Impaired coronary flow reserve as a marker of microvascular dysfunction to predict long-term cardiovascular outcomes, acute coronary syndrome and the development of heart failure.

BACKGROUND: In the absence of obstructive coronary narrowing, impaired coronary flow reserve (CFR) represents coronary microvascular dysfunction. Transthoracic Doppler echocardiography (TTDE) allows non-invasive measurement of CFR in the left anterior descending (LAD) artery. This study aimed to assess the prognostic value of TTDE-derived CFR (as a marker of microvascular function) in predicting long-term cardiovascular events, acute coronary syndrome (ACS) events, and the development of heart failure (HF). METHODS AND RESULTS: This study consisted of 272 patients with coronary artery disease not involving obstructive narrowing (≥50%) in the LAD. Patients underwent TTDE examination for CFR measurement in the LAD. During the follow-up period of 4.0±1.9 years, 32 patients (12%) had cardiovascular events. Cox proportional hazard analysis identified lower CFR as an independent risk factor of cardiovascular events (P<0.001), ACS events (P=0.008), and HF development (P=0.003). A CFR less than 2.4 was the best cut-off value for predicting all events (area under the curve=0.82). CFR excellently predicted the development of HF (area under the curve=0.95), but not ACS events (area under the curve=0.67). CONCLUSIONS: This TTDE study demonstrated that CFR was a significant and independent determinant of long-term cardiovascular events, ACS events and HF in patients with coronary artery disease. A CFR greater than 2.0 was not suitable to predict a favorable long-term outcome, even in the absence of obstructive coronary narrowing.

Multiple plaque rupture and C-reactive protein in acute myocardial infarction.

OBJECTIVES: This study sought to investigate the relationship between multiple plaque ruptures, C-reactive protein (CRP), and clinical prognosis in acute myocardial infarction (AMI). BACKGROUND: Several studies have demonstrated that ruptured or vulnerable plaques exist not only at the culprit lesion but also in the whole coronary artery in some acute coronary syndrome (ACS) patients. Recent studies have reported that a ruptured plaque at the culprit lesion is associated with elevated CRP, which indicates a poor prognosis in patients with ACS. METHODS: We performed intravascular ultrasound in 45 infarct-related arteries and another 84 major coronary arteries in 45 first AMI patients. RESULTS: Plaque rupture was observed in 21 patients (47%) at the culprit site. Intravascular ultrasound revealed 17 additional plaque ruptures at remote sites in 11 patients (24%). Patients with multiple risk factors were more frequently found in our multiple-plaque rupture patients compared with single-plaque rupture or nonrupture patients (82% vs. 40% vs. 29%, p = 0.01). High-sensitive CRP levels had a positive correlation with the number of plaque ruptures (p < 0.01). All culprit lesions were successfully treated by percutaneous coronary intervention. Patients with multiple plaque rupture showed significantly poor prognosis compared with others (p = 0.01). CONCLUSIONS: Multiple plaque rupture is associated with systemic inflammation, and patients with multiple plaque rupture can be expected to show a poor prognosis. Our results suggest that AMI treatment should focus not only on stabilization of the culprit site but also a systemic approach to systemic stabilization of the arteries.

Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris.

Matrix metalloproteinases (MMPs) are important for resorption of extracellular matrixes and may degrade the fibrous cap of an atherosclerotic plaque, thus contributing to coronary plaque rupture. Histologic studies have shown MMP expression in lesions of acute coronary syndrome. In this study, we evaluated the relation between plaque morphology as obtained by intravascular ultrasound before percutaneous coronary intervention and serum MMP levels in patients who had coronary artery disease. We enrolled consecutive 47 patients who had acute myocardial infarction (AMI), 23 who had unstable angina pectoris (UAP), and 19 who had stable effort angina pectoris and underwent intravascular ultrasound before percutaneous coronary intervention followed by successful primary percutaneous coronary intervention. Peripheral blood was obtained from all patients before angiography and serum levels of MMP-1,-2, and -9 were analyzed. Serum levels of MMP-9 in the AMI and UAP groups were significantly higher than that in the stable effort angina pectoris group (p = 0.007 and 0.04, respectively). From the intravascular ultrasound findings before percutaneous coronary intervention, plaque rupture was detected in 26 patients (55%) in the AMI group and in 11 patients (48%) in the UAP group. In these 2 groups, patients with plaque rupture had significantly higher levels of MMP-9 than patients who did not have plaque rupture (p = 0.03 and 0.01, respectively). Multiple logistic regression analysis showed that MMP-9 was the only independent predictor of plaque rupture (p = 0.004). In conclusion, high levels of MMP-9 in patients who have AMI and UAP are related to the presence of plaque rupture in the culprit lesion.

