Southeastern Europe Microcirculation Registry
Conditions: Angina, Microvascular, Coronary Microvascular Dysfunction, Coronary Artery Disease
Sponsor: Institute for Cardiovascular Diseases Dedinje

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SATURATION   
(SoutheAsT eUrope microciRculATION)  registry 
Study protocol version 1.3 
Date 03/21/2024 
 
 
 
 
 
 
 
 
 

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Introduction 
Ischemic heart disease is a leading cause of morbidity and mortality. While cardiologists 
are focused on discrete, visible stenoses of coronary arteries there is increasing awareness of 
the importance of microcirculation in causing angina. Microvascular bed is comprised of vessels 
smaller than 500 microns in diameter. Their network is much greater than the network of 
epicardial vessels and serves important functions such as regulation of myocardial blood flow 
and cellular metabolism.  
Myocardial ischemia is usually caused by significant stenosis of the epicardial coronary 
artery. However, a study that included over 400000 coronary angiograms found that in over 50% 
of cases there was no obstructive coronary artery disease (CAD) or stenoses were less than 
50%1. It was not until recently that the importance of coronary microcirculation in causing 
symptoms and signs of ischemia has been appreciated. Coronary microvascular dysfunction 
(CMD) has an important effect in determining patient outcomes in a number of clinical settings.  
 
 
 Invasive pressure measurements with coronary wire for measurement of pressure and 
temperature is a well-established technique in evaluating coronary artery stenoses. Using the 
same pressure wire, technological advances have allowed estimation of coronary artery flow 
using principles of thermodilution. This method has been validated in an experimental model, 
and also in humans, providing an excellent invasive tool in assessing coronary flow reserve 
(CFR). To assess microcirculation independently, index of microcirculatory resistance (IMR) has 
been developed. Assuming negligible coronary venous pressure, the resistance of coronary 
circulation can be calculated as distal coronary pressure (Pd) divided by absolute coronary flow, 
the latter being proportional to the inverse of mean hyperaemic transit time and thus allowing for 
calculation of IMR. IMR has been shown to be independent of epicardial coronary artery 
stenosis. It has been demonstrated that IMR can have predictive value in patients with ST 
elevation myocardial infarction. A distinct clinical entity known as ischemia with no obstructive 
coronary arteries (INOCA) has been developed to encompass the patients with clear angina 
symptoms, but without visible epicardial coronary artery stenoses.  
The region of Southeast Europe has its specificities regarding morbidity and mortality from 
cardiovascular diseases. It includes transitional countries as well as Mediterranean countries 
where CV diseases are one of the major causes of morbidity. In this registry we wanted to 
evaluate the practice of patient selection for evaluation of microcirculatory bed, including 
indications, ischemia tests done, medications prescribed, procedural aspects of microcirculation 

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evaluation and treatment changes after testing. Also, we want to have an insight regarding 
adverse cardiovascular events in these patients after invasive coronary physiology.   
 
Aims 
 
Aim 1: To assess the regional practice of patient selection for assessment of invasive coronary 
physiology including vasospasm testing and estimation of microcirculation by measuring CFR 
and IMR.  
Aim 2: To assess regional procedural aspects of invasive coronary physiology – how 
aforementioned parameters are measured in the catheterization laboratory 
Aim 3: To assess patients’ treatment and treatment changes after invasive coronary physiology 
measurements at each follow up visit. 
Aim 4: To compare the cardiovascular outcomes and additional procedures (stress testing, 
angiography, etc.) done after comprehensive invasive coronary physiology evaluation.  
 
 
Research design and methods 
 
The study would be prospective, observational and will include patients that underwent 
invasive coronary physiology with Coroflow Coroventis Cardiovascular System software using 
Pressure Wire X (Abbott, Abbott Park, IL, US). Participants will undergo routine coronary 
angiography as well as comprehensive physiologic assessment coronary thermodilution to 
evaluate for coronary microvascular dysfunction (CMD) and possibly with provocative testing for 
diagnosis of vasospastic angina (VSA). The study will include centres in Southeast Europe that 
have obtained Coroventis Coroflow Cardiovascular system and have performed invasive 
coronary physiology procedures.  
 
