Myocardial Infarction
Conditions
Keywords
Myocardial infarction, stem cell, cardiac rehabilitation
Brief summary
One emerging concept is that some form of injury or inflammation is a prerequisite for the success of circulating-cell participation in differentiated tissue structure and function. Once reperfusion is achieved in acute myocardial infarction, an intense inflammatory cascade is unleashed. The architecture of the left ventricle rearranges, leading to ventricular remodeling. The homing processinvolves stem cell migration to the sites of injury or ischemia, which provides an environment that is favorable to growth and function. This microenvironment is a stimulus for homing and differentiation of stem cells of the appropriate lineage. It increases vascular permeability and expression of adhesion proteins like integrin, along with homing receptors that facilitate the attachment, which is mediated by cell-to-cell contact and chemoattractant release from local tissue injury.The migratory capacity of stem cells might be dependent on natural growth factors such as vascular endothelial growth factor (VEGF) , stromal cell-derived factor-1 (SDF-1)and stem cell factor (SCF).The expression of VEGF ,SDF-1 and SCF is highly up-regulated in hypoxic tissue, supporting the hypothesis that these factors may represent homing signals crucial to the recruitment of circulating progenitor cells to assist the endogenous repair mechanisms in the infarcted tissue. This study will examine whether cardiac rehabilitation increases the concentration of stem cell factors released into the bloodstream and if these factors are correlated with the improvement of heart function.
Detailed description
Exercise training has beneficial hemodynamic effects in patients with congestive heart failure.A similar benefit may be seen after MI, with an improvement in functional capacity averaging 20 percent. More important, however, is the possible effect on survival. In a meta-analysis of 24 trials examining the effect of cardiac rehabilitation after MI, there was a significant reduction in mortality with rehabilitation (odds ratio 0.81). Previous studies focused on the effect of rehabilitation comes from the improvement of oxygen utilization in skeletal muscle. The effects on cardiac morphology and perfusion status were rather little to be addressed. In this study, we will collect the questionaires, blood sampling for assay of stem cell factors, maximal O2 consumption, and cardiac MRI before and after cardiac rehabilitation.SDF-1 (stromal cell derived factor-1), SCF(stem cell factor), and VEGF (vasculoendothelial growth factor) will be measured by ELISA. Cardiac MRI will provide the information about (1) LV function, (2) scar size, and (3) perfusion status (dipyridamole stress MRI).
Interventions
BEHAVIORALcardiac rehabilitation
Those in the training group participated in a 3-month rehabilitation training program at an exercise intensity of 55% to 70% of peak oxygen uptake (VO2); those in the nontraining group continued their usual lifestyle.
Sponsors
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
35 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
myocardial infarction with CK more than 3000, status post revascularization therapy, clinical stable with regular follow-up at OPD, NYHA II-III -
Exclusion criteria
sustained ventricular arrhythmia, hypertrophy cardiomyopathy, intolerance to exercise program \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Blood Flow at Baseline and 3-month Follow-up | 3 months | First-pass, contrast-enhanced myocardial perfusion images acquired for 80 heart beats in the left ventricle. Short-axis views were obtained after intravenous administration of gadodiamide. Perfusion studies were performed at rest and during the stress induced by a 4 min infusion of dipyridamole at a concentration of 0.14 mg/kg of body weight per minute.To determine absolute MBF values at rest and stress status, we adopted a model-independent deconvolution method proposed by Jerosch-Herold et al, a method that was previously validated in experimental animal studies by comparison with blood-flow measurements with radiolabelled microspheres. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Angiogenic Cytokines at Baseline and 3-month Follow-up | 3 months | Angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal-derived factor-1 (SDF-1) and stem cell factor (SCF) are known to increase the formation of new vessels at ischaemic sites and thus enhance myocardial perfusion. To rule out any effect of short-term exercise on cytokines levels, blood samples were always taken after at least 72 h of physical inactivity and overnight fasting when the subject had rested in the sitting position for at least 10 min. The plasma samples were immediately frozen and stored at -70°C. High-sensitivity ELISA (Bender MedSystems, R&D) were used to measure plasma levels of SCF, SDF-1 and VEGF according to the manufacturer's protocols. |
Countries
Taiwan
Participant flow
Recruitment details
This prospective randomised controlled study was approved by the ethics committee of the National Taiwan University Hospital. Between August 2004 and December 2005, 91 postinfarction patients were informed about the trial. Thirty-seven refused to participate and 15 did not meet the inclusion criteria.
Pre-assignment details
Inclusion criteria:a successful primary stenting, a clinically stable course after MI, and no ischemia on exercise testing. Exclusion criteria: effort angina, Af, sustained ventricular arrhythmia, NYHA functional class IV, exercise-limiting diseases, severe pulmonary or renal disease, an implanted pacemaker, or claustrophobia.