No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction.

BACKGROUND: The no-reflow phenomenon is associated with poor functional and clinical outcomes for patients with acute myocardial infarction (AMI). In the era of primary intervention, accurately identifying lesions at high risk of no reflow is of crucial importance. At present, no study into the relationship between lesion morphology and no reflow has been performed. The aim of this study was to investigate the relationship between preintervention intravascular ultrasound (IVUS) lesion morphology and the no-reflow phenomenon. METHODS AND RESULTS: This study comprised 100 consecutive patients with AMI who underwent preintervention IVUS and were successfully recanalized with primary balloon angioplasty or stenting. IVUS was again performed to identify and exclude any mechanical vessel obstruction in cases of thrombolysis in myocardial infarction flow grade 0, 1, or 2 after intervention in the absence of angiographic stenosis. Angiographic no reflow was seen in 13 patients (13%). Univariate analysis indicated that hypercholesterolemia, fissure and dissection, lipid pool-like image, lesion, and reference external elastic membrane cross-sectional area correlate with the no-reflow phenomenon. Multivariate logistic regression analysis showed that lipid pool-like image (P<0.05; odds ratio 118; 95% CI, 1.28 to 11 008) and lesion elastic membrane cross-sectional area (P<0.05; odds ratio 1.55; 95% CI 1.01 to 2.38) are independent predictive factors of no-reflow phenomenon after reperfusion for AMI. CONCLUSIONS: Large vessels with lipid pool-like image are at high risk for no reflow after primary intervention for AMI. Also, plaque content may play a role in damage to the microcirculation after primary intervention for AMI.

C-reactive protein and lesion morphology in patients with acute myocardial infarction.

BACKGROUND: Elevated serum C-reactive protein (CRP) is of clinical significance in the management of acute coronary syndromes, but there have been few in vivo studies detailing the relation between lesion morphology and elevated CRP in the setting of acute myocardial infarction (AMI). In this study, we investigated the relation between lesion morphology as seen under preintervention intravascular ultrasound (IVUS) and CRP in the acute phase of AMI. METHODS AND RESULTS: Our patient population comprised 90 consecutive patients with AMI who underwent preintervention IVUS within 6 hours of the onset of symptoms. Patients were divided into an elevated CRP group (> or =3 mg/L) or a normal CRP group on the basis of serum CRP levels. There were no differences in patient characteristics or angiographic findings. We observed significantly more plaque rupture in the elevated CRP group than in the normal CRP group (70% versus 43%, P=0.01). A multivariate logistic regression model revealed that the presence of ruptured plaque alone correlated with elevation of serum CRP (P=0.02; odds ratio, 3.35; 95% CI, 1.22 to 9.18). CONCLUSIONS: Elevated CRP may be related to the presence of ruptured plaque. Our results suggest that in the setting of AMI, elevated CRP levels may reflect the inflammatory activity of a ruptured plaque.

Circulating monocytes and in-stent neointima after coronary stent implantation.

OBJECTIVES: The aim of this study was to investigate the relationship between circulating monocytes and in-stent neointimal volume at six-month follow-up. BACKGROUND: In-stent neointimal hyperplasia is the main contributing factor to in-stent restenosis. There is increasing evidence that white blood cells (WBCs), especially monocytes, play a central role in restenosis after stent implantation. METHODS: We performed coronary stent implantation in 107 patients (107 lesions). Peripheral blood was obtained from all patients immediately before coronary angiography and every day for seven days after the intervention, and each WBC fraction count was analyzed. At scheduled six-month follow-up, all patients received angiographic and volumetric intravascular ultrasound analysis. RESULTS: The circulating monocyte count increased and reached its peak two days after stent implantation (from 350 +/- 167 to 515 +/- 149/mm3, p < 0.01). The maximum monocyte count after stent implantation showed a significant positive correlation with in-stent neointimal volume at six-month follow-up (r = 0.44, p < 0.0001). Other fractions showed neither significant serial changes nor a correlation with in-stent neointimal volume. Multiple regression analysis revealed that in-stent neointimal volume was independently correlated with stent volume immediately after implantation (r = 0.45, p < 0.0001) and maximum monocyte count (r = 0.35, p < 0.001). Angiographic restenosis, defined as percent diameter stenosis >50%, was observed in 22 patients (21%), and these patients showed a significantly larger maximum monocyte count than patients without restenosis (642 +/- 110 vs. 529 +/- 77/mm3, p < 0.01). CONCLUSIONS: Circulating monocytes increased after coronary stent implantation, and the peak monocyte count related to in-stent neointimal volume. Our results suggest that circulating monocytes play a role in the process of in-stent neointimal hyperplasia.

