Early Detection of Silent Myocardial Ischemia (EarlySynergy)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cardiovascular Diseases; Ischemic Heart Disease; Silent Myocardial Ischemia
• Intervention / Treatment: Diagnostic test: CMR stress perfusion imaging

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness	Cost-effectiveness of CMR stress perfusion imaging compared to control group	1 year
Cost-effectiveness	Cost-effectiveness of CMR stress perfusion imaging compared to control group	2.5 years
Cost-effectiveness	Cost-effectiveness of CMR stress perfusion imaging compared to control group	5 years

Collaborators and Investigators

• Sponsor: Pim van der Harst
• Investigators: Principal Investigator: Pim van der Harst, MD, PhD, University Medical Center Groningen

Publications and helpful links

General Publications

• Xia C, Rook M, Pelgrim GJ, Sidorenkov G, Wisselink HJ, van Bolhuis JN, van Ooijen PMA, Guo J, Oudkerk M, Groen H, van den Berge M, van der Harst P, Dijkstra H, Vonder M, Heuvelmans MA, Dorrius MD, De Deyn PP, de Bock GH, Dotinga A, Vliegenthart R. Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study. Eur J Epidemiol. 2020 Jan;35(1):75-86. doi: 10.1007/s10654-019-00519-0. Epub 2019 Apr 23.
• Vonder M, van der Aalst CM, Vliegenthart R, van Ooijen PMA, Kuijpers D, Gratama JW, de Koning HJ, Oudkerk M. Coronary Artery Calcium Imaging in the ROBINSCA Trial: Rationale, Design, and Technical Background. Acad Radiol. 2018 Jan;25(1):118-128. doi: 10.1016/j.acra.2017.07.010. Epub 2017 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Cardiovascular Diseases; Ischemia
• Other Study ID Numbers: NL64860.042.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data management plan in progress
• IPD Sharing Time Frame: In accordance with legal period for study data storage
• IPD Sharing Access Criteria: In correspondence with the principal investigator
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No