Myocardial Ischaemia National Audit Project (MINAP)

The Myocardial Infarction Audit Project (MINAP) began in late 1998 when a broadly based steering group developed a dataset for acute myocardial infarction (AMI). This allowed clinicians to examine the management of myocardial infarction within their hospitals against targets specified by the National Service Framework for Coronary Heart Disease (NSF). The audit project produces annual reports "How the NHS manages heart attacks" to show the performance of hospitals, ambulance services and cardiac networks in England and Wales against national standards and targets for the care of heart attack patients. MINAP has recently changed its name from the Myocardial Infarction National Audit Project to the Myocardial Ischaemia National Audit Project to reflect the importance of all acute coronary syndromes.

Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: Therapeutic potential of mitochondrially targeted antioxidants.

Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6h of reperfusion and peaking at 24h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage.

Cardiac rotation and relaxation after anterolateral myocardial infarction.

BACKGROUND: Both systolic and diastolic dysfunction have been observed in patients with anterolateral myocardial infarction. Diastolic dysfunction is related to disturbances in relaxation and diastolic filling. OBJECTIVE: To analyse cardiac rotation, regional shortening and diastolic relaxation in patients with anterolateral infarction. METHODS: Cardiac rotation and relaxation in controls and patients with chronic anterolateral infarction were assessed by myocardial tagging. Myocardial tagging is based on magnetic resonance imaging and allows us to label specific myocardial regions for imaging cardiac motion (rotation, translation and radial displacement). A rectangular grid was placed on the myocardium (basal, equatorial and apical short-axis plane) of each of 18 patients with chronic anterolateral infarction and 13 controls. Cardiac rotation, change in area and shortening of circumference were determined in each case. RESULTS: The left ventricle in controls performs a systolic wringing motion with a clockwise rotation at the base and a counterclockwise rotation at the apex when viewed from the apex. During relaxation a rotational motion in the opposite direction (namely untwisting) can be observed. In patients with anterolateral infarction, there is less systolic rotation at the apex and diastolic untwisting is delayed and prolonged in comparison with controls. In the presence of a left ventricular aneurysm (n = 4) apical rotation is completely lost. There is less shortening of circumference in infarcted and remote regions. CONCLUSIONS: The wringing motion of the myocardium might be an important mechanism involved in maintaining normal cardiac function with minimal expenditure of energy. This mechanism no longer operates in patients with left ventricular aneurysms and operates significantly less than normal in those with anterolateral hypokinaesia. Diastolic untwisting is significantly delayed and prolonged in patients with anterolateral infarction, which could explain the occurrence of diastolic dysfunction in these patients.

mitoKATP channel activation in the postanoxic developing heart protects E-C coupling via NO-, ROS-, and PKC-dependent pathways.

Whereas previous studies have shown that opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel protects the adult heart against ischemia-reperfusion injury, it remains to be established whether this mechanism also operates in the developing heart. Isolated spontaneously beating hearts from 4-day-old chick embryos were subjected to 30 min of anoxia followed by 60 min of reoxygenation. The chrono-, dromo-, and inotropic disturbances, as well as alterations of the electromechanical delay (EMD), reflecting excitation-contraction (E-C) coupling, were investigated. Production of reactive oxygen species (ROS) in the ventricle was determined using the intracellular fluorescent probe 2',7'-dichlorofluorescin (DCFH). Effects of the specific mitoK(ATP) channel opener diazoxide (Diazo, 50 microM) or the blocker 5-hydroxydecanoate (5-HD, 500 microM), the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 microM), the antioxidant N-(2-mercaptopropionyl)glycine (MPG, 1 mM), and the PKC inhibitor chelerythrine (Chel, 5 microM) on oxidative stress and postanoxic functional recovery were determined. Under normoxia, the baseline parameters were not altered by any of these pharmacological agents, alone or in combination. During the first 20 min of postanoxic reoxygenation, Diazo doubled the peak of ROS production and, interestingly, accelerated recovery of ventricular EMD and the PR interval. Diazo-induced ROS production was suppressed by 5-HD, MPG, or L-NAME, but not by Chel. Protection of ventricular EMD by Diazo was abolished by 5-HD, MPG, L-NAME, or Chel, whereas protection of the PR interval was abolished by L-NAME exclusively. Thus pharmacological opening of the mitoK(ATP) channel selectively improves postanoxic recovery of cell-to-cell communication and ventricular E-C coupling. Although the NO-, ROS-, and PKC-dependent pathways also seem to be involved in this cardioprotection, their interrelation in the developing heart can differ markedly from that in the adult myocardium.

