Ignite Creation Date:
2024-05-05 @ 5:30 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00465868
Status:
COMPLETED
Last Update Posted:
2015-07-28
First Post:
2007-04-24
Brief Title:
MR Myocardial Infarct and Heart Failure
Sponsor:
Helse Stavanger HF
Organization:
Helse Stavanger HF
Study Overview
Official Title:
Magnetic Resonance Imaging Myocardial Infarction and Development of Heart Failure
Status:
COMPLETED
Status Verified Date:
2008-06
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:
KoMPiS
Brief Summary:
KoMPiS is a contrast aided cardiac magnetic resonance study of microvascular obstruction and left ventricular remodelling following acute revascularised anterior myocardial infarction The study will monitor the included patients for 12 months following the acute myocardial infarct and collect data from MR scans and blood samples The study is designed to demonstrate that obstruction of blood flow in the peripheral small vessels of the cardiac muscle is an important factor in the post-MI development of left ventricle dysfunction that occurs in many patients despite of a successful re-opening of the occluded coronary artery that caused the MI
Detailed Description:
Introduction Cardiovascular disease is responsible for 30 of worldwide mortality accounting for approximately 15 million deaths per year Improvement in medical treatment strategies during the last decades has produced a tremendous decrease in mortality in connection with acute myocardial infarction AMI Since the 1960s short-term mortality 30 days has decreased from approximately 30 to the current mortality rate of 65 The success of modern treatment of AMI has however led to an increasing number of patients surviving AMI thus creating a growing group of high-risk patients that need further treatment and care The development of heart failure and the risk of recurrent ischemia and reinfarction are the two main threats to this population To further improve the treatment and outcomes in this high risk population early risk stratification based on a thorough understanding of the operating mechanisms behind the transition from acute infarction to heart failure is necessary
AMI reperfusion and microvascular obstruction Reperfusion therapy has been one of the major successes in the treatment of AMI and there are numerous studies to support the idea of opening occluded coronary arteries especially in the context of an AMI However even in the presence of a patent infarct related artery there may still be inadequate reperfusion at the tissue level This phenomenon known as no-reflow may preclude optimal reperfusion because of microvascular obstruction It is estimated that microvascular obstruction occurs in 30-40 of all revascularised patients in spite of a patent artery the exact underlying pathophysiological mechanisms are partially unknown Microvascular obstruction may possibly be due to sequestration of neutrophils in the microvasculature that subsequently lead to microvascular occlusion by erythrocytes leucocytes and cellular debris It remains unclear whether the stimulus for the development of microvascular obstruction originates during coronary occlusion exclusively or if reperfusion plays an active role in progression of the phenomenon
Microvascular obstruction and heart failure The presence of microvascular obstruction following AMI predicts unfavourable postinfarction prognosis and development of left ventricular dysfunction and left ventricular remodelling Left ventricular remodelling is associated with development of heart failure and is directly related to the magnitude of microvascular obstruction early after experimental and clinical AMI1 as well as 6 months after the acute event The mechanisms by which microvascular obstruction induces ventricular remodelling remain unknown Possibilities include the potentiation of wall thinning and infarct expansion early after infarction as well as potential impairment of infarct healing given the association between presence of microvascular obstruction and greater transmural scar formation 6 months after AMI
Assessment of microvascular obstruction Until recently microvascular obstruction could only be assessed by methods such as radioactive micro-spheres and other histopathological techniques that only could be performed at the terminal phase of an experimental study and not clinically However recent advances in the field of non-invasive cardiac imaging have enabled the serial assessment of this phenomenon by cardiac magnetic resonance imaging CMR thereby facilitating a much greater understanding of its pathophysiological and prognostic significance
Assessment of left ventricular remodelling by CMR The pathologic changes associated with the development of heart failure include changes in geometry and function myocytes and extracellular matrix Assessment of left ventricular remodelling includes estimation of left ventricular size and shape left ventricular mass and a functional assessment including an estimation of ejection fraction
Biochemical markers of scar formation inflammation and LV dysfunction Prognosis after MI is related both to the extent of myocardial cell-loss and the quality and quantity of repair of the infarcted myocardium The fate of fibrous tissue following acute myocardial infarction including regression persistence or progression of fibrosis is important for the understanding of the underlying mechanisms behind the progressive nature of LV remodelling following AMI Non-invasive assessment of fibrous tissue formation may be accomplished by measuring serum markers of collagen turnover
