Inflammatory status as a main determinant of outcome in patients with unstable angina, independent of coagulation activation and endothelial cell function.
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AIMS: Inflammation, endothelial cell function and the coagulation system have been demonstrated to be involved in the onset and course of unstable angina. Whether a proinflammatory state independently determines outcome is unknown and has not been determined yet in a clinically well defined study population of consecutive patients admitted with unstable angina. METHODS AND RESULTS: Markers of inflammation, coagulation activation and endothelial cell function were determined on admission in blood of 211 consecutive patients with severe unstable angina and were related to the in-hospital course. Refractory unstable angina occurred in 76 patients (36%) during their hospital stay. In a univariate analysis, C-reactive protein (P = 0.03), fibrinogen (P < 0.001) and erythrocyte sedimentation rate (P = 0.001) levels were significantly higher in patients with refractory unstable angina, when compared with patients who had an uneventful clinical course. The odds ratios (95% CI) adjusted for age, sex, body mass index, smoking behaviour and cholesterol levels of the occurrence of refractory unstable angina for patients in the highest quartile compared with patients in the lowest quartile of inflammatory markers were 2.19 (0.94-5.11) for C-reactive protein, 2.83 (1.13-7.10) for fibrinogen and 4.72 (1.70-13.09) for the erythrocyte sedimentation rate. The findings were not affected by the presence or absence of myocardial necrosis or the interval between onset of angina and blood collection. No association was found between markers of coagulation activation or markers of endothelial cell function, and in-hospital outcome. CONCLUSION: We found that in a clinically well-defined study population of patients with severe unstable angina, a proinflammatory state is an important and independent determinant of short-term outcome. The data strengthen the importance of inflammation in this syndrome. (+info)
Stents covered by an autologous arterial graft in porcine coronary arteries: feasibility, vascular injury and effect on neointimal hyperplasia.
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OBJECTIVE: The use of stents has improved results after balloon coronary angioplasty. Several materials have been proposed for covering the metallic surface of the stent to reduce the rate of subacute thrombosis and restenosis. In our institution, an autologous arterial graft was used for covering the external surface of a conventional stent. The angiographic and histological response in a porcine coronary artery model was investigated. METHODS: An autologous arterial graft was removed from the femoral artery and carefully prepared. Subsequently, a conventional stent was covered externally by the arterial graft. Twenty-two covered stents and 22 uncovered regular stents were implanted alternatively in the coronary arteries of 22 pigs. One animal died immediately after the procedure, due to thrombus formation in the uncovered stent. Six animals were sacrificed at seven days and the remaining animals were sacrificed at two months. Before the sacrifice, coronary angiography was performed in all animals. RESULTS: Thrombosis was detected in two control segments and in one covered stented segment. After seven days, the luminal surface of the covered stents was covered by a new endothelial layer in contrast to partial endothelial cell appearance in the control group. The angiographic parameters were similar between the two groups. Histologically, the covered stents were associated with less vascular injury compared to uncovered stents. In covered stents a trend towards reduction of maximal intimal hyperplasia was detected (covered: 116.6 +/- 47.75 vs uncovered: 150.25 +/- 46.81 microns, p = 0.08); also the thickness of the arterial media was reduced (covered: 21.34 +/- 10.28 vs uncovered: 102.63 +/- 18.71 microns, p = 0.02). The luminal and vessel areas were similar in the two groups. CONCLUSIONS: The preparation and implantation of the autologous arterial graft-covered stent is technically safe and feasible. This type of covered stent results in accelerated endothelialization, less vascular injury, thinning of the arterial media and a trend to reduce the intimal hyperplasia in normal coronary arteries. (+info)
Angioscopic complex lesions are predominantly compensatory enlarged: an angioscopy and intracoronary ultrasound study.
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OBJECTIVES: Atherosclerotic remodeling of the coronary artery may lead to compensatory enlargement or to shrinkage. Post-mortem data suggest a relation between compensatory enlargement and histopathological markers of plaque vulnerability. In patients that required a coronary intervention, we investigated retrospectively the relation between the angioscopic appearance and the remodeling mode of the culprit lesion. METHODS: In 34 patients, coronary angioscopy and intracoronary ultrasound (ICUS) imaging was performed across the culprit lesion before the intervention. Only single de novo lesions were included. With angioscopy, lesions with a smooth surface without thrombus were classified as smooth, whereas lesions with an irregular surface with or without thrombus were classified as complex. With ICUS, remodeling of the culprit lesions was determined by the relative cross-sectional vessel area (lesion vessel area/reference vessel area) x 100%. Lesions were divided into three groups: compensatory enlargement (relative vessel area > or = 105%), no-remodeling (relative vessel area between 95 and 105%) and shrinkage (relative vessel area < or = 95%). RESULTS: In 22 patients good images were obtained with both imaging modalities. More complex lesions were compensatory enlarged compared to shrunken lesions, whereas more smooth lesions were shrunken compared to compensatory enlarged lesions, 8/9 versus 2/7 and 5/7 versus 1/9, respectively (p = 0.035). CONCLUSIONS: In patients selected for coronary intervention, angioscopic complex atherosclerotic lesions were found predominantly in compensatory enlarged arterial segments, whereas smooth lesions were found predominantly in shrunken arterial segments. (+info)
Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators.
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BACKGROUND: The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. METHODS AND RESULTS: Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including abciximab received low-dose heparin (60-U/kg bolus; infusion of 7 U. kg-1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated alteplase alone was 57% compared with 32% for abciximab alone and 34% to 46% for doses of streptokinase between 500 000 U and 1.25 MU with abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P<0.02). The most promising regimen was 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1) heparin. TIMI 3 flow rates were significantly higher in the 50-mg alteplase plus abciximab group versus the alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major hemorrhage were 6% in patients receiving alteplase alone (n=235), 3% with abciximab alone (n=32), 10% with streptokinase plus abciximab (n=143), 7% with 50 mg of alteplase plus abciximab and low-dose heparin (n=103), and 1% with 50 mg of alteplase plus abciximab with very-low-dose heparin (n=70). CONCLUSIONS: Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding. (+info)
The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes.
