C) or a low dose (1 mg, n = 10; group D1), or a high dose (2 or 3 mg, n = 9; group D2) of diltiazem in a double-blind manner. The agent was administered directly into the coronary artery via a balloon catheter following a control balloon inflation. Chest pain score (maximum, 10) and the magnitude of ischemic ST elevation on standard and intracoronary electrocardiograms (ECGs) during a balloon inflation were assessed in the control and posttreatment periods. After the administration of diltiazem, the chest pain score was significantly decreased in group D1 (control: 5.1 +/- 3.6, posttreatment: 3.8 +/- 3.1, P0.01) and group D2 (3.4 +/- 2.5 vs 2.5 +/- 2.0, P0.01), but not in group C (4.1 +/- 3.1 vs 3.7 +/- 3.3, difference not significant). The magnitude of ST elevation relative to the control on standard and intracoronary ECGs was significantly smaller in groups D1 and D2 than in group C (standard ECG; D1: 51.8 +/- 10.6% of control, D2: 41.6 +/- 28.7% vs C: 93.3 +/- 15.6% and intracoronary ECG; D1: 47.1 +/- 11.7% of control, D2: 27.5 +/- 26.9% vs C: 94.6 +/- 29.3%, all P0.01). Although systolic blood pressure decreased slightly in groups D1 and D2, there was no significant correlation between the change in ST elevation and the change in the rate-pressure product. Pretreatment with a small dose of intracoronary diltiazem attenuated myocardial ischemia during PTCA and this pretreatment may enable us to perform balloon inflation for a longer period.

To elucidate the clinical features of acute myocardial infarction (AMI) and post-MI silent myocardial ischemia (SMI) in the elderly, and efficacy of therapy in an era of coronary intervention, a total of 10,607 patients with AMI who were enrolled in a multicenter survey between 1982 and 1992 were examined. The elderly had a higher ratio of females, noncardiac illness, atypical symptoms at the onset of AMI, severe pump failure at admission, cardiac rupture and multivessel disease. Hospital mortality was markedly higher in patients > or = 75 years, and it was 4-fold compared with patients < 65 years. In the last 5 years, the rate of application of coronary angiography and primary PTCA significantly increased even in the very elderly. In contrast, use of thrombolysis highly diminished. Hospital mortality declined (14.6 vs 11.9%, p < 0.001) in every age group compared with the first 5 years, although it was higher in the elderly even in the last 5 years. Investigation of 642 survivors after AMI admitted to one hospital showed that the elderly had a higher incidence of SMI and post-MI angina compared with the non-elderly. Clinical features of SMI were similar in both groups. However, medical treatment was more prevalent and recurrence of MI and cardiac death during follow-up (average 27 months) were more frequent in the elderly. In this retrospective study, characteristics of AMI and SMI, and effectiveness and limitation of therapy in the elderly were clearly demonstrated. It was evident that hospital mortality of the elderly had improved, although it was still higher than the non-elderly.

To investigate the clinical application of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) in the management of acute myocardial infarction (AMI), we examined 44 patients with AMI within 1 month after onset. Enhanced images were classified into 4 types: nontransmural (type 1), transmural and homogeneous (type 2), transmural and marginal (type 3), and no enhancement (type 4). Each enhancement pattern was correlated with angiographic and thallium-201 imaging results. The redistribution images of thallium were graded on a 4-point scale from 0 (normal) to 3 (markedly reduced or absent activity). The percentage of the perimeter affected by asynergy was obtained from the left ventriculogram. Peak creatine kinase and the percentage of asynergic perimeter were significantly higher in type 3 than in other type patients. End-diastolic volume index was significantly higher in type 3 than in type 2 patients. Left ventricular ejection fraction was lowest, and end-systolic volume index, thallium-201 score, and incidence of wall thinning on MRI were highest in type 3 patients. Therefore, the transmural and marginal enhancement pattern (type 3) was compatible with extensive myocardial infarction with infarct expansion and less viable myocardium. In the other types, the infarction was small to moderate in size and left ventricular function was well preserved. Thus, Gd-DTPA-enhanced MRI may be useful in the evaluation of left ventricular function and myocardial viability of the infarct region after AMI.

