Ignite Creation Date:
2024-05-06 @ 1:52 PM
Last Modification Date:
2024-10-26 @ 1:21 PM
Study NCT ID:
NCT04140019
Status:
UNKNOWN
Last Update Posted:
2021-10-04
First Post:
2019-08-13
Brief Title:
Early Cardiac Magnetic Resonance Imaging in Suspected Non-ST-Elevation Myocardial Infarction
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
Early Cardiac Magnetic Resonance Imaging in Suspected Non-ST-Elevation Myocardial Infarction An Observational Two-Center Study
Status:
UNKNOWN
Status Verified Date:
2021-09
Last Known Status:
RECRUITING
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:
CMR-OBSERVE
Brief Summary:
Background and rationale Evaluating patients with acute chest pain elevated high-sensitive cardiac troponin hs-cTn levels and non-diagnostic electrocardiogram ECG ie suspected non-ST elevation myocardial infarction MI is a daily challenge Although contemporary hs-cTn assay-based algorithms have greatly facilitated clinical decision-making still one-quarter of patients is categorized as observe group and in whom a diagnosis initially remains unknown Although routinely treated as acute MI with referral to invasive coronary angiography ICA up to one-third does not have obstructive coronary artery disease CAD Follow-up cardiac magnetic resonance imaging CMR has been shown to be a very useful diagnostic tool in this setting but is not part of routine clinical care in every patient
Objectives To investigate in patients with suspected non-ST elevation MI meeting the observe criteria and who are scheduled for ICA 1 the prevalence of coronary artery disease as well as non-coronary artery disease related and extra-cardiac diseases by adding CMR early in the diagnostic pathway and 2 the number of major adverse cardiac events MACE and a composite of MACE and major non-cardiac adverse events after 30 days and one year These objectives allow an accurate estimate of the number of potentially avoidable ICA in the future and whether early CMR could be a safe gatekeeper for inappropriate ICA
Study population and design In this prospective observational two-center study in The Netherlands MUMC and VieCuri Medical Center 87 consecutive patients with acute chest pain non-diagnostic ECG and hs-cTn levels meeting the observe criteria and scheduled for ICA will be investigated Patients will undergo a comprehensive CMR examination prior to ICA and will be followed-up at one month and one year After completion of follow-up an independent clinical diagnosis committee will adjudicate a final diagnosis at discharge and after one year The final diagnosis at discharge will be adjudicated twice once with and once without considering the results of CMR For the diagnosis at one-year all clinical variables and CMR results will be considered MACE and complications will be scored after 30 days and one year
Main study parametersendpoints The primary endpoint is the prevalence of coronary artery disease as well as non-coronary artery disease related and extra-cardiac diseases The secondary safety endpoint is the number of major adverse cardiac events MACE and a composite of MACE and major non-cardiac adverse events after 30 days and one year
Nature and extent of the burden and risks associated with participation benefit and group relatedness
CMR is an accepted and safe imaging modality in patients with suspected non-ST-elevation myocardial infarction
Objectives To investigate in patients with suspected non-ST elevation MI meeting the observe criteria and who are scheduled for ICA 1 the prevalence of coronary artery disease as well as non-coronary artery disease related and extra-cardiac diseases by adding CMR early in the diagnostic pathway and 2 the number of major adverse cardiac events MACE and a composite of MACE and major non-cardiac adverse events after 30 days and one year These objectives allow an accurate estimate of the number of potentially avoidable ICA in the future and whether early CMR could be a safe gatekeeper for inappropriate ICA
Study population and design In this prospective observational two-center study in The Netherlands MUMC and VieCuri Medical Center 87 consecutive patients with acute chest pain non-diagnostic ECG and hs-cTn levels meeting the observe criteria and scheduled for ICA will be investigated Patients will undergo a comprehensive CMR examination prior to ICA and will be followed-up at one month and one year After completion of follow-up an independent clinical diagnosis committee will adjudicate a final diagnosis at discharge and after one year The final diagnosis at discharge will be adjudicated twice once with and once without considering the results of CMR For the diagnosis at one-year all clinical variables and CMR results will be considered MACE and complications will be scored after 30 days and one year
Main study parametersendpoints The primary endpoint is the prevalence of coronary artery disease as well as non-coronary artery disease related and extra-cardiac diseases The secondary safety endpoint is the number of major adverse cardiac events MACE and a composite of MACE and major non-cardiac adverse events after 30 days and one year
