Prothrombotic markers in patients with acute myocardial infarction and left ventricular thrombus formation treated with pci and dual antiplatelet therapy.

BACKGROUND: The aim of the present study was to compare circulating levels of selected prothrombotic markers in patients suffering acute myocardial infarction (AMI) with and without left ventricular (LV) thrombus. METHODS: One hundred patients with AMI treated with PCI on the LAD and dual antiplatelet therapy were included. LV thrombus formation was detected by echocardiography and/or MRI in 15 patients. Fasting blood samples were drawn 4-5 days (baseline), 6-7 days, 8-9 days, 2-3 weeks and 3 months after the AMI for determination of haemostatic markers. RESULTS: We found higher levels of soluble tissue factor (TF) and D-dimer in the LV thrombus group 4-5 days, 8-9 days and 3 months (only TF) after the AMI compared to the patients without thrombus formation (p<0.05). Patients with TF in the upper quartile at baseline had significantly higher risk for LV thrombus (OR 4.2; 95% CI 1.2 -14.5; p=0.02, adjusted for infarct size).The levels of prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were significantly lower in the thrombus group after 8-9 days (only ETP), 2-3 weeks and 3 months. The levels of plasminogen activator inhibitor 1 activity and tissue plasminogen activator antigen did not differ between the groups. CONCLUSION: In the acute phase of AMI, we found higher levels of TF and D-dimer in the LV thrombus group, indicating hypercoagulability of possible importance for the generation of mural thrombus. Lower levels of F1+2, ETP and D-dimer in the thrombus group late during follow-up are probably induced by the initiated anticoagulation therapy.

Perfusion MRI at rest in subacute and chronic myocardial infarct.

BACKGROUND: Perfusion magnetic resonance imaging (MRI) and delayed contrast-enhanced MRI (DE-MRI) serve as tools for tissue characterization. PURPOSE: To assess and compare semi-quantitative parameters of myocardial infarct (MI) in the subacute and chronic phase, and to correlate these parameters with qualitative enhancement analysis. MATERIAL AND METHODS: Perfusion MRI at rest and DE-MRI were performed in 63 patients with anterior wall MI at 2-3 weeks after revascularization and repeated after 6 months. Descriptive enhancement parameters of contrast arrival time, initial upslope, enhancement at normal tissue peak (TTPn) and wash-out slope, and kinetic tissue parameters rBF, K (trans), k ep and v e were calculated. Subacute infarct tissue was compared to normal myocardium and chronic infarct tissue. Patients were stratified at baseline according to a qualitative grading of hypoenhancement based on first-pass enhancement and presence of microvascular obstruction (MO) at perfusion MRI and on persistent MO at DE-MRI. The qualitative grade was correlated to semi-quantitative perfusion MRI parameters. RESULTS: Initial upslope, enhancement at TTPn, rBF, and k ep were decreased and wash-out slope and v e were increased in infarct tissue (P < 0.001 for all analyses). Infarct tissue v e decreased from baseline to 6 months (P = 0.045). At baseline infarct tissue with persistent MO revealed decreased K (trans) and delayed contrast arrival, and more pronounced decrease of enhancement at TTPn, rBF and k ep compared to other enhancement groups (P < 0.008 for pairwise analyses). CONCLUSION: Perfusion is decreased in subacute reperfused infarct tissue compared to normal tissue. K (trans) is not decreased, consistent with increased surface area of the vascular bed of the subacute infarct. Infarct tissue v e is increased, and decreases with scarring. The presence of persistent MO correlates to more pronounced perfusion reduction and results in delayed contrast arrival, indicating microvascular collateral circulation.

Regional myocardial function after intracoronary bone marrow cell injection in reperfused anterior wall infarction - a cardiovascular magnetic resonance tagging study.