To assess the efficacy of percutaneous cardiopulmonary support system (PCPS), we studied 16 patients supported urgently by PCPS (11 males, 5 females, mean age: 61 years). The reasons for indicating PCPS were cardiogenic shock in 10 patients, cardiac rupture in 3 patients and ventricular fibrillation (Vf) in 3 patients. Fourteen patients (88%) had ischemic heart disease (IHD). The remaining 2 patients had dilated cadiomyopathy and valvular heart disease, respectively. In five patients (31%), PCPS was used in combination with intraaortic balloon pump support. Finally, 4 patients (25%) survived: 1 patient with Vf and 3 patients with IHD. All of these 3 patients with IHD succeeded in coronary revascularization under the support of PCPS. The remaining patient succeeded in the termination of Vf after operating PCPS. No patient studied in the present study had vascular injury. However, 2 patients had severe mediastinal bleeding due to cardiopulmonary resuscitation, one of whom died of hemorrhagic shock. In conclusion, early coronary revascularization following PCPS is important to recover from cardiogenic shock because cardioprotective effect of PCPS is poor. Anti-coagulation therapy in operating PCPS sometimes induces severe hemorrhagic complications, to which we should pay attention.

Patients with sustained ventricular tachycardia (VT) in the post-infarction period, especially more than 48 h after acute myocardial infarction (AMI), have a high mortality. However, clinical characteristics of these patients are unknown, since previous studies have not clarified the relationship between sustained VT and acute myocardial damage. To clarify the prognostic factors in patients with sustained VT in the early post-infarction period, we retrospectively surveyed 961 consecutive patients with AMI. Eleven patients (9 men and 2 women, aged 54 to 80 years) who had no previous myocardial infarction had at least one documented episode of sustained VT between 3 and 21 days after AMI. Late potentials were detected in 7 of 7 patients who underwent signal-averaged electrocardiography within 2 days after the first occurrence of VT. Entrainment was seen in 2 patients. The 5 patients who died in hospital had the following clinical characteristics: 1) cardiogenic shock, 2) extensive infarction, 3) a short interval from AMI to the onset of VT (mean +/- SD: 4 +/- 2 days), and 4) recurrent and refractory VT. In contrast, the 6 patients who survived had the following clinical characteristics: 1) no cardiogenic shock, 2) a relatively late occurrence of VT (mean = SD: 14 +/- 7 days), 3) few episodes of VT, and 4) no recurrence of VT during the follow-up period of 12 to 58 months. The occurrence of sustained VT within 3 weeks after AMI was influenced by the general condition of the patient, and the prognosis was mainly related to cardiac function.

Therapeutic efficacy of intermittent and continuous injection of isosorbide dinitrate (ISDN) was compared in 22 patients (mean age 64 +/- 10, 18 males and 4 females) with unstable angina at rest. They were randomized into 2 groups that received either continuous (10 mg/h, group A) or intermittent (10 mg/10 min every 2 hours, group B) injection of ISDN for 3 days (phase 1). Each injection protocol was switched (phase 2) and subsequently switched back to the initial protocol (phase 3) in a cross-over fashion. The serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-ISMN were measured serially during both intermittent and continuous injection protocols. In addition, the incidence and duration of angina and changes in systolic blood pressure were analyzed. There were 3 treatment-failure cases during the intermittent injection period and 1 during the continuous injection period. Three of these treatment-failure cases developed small acute myocardial infarcts despite emergent coronary arteriography followed by intra-coronary thrombolysis and percutaneous balloon angioplasty. There was no difference in therapeutic efficacy between continuous and intermittent ISDN in terms of the incidence, duration of angina attacks and the number of patients whose angina was suppressed. After bolus injection of ISDN (10 mg/10 min), the serum concentration of ISDN increased rapidly and returned to the control level at 60 minutes after the injection. The serum 5-ISMN and 2-ISMN concentrations also increased immediately after injection and then decreased gradually reaching statistically insignificant level to the control values at 60 minutes after injection. With continuous injection, ISDN and its metabolites increased gradually and reached similar but slightly lower serum concentrations to the peak levels during intermittent injection. We conclude that the therapeutic efficacy of intermittent and continuous injection of ISDN is similar in patients with unstable angina.

