Coronary Microcirculatory Disease and Inflammation in Patients With Chronic Coronary Syndrome and no Significant Coronary Artery Stenosis

Study Overview
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Brief Summary
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Patients with chronic coronary syndromes (CCS) diagnosed without significant lesions in invasive coronary angiography (ischemia non-obstructive coronary artery disease - INOCA) represent approximately 50% of all patients with CCS. Results of FAME study clearly showed that evaluation of coronary circulation should not be accomplished only with visual assessment in resting conditions. Current European Society of Cardiology Guidelines of diagnosis and treatment of CCS published in 2019 emphasize the necessity of performing complex coronary physiology assessment. Invasive physiological measurements and vasoreactivity provocative tests emerged as key tools to differentiate between vasospastic angina, microcirculatory angina, overlap of both conditions or non-cardiac disease. According to contemporary literature, identification of heterogeneity of patients with INOCA is crucial for determination of adequate treatment. An appropriate pharmacotherapy has a potential to improve outcomes including grade of angina, quality of life, exertional tolerance and most important - MACCE (major adverse cardiac and cardiovascular events) free survival. However, there is a lack of evidence on each of the subtypes of INOCA especially in those with signs and symptoms of vasospasm in provocative test but without visual spasm in epicardial vessels.

Official Title
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Coronary Microcirculatory Disease and Inflammation in Patients With Chronic Coronary Syndrome and no Significant Coronary Artery Stenosis. MOSAIC-COR Study.

Conditions
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Coronary Artery Disease, Ischemia and No Obstructive Coronary Arteries, Ischemic Heart Disease, Microvascular Angina, Vasospastic Angina

Intervention / Treatment
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* Diagnostic Test: Comprehensive functional diagnostics of coronary circulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed chronic coronary syndrome CCS ≥ 2. Evidence of myocardial ischemia (positive result of non-invasive stress test). Informed consent. Age at least 18 years. Exclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1. Coronary microcirculatory disease<br> | Diagnostic Test: Comprehensive functional diagnostics of coronary circulation<br>* Comprehensive functional diagnostics of coronary circulation in patients with INOCA (ischemia and no obstructive coronary arteries) including: echocardiography with assessment of diastolic function flow-mediated dilation of brachial artery coronary angiography functional coronary assessment (RFR, FFR, IMR, CFR, dp/dt, Tau) provocative test with acetylcholine (registration of symptoms, ECG and angiographic spasm) laboratory tests (full blood count, serum creatinine level, eGFR, lipidogram, serum CRP/hsCRP level, serum NT-proBNP level) serum level of inflammatory cytokines and chemokines<br>|
| 2. Epicardial vasospastic angina<br> | Diagnostic Test: Comprehensive functional diagnostics of coronary circulation<br>* Comprehensive functional diagnostics of coronary circulation in patients with INOCA (ischemia and no obstructive coronary arteries) including: echocardiography with assessment of diastolic function flow-mediated dilation of brachial artery coronary angiography functional coronary assessment (RFR, FFR, IMR, CFR, dp/dt, Tau) provocative test with acetylcholine (registration of symptoms, ECG and angiographic spasm) laboratory tests (full blood count, serum creatinine level, eGFR, lipidogram, serum CRP/hsCRP level, serum NT-proBNP level) serum level of inflammatory cytokines and chemokines<br>|
| 3. Microvessel vasospastic angina<br> | Diagnostic Test: Comprehensive functional diagnostics of coronary circulation<br>* Comprehensive functional diagnostics of coronary circulation in patients with INOCA (ischemia and no obstructive coronary arteries) including: echocardiography with assessment of diastolic function flow-mediated dilation of brachial artery coronary angiography functional coronary assessment (RFR, FFR, IMR, CFR, dp/dt, Tau) provocative test with acetylcholine (registration of symptoms, ECG and angiographic spasm) laboratory tests (full blood count, serum creatinine level, eGFR, lipidogram, serum CRP/hsCRP level, serum NT-proBNP level) serum level of inflammatory cytokines and chemokines<br>|
| 4. Non-cardiac disorder<br> | Diagnostic Test: Comprehensive functional diagnostics of coronary circulation<br>* Comprehensive functional diagnostics of coronary circulation in patients with INOCA (ischemia and no obstructive coronary arteries) including: echocardiography with assessment of diastolic function flow-mediated dilation of brachial artery coronary angiography functional coronary assessment (RFR, FFR, IMR, CFR, dp/dt, Tau) provocative test with acetylcholine (registration of symptoms, ECG and angiographic spasm) laboratory tests (full blood count, serum creatinine level, eGFR, lipidogram, serum CRP/hsCRP level, serum NT-proBNP level) serum level of inflammatory cytokines and chemokines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokines (serum levels) |  | baseline | 
| Diastolic Disfunction parameters in ECHO |  | baseline, 12- and 24-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACCE occurrence |  | baseline, 12- and 24-month observation | 
| Hospitalization any |  | baseline, 12- and 24-month observation | 
| symptoms intensity and quality of life (questionnaires) |  | baseline, 12- and 24-month observation | 
| FMD |  | baseline, 12- and 24-month observation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery disease, ischemia and no obstructive coronary arteries, ischemic heart disease, microvascular angina, vasospastic angina, coronary microvascular dysfunction, coronary microcirculation, endothelial dysfunction