Following AMI fibrillar collagen appear both in the infarct scar and remote to the site of the myocardial infarction including viable tissue of the infarcted and noninfarcted ventricles In rats procollagen mRNA for collagens type I and III is increased in the right ventricle from day 2 onwards after a transmural left ventricular MI The increased collagen turnover may last for several months or even years
Aminoterminal propeptide of type I procollagen PINP and aminoterminal propeptide of type III procollagen PIIINP are liberated during collagen biosynthesis and they may be used as markers of this process PIIINP reflects the turnover of soft tissue collagen and is elevated after AMI reaching a plateau after four days with the largest increase in patients with large infarctions and acutely reduced LV function Increased serum PIIINP measured in the subacute phase of myocardial infarction is associated with persistently depressed LV ejection fraction dilatation and restrictive diastolic filling Patency of the infarct related artery reduces the PIIINP response and scar formation
The role of type I collagen following AMI is less clear It has been suggested that there is a late rise in the synthesis of type I collagen after myocardial infarction but this remains to be shown Among patients with heart failure of mixed aetiology ischemic and non-ischemic increased levels of CIPT PINP and PIIINP are associated with an increased risk of death
The modulation of collagen deposition and scar formation is accomplished by an intricate interplay between neurohormones eg aldosterone angiotensin I and II bradykinins catecholamines and natriuretic peptides and the inflammatory system The relationship between CMR collagen markers and neurohormones is not known in this setting
Study aims To characterize disease progression and to elucidate the operative pathophysiological mechanisms in patients with evidence of microvascular obstruction on contrast enhanced CMR following acute AMI
Study plan This is a single centre observational study designed to assess differences between patients with and without CMR evidence of microvascular obstruction To assure a homogenous group of patients only successfully revascularised patients with AMI caused by a single proximalmid LAD CX or RCA occlusion as assessed by coronary angiography will be included Only patients with functionally single vessel disease and without former heart disease will be included Patients will be selected for screening and requested to participate following the acute PCI The first CMR will be performed at 4812 hours following the primary PCI A follow-up CMR will be performed one week two months and one year following the index PCI At every CMR examination including the screening phase blood samples will be collected and clinical examination and an echocardiography will be performed The study population will be managed during and after their AMI according to current optimal guidelines and all patients will be considered for the same medical therapy including ACE inhibitors and beta-blockers The study will evaluate the presence of microvascular obstruction at baseline vs changes over time in CMR data and biochemical markers of collagen turnover neurohormonal activity and inflammation
Sample size estimation To detect a difference in LV mass of 10g with a power of 80 and a p 005 it is necessary to include 14 patients To show a difference in ejection fraction of 5 with a power of 90 and p 005 it is sufficient to include 5 patients In a study by Wu and coworkers late enhancement CMR demonstrated a significant difference in clinical outcome following myocardial infarction when 38 patients with or without congestive heart failure were divided into three groups according to the size of infarction To account for dropout and biological variation we will include a minimum of 20 patients with microvascular obstruction It is estimated that microvascular obstruction persists in around 30-40 of all patients undergoing revascularisation The group of patients without microvascular obstruction will consequently be 40 patients generating a total study population of 60 patients
AMI reperfusion and microvascular obstruction Reperfusion therapy has been one of the major successes in the treatment of AMI and there are numerous studies to support the idea of opening occluded coronary arteries especially in the context of an AMI However even in the presence of a patent infarct related artery there may still be inadequate reperfusion at the tissue level This phenomenon known as no-reflow may preclude optimal reperfusion because of microvascular obstruction It is estimated that microvascular obstruction occurs in 30-40 of all revascularised patients in spite of a patent artery the exact underlying pathophysiological mechanisms are partially unknown Microvascular obstruction may possibly be due to sequestration of neutrophils in the microvasculature that subsequently lead to microvascular occlusion by erythrocytes leucocytes and cellular debris It remains unclear whether the stimulus for the development of microvascular obstruction originates during coronary occlusion exclusively or if reperfusion plays an active role in progression of the phenomenon
Microvascular obstruction and heart failure The presence of microvascular obstruction following AMI predicts unfavourable postinfarction prognosis and development of left ventricular dysfunction and left ventricular remodelling Left ventricular remodelling is associated with development of heart failure and is directly related to the magnitude of microvascular obstruction early after experimental and clinical AMI1 as well as 6 months after the acute event The mechanisms by which microvascular obstruction induces ventricular remodelling remain unknown Possibilities include the potentiation of wall thinning and infarct expansion early after infarction as well as potential impairment of infarct healing given the association between presence of microvascular obstruction and greater transmural scar formation 6 months after AMI