Serum troponin T, a myocardial contractile protein, has been reported to be a sensitive marker for the diagnosis of acute myocardial infarction. However, there have been few reports on its ability to detect coronary reperfusion and to predict left ventricular function in the chronic stage. Twenty two patients (20 males and 2 females, 61 +/- 10 y.o.) with acute myocardial infarction were enrolled in this study. They were divided into 2 groups, one with successful reperfusion (group A: n = 13) and one without reperfusion (Group B: n = 9) and the serial changes of their serum troponin T levels were evaluated. Serum myosin light chain was measured in another group of patients with acute myocardial infarction without history of old myocardial infarction (group C: n = 8). The slope of the logarithm of serum troponin T on a time-value curve was calculated from the time of admission to the first peak within 24 hours of the onset of acute myocardial infarction. The correlation coefficient between the late peak of serum troponin T and the left ventricular ejection fraction in 11 patients with first Q wave acute myocardial infarction was compared with that between the serum myosin light chain peak and the left ventricular ejection fraction in group C. 1) The slope of the logarithm of serum troponin T on the time-value curve in group A was greater than that in group B (0.57 +/- 0.45 vs. 0.22 +/- 0.16) (p < 0.05). 2) There was a good correlation between the late peak level of serum troponin T (78 +/- 10 hours after the onset) and the left ventricular ejection fraction in 11 patients with first Q wave acute myocardial infarction (r = -0.84, p < 0.01), which was similar to that of the serum myosin light chain peak and the left ventricular ejection fraction (r = -0.72, p < 0.05). On the other hand, there was no correlation between the peak level of serum creatine phosphokinase and the left ventricular ejection fraction (r = -0.55, NS). The serum troponin T levels 24, 36, 48 and 60 hours after the onset also correlated well with the left ventricular ejection fraction (r = -0.65, -0.7, -0.65 and -0.89, respectively). We conclude that the serial measurement of serum troponin T in patients with acute myocardial infarction is useful in the evaluation of left ventricular function in the chronic stage and that it is a potential non-invasive predictor of coronary reperfusion.

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is induced by intraplaque hemorrhage and degrades free heme and releases ferrous iron, which is rapidly sequestered by ferritin. In vitro studies have shown that binding of hemoglobin to hemoglobin scavenger receptor (CD163) induces HO-1 and the anti-inflammatory mediator interleukin (IL)-10. We immunohistochemically examined the relationship between CD163 expression in macrophages and intraplaque hemorrhage, HO-1, IL-10, and ferritin using coronary atherectomy specimens from patients with stable (SAP) or unstable angina pectoris (UAP). A total of 67 patients underwent atherectomy for SAP (n = 33) or UAP (n = 34). Samples were stained with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD163, HO-1, IL-10, and ferritin. To identify cell types of HO-1-positive cells, double immunostaining was also performed. Double immunostaining for HO-1 and macrophages revealed that the vast majority of HO-1-positive cells were macrophages. Morphometric analysis demonstrated that CD163-positive macrophage score and the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas were significantly higher in UAP than in SAP patients (CD163, P < .005; glycophorin-A, P < .0001; HO-1, P < .0001; IL-10, P < .005; ferritin, P = .0001). Moreover, CD163-positive macrophage score was positively associated with the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas (glycophorin-A, r = 0.60, P < .0001; HO-1, r = 0.67, P < .0001; IL-10, r = 0.45, P < .0005; ferritin, r = 0.61, P < .0001). These findings suggest that enhanced expression of HO-1 and HO-1-related atheroprotective molecules plays an important role in exerting anti-inflammatory, antioxidant, and scavenging functions, which could contribute to plaque stabilization.

Aims Recent studies have demonstrated that erythrocytes are a potential component in atheromatous lesions and thrombus formation in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to determine the associations of red blood cell (RBC) component of coronary thrombi with oxidative stress and myocardial reperfusion. Methods and results Aspirated thrombi from 178 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, RBCs, fibrin, macrophages, and neutrophils [myeloperoxidase (MPO)]. The thrombi were divided into tertiles according to the percentage of glycophorin-A-positive area: low (glycophorin-A-positive area