Clinical Relevance of Coronary Microvascular Dysfunction Assessments in Myocardial Infarction With Non-Obstructive Coronary Arteries
Conditions: Myocardial Infarction, Coronary Microvascular Dysfunction, Vasospasm, Coronary
Sponsor: Chonnam National University Hospital

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Clinical Relevance of Coronary Microvascular Dysfunction 
Assessments in Myocardial Infarction with Non-Obstructive 
Coronary Arteries 
(CMD-MINOCA) 
 
 
 
 
 
Chonnam National University Hospital, 
Chonnam National University Medical School 
 
 
 
Principal Investigator: Young Joon Hong 
Research Manager: Seung Hun Lee 
 
 

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- Table of Contents - 
1. Title of Study ...................................................................................................................................... 8 
2. Clinical Research Center .................................................................................................................. 8 
3. Principal Investigator, Staff, Co-researchers ................................................................................. 8 
4. Research Grant ................................................................................................................................. 9 
5. Background ....................................................................................................................................... 9 
6. Study Plans ........................................................................................................................................ 9 
6.1. Study Design ............................................................................................................................. 9 
6.2. Study Timeline .......................................................................................................................... 9 
6.3. Study Population ..................................................................................................................... 10 
6.4. Eligibility Criteria ..................................................................................................................... 10 
6.4.1. Inclusion Criteria ........................................................................................................... 10 
6.4.2. Exclusion Criteria .......................................................................................................... 10 
6.5. Patient Follow-up .................................................................................................................... 10 
7. End Points ....................................................................................................................................... 11 
7.1. Primary End Point ................................................................................................................... 11 
7.2. Secondary End Point .............................................................................................................. 11 
8. Patient Enrollment and Withdrawal ............................................................................................... 11 
8.1. Patient Enrollment ................................................................................................................... 11 
8.2. Patient Discontinuation (Withdrawal Criteria) ......................................................................... 11 
8.3. Lost to Follow-up ..................................................................................................................... 12 
9. Study Protocol ................................................................................................................................. 12 
9.1. Flow Chart ............................................................................................................................... 13 
9.2. Study Procedure ..................................................................................................................... 13 
9.3. Schedule of Measurements .................................................................................................... 14 
10. Measurement of study outcome variables ................................................................................. 16 
10.1. Visit 1 Screening & Baseline ................................................................................................. 16 
10.2. Follow-up .............................................................................................................................. 17 
11. Ethical Considerations and Confidentiality .............................................................................. 17 
11.1. Institutional Review Board (IRB) / Ethical Committee Approval............................................ 17 

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11.2. Participant Safety .......................................................................................................... 17 
11.2.1 Elements of Informed Consent ................................................................................. 17 
11.3. Confidentiality ....................................................................................................................... 18 
12. Study Organization ...................................................................................................................... 18 
12.1. Steering Committee and Data Safety Monitoring Board (DSMB) ........................................ 18 
12.2. Clinical Event Adjudication Committee (CEAC) ................................................................. 18 
12.3. Data Coordination and Site Management ........................................................................ 19 
13. Statistical Analysis ...................................................................................................................... 19 
13.1. Primary End point Analysis ................................................................................................ 19 
13.2. Secondary End point Analysis .............................................................................................. 19 
13.3. Multivariable Analyses ......................................................................................................... 20 
13.4. Survival Analyses ................................................................................................................. 20 
14. Publication Policy ........................................................................................................................ 20 
14.1. Data Analysis and Release of Results ............................................................................. 20 
14.2. Review Process ................................................................................................................... 20 
14.3. Authorship: Primary Outcome Paper ................................................................................. 20 
14.4. Other Study Papers, Abstracts and Presentations .......................................................... 20 
15. Quality Assurances, Quality Control and Clinical Monitoring ............................................ 21 
15.1. Protocol Adherence ............................................................................................................. 21 
15.2. Data Collection: Electronic Case Report Forms (eCRF) .................................................. 22 
16. Event Adjudication and Reporting ........................................................................................... 22 
16.1. End point Adjudication ........................................................................................................ 22 
17. Regulatory Responsibilities ........................................................................................................ 22 
17.1. Investigator Responsibilities ................................................................................................. 22 
17.2. Institutional Review Board (IRB) or Ethics Committee Approval ................................... 23 
17.3. Informed Consent ................................................................................................................ 23 
17.4. Study Coordinator ................................................................................................................ 23 
18. Records Retention and Reports ................................................................................................ 23 
18.1. Records ................................................................................................................................. 23 
18.2. Reports ................................................................................................................................. 24 

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19. Investigational Agreement ........................................................................................................... 25 
20. Appendix. Definitions ................................................................................................................... 26 
21. References ..................................................................................................................................... 29 
 
 
 

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Research Summary 
Study Title 
Clinical Relevance of Coronary Microvascular Dysfunction Assessments in 
Myocardial Infarction with Non-Obstructive Coronary Arteries (CMD-MINOCA) 
Principal  
Investigator 
Young Joon Hong, MD, PhD 
 
Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, 
Gwangju, Republic of Korea, 61469, 
Chonnam National University Hospital, 42 Jaebong-ro, Dong-gu, Gwangju, 
Republic of Korea, 61469, 
Telephone: 82-62-220-5778 
E-mail: hyj200@hanmail.net 
Research 
Manager 
Seung Hun Lee, MD, PhD 
Countries 
Involved 
Republic of Korea 
Purpose / Objectives: 
To compare clinical outcomes of myocardial infarction with non-obstructive coronary arteries 
(MINOCA) according to the coronary microvascular dysfunction (CMD), evaluated by optical 
coherence tomography (OCT), invasive and non-invasive coronary physiologic assessment. 
Study Design: 
1. Trial Design 
A prospective observational study 
 
2. Target Population 
Patients with MINOCA   
 
3. Enrollment criteria 
(1) Inclusion criteria 
① Subject with age ≥19 years and acute myocardial infarction 
- 
Rise and/or fall of cardiac troponin with one level >99 percentile plus ischemic 
signs/symptoms 
② Subject with non-obstructive coronary arteries 
- 
<50% diameter stenosis or 
- 
fractional flow reserve (FFR) >0.80 
③ Subject without previous history of coronary artery disease 
④ Subject who performed invasive coronary angiography within 24 hours after presentation 
⑤ Subject who eligible for invasive and non-invasive coronary physiologic assessment 
 