Participants by arm
| Arm | Count |
|---|---|
| Postinfarction Training Patients 39 postinfarction patients randomised to either a 3-month training group (n=20) or a nontraining group (n=19), and 19 normal controls. | 20 |
| Postinfarction Nontraining Patients 39 postinfarction patients randomised to either a 3-month training group (n=20) or a nontraining group (n=19), and 19 normal controls. | 19 |
| Healthy Controls 39 postinfarction patients randomised to either a 3-month training group (n=20) or a nontraining group (n=19), and 19 normal controls. | 19 |
| Total | 58 |
Baseline characteristics
| Characteristic | Postinfarction Nontraining Patients | Healthy Controls | Postinfarction Training Patients | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 19 Participants | 20 Participants | 58 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 9 | 50 years STANDARD_DEVIATION 9 | 52 years STANDARD_DEVIATION 8 | 52 years STANDARD_DEVIATION 8 |
| Region of Enrollment Taiwan | 19 participants | 19 participants | 20 participants | 58 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 20 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Myocardial Blood Flow at Baseline and 3-month Follow-up
First-pass, contrast-enhanced myocardial perfusion images acquired for 80 heart beats in the left ventricle. Short-axis views were obtained after intravenous administration of gadodiamide. Perfusion studies were performed at rest and during the stress induced by a 4 min infusion of dipyridamole at a concentration of 0.14 mg/kg of body weight per minute.To determine absolute MBF values at rest and stress status, we adopted a model-independent deconvolution method proposed by Jerosch-Herold et al, a method that was previously validated in experimental animal studies by comparison with blood-flow measurements with radiolabelled microspheres.
Time frame: 3 months
Population: Eligible patients were randomly assigned to the training group, which underwent a 3-month cardiac rehabilitation program, or the nontraining group in which patients continued their usual lifestyle. Healthy controls underwent the test of myocardial perfusion only at baseline. The analysis was intention-to-treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post-infarction Training | Myocardial Blood Flow at Baseline and 3-month Follow-up | Change of stress MBF in the remote myocardium | 0.62 ml/min/g | Standard Deviation 0.83 |
| Post-infarction Training | Myocardial Blood Flow at Baseline and 3-month Follow-up | Change of stress MBF in the infarcted myocardium | 0.44 ml/min/g | Standard Deviation 0.71 |
| Post-infarction Nontraining | Myocardial Blood Flow at Baseline and 3-month Follow-up | Change of stress MBF in the remote myocardium | -0.27 ml/min/g | Standard Deviation 0.56 |
| Post-infarction Nontraining | Myocardial Blood Flow at Baseline and 3-month Follow-up | Change of stress MBF in the infarcted myocardium | 0 ml/min/g | Standard Deviation 0.46 |
Secondary
Angiogenic Cytokines at Baseline and 3-month Follow-up
Angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal-derived factor-1 (SDF-1) and stem cell factor (SCF) are known to increase the formation of new vessels at ischaemic sites and thus enhance myocardial perfusion. To rule out any effect of short-term exercise on cytokines levels, blood samples were always taken after at least 72 h of physical inactivity and overnight fasting when the subject had rested in the sitting position for at least 10 min. The plasma samples were immediately frozen and stored at -70°C. High-sensitivity ELISA (Bender MedSystems, R&D) were used to measure plasma levels of SCF, SDF-1 and VEGF according to the manufacturer's protocols.
Time frame: 3 months
Population: We calculated that we would need 18 patients in each group to achieve a power of at least 80% to detect a 20% difference in MBF change between study groups, with a two-sided significance level of p\<0.05, and a 20% increase for the stress MBF change from baseline to 3 months' follow-up. The analysis was intention-to-treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post-infarction Training | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of vascular endothelial growth factor | 0.70 pg/ml | Standard Deviation 1.41 |
| Post-infarction Training | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of stromal-derived factor-1 | -196 pg/ml | Standard Deviation 209 |
| Post-infarction Training | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of stem cell factor | 20 pg/ml | Standard Deviation 120 |
| Post-infarction Nontraining | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of vascular endothelial growth factor | 0.95 pg/ml | Standard Deviation 1.46 |
| Post-infarction Nontraining | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of stromal-derived factor-1 | -68 pg/ml | Standard Deviation 175 |
| Post-infarction Nontraining | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of stem cell factor | 17 pg/ml | Standard Deviation 47 |
| Healthy Controls | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of stromal-derived factor-1 | -57 pg/ml | Standard Deviation 200 |
| Healthy Controls | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of stem cell factor | -18 pg/ml | Standard Deviation 60 |
| Healthy Controls | Angiogenic Cytokines at Baseline and 3-month Follow-up | Change of vascular endothelial growth factor | -1.2 pg/ml | Standard Deviation 2.92 |