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OBJECTIVES: The purpose of this study was to assess safety and efficacy of enhanced external counterpulsation (EECP). BACKGROUND: Case series have shown that EECP can improve exercise tolerance, symptoms and myocardial perfusion in stable angina pectoris. METHODS: A multicenter, prospective, randomized, blinded, controlled trial was conducted in seven university hospitals in 139 outpatients with angina, documented coronary artery disease (CAD) and positive exercise treadmill test. Patients were given 35 h of active counterpulsation (active CP) or inactive counterpulsation (inactive CP) over a four- to seven-week period. Outcome measures were exercise duration and time to > or =1-mm ST-segment depression, average daily anginal attack count and nitroglycerin usage. RESULTS: Exercise duration increased in both groups, but the between-group difference was not significant (p > 0.3). Time to > or =1-mm ST-segment depression increased significantly from baseline in active CP compared with inactive CP (p = 0.01). More active-CP patients saw a decrease and fewer experienced an increase in angina episodes as compared with inactive-CP patients (p < 0.05). Nitroglycerin usage decreased in active CP but did not change in the inactive-CP group. The between-group difference was not significant (p > 0.7). CONCLUSIONS: Enhanced external counterpulsation reduces angina and extends time to exercise-induced ischemia in patients with symptomatic CAD. Treatment was relatively well tolerated and free of limiting side effects in most patients. (+info)
Myocardial viability on echocardiography predicts long-term survival after revascularization in patients with ischemic congestive heart failure.
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OBJECTIVES: This study was conducted to evaluate the effect of revascularization on survival in patients with congestive heart failure (CHF) due to ischemic left ventricular (LV) systolic dysfunction based on the presence of myocardial viability (MV). BACKGROUND: There are insufficient data regarding the survival benefit of revascularization in patients with CHF due to ischemic LV systolic dysfunction. METHODS: Follow-up was obtained in 87 consecutive patients with CHF due to ischemic LV systolic dysfunction (New York Heart Association [NYHA] class II-IV; LV ejection fraction <0.35) who underwent low-dose dobutamine echocardiography (DE). MV within each of 12 myocardial segments representing the LV was defined as having either: 1) normal function or mild dyssynergy at rest; 2) severe resting dyssynergy that improved on DE, or 3) worsening of function on DE except in the case of akinesia. RESULTS: At a mean follow-up of 40+/-17 months, 37 patients had received revascularization on the basis of clinical grounds, and there were 22 (25%) cardiac-related deaths. Multivariate Cox regression analysis revealed that when patients with at least five segments showing MV underwent revascularization, mortality was reduced by an average of 93% (confidence interval of 22% to 99%), which was associated with improvement in NYHA class as well as LV ejection fraction. Patients with less than five segments showing MV who underwent revascularization (and thus, showing mostly scar), and those with at least 5 segments demonstrating MV who were treated medically, had a much higher mortality. CONCLUSIONS: Revascularization produces a clear survival benefit in patients with CHF due to ischemic LV systolic dysfunction who have a significant region of the LV demonstrating MV. These data may have wide-ranging implications in the management of patients with coronary artery disease whose main clinical presentation is CHF. (+info)
Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: comparison with stress myocardial perfusion imaging.
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OBJECTIVES: To validate intravascular ultrasound (IVUS) measurements for differentiating functionally significant from nonsignificant coronary stenosis. BACKGROUND: To date, there are no validated criteria for the definition of a flow-limiting coronary artery stenosis by IVUS. METHODS: Preinterventional IVUS imaging (30-MHz imaging catheter) of 70 de novo coronary lesions was performed. The lesion lumen area and three IVUS-derived stenosis indixes comparing lesion lumen area with the lesion external elastic lamina (EEL) area, the mean reference lumen area and the mean reference EEL area were compared with the results of stress myocardial perfusion imaging. RESULTS: The lesion lumen area and three IVUS-derived stenosis indexes showed sensitivities and specificities ranging between 80% and 90% using stress myocardial perfusion imaging as the gold standard. The lesion lumen area < or =4 mm2 is a simple and highly accurate criterion for significant coronary narrowing. CONCLUSIONS: Quantitative IVUS indices can be reliably used for identifying significant epicardial coronary artery stenoses. (+info)
A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study.
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OBJECTIVES: This study examined the effect of a small-molecule, direct thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (TPA) in patients with acute myocardial infarction (AMI). BACKGROUND: Thrombin plays a crucial role in thrombosis and thrombolysis. In vitro and in vivo studies have shown that argatroban has advantages over heparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA. METHODS: One hundred and twenty-five patients with AMI within 6 h were randomized to heparin, low-dose argatroban or high-dose argatroban in addition to TPA. The primary end point was the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 min. RESULTS: TIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-dose argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban patients (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus heparin patients: 57.1% versus 20.0% (p = 0.03 vs. heparin). Major bleeding was observed in 10.0% of heparin, and in 2.6% and 4.3% of low-dose and high-dose argatroban patients, respectively. The composite of death, recurrent myocardial infarction, cardiogenic shock or congestive heart failure, revascularization and recurrent ischemia at 30 days occurred in 37.5% of heparin, 32.0% of low-dose argatroban and 25.5% of high-dose argatroban patients (p = 0.23). CONCLUSIONS: Argatroban, as compared with heparin, appears to enhance reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban. (+info)