(2) Exclusion criteria 
① Subject with obstructive coronary arteries 
② Subject with alternate diagnosis including sepsis, pulmonary embolism, myocarditis, 
Takotsubo syndrome, spontaneous coronary dissection, and other cardiomyopathies. 
③ Subject with cardiogenic shock or cardiac arrest 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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④ Subject who has non-cardiac co-morbid conditions with life expectancy <2 years 
⑤ Subject or lactating women 
⑥ Subject unable to provide consent 
 
4. Outcome Measures 
(1) Primary end point:  
Major adverse cardiovascular and cerebrovascular events (a composite of cardiac death, any 
MI, any revascularization, stroke, readmission due to heart failure) at 2 years 
 
(2) Secondary end points: 
① Cardiac death at 2 years 
② All-cause death at 2 years 
③ Any MI at 2 years 
④ Any revascularization at 2 years 
⑤ Stroke (ischemic or hemorrhagic) at 2 years 
⑥ Readmission due to heart failure at 2 years 
⑦ All-cause death, any MI, or any revascularization at 2 years 
⑧ Left ventricular ejection fraction at 2 years 
⑨ Coronary flow reserve at 6 months 
 
5. Study Procedure 
(1) Flow chart 

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About 150 patients with suspected myocardial infarction underwent invasive coronary angiography, 
but without obstructive coronary arteries will be enrolled. These patients will be evaluated by OCT, 
coronary functional assessment including coronary spasm test, invasive (FFR, CFR, IMR) and non-
invasive coronary physiologic assessment (N-13 ammonia positron emission tomography). Left 
ventricular function will be assessed using echocardiography or left ventriculogram. Cardiac 
magnetic resonance imaging is recommended to exclude other causes for elevating cardiac 
enzymes, if necessary. Patients will be managed with cardioprotective therapies and cause-targeted 
therapies according to the latest recommendation. MINOCA patients with CMD will be followed-up 
their microcirculatory function using non-invasive method.  
 
6. Study Duration and Dates 
IRB approval date ~ 2027.12.31 
 
7. Follow-up 
After the enrollment, clinical follow-up will be done at 1, 6, 12, and 24 months.  
Research Grant: 
The Korean Cardiac Research Foundation (Seoul, Korea) 
Abbott Medical Korea (Seoul, Korea) 
 
 
 

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1. Title of Study 
Clinical Relevance of Coronary Microvascular Dysfunction Assessments in Myocardial 
Infarction with Non-Obstructive Coronary Arteries (CMD-MINOCA) 
 
2. Clinical Research Center 
Chonnam National University Hospital, Chonnam National University Medical School 
 
3. Principal Investigator, Staff, Co-researchers 
 
Name 
Center 
Position 
Principal 
investigator 
Young Joon Hong 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Research 
Manager 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Co-researchers 
Myung Ho Jeong 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Youngkeun Ahn 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Ju Han Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Doo Sun Sim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Min Chul Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Kyung Hoon Cho 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Jun Ho Ahn  
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Dae Young Hyun 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Seok Oh 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Clinical 
Professor 
Yongwhan Lim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Clinical 
Fellow 
Hee-Seung Bom 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Ho-Chun Song 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Sang-Geon Cho 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Yun-Hyeon Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 

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Jong Eun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
 
4. Research Grant 
The Korean Cardiac Research Foundation (Seoul, Korea) 
Abbott Medical Korea (Seoul, Korea) 
 
5. Background 
Approximately 5~10% of patients with acute myocardial infarction (AMI) have been reported 
as myocardial infarction with non-obstructive coronary arteries (MINOCA) in the contemporary clinical 
setting.(1,2) Although those with MINOCA have a better prognosis than with obstructive coronary artery 
disease,(2,3) several observational studies continuously reported that patients with MINOCA showed 
comparable outcomes.(4,5) One plausible explanation of this discrepancy is the heterogeneous and 
variable definition of MINOCA. Possible causes of MINOCA include plaque erosion and/or rupture, 
vasospasm, and CMD. Therefore, it is natural that heterogeneous pathophysiology of MINOCA causes 
diagnostic challenges and proper management.(2,3)  
Recently, there have been efforts for establishing the diagnosis of MINOCA and standardizing 
the systematic management according to the cause of MINOCA. According to the AHA scientific 
statement, patients who suspected MINOCA have been recommended to perform multimodality 
approach, including intravascular imaging (i.e., OCT). Although non-invasive methods, such as N-13 
ammonia positron emission tomography (PET), can be used for evaluating the CMD, invasive coronary 
physiologic assessment using pressure-temperature wire has been recommended. CMD has been 
known as a major sub cause of MINOCA, and it may be required specific treatment.  
Nevertheless, there has no data on the outcomes of MINOCA with or without CMD. Therefore, 
the aim of CMD-MINOCA sought to assess the MINOCA patients regarding the latest clinical pathway 
for diagnosis of CMD and evaluate their clinical outcomes at 2 years. 
 
 
6. Study Plans 
6.1. Study Design 
A prospective observational study. 
 
6.2. Study Timeline 
Overall study will require 5.5~6 years to complete, including 3-year of recruitment and 2-year of 
follow-up followed by close out and reporting of final results. 
 
IRB approval date ~ 2027.12.31 
Subject enrollment: 2022.02.01 ~ 2024.12.31 (roughly 3 years of enrollment) 
End of follow-up period: 2026.12.31 (2 years after the end of recruitment) 
Analysis and report: ~2027.12.31 
 

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6.3. Study Population 
About 150 patients with suspected myocardial infarction underwent invasive coronary angiography, 
but without obstructive coronary arteries will be enrolled. These patients will be evaluated by OCT, 
coronary functional assessment including coronary spasm test, invasive (FFR, CFR, IMR) and non-
invasive coronary physiologic assessment (N-13 ammonia positron emission tomography). Left 
ventricular function will be assessed using echocardiography or left ventriculogram. Cardiac magnetic 
resonance (CMR) imaging is recommended to exclude other causes for elevating cardiac enzymes, if 
necessary. Patients will be managed with cardioprotective therapies and cause-targeted therapies 
according to the latest recommendation. MINOCA patients with CMD will be followed-up their 
microcirculatory function using non-invasive method. 
 