Nature and extent of the burden and risks associated with participation benefit and group relatedness
CMR is an accepted and safe imaging modality in patients with suspected non-ST-elevation myocardial infarction
Detailed Description:
1 OBJECTIVES 11 Primary Objective To investigate the prevalence of coronary artery disease as well as non-coronary artery disease related and extra-cardiac diseases in patients presenting with acute chest pain a non-diagnostic ECG and elevated hs-cTn levels meeting the observe criteria by using CMR early in the diagnostic pathway and at least prior to intended invasive coronary angiography
12 Secondary Objective
To investigate in patients presenting with acute chest pain a non-diagnostic ECG and elevated hs-cTn levels meeting the observe criteria and who are scheduled for ICA
The number of MACE and a composite of MACE and major non-cardiac adverse events after 30 days and one year
The diagnostic accuracy of CMR for the diagnosis of obstructive CAD ie stenosis 70
2 STUDY DESIGN This prospective two-center observational study will be performed in Maastricht University Medical Center MUMC and VieCuri Medical Center Venlo The Netherlands Patients visiting the cardiac ED with acute chest pain a non-diagnostic ECG and hs-cTn levels meeting the observe criteria and who are scheduled for ICA are eligible After written informed consent patients will be included They will be treated according to current guidelines and undergo a comprehensive CMR investigation as soon as possible after inclusion but at least prior to an intended ICA taking into account the guideline requirement of performing ICA 72 hours after admission Early CMR will not interfere with routine clinical care and was previously shown to be feasible16 The interventional cardiologists and treating physicians will be blinded for the CMR results since this is not part of current clinical practice All CMR studies will be analyzed in MUMC ie core lab as soon as possible after ICA is performed Only incidental extra-cardiac findings that may significantly change clinical management will be reported to the treating physician ie malignancy massive pulmonary embolism acute aortic dissection etc Also when a clinical diagnosis remains unknown after ICA and only if clinicians explicitly request to perform additional CMR as a clinical routine the results of the early CMR will be provided Patients will be followed at least after 30 days and one-year and normal clinical variables final diagnosis total number of ICA and outcome MACE and major non-cardiac adverse events will be collected in each patient After all patients have completed their one-year follow-up an independent final diagnosis committee will adjudicate a final diagnosis This committee will adjudicate a final diagnosis 1 after the index discharge and 2 after one year The final diagnosis at discharge will be adjudicated twice by the committee once with and once without considering the results of CMR For the adjudicated final diagnosis at one-year all clinical variables including the results of CMR will be considered
3 STUDY POPULATION
31 Population Patients presenting to the cardiac ED with acute chest pain a non-diagnostic ERCG elevated hs-cTn levels meeting the observe criteria and who are admitted and scheduled for an ICA will be eligible to participate in this study
In MUMC approximately 4000 patients visit the cardiac ED every year of whom half present with acute chest pain25 After excluding 15 of patients with ST-Elevation Myocardial Infarction STEMI 1700 patients with acute chest pain need further evaluation Approximately one-quarter n425 meet the observe criteria8 Although a rather conservative estimate based on pilot data and previous study results 25 the investigators expect that at least 20 of patients n90 will be eligible or willing to participate in a similar research trial per center Because the number of cardiac ED visits in VieCuri Medical Center is comparable to MUMC it is expected that all 87 patients can be included within one year after start of the study
The study will be performed according to Good Clinical Practice GCP guidelines and the data will be analyzed and reported in accordance with the CONSORT Consolidated Standard of Reporting Trials guidelines Prior to inclusion patients will be asked to give written informed consent
32 Inclusion criteria
Acute onset 1 hour chest pain or angina pectoris equivalent suspected of non-ST-elevation myocardial infarction NSTEMI
Hospital admission and scheduling for ICA
Hs-cTn levels meeting the observe criteria
Age between 18 years - 85 years old
Written informed consent 33 Exclusion criteria
Refractory angina or on-going severe ischemia requiring immediate ICA
Patients requiring ICA 24 hours after admission see previous bullet
Hemodynamic instability andor cardiogenic shock mean arterial pressure 60 mmHg
