Myocardial Fibrosis
Conditions
Keywords
MRI, Ventricular function, left
Brief summary
The fascinating role of lymphocyte subtypes in the development of coronary artery disease may be a new strategic target for understanding and therapy of acute myocardial infarction. The determinants of cell viability are unknown, postulating that they arise from factors not only related to microcirculation or energy expenditure, but also to inflammatory and immune responses. Furthermore, the intense mobilization of progenitor cells secondary to myocardial infarction triggers large lymphocyte proliferation that colonizes plaques in development, contributing to recurrent ischemic outcomes. This project aims to evaluate the immune and metabolic mechanisms involved in the recovery of the ischemic myocardium and coronary disease progression.
Detailed description
Specifically, the investigators will study the innate and adaptive immunity, with emphasis on lymphocytes subtypes involved in the early and late surrogate outcomes of patients with acute myocardial infarction, their characterization (B1, B2 and T lymphocytes) in cell culture and by flow-cytometry, and immune responses (IgM and IgG for oxLDL and specific epitopes of apoB). In addition, the project will evaluate new biomarkers identified by studies of metabolomics, as well as the corresponding signaling pathways. Therapeutic pharmacological strategies and changes on intestinal microbiota will be evaluated since the acute phase of myocardial infarction up to 6 months. In the study, the investigators will compared four arms of combined therapy: clopidogrel with rosuvastatin; or clopidogrel with simvastatin; or ticagrelor with rosuvastatin; or ticagrelor with simvastatin. The investigator's hypothesis is that the improvement of microcirculation with rosuvastatin and ticagrelor (synergic pleiotropic effects) may decrease the infarcted mass area, resulting in better left ventricular ejection fraction when compared to the other combined therapies. The monitoring and genotype of microbiota will be examined together the metabolomics and cardiac MRIs obtained at the acute phase of MI and after 1-mo and 6-mo FU.
Interventions
DRUGRosuvastatin plus clopidogrel
Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo
DRUGRosuvastatin plus ticagrelor
Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo
DRUGSimvastatin plus clopidogrel
Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo
DRUGSimvastatin plus ticagrelor
Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1\. Stable patients with ST elevation myocardial infarction (STEMI) treated with thrombolytics in the first 6h or the initial of symptoms of MI.
Exclusion criteria
1. Contraindication or known intolerance to the study drug protocol 2. Those with comorbidities such as neoplasm, renal insufficiency (stage 4 or higher) Patients should be randomized in the first 24 hours of AMI and treated by one of the four combined therapies at least 2h prior to coronary angiogram followed by percutaneous intervention when necessary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the left ventricular function (MRI) between the four combined treatments, after STEMI | 1-mo | The effects of treatments on the left ventricular function will be measured by MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare the effects of the four combined therapies on the left ventricular function after STEMI | 3-d | Variables will be examined by MRI |
| To compare the effects of the four combined therapies on the infarcted mass area after STEMI | 1-mo | Variables will be examined by MRI |
| To compare the effects of the four combined therapies on the percentage of subjects with left ventricular ejection fraction < 40% after STEMI | 1-mo | Variables will be examined by MRI |
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI | 1-d | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI |
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI | 1-d | Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI |
| To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI | 1-d | Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relationship between gut microbiota and diabetes status after STEMI | 1-3d | Intestinal microbiota will be genotyped and diabetes status (non-diabetic, pre-diabetic or diabetic) according to HbA1c levels. |
| Relationship between gut microbiota and diabetes status | 6-mo | Intestinal microbiota will be genotyped and diabetes status (non-diabetic, pre-diabetic or diabetic) according to HbA1c levels. |
| Relationship between gut microbiota and metabolomics | 1-3d | Intestinal microbiota will be genotyped and metabolomics by LC/MS-MS |
| Comparison between the four arm of combined therapies on microparticles and endothelial progenitor cells | 1-d | Endothelial, platelet, and monocyte-derived microparticles as well as endothelial progenitor cells will be quantified by flow-cytometry |
| Correlation between the severity of coronary disease with antibodies against oxidized LDL and peptide D of apolipoprotein B of LDL | 1-d | Antibodies IgG and IgM against oxidized LDL as well as against peptide D of LDL will be quantified by ELISA. Coronary disease severity will be quantified by the Gensini Score |
| Comparison between the four arms of combined therapies on TIMI flow grade and blush grade | 1-d | TIMI flow grade and blush grade will be determined based on coronary angiogram obtained at baseline by two independent and blinded certified invasive cardiologists |
| Relationship between no-reflow images obtained at MRI with metabolomics | 1-d | Metabolomics will be determined by LC/MS-MS and images by MRI |
Countries
Brazil
Contacts
Primary ContactFrancisco A Fonseca, MD, PhD
Backup ContactMaria C Izar, MD, PhD
Outcome results
None listed