6.4. Eligibility Criteria 
6.4.1. Inclusion Criteria 
① Subject with age ≥19 years and acute myocardial infarction 
- 
Rise and/or fall of cardiac troponin with one level >99 percentile plus ischemic 
signs/symptoms 
② Subject with non-obstructive coronary arteries 
- 
<50% diameter stenosis or 
- 
fractional flow reserve (FFR) >0.80 
③ Subject without previous history of coronary artery disease 
④ Subject who performed invasive coronary angiography within 24 hours after presentation 
⑤ Subject who eligible for invasive and non-invasive coronary physiologic assessment 
 
6.4.2. Exclusion Criteria 
① Subject with obstructive coronary arteries 
② Subject with alternate diagnosis including sepsis, pulmonary embolism, myocarditis, 
Takotsubo syndrome, spontaneous coronary dissection, and other cardiomyopathies. 
③ Subject with cardiogenic shock or cardiac arrest 
④ Subject who has non-cardiac co-morbid conditions with life expectancy <2 years 
⑤ Subject or lactating women 
⑥ Subject unable to provide consent 
 
6.5. Patient Follow-up 
Clinical follow-up will occur at 1-month, 6-month and every 12-month after enrollment. The investigator 
may conduct follow-up as telephone contacts or office visits. 
 

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7. End Points 
7.1. Primary End Point 
Major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiac death, 
any MI, any revascularization, stroke, readmission due to heart failure) at 2 years 
 
7.2. Secondary End Point 
① Cardiac death at 2 years 
② All-cause death at 2 years 
③ Any MI at 2 years 
④ Any revascularization at 2 years 
⑤ Stroke (ischemic or hemorrhagic) at 2 years 
⑥ Readmission due to heart failure at 2 years 
⑦ All-cause death, any MI, or any revascularization at 2 years 
⑧ Left ventricular ejection fraction at 2 years 
⑨ Coronary flow reserve at 6 months 
 
 
8. Patient Enrollment and Withdrawal 
8.1. Patient Enrollment 
About 150 patients with MINOCA with undergoing invasive and non-invasive coronary physiologic 
assessments will be enrolled in the study.  
 
8.2. Patient Discontinuation (Withdrawal Criteria) 
Once enrolled, each patient should remain in the study until the required follow-up period is complete. 
However, all patients have the right to withdraw at any point during the study without penalty or loss of 
benefit. The investigator may discontinue any patient at any time if medically necessary. Data obtained 
to the last follow-up will be used for the analysis. It will be documented whether or not each patient 
completed the clinical study. If the study treatment(s) or observations are discontinued in any patient, 
the reason will be recorded and the data coordinating center must be notified promptly.  
 
The following events will result in terminating the patient’s follow-up:  
• Patient voluntary withdrawal  
• Patient withdrawn by investigator as clinically indicated   
 
Every attempt should be made to collect follow-up information, except for those patients who specifically 
withdraw consent for release of such information. All procedures and laboratory specimens or tests 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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requested for evaluation after enrollment in the study should be carried out when possible. Patients will 
not be replaced in this trial. 
 
8.3. Lost to Follow-up 
Patients that do not complete the scheduled follow-up visits and have not officially withdrawn from the 
study are considered lost to follow-up; this term does not apply to missed visits. Site personnel should 
make considerable effort to locate and communicate with the patient using all available methods (eg, 
telephone, emails, and postcards). The following contact procedure is recommended at each time point:  
 
• A minimum of 2 telephone calls on different days over the specified follow-up windows should be 
recorded in the source documentation including date, time, and site personnel initials for staff 
attempting to contact the patient.  
• If these attempts are unsuccessful, a certified letter should be sent to the patient.  
 
If the patient misses 2 consecutive scheduled contact time points and the above-mentioned attempts 
at communicating with the patient are unsuccessful, the patient will be considered lost to follow-up. 
 
9. Study Protocol 
After the patient has been enrolled in the present study, the following procedures will take place. The 
schedule of events for this trial is located in section 9.3. Schedule of Measurements.  
During the index procedure and appropriate medical follow up, it is recommended that enrolling 
investigators try to adhere to current American and European recommendation for MINOCA.(2,3) 
Specific medical treatment is also strongly recommended according to the causes of MINOCA. The 
treatment strategy will be determined by the study-certified cardiologists. 
 

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9.1. Flow Chart 
 
 
9.2. Study Procedure 
(1) Coronary Provocative Spasm Test 
 
Intracoronary infusion of ergonovine was used for the provocation test. Incremental doses of 
20, 40, and 60 mcg were injected into the left coronary arteries and incremental doses of 10, 20, and 
40 mcg were injected into the right coronary artery.(6-8) ‘Definite’ positive result was defined when the 
patient was fulfilled following criteria: 1) typical ischemic angina during provocation test, 2) transient 
total or subtotal coronary artery occlusion (≥90% constriction), and 3) transient ECG changes. 
‘Suspected (or intermediate)’ result was defined as 50~90% coronary artery constriction with or without 
ischemic symptoms and/or ECG changes. Negative result was <50% constriction without ischemic 
symptoms and ECG changes.(7,8) 
 
(2) Invasive Physiologic Assessment 
 
All coronary physiologic measurements were performed after diagnostic angiography and 
provocative vasospasm test.(9) Standardized measurement protocols for resting distal coronary 
pressure (Pd) to aortic pressure (Pa), FFR, CFR, and IMR were adopted before the beginning of the 
study. The pressure sensor was positioned at the distal segment of a target vessel, and intracoronary 
nitrate (100-200 µg) was administered before each physiologic measurement. Three injections of 4mL 
room-temperature saline were performed to obtain resting mean transit time (Tmn) by using a 

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thermodilution curve. Hyperemia was induced by intravenous infusion of adenosine (140µg/kg/min) or 
intracoronary bolus injection of nicorandil (2mg). Hyperemic Pa, Pd, and hyperemic Tmn were 
measured during sustained hyperemia after the pressure curve reached a nadir point. The hyperemic 
period was recognized by a decreased Pd/Pa pattern and a left shift in the Tmn. After measurements 
were complete, the guide wire was pulled back to the guide catheter, and the presence of a pressure 
drift was checked. With a drift larger than >0.03 FFR unit, re-equalizations and repeated measurements 
were recommended. Resting Pd/Pa was calculated as the ratio of mean Pd to mean Pa. CFR was 
calculated as resting Tmn/hyperemic Tmn. FFR was calculated as the lowest average of 3 consecutive 
beats during hyperemia. IMR was calculated by Pd × Tmn during hyperemia and expressed as unit (U). 
All coronary physiologic data were collected and validated at a core laboratory (Chonnam National 
University Hospital) in a blinded fashion. 
Based on the American and European consensus, which proposed definition of CMD based 
on 1) functionally non-obstructive coronary arteries defined by a FFR>0.80 and 2) impaired coronary 
microvascular function determined by abnormal CFR and/or microvascular resistance.(2,3,10) CMD 
was defined as having depressed CFR (<2.0) and/or elevated IMR (≥25U). 
 