BACKGROUND: Trials have brought diverse results of bone marrow stem cell treatment in necrotic myocardium. This substudy from the Autologous Stem Cell Transplantation in Acute Myocardial Infarction trial (ASTAMI) explored global and regional myocardial function after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) in acute anterior wall myocardial infarction treated with percutaneous coronary intervention. METHODS: Cardiovascular magnetic resonance (CMR) tagging was performed 2-3 weeks and 6 months after revascularization in 15 patients treated with intracoronary stem cell injection (mBMC group) and in 13 controls without sham injection. Global and regional left ventricular (LV) strain and LV twist were correlated to cine CMR and late gadolinium enhancement (LGE). RESULTS: In the control group myocardial function as measured by strain improved for the global LV (6 months: -13.1 ± 2.4 versus 2-3 weeks: -11.9 ± 3.4%, p = 0.014) and for the infarct zone (-11.8 ± 3.0 versus -9.3 ± 4.1%, p = 0.001), and significantly more than in the mBMC group (inter-group p = 0.027 for global strain, respectively p = 0.009 for infarct zone strain). LV infarct mass decreased (35.7 ± 20.4 versus 45.7 ± 29.5 g, p = 0.024), also significantly more pronounced than the mBMC group (inter-group p = 0.034). LV twist was initially low and remained unchanged irrespective of therapy. CONCLUSIONS: LGE and strain findings quite similarly demonstrate subtle differences between the mBMC and control groups. Intracoronary injection of autologous mBMC did not strengthen regional or global myocardial function in this substudy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00199823.

Left ventricular systolic and diastolic function improve after acute myocardial infarction treated with acute percutaneous coronary intervention, but are not influenced by intracoronary injection of autologous mononuclear bone marrow cells: a 3 year serial echocardiographic sub-study of the randomized-controlled ASTAMI study.

AIMS: To clarify long-term changes in global, regional, and diastolic left ventricular (LV) function after intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in acute myocardial infarction (AMI). METHODS AND RESULTS: In the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study, 100 patients with anterior ST-elevation myocardial infarction and percutaneous coronary intervention on the left anterior descending artery (LAD) were randomized to receive intracoronary injection of mBMCs or not. Transthoracic echocardiography was performed at baseline, 3, 6, 12 months, and 3 years. Regional LV function was assessed by two-dimensional speckle-tracking echocardiography. From baseline to 3 years, LV ejection fraction changed from 45.7 to 47.5% in the mBMC group, and from 46.9 to 46.8% in the control group (P = 0.87 for difference in change over time between groups). Longitudinal strain in the LAD territory improved from -9.7 to -12.2% in the mBMC group and from -9.9 to -12.8% in the control group (P = 0.45). E/e' decreased from 14.7 to 12.9 in the mBMC group and from 14.8 to 11.9 in the control group (P = 0.31). There were no significant differences between groups in change of LV volumes, global systolic function, regional function, or diastolic function during 3 years follow-up. CONCLUSION: No differences between groups indicating beneficial effect of intracoronary mBMC injection could be identified. Both groups in ASTAMI experienced improvement of global, regional, and diastolic LV function after 3-6 months, with effects sustained at 3 years.

Cell treatment after acute myocardial infarction prevents early decline in circulating IGF-1.

OBJECTIVES: To examine the influence of intracoronary autologous bone marrow cell transplantation after acute myocardial infarction on circulating growth factors and their relationship to left ventricular function. METHODS: Circulating insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), stromal derived factor-1-alpha (SDF-1α), and transforming growth factor beta (TGF-ß) were measured in patients randomized to cell treatment or control, in the ASTAMI study. Autologous cells were injected intracoronary on day 6; blood was sampled on days 5, 9, and at three months. Left ventricular ejection fraction was recorded by electrocardiogram-gated single photon emission computed tomography at six months. RESULTS: Only change in IGF-1 from baseline to three months differed between groups (p = 0.024). A weak but significant correlation was found between left ventricular ejection fraction and the averaged IGF-1 concentrations of all patients (r = 0.24, p = 0.02). Patients with IGF-1 above or below median (102 ng/ml) had a left ventricular ejection fraction of 52.3% (±11.4) versus 46.4% (±12.2) respectively (p = 0.017). CONCLUSIONS: Intracoronary bone marrow cell treatment after myocardial infarction attenuates a reduction in circulating IGF-1. IGF-1 levels over time were weakly, but significantly correlated to left ventricular ejection fraction.

Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.

BACKGROUND: Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment. METHODS: Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size. RESULTS: Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events. CONCLUSIONS: With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function.

Inflammatory responses after intracoronary injection of autologous mononuclear bone marrow cells in patients with acute myocardial infarction.

BACKGROUND: Inflammatory responses after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) are not clarified. The aim of this study was to investigate the influence of intracoronary injection of mBMC on inflammatory mediators in patients with acute myocardial infarction (AMI). METHODS: Patients with AMI in the ASTAMI trial (N = 100) treated with percutaneous coronary intervention were randomized to intracoronary injections of mBMC or control. Fasting blood samples were drawn the day before stem cell transplantation (baseline 4-5 days after AMI) and 1 day, 3 days, 2 to 3 weeks, and 3 months after transplantation for determination of circulating levels of selected inflammatory markers and mRNA levels in whole blood samples. RESULTS: From baseline to day 1, the levels of interleukin 6 and the expression of tumor necrosis factor alpha mRNA increased significantly in the mBMC group compared to the control group (P < .05 for both). The decrease in interleukin 6 levels from baseline to 2 to 3 weeks in the mBMC group was less pronounced than in the controls (P < .05), as was also the decrease in C-reactive protein levels from baseline to day 1 and day 3 in the mBMC group (P < .05). However, from baseline to 3 months the levels of tumor necrosis factor alpha and monocyte chemoattractant protein 1 increased less in the mBMC group (P < .05 for both). CONCLUSION: Intracoronary injection of mBMC in patients with AMI induces a marked short-term inflammatory response, but a slightly reduced inflammation after 3 months which may have implications for the timing of stem cell transplantation in AMI.

Exercise capacity and quality of life after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: results from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) randomized controlled trial.

BACKGROUND: The effects on left ventricular function of intracoronary injection of bone marrow cells in acute myocardial infarction (AMI) have been studied with conflicting results. The aim of this substudy of the ASTAMI trial was to examine the effects of this novel treatment on exercise capacity and quality of life. METHODS: We studied 100 patients with anterior wall ST-elevation AMI. All had percutaneous coronary intervention with stent in the proximal or mid left anterior descending coronary artery 2 to 12 hours after start of symptoms. Patients were randomized to intracoronary injection of mononuclear bone marrow cells (mBMCs) in left anterior descending coronary artery 6 +/- 1.3 days after AMI (n = 50) or control (n = 50). Assessment of physical capacity by maximal symptom-limited bicycle ergometer exercise tests and quality of life by the Short Form 36 health survey was performed 2 to 3 weeks and 6 months after the AMI. RESULTS: There was a significantly greater improvement in exercise time in the mBMC group than in the control group (treatment effect 0.9 minute, 95% CI 0.3-1.6, P < .01), and a similar improvement in peak oxygen consumption in the groups (2.8 +/- 3.9 mL/[kg min] in the mBMC group vs 2.4 +/- 3.5 mL/[kg min] in controls, P = .62). Peak heart rate and percentage of heart rate reserve increased significantly more in the treatment group than in the control group. Treatment with mBMCs did not influence quality of life. CONCLUSIONS: In this randomized open-labeled study, the mBMC group significantly improved exercise time and heart rate responses to exercise compared with the control group. There was no treatment effect on peak oxygen consumption.

Continued symptomatic improvement three to five years after transmyocardial revascularization with CO(2) laser: a late clinical follow-up of the Norwegian Randomized trial with transmyocardial revascularization.