Heart failure Killip Class III requiring intravenously medication nitroglycerine diuretics etc
ST-Elevation Myocardial Infarction ST-elevation in 2 contiguous leads 02mV in men or 015 mV in women in leads V2-V3 andor 01 mV in other leads or new left bundle branch block
Symptoms highly suggestive of non-cardiac origin at presentation as judged by the cardiac ED physiciancardiologist
Symptoms highly suggestive of AAD PE or acute peri-myocarditis
Inability to organize ICA and CMR 72 hours after admission especially for patients admitted on Friday eveningsnights logistic restrictions
Life threatening arrhythmias prior to or during presentation sustained ventricular tachycardia repetitive non-sustained ventricular tachycardia ventricular fibrillation sinoatrial or atrio-ventricular block
Atrial fibrillation with persistent ventricular rate 100 beats per minute bpm after treatment
Ongoing tachycardia 100bpm
Angina pectoris secondary to anemia 56 mmolL untreated hyperthyroidism or severe hypertension 200110 mmHg
More than mild aortic and mitral valve calcification or stenosis by latest echocardiography
Recent revascularization or ACUTE MI 6 months
Known CAD not suitable for further interventions PCI or CABG
Pregnancy
Breast feeding women
Life expectancy 1 year malignancy etc
Refusal of data storage until 15 years after end of study
Participation in another investigational study that has not reached its primary endpoint
Contraindications to CMR
ODIN-protocol Uitvoering van MRI-onderzoek bij patiënten met een cardiaal implanteerbaar elektronisch device CIED waaronder een pacemaker en ICD ODIN-protocol Voorbereiding klinische patiënten voor MRI-onderzoek
Metallic implant vascular clip neuro-stimulator cochlear implant
Pacemaker or implantable cardiac defibrillator ICD
Claustrophobia
Body weight 130 kg or body habitus that does not fit into the gantry
Renal failure estimated Glomerular Filtration Rate eGFR 30 mLmin173m2 chronic renal failure stage 4-5
Known severe allergy to gadolinium contrast agents patient with mild allergy is eligible for inclusion when pre-medication according to hospital guidelines can be administered
Contraindications to adenosine
High degree atrio-ventricular block 2nd or 3rd degree
Severe bronchial asthma
Chronic obstructive pulmonary disease GOLD III
Concomitant use of Dipyridamole Persantin
Long QT syndrome congenital
34 Patient inclusion process Eligible patients need to have acute chest pain or angina pectoris equivalent for at least one hour a non-diagnostic ECG and hs-cTn levels meeting the observe criteria and need to be admitted and scheduled for ICA The physician working on the cardiac ED will screen patients When eligible patients will be informed about the study and asked for oral permission to be approached by a member of the research team Two hours after written information is given the patient is asked to participate After written informed consent the patient is included in the study
35 Sample size calculation This is an observational study primarily aiming to investigate the prevalence of non-coronary artery and extra-cardiac diseases in patients presenting with acute chest pain non-diagnostic ECG and elevated hs-cTn levels meeting the observe criteria ie patients with suspected NSTEMI and who are scheduled for ICA Knowing this prevalence will help to determine the number of potentially avoidable ICA in the future
Based on studies performed in comparable but not similar patients in the conventional troponin assay non-hs-cTn era the investigators transpose a prevalence of at least 20 having non-obstructive CAD to the current population This is a rather conservative estimation and the prevalence is expected to be even higher in the current high-sensitive troponin assay era Similarly the investigators transpose the results of additional CMR in patients with ST-elevation myocardial infarction and non-obstructive CAD where CMR was helpful providing a diagnosis in 70 Using follow-up CMR in this setting myocarditis can be diagnosed in 34 stress cardiomyopathy in 15 PE or AAD in 1 and other diseases in 2 of patients Interestingly MI or myocardial ischemia can still be diagnosed in 20 of patients in the absence of obstructive CAD CMR is expected to be normal in 25 and non-diagnostic in 5
ICA will be considered appropriate when obstructive CAD is found at ICA and for safety reasons when CMR shows MI or myocardial ischemia despite non-obstructive CAD at follow-up ICA in 20 or when CMR is non-diagnostic in 5 The total proportion of appropriate ICA is thus expected to be 85 ie patients with obstructive CAD at ICA 80 of total 25 of 20 of patient with non-obstructive CAD 5 of total
To accurately estimate this proportion of appropriate ICA the investigators aim to include a sample large enough so that the total width of the 95 confidence interval does not exceed 15 and thus the maximum margin of error ie the half-width of the confidence interval does not exceed 75 Assuming a proportion of 85 the investigators need to include at least 87 patients
