Early Detection of Silent Myocardial Ischemia

Study Overview
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Brief Summary
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Early-Synergy investigates a diagnostic imaging approach in asymptomatic individuals from the general population for early detection of silent myocardial ischemia and cardiac dysfunction. The diagnostic imaging approach consists of cardiac computed tomography for coronary artery calcium scoring (CT-CAC) and cardiac magnetic resonance (CMR) stress perfusion imaging. Early-Synergy investigates the effect of early detection of silent myocardial ischemia and cardiac dysfunction by CMR in asymptomatic individuals with increased CAC. In addition, the diagnostic yield of CMR for early detection of silent myocardial ischemia and cardiac dysfunction is investigated. Asymptomatic individuals at increased risk (CAC ≥ 300) are therefore randomized 1:1 to either CMR stress perfusion imaging or a control group.

Detailed Description
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Early-Synergy is a prospective multi-center study performed in the Netherlands. Potential candidates for participation in Early-Synergy have had CT-CAC scanning as part of participation in two ongoing population-based studies (ROBINSCA and ImaLife) and had CAC ≥300. Participants are randomized in a 1:1 fashion to (1.) CMR stress perfusion imaging with feedback of clinically actionable findings or (2.) control group. In the CMR group, feedback on CMR stress perfusion imaging is provided to the participant and general practitioner only in case of CMR findings that require further management based on current clinical guidelines. Participants in the control group will not receive stress CMR perfusion imaging but will be followed in time to evaluate the clinical presentation of the natural course of coronary atherosclerosis. Follow-up will be performed up to 5 years in both groups by sending questionnaires and collecting medical information from health care providers and registries. Additionally, blood is drawn from participants in the CMR group during the hospital visit for CMR scanning and is stored to allow evaluation of cardiac blood markers as predictors of CMR findings.

Official Title
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Early Detection of Silent Myocardial Ischemia and Cardiac Dysfunction in Asymptomatic Individuals With Increased Coronary Artery Calcium Scores

Conditions
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Ischemic Heart Disease, Silent Myocardial Ischemia, Cardiovascular Diseases

Intervention / Treatment
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* Diagnostic Test: CMR stress perfusion imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in ROBINSCA or ImaLife study CT-CAC ≥300 Exclusion Criteria: History of ischemic heart disease or other cardiac disease (myocardial infarction, sudden cardiac arrest, heart failure, cardiomyopathy, congenital cardiac disease, percutaneous coronary intervention, coronary artery bypass grafting surgery, valvular surgery, other major cardiac surgery (e.g. cardiac transplantation) and/or previous invasive coronary angiography or catheter ablation) Contra-indication for stress CMR perfusion imaging (claustrophobia, CMR incompatible device (e.g., Implantable Cardioverter Defibrillator/pacemaker), contrast agent or vasodilator intolerance, contra-indications for adenosine or regadenoson (e.g. 2nd/3rd degree atrioventricular block, severe hypotension) and/or weight > 125 kg) Severe comorbidity and/or a life expectancy of less than 1 year Unable to provide written informed consent Pregnancy

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cardiac magnetic resonance imaging<br>Cardiac magnetic resonance (CMR) stress perfusion imaging with feedback of clinically actionable findings | Diagnostic Test: CMR stress perfusion imaging<br>* CMR stress perfusion imaging with feedback of clinically actionable findings to general practitioner and participant<br>|
| No Intervention: Control<br>No intervention, following the natural course of coronary atherosclerosis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major adverse cardiac events | Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest | 1 year | 
| Rate of major adverse cardiac events | Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest | 2.5 years | 
| Rate of major adverse cardiac events | Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest | 5 years | 
| Diagnostic yield of CMR stress perfusion imaging | Prevalence and extent of silent myocardial ischemia and cardiac dysfunction | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of individual components of primary outcome 1 | Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest | 1 year | 
| Rate of individual components of primary outcome 1 | Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest | 2.5 years | 
| Rate of individual components of primary outcome 1 | Cardiovascular death, non-fatal myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest | 5 years | 
| All-cause mortality rate | Death from any disease | 1 year | 
| All-cause mortality rate | Death from any disease | 2.5 years | 
| All-cause mortality rate | Death from any disease | 5 years | 
| Rate of invasive cardiovascular procedures | percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) surgery, invasive coronary angiography (ICA) and other invasive cardiovascular procedures | 1 year | 
| Rate of invasive cardiovascular procedures | percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) surgery, invasive coronary angiography (ICA) and other invasive cardiovascular procedures | 2.5 years | 
| Rate of invasive cardiovascular procedures | percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) surgery, invasive coronary angiography (ICA) and other invasive cardiovascular procedures | 5 years | 
| Rate of hospitalization for cardiovascular disease | Hospitalization for cardiovascular disease (e.g. stroke, peripheral vascular disease) | 1, 2.5, 5 years | 
| Rate of hospitalization for cardiovascular disease | Hospitalization for cardiovascular disease (e.g. stroke, peripheral vascular disease) | 1 year | 
| Rate of hospitalization for cardiovascular disease | Hospitalization for cardiovascular disease (e.g. stroke, peripheral vascular disease) | 2.5 years | 
| Rate of non-invasive cardiac imaging procedures | Rate of non-invasive cardiac imaging procedures (e.g., myocardial stress perfusion imaing, echocardiography) | 5 years | 
| Rate of medical therapy initiation | Initiation of preventive or cardio-active medication (e.g., ACE-inhibiters, statins, calcium antagonists, beta-blockers etc.) | 1 year | 
| Rate of medical therapy initiation | Initiation of preventive or cardio-active medication (e.g., ACE-inhibiters, statins, calcium antagonists, beta-blockers etc.) | 2.5 years | 
| Rate of medical therapy initiation | Initiation of preventive or cardio-active medication (e.g., ACE-inhibiters, statins, calcium antagonists, beta-blockers etc.) | 5 years | 
| Quality of Life as reflected by EQ-5D-5S score | Quality of life as assessed by EQ-5D-5S questionnaire | 1 year | 
| Quality of Life as reflected by EQ-5D-5S score | Quality of life as assessed by EQ-5D-5S questionnaire | 2.5 years | 
| Quality of Life as reflected by EQ-5D-5S score | Quality of life as assessed by EQ-5D-5S questionnaire | 5 years | 
| Quality of Life as reflected by HeartQoL score | Quality of life as assessed by HeartQoL questionnaire | 1 year | 
| Quality of Life as reflected by HeartQoL score | Quality of life as assessed by HeartQoL questionnaire | 2.5 years | 
| Quality of Life as reflected by HeartQoL score | Quality of life as assessed by HeartQoL questionnaire | 5 years |