OBJECTIVES: The goals of this study were to assess late clinical outcome and left ventricular ejection fraction (LVEF) after transmyocardial revascularization with CO(2) laser (TMR). BACKGROUND: During the 1990s TMR emerged as a treatment option for patients with refractory angina not eligible for conventional revascularization. Few reports exist on clinical effects and LVEF >3 years after TMR. METHODS: One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized 1:1 to receive continued medical treatment or medical treatment combined with TMR. The patients were evaluated at baseline and after 3, 12 and 43 (range: 32 to 60) months with end points to angina, hospitalizations due to acute myocardial infarctions or unstable angina, heart failure and LVEF. Mortality was registered and MOS 36 Short-Form Health Survey answered at baseline and after 3, 6 and 12 months. RESULTS: Forty-three months after TMR, angina symptoms were still significantly improved, and unstable angina hospitalizations reduced by 55% (p < 0.001). Heart failure treatment (p < 0.01) increased, whereas the number of acute myocardial infarctions, LVEF and mortality was not affected. Quality of life was improved 3, 6 and 12 months after TMR. CONCLUSIONS: Forty-three months after TMR, angina symptoms and hospitalizations due to unstable angina were significantly reduced, heart failure treatment increased and LVEF and mortality were seemingly unaffected.

A descriptive study of early nonspecific chest pain after PTCA: important area for the acute health care personnel.

BACKGROUND: Many patients report chest pain of varying intensity at various locations during the first hours after percutaneous transluminal coronary angioplasty (PTCA). OBJECTIVES: The aim of the study was to increase knowledge regarding differentiating between harmless chest pain versus ischemic chest pain, focusing on patients description of their pain. METHODS: A total of 192 patients after elective PTCA were interviewed twice. In addition patients experiencing chest pain within 6 hours after the procedure completed the McGill Pain Questionnaire (MPQ). RESULTS: Nonspecific chest pain occurred in 34 patients (18%) and ischemic chest pain in 6 (3%), whereas 152 (79%) did not report early chest pain after PTCA. The nonspecific pain group reported statistically significant less pain intensity (VAS P =.001), used fewer (P =.006) and qualitatively weaker (P =.008) words compared to the ischemic pain group. No predisposing factors that could predict chest pain were identified. CONCLUSIONS: Discriminators appear to be the pain intensity and the word descriptors. MPQ combined with a VAS could be valuable clinical tools with regard to patients' description of pain.

The influence of intracoronary injection of bone marrow cells on prothrombotic markers in patients with acute myocardial infarction.

INTRODUCTION: The effects of intracoronary injection of mononuclear bone marrow cells (mBMC) on haemostasis are not clarified. The aim of the present substudy of the autologous stem cell transplantation in acute myocardial infarction (ASTAMI) trial was to investigate the influence of intracoronary injection of mBMC on selected circulating prothrombotic markers. MATERIALS AND METHODS: One hundred patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) on the left descending coronary artery were randomized to receive mBMC (Tx) (median 6 days after the STEMI) or to a control group. Fasting blood samples were drawn the day before Tx (day-1, 4-5 days after the STEMI), and 1 day, 3 days, 2-3 weeks and 3 months after Tx. RESULTS: No significant differences in changes between the groups were observed from day-1 to any later time points in the levels of TF (tissue factor), F1+2 (prothrombin fragment 1+2), D-dimer, ETP (endogenous thrombin potential), PAI-1 (plasminogen activator inhibitor 1) or tissue plasminogen activator. However, TF and F1+2 decreased from day-1 to the subsequent time points in both groups, except from a small increase of TF at 3 months in the control group. In both groups, D-dimer and ETP decreased from day-1 to 2-3 weeks and 3 months, whereas PAI-1 increased to 2-3 weeks and 3 months. CONCLUSIONS: Intracoronary injection of mBMC did not influence on prothrombotic markers in patients with STEMI. Reduction in several prothrombotic markers from day-1 to 2-3 weeks and 3 months could be demonstrated in both groups indicating decreased hypercoagulability. This is a substudy of the ASTAMI trial which is registered at www.clinicaltrials.gov, NCT 00199823.

Frequency of left ventricular thrombus in patients with anterior wall acute myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy.