(3) N-13 Ammonia PET  
 
All patients were performed N-13 ammonia PET according to the standardized method. The 
details of protocol was previously reported.(11) If the patients showed CMD at baseline, those patients 
were recommended 6-month follow-up PET for assessing the effect of CMD-specific medical treatment 
after enrollment.  
 
9.3. Schedule of Measurements 
Visit 
Screening & 
Baseline 
 
Follow-Up 
1-month 
±14days 
6-month 
±30days 
12-month 
±30days 
24-month 
±30days 
SCV 
Medical/Clinical/His
tory (age, sex, risk 
factors) 
× 
 
 
 
 
 
Informed Consent 
× 
 
 
 
 
 
Enrollment1) 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
× 
 
 
 
 
 
Brief Physical 
Examination 
× 
 
 
 
 
 
Vital status 
× 
× 
× 
× 
× 
× 
Weight, height 
× 
 
 
 
 
 
12-lead ECG 
× 
×2) 
×2) 
×2) 
×2) 
×2) 
Coronary 
angiography 
× 
 
 
 
 
 
Coronary spasm 
test 
× 
 
 
 
 
 
OCT 
 
 
 
 
 
 
Invasive 
physiologic 
assessment 
(FFR, CFR, IMR) 
× 
 
 
 
 
 

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Visit 
Screening & 
Baseline 
 
Follow-Up 
1-month 
±14days 
6-month 
±30days 
12-month 
±30days 
24-month 
±30days 
SCV 
N-13 ammonia 
PET 
× 
 
× 
 
 
 
Contrast CMR 
× 
 
 
 
 
 
CBC 
× 
× 
× 
× 
× 
× 
Electrolytes, LFT 
× 
× 
× 
× 
× 
× 
Creatinine, BUN 
× 
× 
× 
× 
× 
× 
Fasting plasma TG, 
LDL, HDL, total 
cholesterol 
× 
× 
× 
× 
× 
× 
Fasting glucose 
level, HbA1c 
× 
 
 
 
 
 
CK-MB, Troponin-I 
or Troponin-T, 
proBNP 
× 
× 
× 
× 
× 
× 
Medications3) 
× 
× 
× 
× 
× 
× 
Echocardiography4) 
× 
 
 
× 
× 
× 
Clinical event5) 
 
× 
× 
× 
× 
× 
 
* Follow-up visits will allow telephone contact if clinic visits are unavailable. 
* Because all test results are collected only when performed with clinical requirements, it will not be 
recorded as a protocol violence whether or not the tests are done. 
* The last visit will be conducted within 1 month from the time when the participating center declares 
the end of follow-up. 
 
1) The subject identification code will be assigned consecutively from CNUH-0001 by the interactive 
web response system of e-CRF.  
2) Electrocardiogram at follow up visits will only be obtained when clinically indicated such as recurrent 
chest pain, ischemia, significant arrhythmias, heart failure or other signs or symptoms of clinical 
instability.  
3) Medication data included medication at baseline (before admission) and post-discharge. 
4) Echocardiography will be recorded with the closest result from the enrollment among the tests 
performed before and after the enrollment. 
5) Only end point-related clinical events (all-cause death, cardiac death, any MI, any revascularization, 
stroke, readmission due to heart failure) will be collected. 
 

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10. Measurement of study outcome variables 
10.1. Visit 1 Screening & Baseline 
(1) Medical/Clinical/ History  
Demographic information (age, sex, risk factors, cardiac history, and cardio-cerebral event) will be 
recorded at Screening& Baseline. 
Relevant medical history, including history of current disease, other pertinent cardiac history, and 
information regarding underlying diseases will be recorded at Screening & Baseline. 
(2) Informed consent 
Before any examination, they will be informed about the study aims, procedures, and possible risks 
and the Investigator will ensure that the patient or the patient’s legally acceptable representative 
has provided written informed consent. Written consent should include signature and date of legally 
authorized representatives and investigator. 
A copy of the signed consent form will be given to the subject or legal representative of the subject 
and the original will be maintained with the subject’s records.  
(3) Inclusion/Exclusion Criteria 
Review of subject eligibility. 
(4) Brief Physical Examination, Height and Weight, Vital signs 
Height, weight, blood pressure and pulse will be measured 
(5) 12-Lead ECG, Angiogram 
Electrocardiogram at follow up visits will only be obtained when clinically indicated such as 
recurrent chest pain, ischemia, significant arrhythmias, heart failure or other signs or symptoms of 
clinical instability. 
(6) Coronary Angiogram 
Angiographic data will be obtained at Screening & baseline visits.  
(7) Coronary Provocative Spasm Test  
Coronary provocative spasm test will be performed at Screening & baseline visits. 
(8) Intravascular Imaging (OCT), Invasive Physiologic Assessment 
OCT and invasive physiologic assessment data will be obtained at Screening & baseline visits.  
(9) N-13 Ammonia PET 
N-13 Ammonia PET data will be obtained at Screening & baseline visits.  
(10) Contrast Cardiac MR 
Contrast cardiac MR data will be obtained at Screening & baseline visits.  
(11) Laboratory data 
Complete blood count, liver function test, renal function test, electrolytes, fasting plasma glucose, 
lipid profile, cardiac enzyme, and proBNP will be obtained. 
(12) Concomitant Medication 
Concomitant medication will be documented at Baseline/Screening and at follow-up. Dose, route, 
unit frequency of administration, and indication for administration and dates of medication will be 
captured. 

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(13) Echocardiography 
Echocardiography data will be obtained at Screening & baseline visits.  
 
10.2. Follow-up 
After enrollment, follow-up will occur at 1-month, 6-month, 12-month and 24-month. Investigator or 
designee may conduct follow-up as office visits. 
(1) Vital Signs 
Blood pressure and heart rate will be performed 
(2) 12-Lead ECG 
ECG at follow up visits will only be obtained when clinically indicated such as recurrent chest 
pain, ischemia, significant arrhythmias, heart failure or other signs or symptoms of clinical 
instability 
(3) Concomitant medications 
(4) Clinical Event 
Information regarding occurrence of clinical events (all-cause death, cardiac death, any MI, any 
revascularization, stroke, readmission due to heart failure etc.) will be captured throughout the 
study.  
(5) N-13 Ammonia PET 
If the patients showed CMD, follow-up N-13 Ammonia PET data will be obtained at 6-month.  
 