The decrease of plaque volume during percutaneous coronary intervention has a negative impact on coronary flow in acute myocardial infarction: a major role of percutaneous coronary intervention-induced embolization.

OBJECTIVES: The aim of this study was to evaluate how decreased plaque volume during percutaneous coronary intervention (PCI) affects coronary flow in patients with acute myocardial infarction (AMI). BACKGROUND: Coronary flow after reperfusion therapy is a major determinant of clinical outcomes in patients with AMI. However, little is still known about the changes in coronary flow that appear after PCI in response to the decreased plaque during the procedure. METHODS: The study group comprised 60 patients with AMI who underwent pre- and post-PCI intravascular ultrasound (IVUS). Qualitative and quantitative analyses were performed on all IVUS procedures. External elastic membrane volume (EEMV), lumen volume (LV), and plaque volume (PV) were measured every 1.0 mm to include the lesion and reference segments 3.0 mm proximal and distal to the lesion. The difference between pre- and post-PCI PV was defined as the index of the decrease in plaque volume (DeltaPV). The corrected TIMI frame count (CTFC) was used to evaluate coronary flow after PCI. RESULTS: Plaque volume was decreased at post-PCI IVUS in all 60 patients. Inadequate reflow (CTFC >40) was observed in 13 patients (21.7%). The decrease in PV was significantly larger in patients with inadequate reflow than in those with reflow (49.4 +/- 18.9 vs. 31.7 +/- 15.5 mm(3), p = 0.0010). Also, DeltaPV was significantly correlated with CTFC after PCI (r = 0.415, p = 0.0012). CONCLUSIONS: The decrease in PV during PCI has a negative impact on coronary flow after PCI in patients with AMI. Embolization induced by PCI may occur in all patients with AMI.

Primary cardiac malignant fibrous histiocytoma with abdominal wall metastasis.

We present a rare case of cardiac malignant fibrous histiocytoma (MFH; undifferentiated pleomorphic sarcoma); to date, fewer than 100 cases of cardiac MFH have been reported. In this case, transthoracic echocardiography revealed cardiac tumors in the left atrium (LA) of a 53-year-old woman with a 3-month history of worsening dyspnea; the largest tumor was found to protrude through the mitral valve in diastole, causing stenosis. Three of the four tumors were resected during emergency surgery; however, the residual tumor extension into the left pulmonary vein could not be removed. Histological findings of the resected tumors, such as organized thrombus and myxomatous tissue changes, indicated that the tumors were benign. After 3 months, the patient underwent total resection for a small mass that developed on her right abdominal wall, which was revealed histologically to be MFH; additionally, the residual mass in the LA had enlarged progressively. After undergoing radiation therapy without further surgery, she died of cerebral bleeding 6 months after cardiac surgery. Postmortem examination revealed that the tumor in the LA was an MFH. Thus, cardiac MFH should be considered as a differential diagnosis for tumors on the posterior wall of the LA. .

Predicting angiographic distal embolization following percutaneous coronary intervention in patients with acute myocardial infarction.

The aim of this study was to investigate the relation between lesion morphology identified by intravascular ultrasound (IVUS) before intervention and angiographic distal embolization after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). PCI for AMI has already been established as beneficial therapy, although some complications remain unresolved. Distal embolization is 1 of the important complications of PCI. Recently, some new devices have been developed for the prevention of distal embolization. However, few studies exist that look into the relation between lesion morphology and distal embolization. IVUS was performed safely in 140 consecutive patients with AMI before coronary intervention. No patient received thrombolytic therapy. From the incidence of angiographic distal embolization, patients were divided into 2 groups--an embolization group and a nonembolization group--and clinical background, IVUS, and angiographic information were evaluated. Distal embolization was observed in 12 patients (9%). Peak creatine kinase levels (3,877 +/- 2,285 vs 2,293 +/- 1,792 IU/L, p <0.05) and the incidence of angiographic thrombus (25% vs 5%, p <0.05) and intracoronary mobile mass detected by IVUS (75% vs 16%, p <0.001) were higher for patients in the embolization group. From the multivariate logistic regression analysis, only an intracoronary mobile mass detected by IVUS emerged as a predictor of distal embolization (odds ratio 53, 95% confidence interval 2.7 to 1,040, p <0.01). Patients with an intracoronary mobile mass detected by IVUS are prone to distal embolization after PCI and larger infarction. IVUS imaging before PCI may be useful for determining which patients need a distal protection device.

