Myocardial Infarction With Non-Obstructive Coronary Arteries in the Greek Population

Acute Myocardial Infarction Clinical Trial

— MINOCA-GR  

Official title:

Myocardial Infarction With Non-Obstructive Coronary Arteries in the Greek Population: Diagnosis and Management (The MINOCA-GR Registry)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04186676
• Other study ID #: CIP_001_MINOCA_GR_27.11.2019
• Status: Completed
• Start date: January 1, 2021
• Est. completion date: January 30, 2024

Study information

• Verified date: January 2024
• Source: AHEPA University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The MINOCA-GR registry will be the first nationwide study aiming to obtain data regarding prevalence, demographics, clinical profile, previous anginal status, presence of cardiovascular risk factors, management and outcomes in patients with Myocardial Infarction with Non-Obstructive Coronary Arteries. An additional purpose of the registry is to highlight, for the first time worldwide to the best of the investigator's knowledge, the role of cardiac computed tomography angiography for risk stratification and personalized therapeutic approach in MINOCA patients.

Description:

MINOCA occurs in 5%-10% of all patients with Acute Myocardial Infarction (AMI) and these patients are younger and more often women in comparison with patients with AMI and obstructive Coronary Artery Disease (CAD). The underlying pathophysiological mechanisms are poorly understood, although several different mechanisms have been proposed, including plaque disruption, spasm, thromboembolism, dissection, microvascular dysfunction and ischemic myocardial injury attributable to supply/demand mismatch. In most, but not all, studies of prognosis, MINOCA patients had better outcomes than their AMI counterparts with coronary artery disease but faced a high risk for recurrent events, with one study finding that 25% of patients with MINOCA experience angina in the following year. Optimal patient management requires early diagnosis as well as understanding which of the myriad of mechanisms (atherosclerotic or non-atherosclerotic as well as a combination of both) may be underlying the initial diagnosis. The effects of secondary preventive treatments proven beneficial in patients with classical type I AMI are unknown in MINOCA patients; randomized clinical trials, and large observational studies, as well, evaluating different treatments in MINOCA patients do not exist. Hence, evidence-based guidelines for treatment of MINOCA are lacking. Elucidating the associations between different treatments and outcome may also increase the understanding of underlying mechanisms of MINOCA. The underlying mechanisms strongly determine prognosis and more importantly, therapeutic interventions as well as their success. Likewise, multimodality imaging could provide new insights into the management of MINOCA patients. The current research reveals the utility of Cardiac Magnetic Resonance for diagnosis and risk stratification of suspected MINOCA patients but at the same time shows how much more information is needed to further characterize risk and ultimately develop therapeutic approaches to alter its natural history. Computed tomography has a suite of strengths including diagnosis of CAD, identification of plaque characteristics, morphology and perfusion data, and even possibly delayed enhancement; its ability to detect nonobstructive coronary disease by way of visualizing not only the lumen but also plaques is very helpful in our efforts trying to understand microvascular disease, plaque erosion, and myocardial infarction with no obstructive coronary artery. Furthermore, up until recently, high-risk plaque features and lesion specific ischemia are thought to be not directly related. However, emerging evidence suggests a possible relationship between high-risk plaque features, particularly low attenuation plaque volume and positive remodeling, with lesion specific ischemia by fractional flow reserve. Such relationship is independent of degree of luminal stenosis. As a result of the above, it is obvious that Cardiac Computed Tomography Angiography (CCTA) may have a potential role in some selected patients with MINOCA, depending on their clinical picture and stability. Regarding Greece, the MINOCA-GR registry will be the first prospectively enrolling medical database of this magnitude.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 30, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients older than 18 years

2. Patients without known history of coronary artery disease

3. Patients with acute coronary syndrome with and/or without ST-segment elevation who underwent coronary angiography within 24h after onset of the disease

4. Absence of obstructive coronary atherosclerosis (normal coronary arteries or plaques <50% stenosis) based on the results of invasive coronary angiography

5. Subject has provided written informed consent

6. Subject is willing to comply with study follow-up requirements

Exclusion Criteria:

1. Patients < 18 years old at time of coronary angiography

2. Patients with a previous history of coronary artery disease and/or prior revascularization

3. Patients with serious concurrent disease and life expectancy of < 1 year

4. Patients who refuse to give written consent for participation in the study

5. In the investigator's opinion, subject will not be able to comply with the follow-up requirements

6. Subject is pregnant and/or breastfeeding or intends to become pregnant during the study

7. Subject has a known allergy to contrast agent that cannot be adequately pre-medicated

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Angina Pectoris
• Atherosclerosis
• Coronary Artery Disease
• Coronary Microvascular Disease
• Heart Diseases
• Infarction
• Ischemic Heart Disease
• Microvascular Angina
• Myocardial Infarction
• Myocardial Ischemia
• Non-Obstructive Coronary Atherosclerosis

Intervention

Other:
• MINOCA registry
Prevalence, demographics, clinical profile, anginal status, presence of cardiovascular risk factors, management and outcomes

Diagnostic Test:
• CCTA Phenotypes
Complete normal coronary arteries Diffuse non-obstructive coronary artery disease Non-obstructive high-risk plaques Myocardial bridges

Locations

Country	Name	City	State
Greece	National & Kapodistrian University of Athens, First Department of Cardiology, Hippokration Hospital	Athens
Greece	AHEPA University Hospital	Thessaloníki
Greece	General Hospital of Veroia	Véroia	Imathia

Sponsors (3)

Lead Sponsor	Collaborator
AHEPA University Hospital	New York University, University of Zurich

Country where clinical trial is conducted

Greece, 

References & Publications (10)

Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P; WG on Cardiovascular Pharmacotherapy. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143-153. doi: 10.1093/eurheartj/ehw149. No abstract available. — View Citation

Ahmadi A, Leipsic J, Ovrehus KA, Gaur S, Bagiella E, Ko B, Dey D, LaRocca G, Jensen JM, Botker HE, Achenbach S, De Bruyne B, Norgaard BL, Narula J. Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis. JACC Cardiovasc Imaging. 2018 Apr;11(4):521-530. doi: 10.1016/j.jcmg.2017.11.020. Epub 2018 Jan 5. — View Citation

Benetos G, Buechel RR, Goncalves M, Benz DC, von Felten E, Rampidis GP, Clerc OF, Messerli M, Giannopoulos AA, Gebhard C, Fuchs TA, Pazhenkottil AP, Kaufmann PA, Grani C. Coronary artery volume index: a novel CCTA-derived predictor for cardiovascular events. Int J Cardiovasc Imaging. 2020 Apr;36(4):713-722. doi: 10.1007/s10554-019-01750-2. Epub 2020 Jan 1. — View Citation

Benz DC, Benetos G, Rampidis G, von Felten E, Bakula A, Sustar A, Kudura K, Messerli M, Fuchs TA, Gebhard C, Pazhenkottil AP, Kaufmann PA, Buechel RR. Validation of deep-learning image reconstruction for coronary computed tomography angiography: Impact on noise, image quality and diagnostic accuracy. J Cardiovasc Comput Tomogr. 2020 Sep-Oct;14(5):444-451. doi: 10.1016/j.jcct.2020.01.002. Epub 2020 Jan 13. — View Citation

Grodzinsky A, Arnold SV, Gosch K, Spertus JA, Foody JM, Beltrame J, Maddox TM, Parashar S, Kosiborod M. Angina Frequency After Acute Myocardial Infarction In Patients Without Obstructive Coronary Artery Disease. Eur Heart J Qual Care Clin Outcomes. 2015;1(2):92-99. doi: 10.1093/ehjqcco/qcv014. Epub 2015 Jul 23. — View Citation

Nordenskjold AM, Lagerqvist B, Baron T, Jernberg T, Hadziosmanovic N, Reynolds HR, Tornvall P, Lindahl B. Reinfarction in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): Coronary Findings and Prognosis. Am J Med. 2019 Mar;132(3):335-346. doi: 10.1016/j.amjmed.2018.10.007. Epub 2018 Oct 25. — View Citation

Rampidis GP, Benetos G, Benz DC, Giannopoulos AA, Buechel RR. A guide for Gensini Score calculation. Atherosclerosis. 2019 Aug;287:181-183. doi: 10.1016/j.atherosclerosis.2019.05.012. Epub 2019 May 10. No abstract available. — View Citation

Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian-Engoren C, Bolger AF, Beltrame JF; American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research. 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 Apr 30;139(18):e891-e908. doi: 10.1161/CIR.0000000000000670. — View Citation

Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. No abstract available. — View Citation

van Rosendael AR, Shaw LJ, Xie JX, Dimitriu-Leen AC, Smit JM, Scholte AJ, van Werkhoven JM, Callister TQ, DeLago A, Berman DS, Hadamitzky M, Hausleiter J, Al-Mallah MH, Budoff MJ, Kaufmann PA, Raff G, Chinnaiyan K, Cademartiri F, Maffei E, Villines TC, Kim YJ, Feuchtner G, Lin FY, Jones EC, Pontone G, Andreini D, Marques H, Rubinshtein R, Achenbach S, Dunning A, Gomez M, Hindoyan N, Gransar H, Leipsic J, Narula J, Min JK, Bax JJ. Superior Risk Stratification With Coronary Computed Tomography Angiography Using a Comprehensive Atherosclerotic Risk Score. JACC Cardiovasc Imaging. 2019 Oct;12(10):1987-1997. doi: 10.1016/j.jcmg.2018.10.024. Epub 2019 Jan 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of post-MI angina [Seattle Angina Questionnaire (SAQ)]	The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Scores range from 0 to 100, where higher scores indicate better function (less physical limitation, less angina and better quality of life).	1 month
Primary	Frequency of post-MI angina [Seattle Angina Questionnaire (SAQ)]	The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Scores range from 0 to 100, where higher scores indicate better function (less physical limitation, less angina and better quality of life).	6 months
Primary	Frequency of post-MI angina [Seattle Angina Questionnaire (SAQ)]	The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Scores range from 0 to 100, where higher scores indicate better function (less physical limitation, less angina and better quality of life).	12 months
Primary	Extent of coronary atherosclerosis	Total atherosclerotic plaque volume (mm3)	15 days after the acute event
Primary	Extent of coronary atherosclerosis using Leiden CTA risk score	Leiden CTA risk score incorporates the presence, extent, severity, location, and composition of coronary artery disease (CAD). Leiden CTA score is calculated using the following approach. First, the presence of CAD is determined in each segment. When plaque is absent the score is 0. When plaque is present a score of 1.1, 1.2 or 1.3 is given according to plaque composition (calcified, noncalcified, and mixed plaque, respectively). Subsequently, this score is multiplied by a weight factor for the location of the segment in the coronary artery tree (0.5 through 6 according to vessel, proximal location and system dominance) and multiplied by a weight factor for stenosis severity (1.4 for =50% stenosis and 1.0 for stenosis <50%). The final score (range 0 to 42) is calculated by addition of the individual segment scores. Leiden CTA risk score calculator is available at: http://18.224.14.19/calcApp/.	15 days after the acute event
Primary	Extent of coronary atherosclerosis using Gensini score	The relative severity of a lesion is indicated using a score of 1 for 1-25% obstruction and doubling that number as the severity of obstruction progresses with each step in the 25-50-75-90-99-100% diameter reduction. Thus, the severity score for each lesion may range from 1 to 32. Furthermore, the score weighed according to the usual blood flow to the left ventricle in each vessel or vessel segment. A multiplying factor is applied to each lesion score based upon its location in the coronary tree, depending on the functional significance of the area supplied by that segment. If a segment is totally occluded or 99% stenosed and receiving collaterals, a collateral adjustment factor is used, and the adjustment is reduced by the extent of disease in the vessel that is the source of collaterals. The final score is the sum of all the lesion scores (Reference: Rampidis GP et al. A guide for Gensini Score calculation. Atherosclerosis 2019 August 2019;287:181-183).	15 days after the acute event
Secondary	Indexed Coronary Volume	Calculated by dividing the total coronary volume to the left ventricle (LV) mass, both derived from CCTA (mm3/gr)	15 days after the acute event
Secondary	Generic health status [Medical Outcomes Study 12-Item Short Form (SF-12)]	The Medical Outcomes Study 12-Item Short Form (SF-12) is a general health questionnaire and is computed using the scores of 12 questions ranging from 0 to 100, where 0 indicates the lowest level of health and 100 indicates the highest level of health.	12 months
Secondary	Chest-pain rehospitalization	Frequency (%) of chest-pain rehospitalization	12 months
Secondary	Hospitalization for a bleeding event	Frequency (%) of hospitalization for a bleeding event	12 months
Secondary	Frequency of occurrence of high-risk plaques	Frequency (%) of occurrence of high-risk plaque features (HU <30, remodelling index > 1.1, napkin-ring sign, spotty calcium)	15 days after the acute event
Secondary	Atrial Fibrillation	Frequency (%) of occurrence of atrial fibrillation	12 months
Secondary	Heart Failure	Frequency (%) of occurrence of acute decompensated heart failure with or without cardiogenic shock	12 months