11. Ethical Considerations and Confidentiality 
11.1. Institutional Review Board (IRB) / Ethical Committee Approval 
Institutional Review Board / Ethical Committee approval for the protocol and informed consent form will 
be obtained by the investigator prior to study participation. The approval letter must be signed by the 
IRB Chairperson or authorized representative prior to beginning the present study. No changes will be 
made to the protocol or informed consent form without appropriate approval from the IRB. According to 
IRB requirements, the investigator will report study progress until it is completed. Further, any protocol 
amendments as well as associated informed consent changes will be submitted to the IRB and written 
approval must be obtained prior to implementation. 
 
11.2. Participant Safety 
11.2.1 Elements of Informed Consent 
This study will involve patients with MINOCA and underwent intravascular imaging, invasive, and non-
invasive physiologic assessment. We anticipate enrolling 150 patients with a mean age in the 60s. 
Patients under the age of 19 will be excluded from the study for ethical and safety concerns. Women of 
child-bearing potential must have a negative serum/urine pregnancy test prior to enrollment and 
sexually-active females must use contraception for up to 2-year following the index procedure. 
Prior to collecting study data, the details of the study will be explained to the participant including: (1) 
that the study represents a prospective observational study, (2) that participation is voluntary, and there 
is no penalty for withdrawal, (3) anticipated costs to the patient for participation, (4) potential risks and 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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benefits for participation, and (5) contact information for additional concerns. Patients are informed of 
the purpose of the study, the treatment alternative, the need to be available for telephone follow-up and 
return clinic visits at regular intervals for questionnaires and/or medical tests, and of their options to 
accept or refuse entry into the study without affecting their clinical care. 
All patients or legally authorized patient representatives must sign the current IRB approved informed 
consent form prior to any study-related activities and the index procedure. Failure to obtain signed 
informed consent will render the patient ineligible for the study. The signed informed consent will be 
kept in the patient’s medical records and a copy given to the patient or legally authorized patient 
representative.  
All sources of research materials will be in the form of medical records, coronary angiograms, 
electrocardiograms and routine blood work. This material will be obtained both for routine medical care 
as well as for research purposes. 
 
11.3. Confidentiality 
The confidentiality of protected health information shall be maintained by all parties involved at all times 
throughout the clinical trial. All data should be secured against unauthorized access. Study patients will 
be assigned a unique coded identifier on eCRFs. Patient data will be protected by the use of locked 
cabinets at the Clinical Centers and use of passwords, data encryption and secure, limited access 
storage of electronic data. The DCC has programs, policies and procedures in use at all times to ensure 
the security and confidentiality of the data. The explicit issue of privacy and confidentiality is outlined in 
the Informed Consent Form.  
 
12. Study Organization 
12.1. Steering Committee and Data Safety Monitoring Board (DSMB) 
The executive steering committee comprised of the chairperson and the principal investigator 
approved the study design, protocol, and amendments issued to the DSMB and the participating 
centers. An independent DSMB will review the safety data from the study and construct 
recommendations for adverse events/serious adverse events, protocol deviation, and follow-up case 
reports. Scheduled DSMB meetings will discuss safety or compliance issues and will provide advice 
on modifying or stopping the study as needed. However, the final decisions regarding changes in the 
study protocol remain in the hands of the executive steering committee. In addition, the DSMB will 
help to conduct the trial appropriately by reviewing and reporting the cumulative investigational data 
for accuracy and completeness, ensuring protocol compliance. The DSMB will develop a consensus 
understanding of all trial end points and definitions used in the event adjudication process. 
 
12.2. Clinical Event Adjudication Committee (CEAC) 
CEAC is comprised of interventional and non-interventional cardiologists who are not participants in the 
study. The CEAC is charged with the development of specific criteria used for the categorization of 
clinical events and clinical end points in the study which are based on protocol. At the onset of the trial, 
the CEAC will establish explicit rules outlining the minimum amount of date required, and the algorithm 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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followed in order to classify a clinical event. All members of the CEAC will be blinded to the primary 
results of the trial. 
The CEAC will meet regularly to review and adjudicate all clinical events. The Committee will also 
review and rule on all deaths that occur throughout the trial. 
 
12.3. Data Coordination and Site Management 
Data coordination and site management services will be performed at the Heart Center and Biomedical 
Research Institute of Chonnam National University Hospital. 
 
13. Statistical Analysis 
13.1. Primary End point Analysis 
Primary end points (the composite rate of cardiac death, any MI, any revascularization, stroke, or 
readmission due to heart failure) will be analyzed with Kaplan-Meier survival with log-rank test.  
 
13.2. Secondary End point Analysis 
The individual components of events will be with Kaplan-Meier survival with log-rank test at 2 years 
after enrollment. 
 
Primary End point 
Statistical methods 
Time point of analysis 
MACCE (a composite of cardiac death, 
any MI, any revascularization, stroke, or 
readmission due to heart failure) 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
 
Secondary End point 
Statistical methods 
Time point of analysis 
All-cause and cardiac death 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
Any myocardial infarction  
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
Any revascularization (clinically driven 
revascularization) 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
Stroke (ischemic or hemorrhagic) 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
Re-admission due to heart failure 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
Composite of all-cause death, any MI, or 
any revascularization 
Kaplan-Meier survival esti
mates and log-rank tests 
2 years after enrollment 
Left ventricular ejection fraction 
Paired T-test 
2 years after enrollment 
Coronary flow reserve 
Paired T-test 
6 months after enrollment 
 
 

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13.3. Multivariable Analyses 
Multivariable predictors of all primary and secondary end points will be determined using multiv
ariable regression models, using either binary or Cox’s proportional hazard method. Forward or 
backward stepwise selection algorithms will be used to select predictors as needed. Baseline de
mographic and clinical variables that are predictive at the 0.1 level will be included in the mod
els. The purpose of this is two-fold: to do a covariate adjusted analysis of treatment for all pri
mary and secondary end points and to identify the risk factors which are associated with the s
tudy end points.  
 
13.4. Survival Analyses 
All time-to-event outcomes will be summarized using Kaplan-Meier survival estimates and comp
ared between groups using log-rank tests. 
 
14. Publication Policy  
Study derived data are the property of the participating investigators. However, individual investigators 
will not use study related data for any purpose other than study completion or for generating publication 
material as stated in the study site agreement without prior consent from the executive committee.  
 