Circadian variation of plaque rupture in acute myocardial infarction.

Studies have reported a circadian variation in the onset of acute myocardial infarction (AMI). Pathologic studies have revealed that plaque rupture is 1 of the major causes of AMI, but none of these has looked specifically at the circadian variation of plaque rupture. The aim of this study was to use intravascular ultrasound (IVUS) to investigate the circadian variation of plaque rupture in AMI. This study included 174 consecutive patients with AMI who underwent preinterventional IVUS. All patients were assigned to either a rupture group or a nonrupture group according to the preinterventional IVUS. In the 81 patients (47%) in the rupture group, the frequency of the onset of AMI increased significantly in the period from 6 A.M. to 12 P.M. compared with all other time periods (p <0.05). The clinical features of AMI in the rupture group were characterized as occurring significantly more at rest (67% vs 31%, p <0.01) and after significantly less preinfarction angina (22% vs 57%, p <0.01) compared with the nonrupture group. A different circadian variation was identified in the nonrupture group, characterized as a significant nocturnal nadir (12 to 6 A.M. compared with all other periods, p <0.05). The circadian variation of AMI is the result of a morning increase in incidence of plaque rupture.

Use of preintervention intravascular ultrasound in patients with acute myocardial infarction.

This study was designed to determine whether preintervention intravascular ultrasound (IVUS) imaging can assist in predicting the likelihood of acute coronary occlusion after primary angioplasty. Primary angioplasty is in widespread use for the treatment of acute myocardial infarction (AMI), although its usefulness is sometimes compromised by postprocedural acute coronary occlusion. If preintervention IVUS could be used to predict acute coronary occlusion, the task of determining treatment strategies for AMI would be significantly eased. Preintervention IVUS was performed without complications in 46 patients with AMI using manually prepared contrast medium. Coronary angiography was performed 1 hour after successful percutaneous transluminal coronary angioplasty. Acute coronary occlusion was seen in 13 of 46 patients (28%). There were no differences in the clinical characteristics and angiographic results between the patients with and without occlusion. In patients with acute occlusion, the incidence of eccentric plaque (85% vs 36%, p <0.01) and echolucent area (92% vs 15%, p <0.01) was significantly higher than in the occlusion-free patients. Most of the echolucent areas were associated with eccentric plaques (88%). Eccentric plaques characterized by echolucent areas are prone to acute occlusion after primary balloon angioplasty for AMI. Preintervention IVUS is both a safe and a useful adjunct to primary angioplasty.

Comparison of risk factors in acute myocardial infarction and unstable angina pectoris in patients < or =66 versus >66 years of age.

A prospective study was conducted of the differences in clinical characteristics between patients with acute myocardial infarction and those with unstable angina pectoris admitted to hospitals in the South-Osaka district of Japan. Gender and smoking were identified as discriminant risk factors for the incidence of acute myocardial infarction in patients < or =66 years with acute coronary syndromes; however, age alone affected the mode of presentation in older patients.

In-stent restenosis and lesion morphology in patients with acute myocardial infarction.

We investigated the correlation between lesion morphology with preintervention intravascular ultrasound and in-stent restenosis in 72 patients with acute myocardial infarction (AMI). Multivariate logistic regression analysis showed that the presence of ruptured plaque was the only predictive factor of in-stent restenosis after primary stenting for AMI.

Oolong tea increases plasma adiponectin levels and low-density lipoprotein particle size in patients with coronary artery disease.

BACKGROUND: Oolong tea has been studied for its effect on cardiovascular disease and obesity. Plasma adiponectin levels are reduced in obesity, in patients with type 2 diabetes mellitus and in coronary artery disease (CAD). OBJECTIVE: To investigate prospectively, whether intake of Oolong tea influences plasma adiponectin levels, low-density lipoprotein (LDL) particle size, total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, serum triglyceride and plasma glucose levels in patients with CAD. METHODS: Twenty two patients in our study consumed Oolong tea (1000 ml) or water for 1 month in our randomized cross-over study design. RESULTS: There was a significant difference in plasma adiponectin levels before and after 1 month intake of Oolong tea (6.26 +/- 3.26 microg/ml versus 6.88 +/- 3.28 microg/ml, P < 0.05), and in plasma level LDL particle size (25.02+/-0.67 nm versus 25.31+/-0.60 nm, P < 0.01). The water-consuming control group showed no changes (6.28+/-3.28 microg/ml versus 6.23+/-3.21 microg/ml) in adiponectin levels or LDL particle sizes (25.03+/-0.70 nm versus 25.02+/-0.72 nm). We also observed a significant difference in hemoglobin A1c levels (7.23 +/- 4.45% versus 6.99 +/- 4.30%, P < 0.05) before and after intake of Oolong tea. CONCLUSION: Oolong tea may have beneficial effects on the progression of atherosclerosis in patients with CAD.

