Modulation of Fibrosis-inducing Pathways in Acute Myocardial Infarction

Modulation of the WNT/Beta-Catenin Pathway in Patients With Acute Myocardial Infarction

This is a single-center, prospective, observational controlled cohort study designed to describe the role of WNT/B-catenin signaling and adenosine system after an acute myocardial infarction, correlating it with clinical markers of fibrosis/remodeling (primary objective). The modulation of the aforementioned molecular patterns will also be evaluated in light of the type of P2Y12 inhibitor implemented (ticagrelor or prasugrel) to identify variations in response (secondary objective).

A total of 50 patients will be enrolled in the study, 40 with clinical presentation of acute myocardial infarction and eligible for treatment with either prasugrel or ticagrelor, and a control cohort of 10 patients with stable coronary artery disease, matched for age, sex and major risk factors, and with no history of prior myocardial infarction.

The study has been approved by the local ethics committee on 22/09/2021. Pre-enrollment screening will start from 01/11/2021. Blood samples will be obtained at 5 time-points: before and immediately after coronary revascularization (PCI) through the arterial introducer, and in the ward / clinic at a distance of 3, 5 days and 45±15 days from the procedure during normal routine examinations.

These will be used to study the expression of messenger RNA encoding for beta-catenin and to dose concentrations of beta-catenin, adenosine and cyclic adenosine monophosphate (cAMP) on serum. The extraction of RNA from blood samples will be carried out with a Real-time PCR method and the determination of molecules using ELISA colorimetric method, using specific kits.

Clinical-laboratory markers of left ventricular remodeling such as NT-proBNP, hsTnT, C-reactive protein, CK-MB, 12-lead ECG, transthoracic echocardiogram and cardiac magnetic resonance imaging, will be evaluated during hospitalization (at 3 and 5 days) and at the control visit (at 45 ± 15 days) as per standard clinical practice.

Inclusion Criteria:

• Patients with ST segment elevation acute myocardial infarction undergoing coronary angiography and interventional treatment.*

  * Patients with chronic coronary syndrome matched by age, sex and risk factors will also be screened and included as per study design.

• Patients with an indication to potent P2Y12 inhibitor therapy (i.e. ticagrelor or prasugrel) for acute myocardial infarction.

• Population equally amenable to ticagrelor or prasugrel therapy according to the italian drug instruction of use (IFU)

Exclusion Criteria:

• Patients with a poor prognosis (less than 12 months)
• Patients admitted with cardiogenic shock or advanced cardiac failure (NYHA 4)
• Patients pre-treated before coronary angiography or in chronic therapy with a P2Y12 inhibitor
• Patients undergoing a medical only approach without percutaneous myocardial revascularization
• Patients undergoing surgical coronary revascularization
• Patients with prior history of myocardial infarction or prior coronary revascularization.
• Patients with contraindications or intolerance to antiplatelet therapy (ticagrelor, prasugrel, clopidogrel or cardioaspirin)
• Patients scheduled for a treatment with with cangrelor or GPIIb/IIIa inhibitors
• Patients with active bleeding at the time of inclusion
• Hemorrhagic diathesis
• Confirmed history of renal failure with glomerular filtration rate of <30ml/min
• Severe hepatopathy
• Patients treated or scheduled for treatment with oral anticoagulant therapy
• Active cancer or diagnosis any proliferative disease within 5 years.
• Prior TIA or stroke (ischemic or hemorrhagic)
• Age >75 years
• Weight <60kg