14.1. Data Analysis and Release of Results 
No results will be released publicly before completion of the final analysis regarding the primary end 
point of this study. The statistical analysis will be performed according to the pre-specified analysis plan 
as described in this protocol. Any decisions on release of results will be undertaken by the Executive 
Committee after the approval of the DSMB. 
 
14.2. Review Process 
The Executive Committee will review the primary outcome data according to the pre-specified statistical 
analysis plan, and then will (i) decide on the early dissemination of the information at national and 
international scientific meetings (ii) provide the data to the publications committee which will in turn (a) 
first prepare a formal presentation to the Steering Committee members and (b) after taking under 
account the input and comments of the Steering Committee will proceed with submitting the manuscript 
to the Executive Committee. No study results will be released to the scientific or lay community without 
the approval of the Executive Committee. 
 
14.3. Authorship: Primary Outcome Paper 
Authorship of the primary outcome paper will be credited collectively to the “Investigators”. 
 
14.4. Other Study Papers, Abstracts and Presentations 
Manuscripts on Ancillary Studies or Subset Analyses should be approved by the Executive Committee. 
The investigators significantly contributing to the study, considering both the number of patients enrolled 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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by the specific investigators and their contribution to the study design will have the priority in the 
authorships of the ancillary studies or subset analysis. Each presentation of results on behalf of the 
investigators should have the approval of the Executive Committee.  
 
15. Quality Assurances, Quality Control and Clinical Monitoring 
The purposes are: 
• To ensure accuracy of study data; 
• To provide constructive feedback to site and core laboratory staff to improve and/or maintain high 
performance; 
• To document data quality for the study record. 
This section addresses of issues with respect to protocol adherence, data collection at the clinical 
centers, and interpreter variability at the core laboratories. 
 
15.1. Protocol Adherence 
There are three key components, each of which is pre-specified. The DATABASE will be programmed 
to monitor: eligibility criteria, correct treatment administration, and completion in a timely manner of all 
required data collection (no missed visits, missed studies or specimens). Eligibility criteria are also 
checked for all or a random sample of patients at every clinic site visit by auditing the patient’s 
record/worksheet. 
It is the Investigator's responsibility to ensure that there are no deviations from the protocol except in 
cases of medical emergencies, when the deviation is necessary to protect the life or physical well-being 
of the patient. The DCC will monitor these aspects of protocol adherence continually. In addition, clinic 
site personnel will have clearly specified timeframes for entry of all data and for resolution of any edit 
queries. All of these aspects of protocol can be monitored at the DCC via real-time reporting, in 
aggregate and by clinic site. 
Any of the protocol violations listed below will be reviewed immediately by the DCC and communicated 
to the principal investigator. All remedial actions will be jointly decided and, in general, implemented by 
the DCC. Any clinical site being considered for temporary or permanent termination of patient 
recruitment may be visited administratively by the monitoring group. The major protocol violations for 
this study consist of, but are not limited to, the following:  
 
Protocol Violations: 
• Eligibility not confirmed, or subject found to be ineligible; 
• Informed consent not obtained (or not obtained in a timely manner); 
• Failure to conduct protocol required clinical follow-ups and within time windows; 
 
In the event of any deviation from the protocol, the Investigator will be notified of the site’s non-
compliance. Corrective actions will be required if necessary. After any one violation, the DCC will work 
closely with the site PI to ensure further violations are avoided. Any clinic investigator, certified for the 
trial, who commits any two of the above violations will be immediately considered for suspension from 
participation in the trial and the clinic site principal investigator will also be given notice that further 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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violations by investigators at that site may result in site suspension (after an administrative site visit). If 
a site is suspended early in the trial, all patient recruitment and follow-up (except for vital status and 
safety) may be terminated. A site suspended later in the trial may still be required to complete follow-
up on those subjects already randomized, assuming that the site’s adherence to the follow-up protocol 
is satisfactory or can be remediated.  
 
15.2. Data Collection: Electronic Case Report Forms (eCRF) 
DCC personnel will determine form content, considering (1) Identify the minimal set of measurements 
for the specified variables; (2) Choose those measurements (if more than one candidate) which are 
valid and reliable and, other considerations being equal, are least burdensome to the subject; and (3) 
Develop, test and assess reliability of new measures as required. Experienced DCC staff will then order 
and format items to ensure clarity, smooth flow and to minimize missing information, using clear skip 
patterns, consistent coding for all close-ended items, and standard "footers" to identify form name, 
version date, and page number. Standard, modular data forms will be identified and developed to be 
used in both the Trial and Registry as needed.  
Case report forms will be developed by the Clinical Research Center as an online electronic form where 
investigators from individual site can access and input the data via the internet 
 
16. Event Adjudication and Reporting 
16.1. End point Adjudication 
With the exception of all-cause mortality, most end points will require clear, prespecified criteria, and 
centralized review. These end points will be captured during patient interview, supplemented by death 
certificates; hospital record abstracts and related reports (autopsy, biopsy, diagnostic output).  
From extensive experience, the following approach is proposed. First, all required documents, reports, 
hospital records will be identified, made anonymous, and copied to the DCC by clinical staff. Second, 
the DCC will check to ensure confidentiality and, if required, have the records centrally abstracted onto 
standard forms by trained DCC staff. Central abstraction in large (>30) batches is recommended to 
reduce variability and secular drift and maintain adequate accuracy and completeness. Third, centrally 
prepared forms and documents will be circulated to CEAC members for assessment. 
 
17. Regulatory Responsibilities 
17.1. Investigator Responsibilities  
The investigator is responsible for ensuring that the trial is conducted according to all signed 
agreements, the study protocol and good clinical practice (GCP) requirements. Also, each investigator 
must complete and sign the Investigator's Agreement. In signing, the investigator agrees to: 
• Sign and adhere to the Investigator Agreement 
• Participate in Investigator meetings and training sessions as scheduled by Sponsor 
• Maintain up-to-date angiographic and intravascular ultrasound equipment (if applicable) 
• Be willing to provide original cine films/CD ROMs/intravascular ultrasound videotape for analysis 
• Have access to cardiac surgery 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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• Be willing to perform and be capable of performing treatment procedures as outlined in this protocol 
• Comply with all required elements of this protocol (e.g., perform testing and follow-up as specified, 
especially during personnel transitions) and supply angiographic material suitable for quantitative 
analysis 
• Obtain written Informed Consent from each study participant before any study specific procedures 
are performed in accordance with GCP 
• Complete all electronic case report forms for completed patients visits and/or applicable events prior 
to scheduled monitoring visits 
• Adhere to all relevant Core Laboratory requirements and, 
 
 
17.2. Institutional Review Board (IRB) or Ethics Committee Approval 
The investigator must submit the study protocol to IRB or Ethics Committee and obtain their written 
approval before being allowed to conduct and participate in the study. The investigator is also 
responsible for fulfilling any conditions of approval imposed by the IRB, such as regular reporting, study 
timing, etc. The investigator will provide the Sponsor with copies of such approvals and reports. 
 