Spinal cord ischemia : clinical and imaging patterns, pathogenesis, and outcomes in 27 patients

RÉSUMÉ Introduction: l'histoire naturelle et la physiopathologie des infarctus de la moelle épinière restent largement inconnues. En effet, la plupart des études cliniques portent sur des patients qui ont souffert d'infarctus médullaire secondaire à des chirurgies aortiques ou des hypotensions prolongées. Méthode: ce travail analyse les données cliniques, le laboratoire, l'imagerie (IRM) et l'évolution de 27 patients souffrant d'infarctus de la moelle épinière admis dans le service de Neurologie du CHUV. Parmi ces patients, il y avait 11 hommes et 16 femmes (âge moyen de 56 ans, tranche d'âge de 19 à 80 ans). Résultats: dix patients (37%) souffraient d'infarctus de l'artère spinale antérieure, 4 (15%) d'infarctus unilatéraux antérieurs, 4 (15%) unilatéraux postérieurs, 3 (11%) d'infarctus centraux, 2 (7%) d'infarctus des artères spinales postérieures, 2 (7%) d'infarctus transverse tandis que 2 patients présentaient des tableaux cliniques inclassables. Vingt patients (74%) n'avaient pas d'étiologie identifiable. Les patients avec infarctus centraux ou transverses présentaient fréquemment (40%) des artériopathies périphériques et tous les infarctus transverses survenaient à la suite d'hypotensions artérielles prolongées. Le début de tous les autres types d'infarctus était associé à des facteurs mécaniques (p=0.02} et ces patients avaient fréquemment des pathologies du rachis (p=0.003) au niveau de la lésion médullaire. Dans ces cas, les données cliniques suggèrent une lésion d'une racine nerveuse au niveau de l'infarctus médullaire compromettant mécaniquement le flux de son artère radiculaire. L'évolution clinique était généralement favorable, seuls 13 patients (48%) présentaient une atteinte significative de la marche à la sortie de l'hôpital. Conclusion: ce travail montre qu'il existe 2 types principaux d'infarctus de la moelle épinière : d'une part les infarctus dans le territoire d'une artère radiculaire (infarctus de l'artère spinale antérieure, des artères spinales postérieures et infarctus unilatéraux) et d'autre part les hypoperfusions régionales globales de la moelle épinière (infarctus centraux et transverses). Chacune de ces 2 catégories d'infarctus ont des caractéristiques cliniques, radiologiques, physiopathologiques et pronostiques distinctes.

Neuroprotective role of lactate after cerebral ischemia.

It is well established that lactate can be used as an energy substrate by the brain by conversion to pyruvate and a subsequent oxidation in the mitochondria. Knowing the need for readily metabolizable substrates directly after ischemia and the protective effect of lactate after excitotoxicity, the aim of this study was to investigate whether lactate administration directly after ischemia could be neuroprotective. In vitro, the addition of 4 mmol/L L-lactate to the medium of rat organotypic hippocampal slices, directly after oxygen and glucose deprivation (OGD), protected against neuronal death, whereas a higher dose of 20 mmol/L was toxic. In vivo, after middle cerebral artery occlusion in the mouse, an intracerebroventricular injection of 2 microL of 100 mmol/L L-lactate, immediately after reperfusion, led to a significant decrease in lesion size, which was more pronounced in the striatum, and an improvement in neurologic outcome. A later injection 1 h after reperfusion did not reduce lesion size, but significantly improved neurologic outcome, which is an important point in the context of a potential clinical application. Therefore, a moderate increase in lactate after ischemia may be a therapeutic tool.

