Ignite Creation Date:
2024-05-06 @ 3:58 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04829825
Status:
RECRUITING
Last Update Posted:
2024-06-10
First Post:
2021-03-31
Brief Title:
The MyoThrombus Study
Sponsor:
University of Edinburgh
Organization:
University of Edinburgh
Study Overview
Official Title:
Exploration of Cardiovascular Thrombus Activity Post Myocardial Infarction by Using 18F-GP1 MRPET
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Left ventricular thrombus is a recognised complication of acute myocardial infarction 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 Advanced non-invasive imaging holds major promise in improving our understanding of the incidence and the natural history of left ventricular thrombus as well as providing potential biomarkers to assess disease activity and treatment efficacy
In this prospective observational study the investigators will recruit patients with recent acute anterior myocardial infarction and screen them for evidence of left ventricular thrombus and subclinical stroke using hybrid positron emission tomography and magnetic resonance imaging PETMR Each patient will undergo PETMR of the heart and head 72 days after acute myocardial infarction If left ventricular thrombus is present on baseline MR patients will be started on anticoagulation at the discretion of the attending physician who will determine the agent used warfarin or direct oral anticoagulant and the duration of therapy 3-6 months Patients will then undergo repeat PETMR at completion of anti-coagulant therapy and then again after another 3 months Patients with increased 18F- GP1 activity but no overt thrombus on MR will undergo repeat PETMR of the head and heart at 3 and 6 months to establish the natural history of this observation and its association with thromboembolism in the brain They will not routinely receive anticoagulation given the exploratory nature of this study
In this prospective observational study the investigators will recruit patients with recent acute anterior myocardial infarction and screen them for evidence of left ventricular thrombus and subclinical stroke using hybrid positron emission tomography and magnetic resonance imaging PETMR Each patient will undergo PETMR of the heart and head 72 days after acute myocardial infarction If left ventricular thrombus is present on baseline MR patients will be started on anticoagulation at the discretion of the attending physician who will determine the agent used warfarin or direct oral anticoagulant and the duration of therapy 3-6 months Patients will then undergo repeat PETMR at completion of anti-coagulant therapy and then again after another 3 months Patients with increased 18F- GP1 activity but no overt thrombus on MR will undergo repeat PETMR of the head and heart at 3 and 6 months to establish the natural history of this observation and its association with thromboembolism in the brain They will not routinely receive anticoagulation given the exploratory nature of this study
Detailed Description:
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 IIbIIIa GP IIbIIIa increasing platelet ability to bind fibrinogen The activated platelets then change shape from spherical to stellate and the fibrinogen cross-links with glycoprotein IIbIIIa 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 IIbIIIa 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 IIbIIIa 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 51 increasing to 115 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 25 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 26Furthermore 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
Stroke
The incidence of stroke after acute myocardial infarction during the hospital stay ranges from 07 to 22 Despite contemporary antithrombotic treatment LV thrombus detected by LGE-CMR is associated with a 4-fold higher long-term incidence of embolism In a large cohort of patients with LV thrombus detected by LGE-CMR there was an annualized incidence of embolism of 37 despite the use of contemporary anticoagulant treatment in 89 of patients This was 4-fold higher than the 08 annualized incidence of embolism in matched patients without LV thrombus Moreover among patients with LV thrombus detected by LGE-CMR the rate of embolism was the same irrespective of whether or not the LV thrombus had been observed on echocardiography
The incidence of subclinical ischaemic stroke in patients with anterior myocardial infarction has not been investigated previously However mounting epidemiologic evidence has shown that subclinical stroke is clinically important contributing to cognitive dysfunction dementia and increased overall mortality
Understanding Platelet Biology
As platelet aggregation is a major component of both arterial and venous thrombi the investigators will use 18F-GP1 - a radiolabelled ligand of the glycoprotein IIbIIIa GPIIbIIIa receptor- to detect activated platelets on thrombus GPIIbIIIa receptors mediate platelet adherence and aggregation They are expressed in greater numbers and assume a more ligand binding conformation on activation The receptor can then bind protein ligands including von Willebrand factor and Fibrinogen facilitating platelet bridging and aggregation Accordingly 18F-GP1 PET will provide important information on LV thrombus formation following myocardial infarction allowing us to better understand and time course of this pathology
The haemostatic process is fluid and dynamic with the expression of activated membrane proteins and coagulation factors changing throughout Platelet expression of GP IIbIIIa 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 IIbIIIa 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 51 increasing to 115 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 25 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 26Furthermore 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
Stroke
The incidence of stroke after acute myocardial infarction during the hospital stay ranges from 07 to 22 Despite contemporary antithrombotic treatment LV thrombus detected by LGE-CMR is associated with a 4-fold higher long-term incidence of embolism In a large cohort of patients with LV thrombus detected by LGE-CMR there was an annualized incidence of embolism of 37 despite the use of contemporary anticoagulant treatment in 89 of patients This was 4-fold higher than the 08 annualized incidence of embolism in matched patients without LV thrombus Moreover among patients with LV thrombus detected by LGE-CMR the rate of embolism was the same irrespective of whether or not the LV thrombus had been observed on echocardiography
The incidence of subclinical ischaemic stroke in patients with anterior myocardial infarction has not been investigated previously However mounting epidemiologic evidence has shown that subclinical stroke is clinically important contributing to cognitive dysfunction dementia and increased overall mortality
Understanding Platelet Biology
As platelet aggregation is a major component of both arterial and venous thrombi the investigators will use 18F-GP1 - a radiolabelled ligand of the glycoprotein IIbIIIa GPIIbIIIa receptor- to detect activated platelets on thrombus GPIIbIIIa receptors mediate platelet adherence and aggregation They are expressed in greater numbers and assume a more ligand binding conformation on activation The receptor can then bind protein ligands including von Willebrand factor and Fibrinogen facilitating platelet bridging and aggregation Accordingly 18F-GP1 PET will provide important information on LV thrombus formation following myocardial infarction allowing us to better understand and time course of this pathology
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| E202276 | OTHER | CRF | None |