17.3. Informed Consent 
Part of the IRB/Ethics Committee approval must include approval of an Informed Consent text specific 
to the study. The investigator must administer this approved Informed Consent text to each prospective 
study patient and obtain the patient's signature on the text prior to enrollment in the study. This may be 
modified to suit the requirements of the individual site. The investigator will provide the Sponsor with a 
copy of the approved Informed Consent for his/her site. 
 
17.4. Study Coordinator 
To assure proper execution of the study protocol, each investigator must identify at least one study 
coordinator. Working with and under the authority of the investigator, the study coordinator assures that 
all study requirements are fulfilled and is the contact person at the site for all aspects of study 
administration. 
 
18. Records Retention and Reports  
To comply with ICH guidelines, the Primary Investigator will maintain all records relevant to this study 
for 2 years following study completion, unless the records are archived by an external vendor. The 
investigator shall take responsibility for maintaining adequate and accurate hard copy source 
documents of all observations and data generated as required during this study. Such documentation 
may be subject to inspection by appropriate regulatory agencies.  
 
18.1. Records 
investigator must maintain the following accurate, complete, and current records relating to the conduct 
of the investigation. (The data for some of these records may be available in computerized form from 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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the Data Coordinating Center; however the final responsibility for maintaining remains with the 
investigator.)   
• All correspondence with another investigator, an IRB, a Core Laboratory, the Sponsor, a monitor, 
Data Coordinating Center, including required reports. 
 
• Records of each subject's case history, including study-required Case Report Forms, evidence of 
informed consent, the condition of each subject upon entering and during the course of the 
investigation, relevant medical history, the results of all diagnostic testing, and the date of each 
study treatment. 
 
18.2. Reports 
Below is a list of the reports which are the investigator's responsibility to generate. The table also 
shows to whom the report is to be sent and with what frequency or within what time constraints. While 
some of these reports will be developed by or with the assistance of the Data Coordinating Center, 
the final responsibility for them rests with the investigator.  
 
Reports Required from Clinical Investigators: 
Type of Report 
Prepared by Investigator For: 
Time Constraints of 
Notification 
Patient withdrawal 
DCC 
Notify within 7 days 
Annual progress report 
EC/Principal investigator 
Submitted per 1 year 
Deviations from investigational plan 
IRB 
Per local standard. 
EC/Principal investigator 
Notify within 7 days. 
Informed consent not obtained 
DCC/IRB 
Notify within 7 days. 
Final summary report 
EC/Principal investigator 
Within 1 month. 
* DCC: Data Coordinating Center; DSMB; Data Safety Monitoring Board; EC: Executive Committee 
(Co-researchers) 
 
 

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19. Investigational Agreement  
I have read and understand the protocol (including the Investigator’s Brochure) and agree that it 
contains all the ethical, legal and scientific information necessary to conduct this trial. I will personally 
conduct the study as described and agree to adhere strictly to the attached protocol.  
I will provide copies of the protocol to all physicians, nurses and other professional personnel, who 
under my responsibility will participate in this study. I will discuss the protocol with them to assure that 
they are sufficiently informed regarding the drugs used in the study, the concurrent medications, the 
efficacy and safety parameters, and the overall execution of the study in general. I am aware that this 
protocol must be approved by the Institutional Review Board (IRB) or Ethics Committee (EC) 
responsible for such matters in the clinical study facility where the drug will be tested, prior to 
commencement of this study. I agree that clinical data entered on case report forms by the staff and I, 
can be utilized in various ways including, but not limited to, publication in peer journals, submission as 
abstracts, submission to governmental regulatory authorities and/or in combination with clinical data 
gathered from other research sites, whenever applicable. I agree to allow monitors and auditors as well 
as inspectors from regulatory authorities, full access to all medical records at the research facility for 
patients screened in the study. 
I agree to provide all patients with informed consent forms, as required by government and ICH 
regulations. I further agree to report to the DCC any adverse experiences in accordance with the terms 
of this protocol, KFDA regulation, and ICH guideline. 
 
 
 
 
 
 
 
 
 
Principal Investigator 
(print) 
 
 
Principal Investigator (signature) 
 
Date 
Institution Name/Location 
 

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20. Appendix. Definitions 
Cerebrovascular accident (CVA) or Stroke 
Sudden onset of vertigo, numbness, dysphasia, dysarthria or central neurologic deficit secondary to 
vascular lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that 
persists for > 72 hours 
 
* CVA type 
1. 
Hemorrhagic: A stroke with documentation on imaging (e.g., CT scan or MRI of hemorrhage 
in the cerebral parenchyma, or a subdural or subarachnoid hemorrhage). Evidence of 
hemorrhagic stroke obtained from lumbar puncture, neurosurgery, or autopsy can also 
confirm the diagnosis. 
2. 
Nonhemorrhagic: A focal neurological deficit that results from a thrombus or embolus (and 
not due to hemorrhage) that appears and is still partially evident for more than 24 hours 
3. 
Unknown/no imaging performed: if the type of stroke could not be determined by imaging or 
other means (from lumbar puncture, neurosurgery, or autopsy) 
 
Death  
Death defined by the Academic Research Consortium is as follows:  
All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. 
Specifically, any unexpected death even in patients with coexisting potentially fatal noncardiac disease 
(eg, cancer, infection) should be classified as cardiac. The cause of death (cardiac vs. non-cardiac) will 
be adjudicated by an independent clinical event adjudication committee 
Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output 
failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure-related 
deaths, including those related to concomitant treatment, will be classified as cardiac death.  
Vascular death: Death caused by noncoronary vascular causes, such as cerebrovascular disease, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular diseases.  
Non-cardiovascular death: Any death not covered by the above definitions, such as death caused by 
infection, malignancy, sepsis, pulmonary causes, accident, suicide, or trauma.  
 