4 TREATMENT OF SUBJECTS Patients will be treated according to current international guidelines and local practice CMR will be performed as soon as possible prior to ICA taking into account the requirement of ICA 72 hours after admission and does not interfere with routine clinical care
12 Secondary Objective
To investigate in patients presenting with acute chest pain a non-diagnostic ECG and elevated hs-cTn levels meeting the observe criteria and who are scheduled for ICA
The number of MACE and a composite of MACE and major non-cardiac adverse events after 30 days and one year
The diagnostic accuracy of CMR for the diagnosis of obstructive CAD ie stenosis 70
2 STUDY DESIGN This prospective two-center observational study will be performed in Maastricht University Medical Center MUMC and VieCuri Medical Center Venlo The Netherlands Patients visiting the cardiac ED with acute chest pain a non-diagnostic ECG and hs-cTn levels meeting the observe criteria and who are scheduled for ICA are eligible After written informed consent patients will be included They will be treated according to current guidelines and undergo a comprehensive CMR investigation as soon as possible after inclusion but at least prior to an intended ICA taking into account the guideline requirement of performing ICA 72 hours after admission Early CMR will not interfere with routine clinical care and was previously shown to be feasible16 The interventional cardiologists and treating physicians will be blinded for the CMR results since this is not part of current clinical practice All CMR studies will be analyzed in MUMC ie core lab as soon as possible after ICA is performed Only incidental extra-cardiac findings that may significantly change clinical management will be reported to the treating physician ie malignancy massive pulmonary embolism acute aortic dissection etc Also when a clinical diagnosis remains unknown after ICA and only if clinicians explicitly request to perform additional CMR as a clinical routine the results of the early CMR will be provided Patients will be followed at least after 30 days and one-year and normal clinical variables final diagnosis total number of ICA and outcome MACE and major non-cardiac adverse events will be collected in each patient After all patients have completed their one-year follow-up an independent final diagnosis committee will adjudicate a final diagnosis This committee will adjudicate a final diagnosis 1 after the index discharge and 2 after one year The final diagnosis at discharge will be adjudicated twice by the committee once with and once without considering the results of CMR For the adjudicated final diagnosis at one-year all clinical variables including the results of CMR will be considered
3 STUDY POPULATION
31 Population Patients presenting to the cardiac ED with acute chest pain a non-diagnostic ERCG elevated hs-cTn levels meeting the observe criteria and who are admitted and scheduled for an ICA will be eligible to participate in this study
In MUMC approximately 4000 patients visit the cardiac ED every year of whom half present with acute chest pain25 After excluding 15 of patients with ST-Elevation Myocardial Infarction STEMI 1700 patients with acute chest pain need further evaluation Approximately one-quarter n425 meet the observe criteria8 Although a rather conservative estimate based on pilot data and previous study results 25 the investigators expect that at least 20 of patients n90 will be eligible or willing to participate in a similar research trial per center Because the number of cardiac ED visits in VieCuri Medical Center is comparable to MUMC it is expected that all 87 patients can be included within one year after start of the study
The study will be performed according to Good Clinical Practice GCP guidelines and the data will be analyzed and reported in accordance with the CONSORT Consolidated Standard of Reporting Trials guidelines Prior to inclusion patients will be asked to give written informed consent
32 Inclusion criteria
Acute onset 1 hour chest pain or angina pectoris equivalent suspected of non-ST-elevation myocardial infarction NSTEMI
Hospital admission and scheduling for ICA
Hs-cTn levels meeting the observe criteria
Age between 18 years - 85 years old
Written informed consent 33 Exclusion criteria
Refractory angina or on-going severe ischemia requiring immediate ICA
Patients requiring ICA 24 hours after admission see previous bullet
Hemodynamic instability andor cardiogenic shock mean arterial pressure 60 mmHg
Heart failure Killip Class III requiring intravenously medication nitroglycerine diuretics etc
ST-Elevation Myocardial Infarction ST-elevation in 2 contiguous leads 02mV in men or 015 mV in women in leads V2-V3 andor 01 mV in other leads or new left bundle branch block
Symptoms highly suggestive of non-cardiac origin at presentation as judged by the cardiac ED physiciancardiologist