Increased cardiac mortality in women compared with men in patients with acute myocardial infarction.

OBJECTIVE: It has been reported that women with acute myocardial infarction (AMI) have a higher short-term mortality rate than men, but the reason is not known. The profile in relation to age, gender and risk factors was evaluated to compare AMI and unstable angina pectoris (UAP). METHODS: Findings from 984 patients including 580 patients with AMI (129 women, 451 men) and 404 patients with UAP (131 women, 273 men) were analyzed by the South Osaka Acute Coronary Syndrome Study Group (SACS). The primary endpoint of the study was in-hospital death. The primary endpoints of interest (cardiac death) were fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. RESULTS: Cardiac death during hospitalization within 30 days in AMI was higher in women than in men (12.4% vs 6.7%, p < 0.05). On the other hand, in UAP there was no significant difference between women and men (1.5% vs 0.7%, NS). The incidence of cardiac death in AMI was significantly higher for patients 75 years old and older (19.0%) than for patients less than 55 years old (4.2%), 55-64 years old (3.5%) and 65-74 years old (4.7%) (p < 0.001, respectively). CONCLUSIONS: Cardiac death was higher for women compared with men in patients with AMI. The worse prognosis for the AMI women patients was likely to be derived from less performance of percutaneous coronary intervention, and a high incidence of severe myocardial infarction. Further research should be focused on the analysis of various clinical backgrounds.

[Cerebral embolism associated with Becker muscular dystrophy-related dilated cardiomyopathy].

A 65-year-old man with previous history of congestive heart failure and genetically proven Becker muscular dystrophy (BMD) was suddenly suffered from aphasia and right hemiplegia. Physical examination showed severe motor aphasia, right hemiplegia, and signs of left heart failure. An echocardiogram before the onset of aphasia showed markedly dilated left ventricle and decreased ventricular contraction. Intracardiac thrombus was not detected. Although his electrocardiogram on admission showed sinus rhythm, atrial fibrillation was noted at the time of neurological deterioration. MRI of the brain revealed acute infarction in the territory of the left middle cerebral artery and the left anterior inferior cerebellar artery. MR angiography showed vascular occlusion at the left M2 segment. Cerebral embolism due to atrial fibrillation associated with BMD-related DCM was diagnosed. While an administration of anti-coagulant, diuretics, and dopamine relieved his respiratory distress and right hemiplegia, severe motor aphasia persisted. Cerebral embolism may be a notable complication in patients with BMD presenting with late-life expression of skeletal muscular weakness and antecedent cardiac involvement.

Prognostic value of coronary flow reserve on long-term cardiovascular outcomes in patients with chronic kidney disease.

Cardiovascular (CV) diseases and chronic kidney disease (CKD) have common predisposing factors that subsequently cause microvascular dysfunction. In the absence of obstructive coronary artery disease, coronary flow reserve (CFR) represents the status of coronary microcirculation. This study aimed to investigate the prognostic importance of impaired CFR, as a marker of microvascular dysfunction, on long-term CV outcomes in patients with CKD. This study consisted of 139 patients with an estimated glomerular filtration rate of <60 ml/min/1.73 m(2) who had no obstructive narrowing of the left anterior descending artery. Transthoracic Doppler echocardiography was used to measure CFR in the left anterior descending artery. During the follow-up period (3.3 ± 1.6 years), CV events occurred in 26 patients (18.7%). Multivariate analysis that included CFR as a continuous value identified a serum level of C-reactive protein (hazard ratio 1.41, p = 0.03) and a value of CFR (hazard ratio 0.21, p = 0.009) as determinants for CV events, independent of traditional CV risk factors. Patients with a CFR of <2.0 had worse CV outcomes compared with those with a CFR of ≥2.0 (p <0.001). In conclusion, transthoracic Doppler echocardiographically derived CFR was useful for the risk stratification of CV outcomes in patients with CKD. The presence of microvascular dysfunction may play an important role in the association between CKD and future CV events.