Diabetes 
Defined as 
1. 
History of diabetes, regardless of duration of disease, need for antidiabetic agents, or  
2. 
a fasting blood glucose > 126 mg/dl. 
The type of diabetic control should be noted: 
① None 
② Diet: Diet treatment 
③ Oral: Oral agent treatment 
④ Insulin: Insulin treatment (includes any combination of insulin) 
 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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Enrolled Patient  
The point of enrollment occurs when a patient or patient’s legally authorized representative has provided 
written informed consent to participate in the trial 
 
Myocardial Infarction (MI)  
Myocardial Infarction Classification and Criteria for Diagnosis is defined by the Fourth Universal 
Definition of Myocardial Infarction (12) as follows: 
Type  
Biomarker criteria 
Time frame 
Necessary additional criteria 
Type 1: 
Spontaneous 
Rise and/or fall of cTn values 
with at least one value above 
99th percentile URL 
None 
Requiring at least one of the following:  
- Symptoms of acute myocardial ischemia 
- New ischemic ECG changes 
- Development of pathological Q waves 
- Imaging evidence of new loss of viable myocardium 
or new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology 
- Identification of a coronary thrombus by angiography 
including intracoronary imaging or by autopsy 
Type 2: 
Ischemic 
imbalance 
Rise and/or fall of cTn values 
with at least one value above 
99th percentile URL 
None 
Requiring at least one of the following:  
- Symptoms of acute myocardial ischemia 
- New ischemic ECG changes 
- Development of pathological Q waves 
- Imaging evidence of new loss of viable myocardium 
or new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology 
Type 3: 
Cardiac death 
before 
biomarkers 
drawn 
None 
None 
- Symptoms suggestive of myocardial ischemia 
accompanied by presumed new ischemic ECG 
changes or ventricular fibrillation 
- Myocardial infarction is detected by autopsy 
Type 4a: 
After 
percutaneous 
coronary 
intervention 
(PCI) 
One of the following: 
Elevation of cTn values >5 
times the 99th percentile URL 
in patients with normal 
baseline values 
Rise of postprocedural cTn 
values >20% in patients with 
cTn level are stable or falling 
Within 48 
hours after 
PCI 
Requiring at least one of the following:  
- New ischemic ECG changes 
- Development of new pathological Q waves 
- Imaging evidence of new loss of viable myocardium 
or new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology 
- Angiographic findings consistent with a procedural 
flow-limiting complication such as coronary dissection, 
occlusion of a major epicardial artery or a side branch 
occlusion/thrombus, disruption of collateral flow, or 
distal embolization 
Type 4b: 
Stent thrombosis 
Rise and/or fall of cTn values 
with at least one value above 
99th percentile URL 
Acute, 0~24 
hours; 
Subacute, 
>1~30 days; 
Late, >30 
days~1 
year; 
Very late, 
> 1 year 
Documented by angiography or autopsy using the same 
criteria utilized for type 1 myocardial infarction  
Type 4c: 
PCI restenosis 
Focal or diffuse restenosis, or 
a complex lesion associated 
with a rise and/or fall of cTn 
values above the 99th 
percentile URL 
None 
Same criteria utilized for type 1 myocardial infarction 

CMD-MINOCA_CNUH-2021-413_March 1, 2022 
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Type 5: 
After coronary 
artery bypass 
grafting (CABG) 
Elevation of cTn values >10 
times the 99th percentile URL 
in patients with normal 
baseline cTn values.  
In patients with elevated 
preprocedure cTn in whom 
cTn levels are stable (≤20% 
variation) or falling, the 
postprocedure cTn must rise 
by >20%.  
Within 48 
hours after 
CABG 
Requiring at least one of the following: 
- Development of new pathological Q waves 
- Angiographic documented new graft occlusion or new 
native coronary artery occlusion 
- Imaging evidence of new loss of viable myocardium 
or new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology. 
cTn = cardiac troponin; ECG = electrocardiogram; URL = Upper Reference Limit (defined 99th 
percentile of normal reference range).  
 
Principal Investigator  
A physician-specialist responsible for overseeing trial conduct at all sites, protocol compliance, and 
relevant KFDA regulations  
 
Repeat coronary revascularization 
See revascularization 
 
Revascularization  
Revascularization is defined by the Academic Research Consortium as follows:  
 
*Clinically indicated revascularization: A revascularization is considered clinically indicated if 
angiography at follow-up shows a percent diameter stenosis ≥ 50% (core laboratory quantitative 
coronary angiography assessment) and if one of the following occurs:  
(1) A positive history of recurrent angina pectoris, presumably related to the target vessel;  
(2) Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), 
presumably related to the target vessel;  
(3) Abnormal results of any invasive functional diagnostic test (eg, Doppler flow velocity reserve, 
fractional flow reserve);  
 
Transient Ischemic Neurological Attack (TIA)  
A sudden onset of reversible focal neurological deficits due to vascular lesions of the brain that lasts ≤ 
24 hours  
 
 

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with suspected myocardial infarction and nonobstructive coronary arteries. Circulation 2015;131:861-
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2.  Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary Diagnosis and Management of 
Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific 
Statement From the American Heart Association. Circulation 2019;139:e891-e908. 
3.  Agewall S, Beltrame JF, Reynolds HR, et al. ESC working group position paper on myocardial 
infarction with non-obstructive coronary arteries. Eur Heart J 2017;38:143-53. 
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Study. J Am Heart Assoc 2018;7. 
5.  Choo EH, Chang K, Lee KY, et al. Prognosis and Predictors of Mortality in Patients Suffering 
Myocardial Infarction With Non-Obstructive Coronary Arteries. J Am Heart Assoc 2019;8:e011990. 
6.  Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic 
Angina) (JCS 2013). Circ J 2014;78:2779-801. 
7.  Shin DI, Baek SH, Her SH, et al. The 24-Month Prognosis of Patients With Positive or Intermediate 
Results in the Intracoronary Ergonovine Provocation Test. JACC Cardiovasc Interv 2015;8:914-23. 
8.  Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for 
vasospastic angina. Eur Heart J 2017;38:2565-8. 
9.  Lee JM, Jung JH, Hwang D, et al. Coronary Flow Reserve and Microcirculatory Resistance in 
Patients With Intermediate Coronary Stenosis. J Am Coll Cardiol 2016;67:1158-69. 
10.  Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia 
with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working 
Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders 
International Study Group. Eur Heart J 2020;41:3504-20. 
11.  Kang KW, Kim JS, Cho SG, Kim J, Song HC. Acquisition of dynamic N-13 ammonia PET for 
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