Inclusion Criteria 
- 
Adults of both sexes older than 18 years 
- 
Angina symptoms or angina equivalent 
- 
Referred to  Cath lab for evaluation of CAD  
- 
Invasive physiology testing performed (microcirculation testing +/- vasospasm testing) 
using Coroflow Coroventis Cardiovascular system (Abbott, Abbott Park, IL, US) 

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Exclusion Criteria 
- 
persons under the age of 18 
- 
pregnant of nursing 
- 
no coronary physiology measurements performed 
 
Outcomes 
Outcomes will be evaluated every 6 months for 2 years via direct patient contact by research 
staff or at follow up visits. 
- 
Primary outcomes:  
o all-cause death and non-fatal MI 
o composite MACE: all-cause death, non-fatal MI, coronary revascularization, 
hospitalization for cardiovascular causes (acute coronary syndrome, heart failure, 
angina, repeated coronary angiography) 
- 
Secondary outcomes: all-cause death, cardiovascular death, MI, coronary 
revascularization, stroke, hospitalization for heart failure, hospitalization for acute 
coronary syndrome, repeated coronary angiography 
- 
Patient-centred outcomes 
o Freedom from angina (SAQ questionnaire) 
o Quality of life using EQ-5D-5L questionnaire  
o Follow up non-invasive ischemia testing (if performed) 
 
Study protocol must be approved by the institutional Ethics committee prior to enrolling 
patients in the study. Patients will be enrolled in the study by the investigators familiar with the 
study protocol. Patients will be enrolled after invasive coronary physiology procedure. Patients 
will sign informed consent (IC) form provided and explained by the study team member. After 
signing IC form patients will be eligible for entering the study. Patients’ treatment is responsibility 
of the treating physician and the participation in the study will not alter patients’ treatment.  
After enrolling the patients in the study, they will be treated according to local protocols and 
current recommendations for INOCA. 
The patients’ data will be stored in an online database managed by Castor EDC organization. 
Every centre will have the opportunity to access the database and enter patients’ data into it. 
The data collected for a patient in the study will be the following: 

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Enrollment 
1. Demographics 
Date of birth 
Date of invasive physiology assessment 
Sex 
Race 
Height  
Weight 
BMI 
Site of enrollment 
2. Risk factors 
Comorbidities 
Recent lab studies 
Smoking status 
Family history of premature coronary disease 
3. Previous cardiovascular events 
Myocardial infarction (ever and in the past 30 days) 
TIA/stroke 
Other cardiovascular diseases 
Prior angiographies 
Prior PCIs 
NYHA class 
CCS class 
4. Medications 
5. Baseline echocardiography 
6. Non-invasive ischemia testing 
7. Seattle Angina Questionnaire 
8. EQ-5D-5L 

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9. Coronary angiography findings 
Presence of obstructive coronary artery disease (CAD) 
Coronary vessel(s) with obstructive CAD 
Previous PCI procedure in coronary vessel(s) 
10. Invasive physiology procedure 
Primary indication 
Access site 
Radial sheath medications 
Withholding the calcium channel blocker, beta blocker, nitrate 
Vasospastic angina testing (which artery, what test, result) 
Microvascular angina testing (which artery, CFR, IMR, RRR, FFR, Pd, Pa and all transit 
times) 
Complications 
 
Follow up visit 
1. Demographics 
2. Events (MACE) 
3. Medications 
4. SAQ 
5. EQ-5D-5L 
6. New non-invasive ischemia testing 
 
Author correspondence 
Dr Ivan Ilic 
Department of interventional cardiology 
Cardiology clinic, Institute for cardiovascular diseases Dedinje,  
Heroja Milana Tepica 1, 11040 Belgrade, Serbia 
Email: Ivan1ilic@yahoo.com, phone +381(11) 3601-700; cell +381(64) 137-4455