Exploration of Cardiovascular Thrombus Activity Post Myocardial Infarction by Using 18F-GP1 MR/PET

Cardiovascular thrombotic conditions were estimated to account for 1 in 4 deaths worldwide in 2010 and are the leading cause of global mortality. Thrombosis begins with damage to the vascular wall. Physiological haemostasis is triggered when underlying collagen is exposed to circulating platelets which bind directly to collagen with collagen-specific glycoprotein surface receptors. After an initial signalling cascade involving release of platelet binder von Willebrand Factor, platelets become activated which allows adherence to the site of injury. Following activation, phospholipase A2 modifies the integrin membrane glycoprotein IIb/IIIa (GP IIb/IIIa) increasing platelet ability to bind fibrinogen. The activated platelets then change shape from spherical to stellate, and the fibrinogen cross-links with glycoprotein IIb/IIIa aiding aggregation of more platelets and completing primary haemostasis. Secondary haemostasis involves activation of the coagulation cascade through extrinsic and intrinsic pathways and ends with cross linked fibrin deposition and a mature thrombus.

The haemostatic process is fluid and dynamic with the expression of activated membrane proteins and coagulation factors changing throughout. Platelet expression of GP IIb/IIIa falls as a thrombus matures hence why it is a pharmacological target for antithrombotic therapies. The investigators aim to explore the expression and distribution of GP IIb/IIIa receptors in the cardiovascular system. Improving our understanding of how clinical presentation relates to platelet activation over a range of conditions, will help optimise the appropriate use of anti-thrombotic therapies.

In the aftermath of major acute myocardial infarction, the combination of blood stasis and activated tissue factor frequently leads to the formation of left ventricular (LV) thrombus which is associated with stroke, recurrent myocardial infarction and adverse cardiac remodelling. The prevention, treatment and resolution of thrombus is hampered by a lack of understanding of its initiation, propagation and dissolution. Moreover, the current clinical approach fails to diagnose a high proportion of LV thrombi and we lack evidence regarding the optimal anti-coagulant therapy to use and duration of therapy. Non-invasive imaging techniques hold major promise in improving our understanding of the incidence and the natural history of LV thrombus as well as providing potential biomarkers to determine the optimal treatment strategy.

Left ventricular (LV) thrombus post myocardial infarction (MI):

Before thrombolytic therapy was available, LV thrombus occurred in 20% to 60% of patients with acute myocardial infarction. In the thrombolytic trials, the incidence of LV thrombosis detected by echocardiography was 5.1% increasing to 11.5% in those who had an anterior myocardial infarction. The incidence has further declined with the advent of primary percutaneous coronary intervention, likely due to enhanced myocardial salvage, and now ranges from 2.5% to 15%. However, the incidence is much higher in patients with anterior myocardial infarction, with studies using cardiac magnetic resonance imaging reporting an incidence of LV thrombus of 26%.Furthermore, the natural history of this condition is rather vague. Indeed, in most published studies, thrombi were assessed at a single time, and their size, mobility, and characteristics were not reported. Although echocardiography is currently used to identify LV thrombus in the clinic, it lacks sensitivity and leaves many cases undetected. In some studies, the sensitivity of transthoracic echocardiography compared to cardiac magnetic resonance imaging with contrast delayed enhancement (LGE-CMR) was 20-25%. We therefore need a more highly specific and sensitive imaging technique to detect the presence LV thrombus early after myocardial infarction. In this study the investigators will use 18F-GP1 PET to describe the prevalence and natural history of LV thrombus in patients after myocardial infarction and to differentiate old from new LV thrombus. This study will also facilitate the identification of features that predict thrombus formation as well as providing a useful biomarker for potential therapeutic interventions.