Cutting edge: IL-1α is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.

Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88(-/-) fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1β, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1α-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1α in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1α as a crucial early danger signal triggering post-MI inflammation.

A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.

ABSTRACT: BACKGROUND: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. METHODS: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). RESULTS: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = -0.63, p < 0.01), while extent of necrosis showed borderline correlation (r2 = -0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p < 0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. CONCLUSIONS: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase.

Primary percutaneous coronary intervention for unprotected left main disease in patients with acute ST-segment elevation myocardial infarction the AMIS (Acute Myocardial Infarction in Switzerland) plus registry experience.

OBJECTIVES: This study sought to assess outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) for unprotected left main (LM) disease. BACKGROUND: Limited data are available on outcomes in patients with ST-segment elevation myocardial infarction undergoing LM PCI. METHODS: Of 9,075 patients with ST-segment elevation myocardial infarction enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus registry between 2005 and June 30, 2010, 6,666 underwent primary PCI. Of them, 348 (5.2%; mean age: 63.5 ± 12.6 years) underwent LM PCI, either isolated (n = 208) or concomitant to PCI for other vessel segments (n = 140). They were compared with 6,318 patients (94.8%; mean age: 61.9 ± 12.5 years) undergoing PCI of non-LM vessel segments only. RESULTS: The LM patients had higher rates of cardiogenic shock (12.2% vs. 3.5%; p < 0.001), cardiac arrest (10.6% vs. 6.3%; p < 0.01), in-hospital mortality (10.9% vs. 3.8%; p < 0.001), and major adverse cardiac and cerebrovascular events (12.4% vs. 5.0%; p < 0.001) than non-LM PCI. Rates of mortality and major adverse cardiac and cerebrovascular events were highest for concurrent LM and non-LM PCI (17.9% and 18.6%, respectively), intermediate for isolated LM PCI (6.3% and 8.3%, respectively), and lowest for non-LM PCI (3.8% and 5.0%, respectively). Rates of mortality and major adverse cardiac and cerebrovascular events for LM PCI were higher than for non-LM multivessel PCI (10.9% vs. 4.9%, p < 0.001, and 12.4% vs. 6.4%, p < 0.001, respectively). LM disease independently predicted in-hospital death (odds ratio: 2.36; 95% confidence interval: 1.34 to 4.17; p = 0.003). CONCLUSIONS: Emergent LM PCI in the context of acute myocardial infarction, even including 12% cardiogenic shock, appears to have a remarkably high (89%) in-hospital survival. Concurrent LM and non-LM PCI has worse outcomes than isolated LM PCI.

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

Background. In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR). Methods. We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB). Results. 160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant]. We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events. Conclusions. Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.

Comparison of multislice computerized tomography angiography and digital subtraction angiography in the postoperative evaluation of patients with clipped aneurysms.

OBJECT: In this study the accuracy of multislice computerized tomography (MSCT) angiography in the postoperative examination of clip-occluded intracranial aneurysms was compared with that of intraarterial digital subtraction (DS) angiography METHODS: Forty-nine consecutive patients with 60 clipped aneurysms (41 of which had ruptured) were studied with the aid of postoperative MSCT and DS angiography. Both types of radiological studies were reviewed independently by two observers to assess the quality of the images, the artifacts left by the clips, the completeness of aneurysm occlusion, the patency of the parent vessel, and the duration and cost of the examination. The quality of MSCT angiography was good in 42 patients (86%). Poor-quality MSCT angiograms (14%) were a result of the late acquisition of images in three patients and the presence of clip or motion artifacts in four. Occlusion of the aneurysm on good-quality MSCT angiograms was confirmed in all but two patients in whom a small (2-mm) remnant was confirmed on DS angiograms. In one patient, occlusion of a parent vessel was seen on DS angiograms but missed on MSCT angiograms. The sensitivity and specificity for detecting neck remnants on MSCT angiography were both 100%, and the sensitivity and specificity for evaluating vessel patency were 80 and 100%, respectively (95% confidence interval 29.2-100%). Interobserver agreements were 0.765 and 0.86, respectively. The mean duration of the examination was 13 minutes for MSCT angiography and 75 minutes for DS angiography (p < 0.05). Multislice CT angiography was highly cost effective (p < 0.01). CONCLUSIONS: Current-generation MSCT angiography is an accurate noninvasive tool used for assessment of clipped aneurysms in the anterior circulation. Its high sensitivity and low cost warrant its use for postoperative routine control examinations following clip placement on an aneurysm. Digital subtraction angiography must be performed if the interpretation of MSCT angiograms is doubtful or if the aneurysm is located in the posterior circulation.

Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry

There is little literature about the clinical presentation and time-course of postoperative venous thromboembolism (VTE) in different surgical procedures. RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we analysed the baseline characteristics, thromboprophylaxis and therapeutic patterns, time-course, and three-month outcome of all patients with postoperative VTE. As of January 2006, there were 1,602 patients with postoperative VTE in RIETE: 393 (25%) after major orthopaedic surgery (145 elective hip arthroplasty, 126 knee arthroplasty, 122 hip fracture); 207 (13%) after cancer surgery; 1,002 (63%) after other procedures. The percentage of patients presenting with clinically overt pulmonary embolism (PE) (48%, 48%, and 50% respectively), the average time elapsed from surgery to VTE (22 +/- 16, 24 +/- 16, and 21 +/- 15 days, respectively), and the three-month incidence of fatal PE (1.3%, 1.4%, and 0.8%, respectively), fatal bleeding (0.8%, 1.0%, and 0.2%, respectively), or major bleeding (2.3%, 2.9%, and 2.8%, respectively) were similar in the three groups. However, the percentage of patients who had received thromboprophylaxis (96%, 76% and 52%, respectively), the duration of prophylaxis (17 +/- 9.6, 13 +/- 8.9, and 12 +/- 11 days, respectively) and the mean daily doses of low-molecular-weight heparin (4,252 +/- 1,016, 3,260 +/- 1,141, and 3,769 +/- 1,650 IU, respectively), were significantly lower in those undergoing cancer surgery or other procedures. In conclusion, the clinical presentation, time-course, and three-month outcome of VTE was similar among the different subgroups of patients, but the use of prophylaxis in patients undergoing cancer surgery or other procedures was suboptimal.

Perioperative in-stent thrombosis after lung resection performed within 3 months of coronary stenting

BACKGROUND: Incidence of perioperative in-stent thrombosis associated with myocardial infarction in patients undergoing major lung resection within 3 months of coronary stenting. METHODS: Retrospective multi-institutional trial including all patients undergoing major lung resection (lobectomy or pneumonectomy) within 3 months of coronary stenting with non-drug-eluting stents between 1999 and 2004. RESULTS: There were 32 patients (29 men and 3 women), with age ranging from 46 to 82 years. One, two or four coronary stents were deployed in 72%, 22% and 6% of the patients, respectively. The time intervals between stenting and lung surgery were <30 days, 30-60 days and 61-90 days in 22%, 53% and 25% of the patients, respectively. All patients had dual antiplatelet therapy after stenting. Perioperative medication consisted of heparin alone or heparin plus aspirin in 34% and 66% of the patients, respectively. Perioperative in-stent thrombosis with myocardial infarction occurred in three patients (9%) with fatal outcome in one (3%). Twenty patients underwent lung resection after 4 weeks of dual antiplatelet therapy as recommended by the ACC/AHA Guideline Update; however, two out of three perioperative in-stent thrombosis occurred in this group of patients. CONCLUSIONS: Major lung resection performed within 3 months of coronary stenting may be complicated by perioperative in-stent thrombosis despite 4 weeks of dual antiplatelet therapy after stenting as recommended by the ACC/AHA Guideline Update.

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function.

BACKGROUND: Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.