The aim of the present study was to investigate the prevalence of left ventricular (LV) thrombus formation and important determinants in patients with acute ST elevation myocardial infarction localized to the anterior wall treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy. One hundred selected patients with ST elevation myocardial infarctions revascularized with PCI in the left anterior descending coronary artery were included. The patients participated in the Autologous Stem Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial. All were treated with aspirin 75 mg/day and clopidogrel 75 mg/day and underwent serial echocardiography and magnetic resonance imaging during the first 3 months after PCI. After 4 to 5 days, the ejection fraction and infarct size in percentage of the left anterior descending coronary artery area were assessed using single photon-emission computed tomography in addition to the ejection fraction by echocardiography. LV thrombi were detected in 15 patients during the first 3 months, 2/3 of them within the first week. No differences in baseline characteristics between the groups with and without LV thrombi were shown. However, in the thrombus group, significantly higher peak creatine kinase levels (6,128 vs 2,197 U/L, p <0.01), larger infarct sizes (82.5% vs 63.8%, p <0.01), and lower ejection fractions on single photon-emission computed tomography (35.5% vs 40.0%, p = 0.03) and on echocardiography (43.0% vs 46.0%, p = 0.03) were found compared to patients without LV thrombi. In conclusion, LV thrombus formation is a frequent finding in patients with anterior wall ST elevation myocardial infarction treated acutely with PCI and dual-antiplatelet therapy and should be assessed by echocardiography within the first week.

Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on beta-blockers.

AIMS: The aim of this study is to compare the effects of a 24 h intravenous infusion of levosimendan and a 48 h infusion of dobutamine on invasive haemodynamics in patients with acutely decompensated chronic NYHA class III-IV heart failure. All patients were receiving optimal oral therapy including a beta-blocker. METHODS AND RESULTS: This was a multinational, randomized, double-blind, phase IV study in 60 patients; follow-up was 1 month. There was a significant increase in cardiac index and a significant decrease in pulmonary capillary wedge pressure (PCWP) at 24 and 48 h for both dobutamine and levosimendan. The improvement in cardiac index with levosimendan was not significantly different from dobutamine at 24 h (P = 0.07), but became significant at 48 h (0.44 +/- 0.56 vs. 0.66 +/- 0.63 L/min/m(2); P = 0.04). At 24 h, the reduction in the mean change in PCWP from baseline was similar for levosimendan and dobutamine, however, at 48 h the difference was more marked for levosimendan (-3.6 +/- 7.6 vs. -8.3 +/- 6.7 mmHg; P = 0.02). No difference was observed between the groups for change in NYHA class, beta-blocker use, hospitalizations, treatment discontinuations or rescue medication use. Reduction in B-type natriuretic peptide (BNP) was significantly greater with levosimendan at 48 h (P = 0.03). According to physician's assessment, the improvement in fatigue (P = 0.01) and dyspnoea (P = 0.04) was in favour of dobutamine treatment, and hypotension was significantly more frequent with levosimendan (P = 0.007). No increase in atrial fibrillation or ventricular tachycardia was seen in either group. CONCLUSION: A 24 h levosimendan infusion achieved haemodynamic and neurohormonal improvement that was at least comparable at 24 h and superior at 48 h to a 48 h dobutamine infusion.

Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects.

OBJECTIVES: Intracoronary transplantation of different cell populations has been used in acute myocardial infarction (AMI) with promising results. The primary objective of the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study is to test whether intracoronary transplantation of autologous mononuclear bone marrow cells (mBMC) improves left ventricular ejection fraction (LVEF) after anterior wall AMI. DESIGN: The ASTAMI study is a randomized, controlled, prospective study. One hundred patients with acute anterior wall ST-elevation myocardial infarction (STEMI) treated with acute percutaneous coronary intervention (PCI) are randomized in a 1:1 way to either intracoronary transplantation of autologous mBMC 5-8 d after PCI or to control. Left ventricular function, exercise capacity, biochemical status, functional class, quality of life and complications are validated at baseline and during a 12-month follow-up. RESULTS: By August 2004, out of 1004 patients with STEMI, 49 patients have been included in the study. Twenty-four patients have been randomized to intracoronary mBMC transplantation. Twenty patients had chest pain and 16 patients had ischemic ECG changes during the mBMC transplantation procedure. One patient had ventricular fibrillation 24 h after transplantation. CONCLUSIONS: Intracoronary transplantation of autologous mBMC in the acute phase after AMI is feasible and seems safe in the short term.