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1.
AIMS: To investigate the clinical outcome after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled multicentre trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone-marrow-derived progenitor cells (BMCs) or placebo medium into the infarct artery 3-7 days after successful infarct reperfusion therapy. At 12 months, the pre-specified cumulative endpoint of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (P=0.009). Likewise, the combined endpoint death, recurrence of myocardial infarction, and rehospitalization for heart failure was significantly (P=0.006) reduced in patients receiving intracoronary BMC administration. Intracoronary administration of BMC remained a significant predictor of a favourable clinical outcome by Cox regression analysis, adjusting for classical predictors of poor outcome after AMI. CONCLUSION: Intracoronary administration of BMCs is associated with a significant reduction of the occurrence of major adverse cardiovascular events after AMI. Large-scale studies are warranted to confirm the effects of BMC administration on mortality and morbidity in patients with AMIs.  相似文献   

2.
AIMS: We have recently shown in the randomized-controlled BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial that intracoronary autologous bone marrow cell (BMC) transfer improves left ventricular (LV) ejection fraction recovery in patients after acute myocardial infarction (AMI). However, the impact of BMC therapy on LV diastolic function in patients after AMI has remained uncertain. METHODS AND RESULTS: Using (tissue) Doppler echocardiography, we evaluated the effects of BMC transfer on LV diastolic function in patients enrolled in the BOOST trial. After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (MI), patients were randomized to a control (n = 29) or BMC transfer group (n = 30). Diastolic function was determined 4.5+/-1.5 days after PCI, at 6 months, and at 18 months by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall effect of BMC transfer on E/A [0.33+/-0.12; 95% confidence interval (CI): 0.09-0.57; P = 0.008] and Ea/Aa ratios (0.29+/-0.14; 95% CI: 0.01-0.57; P = 0.04). In contrast, we found no effect of BMC transfer on DT (-5+/-14 ms; 95% CI: -33 to 22; P = 0.70), IVRT (-7+/-7 ms; 95% CI: -20 to 6; P = 0.29), and E/Ea ratio (0.35+/-0.14; 95% CI: -0.92 to 1.62; P = 0.57). CONCLUSION: Intracoronary autologous BMC transfer improves echocardiographic parameters of diastolic function in patients after AMI.  相似文献   

3.
To assess the impact of spontaneous anterograde flow of the infarct artery on outcomes in patients with acute myocardial infarction (AMI), we studied 478 patients with a first anterior wall AMI who underwent coronary angiography within 12 hours after the onset of chest pain; Thrombolysis In Myocardial Infarction (TIMI) 3 flow was obtained after reperfusion therapy. Patients were divided into 3 groups: 119 patients with spontaneous anterograde flow (initial TIMI 2 or 3 flow) of the infarct artery, 118 patients with an initially occluded artery (TIMI 0 or 1 flow) and time to angiography or=55% (odds ratio 7.13, 95% confidence interval 3.10 to 16.4, p <0.001). In conclusion, although very early reperfusion improved LV function more than late reperfusion, spontaneous anterograde flow was associated with better acute and predischarge LV function after AMI compared with very early reperfusion of an initially occluded artery.  相似文献   

4.
BACKGROUND: Transplantation of bone marrow derived adult stem cells (BMC) improves cardiac function after acute myocardial infarction (MI). However, the cell population mediating myocardial recovery and the fate of the transplanted cells are still controversial. AIMS: We determined the effects of Sca-1+ c-kit+ lin- haematopoietic BMC on cardiac function after MI and the cell fate after transplantation. METHODS: Sca-1+ c-kit+ lin- BMC of male donor C57BL/6 mice were transplanted by intravenous injection into syngenic females after permanent MI. LV dimensions and function were determined by echocardiography and cardiac magnetic resonance imaging, transplanted BMC were identified by Y chromosome DNA in situ hybridization. RESULTS: BMC treatment completely prevented LV dilation (LV end-diastolic volume BMC 70 +/- 16 microl vs. control 122 +/- 41 microl; p < 0.05) and improved fractional shortening (BMC 22.9 +/- 8% vs. control 15.4 +/- 8.4%; p < 0.05) and ejection fraction BMC 68.2 +/- 6.6% vs. control 52 +/- 14.3%; p < 0.05) as early as 3 days after transplantation, but did not decrease infarct size (BMC 27 +/- 6% vs. control 28 +/- 7%, p = n.s.). After 4 weeks, only sporadic cells of male origin were identified in infarcted hearts (< 0.01% of periinfarct cells). CONCLUSION: Intravenous injection of Sca-1+ c-kit+ lin- in BMC after MI improves LV dimensions and function without evidence for long term engraftment.  相似文献   