Assessment of microvascular obstruction Until recently microvascular obstruction could only be assessed by methods such as radioactive micro-spheres and other histopathological techniques that only could be performed at the terminal phase of an experimental study and not clinically However recent advances in the field of non-invasive cardiac imaging have enabled the serial assessment of this phenomenon by cardiac magnetic resonance imaging CMR thereby facilitating a much greater understanding of its pathophysiological and prognostic significance
Assessment of left ventricular remodelling by CMR The pathologic changes associated with the development of heart failure include changes in geometry and function myocytes and extracellular matrix Assessment of left ventricular remodelling includes estimation of left ventricular size and shape left ventricular mass and a functional assessment including an estimation of ejection fraction
Biochemical markers of scar formation inflammation and LV dysfunction Prognosis after MI is related both to the extent of myocardial cell-loss and the quality and quantity of repair of the infarcted myocardium The fate of fibrous tissue following acute myocardial infarction including regression persistence or progression of fibrosis is important for the understanding of the underlying mechanisms behind the progressive nature of LV remodelling following AMI Non-invasive assessment of fibrous tissue formation may be accomplished by measuring serum markers of collagen turnover
Following AMI fibrillar collagen appear both in the infarct scar and remote to the site of the myocardial infarction including viable tissue of the infarcted and noninfarcted ventricles In rats procollagen mRNA for collagens type I and III is increased in the right ventricle from day 2 onwards after a transmural left ventricular MI The increased collagen turnover may last for several months or even years
Aminoterminal propeptide of type I procollagen PINP and aminoterminal propeptide of type III procollagen PIIINP are liberated during collagen biosynthesis and they may be used as markers of this process PIIINP reflects the turnover of soft tissue collagen and is elevated after AMI reaching a plateau after four days with the largest increase in patients with large infarctions and acutely reduced LV function Increased serum PIIINP measured in the subacute phase of myocardial infarction is associated with persistently depressed LV ejection fraction dilatation and restrictive diastolic filling Patency of the infarct related artery reduces the PIIINP response and scar formation
The role of type I collagen following AMI is less clear It has been suggested that there is a late rise in the synthesis of type I collagen after myocardial infarction but this remains to be shown Among patients with heart failure of mixed aetiology ischemic and non-ischemic increased levels of CIPT PINP and PIIINP are associated with an increased risk of death
The modulation of collagen deposition and scar formation is accomplished by an intricate interplay between neurohormones eg aldosterone angiotensin I and II bradykinins catecholamines and natriuretic peptides and the inflammatory system The relationship between CMR collagen markers and neurohormones is not known in this setting
Study aims To characterize disease progression and to elucidate the operative pathophysiological mechanisms in patients with evidence of microvascular obstruction on contrast enhanced CMR following acute AMI
Study plan This is a single centre observational study designed to assess differences between patients with and without CMR evidence of microvascular obstruction To assure a homogenous group of patients only successfully revascularised patients with AMI caused by a single proximalmid LAD CX or RCA occlusion as assessed by coronary angiography will be included Only patients with functionally single vessel disease and without former heart disease will be included Patients will be selected for screening and requested to participate following the acute PCI The first CMR will be performed at 4812 hours following the primary PCI A follow-up CMR will be performed one week two months and one year following the index PCI At every CMR examination including the screening phase blood samples will be collected and clinical examination and an echocardiography will be performed The study population will be managed during and after their AMI according to current optimal guidelines and all patients will be considered for the same medical therapy including ACE inhibitors and beta-blockers The study will evaluate the presence of microvascular obstruction at baseline vs changes over time in CMR data and biochemical markers of collagen turnover neurohormonal activity and inflammation
Sample size estimation To detect a difference in LV mass of 10g with a power of 80 and a p 005 it is necessary to include 14 patients To show a difference in ejection fraction of 5 with a power of 90 and p 005 it is sufficient to include 5 patients In a study by Wu and coworkers late enhancement CMR demonstrated a significant difference in clinical outcome following myocardial infarction when 38 patients with or without congestive heart failure were divided into three groups according to the size of infarction To account for dropout and biological variation we will include a minimum of 20 patients with microvascular obstruction It is estimated that microvascular obstruction persists in around 30-40 of all patients undergoing revascularisation The group of patients without microvascular obstruction will consequently be 40 patients generating a total study population of 60 patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None