Symptoms highly suggestive of AAD PE or acute peri-myocarditis
Inability to organize ICA and CMR 72 hours after admission especially for patients admitted on Friday eveningsnights logistic restrictions
Life threatening arrhythmias prior to or during presentation sustained ventricular tachycardia repetitive non-sustained ventricular tachycardia ventricular fibrillation sinoatrial or atrio-ventricular block
Atrial fibrillation with persistent ventricular rate 100 beats per minute bpm after treatment
Ongoing tachycardia 100bpm
Angina pectoris secondary to anemia 56 mmolL untreated hyperthyroidism or severe hypertension 200110 mmHg
More than mild aortic and mitral valve calcification or stenosis by latest echocardiography
Recent revascularization or ACUTE MI 6 months
Known CAD not suitable for further interventions PCI or CABG
Pregnancy
Breast feeding women
Life expectancy 1 year malignancy etc
Refusal of data storage until 15 years after end of study
Participation in another investigational study that has not reached its primary endpoint
Contraindications to CMR
ODIN-protocol Uitvoering van MRI-onderzoek bij patiënten met een cardiaal implanteerbaar elektronisch device CIED waaronder een pacemaker en ICD ODIN-protocol Voorbereiding klinische patiënten voor MRI-onderzoek
Metallic implant vascular clip neuro-stimulator cochlear implant
Pacemaker or implantable cardiac defibrillator ICD
Claustrophobia
Body weight 130 kg or body habitus that does not fit into the gantry
Renal failure estimated Glomerular Filtration Rate eGFR 30 mLmin173m2 chronic renal failure stage 4-5
Known severe allergy to gadolinium contrast agents patient with mild allergy is eligible for inclusion when pre-medication according to hospital guidelines can be administered
Contraindications to adenosine
High degree atrio-ventricular block 2nd or 3rd degree
Severe bronchial asthma
Chronic obstructive pulmonary disease GOLD III
Concomitant use of Dipyridamole Persantin
Long QT syndrome congenital
34 Patient inclusion process Eligible patients need to have acute chest pain or angina pectoris equivalent for at least one hour a non-diagnostic ECG and hs-cTn levels meeting the observe criteria and need to be admitted and scheduled for ICA The physician working on the cardiac ED will screen patients When eligible patients will be informed about the study and asked for oral permission to be approached by a member of the research team Two hours after written information is given the patient is asked to participate After written informed consent the patient is included in the study
35 Sample size calculation This is an observational study primarily aiming to investigate the prevalence of non-coronary artery and extra-cardiac diseases in patients presenting with acute chest pain non-diagnostic ECG and elevated hs-cTn levels meeting the observe criteria ie patients with suspected NSTEMI and who are scheduled for ICA Knowing this prevalence will help to determine the number of potentially avoidable ICA in the future
Based on studies performed in comparable but not similar patients in the conventional troponin assay non-hs-cTn era the investigators transpose a prevalence of at least 20 having non-obstructive CAD to the current population This is a rather conservative estimation and the prevalence is expected to be even higher in the current high-sensitive troponin assay era Similarly the investigators transpose the results of additional CMR in patients with ST-elevation myocardial infarction and non-obstructive CAD where CMR was helpful providing a diagnosis in 70 Using follow-up CMR in this setting myocarditis can be diagnosed in 34 stress cardiomyopathy in 15 PE or AAD in 1 and other diseases in 2 of patients Interestingly MI or myocardial ischemia can still be diagnosed in 20 of patients in the absence of obstructive CAD CMR is expected to be normal in 25 and non-diagnostic in 5
ICA will be considered appropriate when obstructive CAD is found at ICA and for safety reasons when CMR shows MI or myocardial ischemia despite non-obstructive CAD at follow-up ICA in 20 or when CMR is non-diagnostic in 5 The total proportion of appropriate ICA is thus expected to be 85 ie patients with obstructive CAD at ICA 80 of total 25 of 20 of patient with non-obstructive CAD 5 of total
To accurately estimate this proportion of appropriate ICA the investigators aim to include a sample large enough so that the total width of the 95 confidence interval does not exceed 15 and thus the maximum margin of error ie the half-width of the confidence interval does not exceed 75 Assuming a proportion of 85 the investigators need to include at least 87 patients
4 TREATMENT OF SUBJECTS Patients will be treated according to current international guidelines and local practice CMR will be performed as soon as possible prior to ICA taking into account the requirement of ICA 72 hours after admission and does not interfere with routine clinical care
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