5.
Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 microg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, > or =5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 +/- 6% to 45 +/- 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 +/- 33 to 144 +/- 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 +/- 35 to 168 +/- 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 +/- 6% to 38 +/- 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention.  相似文献   

6.
AIMS: Recent data suggest that the administration of bone marrow-derived stem cells (BMSC) might improve myocardial perfusion and left ventricular (LV) function after acute myocardial infarction (AMI). The aim of this study was to assess spontaneous mobilization of BMSC expressing the haematopoietic and endothelial progenitor cell-associated antigen CD34+ after AMI and its relation to post-infarction remodelling. METHODS AND RESULTS: Peripheral blood concentration of CD34+ BMSC was measured by flow cytometry in 54 patients with AMI, 26 patients with chronic stable angina (CSA), and 43 normal healthy subjects. In patients with AMI, LV function was measured by 2D-echocardiography. Eighteen AMI patients were reassessed at 1 year. BMSC concentration was higher in patients with AMI (mean peak value: 7.04+/-6.27 cells/microL), than in patients with CSA (3.80+/-2.12 cells/microL, P=0.036) and in healthy controls (1.87+/-1.52 cells/microL, P<0.001). At multivariable analysis statin use (P<0.001), primary percutaneous intervention (P=0.048) and anterior AMI (P=0.05) were the only independent predictors of increased BMSC mobilization after AMI. In the 28 patients without subsequent acute coronary events reassessed at 1 year follow-up, CD34+ cell concentration was an independent predictor of global and regional improvement of LV function (r=0.52, P=0.004 and r=-0.41, P=0.03, respectively). CONCLUSION: AMI is followed by enhanced spontaneous mobilization of BMSC, in particular, in patients on statin therapy and following a primary percutaneous intervention. More importantly persistent spontaneous mobilization of BMSC might contribute to determine a more favourable post-AMI remodelling.  相似文献   

7.
BACKGROUND: Elevation of white blood cell (WBC) count at admission is associated with adverse outcome after acute myocardial infarction (AMI). Prodromal angina, by the mechanism of ischemic preconditioning, improves left ventricular (LV) function and survival after reperfusion therapy in patients with AMI. Recent experimental studies have reported that preconditioning has anti-inflammatory effect. METHODS: This study consisted of 598 patients with first anterior wall AMI who underwent coronary angiography within 12 h after symptom onset. WBC count was measured at the time of hospital admission. Prodromal angina was defined as angina occurring within 24 h before the onset of AMI. Serial measurements of LV ejection fraction (EF) were obtained before reperfusion therapy and before discharge in 421 patients (71%). RESULTS: High WBC count (>10.2 x 103/mm3, n=297) was associated with higher 30-day mortality (8% vs. 4%, p=0.02) and lower predischarge LVEF (51+/-15% vs. 57+/-14%, p<0.001), although there was no significant difference in acute LVEF (47+/-10% vs. 49+/-11%, p=0.07). High WBC count was an independent predictor of 30-day mortality (p=0.009) and predischarge LVEF (p=0.002). Prodromal angina was associated with lower 30-day mortality (3% vs. 7%, p=0.02) and preserved predischarge LVEF (57+/-15% vs. 53+/-14%, p=0.006). Patients with prodromal angina had lower WBC count (10.0+/-3.3 x 10(3)/mm3 vs. 11.0+/-3.9 x 10(3)/mm3, p=0.001) and prodromal angina was an independent predictor of WBC count (p<0.001). CONCLUSIONS: Elevation of WBC count and lack of prodromal angina were associated with impaired LV function and mortality after reperfusion in patients with AMI. Prodromal angina might have contributed to favorable outcome after AMI through its anti-inflammatory effect.  相似文献   

