Pan-Cardio-Genetics Clot Assessment in Acute Coronary Syndromes

Study Overview
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Brief Summary
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Acute myocardial infarction with ST elevation (STEMI) is one of the leading causes of mortality. Although the presence of thrombus in STEMI patients has been linked to adverse outcomes, routine thrombus aspiration has not been proven effective. A potential explanation could be that patients with STEMI should be risk-stratified. Thus, a more personalized approach in treating these patients is stressfully required. This proposal aims to establish the required interdisciplinary infrastructure for developing a risk-stratification model by implementing clinical, laboratory and angiographic data with molecular knowledge obtained by using innovative technologies, such as data from nano/micro-Computed tomography and circulating microRNAs. Two hundred consecutive patients with STEMI undergoing thrombus aspiration will be enrolled in the study and will be followed-up for one year for Major Adverse Cardiac and Cerebrovascular events (MACCE). The proposed approach will shed light on the pathophysiological mechanisms and broaden the investigator's understanding of the complex cellular and molecular interactions in the STEMI setting that, along with clinical parameters, affect patient outcomes. Furthermore, it will enable the identification of certain circulating micro-RNAs as cardiovascular disease biomarkers and it will help clinicians to better stratify the cardiovascular and cerebrovascular risk of patients with STEMI. As part of the work, important characteristics of aspirated thrombi will be assessed for the first time (such as volume, density and shape) and will be linked to patient outcomes. All this information will be incorporated into one in-vitro model, which will be developed using bioprinting and microfluidics methodologies. The in-vitro model will facilitate: (i) the in-depth exploration of the pathophysiological mechanisms in patients with STEMI; and (ii) the therapeutic optimization of innovative nanocarriers/nanomedicines with thrombolytic efficacy. Clearly, the study improves personalized cardiovascular medicine approaches, by considering individual patient clinical assessment in a way that empowers the precision in diagnosis and therapy.

Official Title
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Pan-Cardio-Genetics Clot Assessment in Acute Coronary Syndromes

Conditions
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STEMI - ST Elevation Myocardial Infarction, Thrombi, MicroRNA

Intervention / Treatment
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* Procedure: thrombus aspiration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptoms of myocardial ischemia lasting for more than 30 minutes Definite ECG changes indicating STEMI Patients undergoing primary PCI within 12 hours from symptom onset Possibility to perform thrombus aspiration Written informed consent Exclusion Criteria: Treatment with fibrinolytic therapy for qualifying index STEMI event Patients with known intolerance to aspirin, ticagrelor or heparin Patients with active internal bleeding Patients with a recent history of intracranial hemorrhage

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with low thrombus burden<br>patients with the lower volume of aspirated thrombi, as measured using micro-CT | Procedure: thrombus aspiration<br>* Thrombus aspiration will be performed by experienced interventional cardiologists according to standard practices, as previously described. The intracoronary blood samples will be collected as well during the same procedure and- along with peripheral blood samples- they will be analyzed for the presence of specific miRNAs. The aspirated thrombi will be preserved in 10% formalin solution and will be analyzed using the micro/nano-CT scanners.<br>|
| patients with high thrombus burden<br>patients with the higher volume of aspirated thrombi, as measured using micro-CT | Procedure: thrombus aspiration<br>* Thrombus aspiration will be performed by experienced interventional cardiologists according to standard practices, as previously described. The intracoronary blood samples will be collected as well during the same procedure and- along with peripheral blood samples- they will be analyzed for the presence of specific miRNAs. The aspirated thrombi will be preserved in 10% formalin solution and will be analyzed using the micro/nano-CT scanners.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold changes of differentially-expressed microRNA from peripheral blood from patients suffering from STEMI (measured in log2 scale) | The expression profiles of the total number of microRNAs that exist in the peripheral blood of patients suffering from STEMI will be analyzed using Next Generation Sequencing (NGS). Blood samples collected from the patients will be used to extract microRNAs through the application of suitable microRNA isolation kit (miRNeasy Serum/Plasma kit). Following, the miRNA library construction will be prepared using commercially available reagents (QIAseq miRNA Library kit). The quantification of miRNAs will be done by the Qubit dsDNA HS assay kit in the Qubit fluorometer before the cDNA library generation.Statistical analyses of differentially expressed miRNAs will be carried out using EdgeR by the generalized linear model. Fold changes of differentially-expressed microRNA will be measured in log2 scale. | 12 months | 
| Volume of aspirated thrombus burden | The volume of aspirated thrombi will be quantified (in mm3) using micro-CT. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between fold changes of microRNA expression and post-procedural Thrombolysis in Myocardial Infarction (TIMI) flow | Fold changes of differentially-expressed microRNAs (measured in log2 scale as described above) will be correlated to post-procedural TIMI flow (classified as previously described: TIMI flow 0,1,2 or 3). | 12 months | 
| Association between fold changes of microRNA expression (measured in log2 scale) with distal embolization | Fold changes of differentially-expressed microRNAs (measured in log2 scale, as described above) will be correlated to distal embolization (dichotomous variable-yes/no). | 12 months | 
| Association between fold changes of microRNAs expression and volume of aspirated thrombus. | Fold changes of differentially-expressed microRNA (measured in log2 scale) will be correlated to the volume of aspirated thrombi (measured in mm3), as it will be quantified using micro-CT. | 12 months | 
| Association between fold changes of microRNA expression and Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) | Fold changes of differentially-expressed microRNAs (measured in log2 scale) will be correlated to MACCE. MACCE are defined as any of the following: cardiac death, cerebrovascular death, acute myocardial infarction, target lesion revascularization, stent thrombosis or stroke. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioprinting, thrombus aspiration, micro-CT