8.
Left ventricular (LV) diastolic filling is characterized by the formation of intraventricular rotational bodies of fluid (termed "vortex rings") that optimize the efficiency of LV ejection. The aim of the present study was to evaluate the morphology and dynamics of LV diastolic vortex ring formation early after acute myocardial infarction (AMI), in relation to LV diastolic function and infarct size. A total of 94 patients with a first ST-segment elevation AMI (59 ± 11 years; 78% men) were included. All patients underwent primary percutaneous coronary intervention. After 48 hours, the following examinations were performed: 2-dimensional echocardiography with speckle-tracking analysis to assess the LV systolic and diastolic function, the vortex formation time (VFT, a dimensionless index for characterizing vortex formation), and the LV untwisting rate; contrast echocardiography to assess LV vortex morphology; and myocardial contrast echocardiography to identify the infarct size. Patients with a large infarct size (≥ 3 LV segments) had a significantly lower VFT (p <0.001) and vortex sphericity index (p <0.001). On univariate analysis, several variables were significantly related to the VFT, including anterior AMI, LV end-systolic volume, LV ejection fraction, grade of diastolic dysfunction, LV untwisting rate, and infarct size. On multivariate analysis, the LV untwisting rate (β = -0.43, p <0.001) and infarct size (β = -0.33, p = 0.005) were independently associated with VFT. In conclusion, early in AMI, both the LV infarct size and the mechanical sequence of diastolic restoration play key roles in modulating the morphology and dynamics of early diastolic vortex ring formation.  相似文献   

9.
BACKGROUND: Transplantation of non-expanded peripheral blood mononuclear cells (PBMNCs) enhances neovessel formation in ischemic myocardium and limbs by releasing angiogenic factors. This study was designed to examine whether intracoronary transplantation of PBMNCs improves cardiac function after acute myocardial infarction (AMI). METHODS AND RESULTS: After successful percutaneous coronary intervention (PCI) for a ST-elevation AMI with occlusion of proximal left anterior descending coronary artery within 24 h, patients were assigned to either a control group or the PBMNC group that received intracoronary infusion of PBMNCs within 5 days after PCI. PBMNCs were obtained from patients by COBE spectra-apheresis and concentrated to 10 ml, 3.3 ml of which was infused via over-the-wire catheter. The primary endpoint was the global left ventricular ejection fraction (LVEF) change from baseline to 6 months' follow-up. The data showed that the absolute increase in LVEF was 7.4% in the control group and 13.4% (p=0.037 vs control) in the PBMNC group. Cell therapy resulted in a greater tendency of DeltaRegional ejection fraction (EF) or significant improvement in the wall motion score index and Tc-99m-tetrofosmin perfusion defect score associated with the infarct area, compared with controls. Moreover, intracoronary administration of PBMNCs did not exacerbate either left ventricular (LV) end-diastolic and end-systolic volume expansion or high-risk arrhythmia, without any adverse clinical events. CONCLUSION: Intracoronary infusion of non-expanded PBMNCs promotes improvement of LV systolic function. This less invasive and more feasible approach to collecting endothelial progenitor cells may provide a novel therapeutic option for improving cardiac function after AMI.  相似文献   

10.
This study sought to analyze the evolution of myocardial perfusion during follow-up after primary angioplasty for acute myocardial infarction (AMI) and relate it to final left ventricular (LV) function. In 101 patients with a first AMI, angiographic myocardial blush grade (MBG) was analyzed immediately after intervention and at follow-up 7.5 +/- 5.6 months later. Cine ventriculography was performed at follow-up angiography to define LV function. Five patients had occluded stents or flow-limiting restenosis. In the remaining patients, myocardial perfusion at follow-up, as defined by MBG, was persistently abnormal in 19 patients (20%), had become normalized from previously abnormal MBG in 30 patients (31%), remained normal in 40 patients (42%), and deteriorated from normal to abnormal in 7 patients (7%). Patients with improvement of abnormal blush determined immediately after intervention to normal blush at follow-up (n = 30) compared with patients with persistently abnormal blush (n = 19) had a better LV ejection fraction at follow-up (53.7 +/- 11.1 vs. 37.4 +/- 9.7%, p <0.001). Evolution of MBG had a better predictive value for LV ejection fraction at follow-up than acute MBG only. Multivariate analysis proved evolution of MBG from AMI to follow-up to be an independent predictor of LV function (R(2) = 0.177, p <0.001) in addition to the initial size of jeopardized myocardium as defined by the sum of ST-segment elevation (R(2) = 0.138, p = 0.001) and infarct location (R(2) = 0.044, p = 0.033). In conclusion, tissue reperfusion after angioplasty for AMI is characterized by frequent improvement over time, as indicated by repeated MBG analysis. Patients with recovery of perfusion have better, final LV function.  相似文献   

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