A Prospective, Multi-center Clinical Trial for Evaluating the Effectiveness and Safety of Online Coronary Angiography-Derived Index of Microcirculatory Resistance (caIMR)

Study Overview
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Brief Summary
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More than 50% of patients with stable or unstable angina pectoris have no obstructive coronary arteries by angiographic visual estimation, in which coronary microvascular dysfunction (CMD) is one of the causes of myocardial ischemia and chest pain. A coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed for physiological assessment of microvascular diseases in coronary circulation. The aim of the trial is to assess diagnostic performance of caIMR, using wire-derived index of microcirculatory resistance (IMR) as the reference standard.

Detailed Description
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More than 50% of patients with stable or unstable angina pectoris have no obstructive coronary arteries by angiographic visual estimation, in which coronary microvascular dysfunction (CMD) is one of the causes of myocardial ischemia and chest pain. Presently, the index of microcirculatory resistance (IMR) measured by the pressure wire is recognized as standard for evaluating coronary microcirculatory function. A coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed for physiological assessment of microvascular diseases in coronary circulation without pressure wire, hyperemic agents, or thermodilution method. This study is a prospective, multi-center clinical trial. In the study, IMR (measured by pressure wire) will be used as a reference standard to evaluate the feasibility, accuracy and safety of caIMR measured by a non-invasive diagnosis system (FM21a) based on angiography images and aortic pressure wave. 116 patients eligible for inclusion criteria will be enrolled in the study. Both IMR and caIMR measurement will be performed in the same patient in a random order after angiography. The definitions of IMR and caIMR for coronary microcirculatory ischemia are IMR≥25 and caIMR≥25. The primary endpoint is the diagnostic accuracy of caIMR. The secondary endpoint is caIMR's sensitivity, specificity, positive predictive value, negative predictive value, ROC curve and AUC of caIMR diagnosis, and the diagnostic characteristics of caIMR at the vascular level.

Official Title
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A Prospective, Multi-center Clinical Trial for Evaluating the Effectiveness and Safety of Coronary Angiography-Derived Index of Microcirculatory Resistance Measured Online by a Coronary Functional Measurement System

Conditions
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Coronary Microvascular Dysfunction

Intervention / Treatment
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* Device: Angiography-derived Index of Microcirculatory Resistance
* Device: Pressure wire-based Index of Microcirculatory Resistance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 years and above, 80 years old and below, with no gender limitation; Patients with stable or unstable angina or suspected myocardial ischemia; Patients voluntarily participated in this clinical trial and signed an informed consent form; Target coronary with <50% diameter stenosis (DS%) by visual estimation. Exclusion Criteria: Patients with suspected acute myocardial infarction; Patients with old myocardial infarction; Patients with primary or secondary cardiomyopathy; Patients with primary or secondary heart valve disease; Patients with severe cardiac insufficiency and LVEF≤35%; Patients with renal insufficiency (eGFR<60ml/min (1.73m^2)) or patients undergoing dialysis; Patients who are allergic to iodine contrast agents, adenosine, and ATP; Patients with severe organ disease or life expectancy less than 24 months; Patients who are participating in other clinical studies of investigational drugs or devices and have not reached their primary endpoint; The patient who has other conditions that are not suitable for clinical trials; Patients with coronary artery involved in coronary fistula and myocardial bridge; The contrast media is not filled, the blood vessels are overlapped, or the target blood vessel is severely distorted, and the lesion location cannot be fully exposed, or the image quality is poor and cannot be recognized; Left main coronary artery disease and right coronary artery orifice disease; After angiography, the investigator believes that the patient cannot tolerate any of the detection methods between caIMR and IMR; The investigator believes that the patient is not suitable for clinical trials after angiography;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IMR first group<br>In this group, IMR based on pressure wire and arterial physiological detector will be measured first, and then caIMR base on angiography images and pressure sensor will be measured secondly. | Device: Angiography-derived Index of Microcirculatory Resistance<br>* caIMR will be measured by pressure sensors which are produced by Suzhou Rainmed Medical Technology Co., Ltd. caIMR is calculated based on angiography images and Hyperemic Pa estimated from resting Pa according to prespecified equation.<br>Device: Pressure wire-based Index of Microcirculatory Resistance<br>* IMR will be measured by thermodilution method with pressure wire and arterial physiological detector which are produced by St. Jude Medical. IMR = Pd ∙Tmn<br>|
| caIMR first group<br>In this group, caIMR based on angiography images and pressure sensor will be measured first, and then IMR based on pressure wire and arterial physiological detector will be measured secondly. | Device: Angiography-derived Index of Microcirculatory Resistance<br>* caIMR will be measured by pressure sensors which are produced by Suzhou Rainmed Medical Technology Co., Ltd. caIMR is calculated based on angiography images and Hyperemic Pa estimated from resting Pa according to prespecified equation.<br>Device: Pressure wire-based Index of Microcirculatory Resistance<br>* IMR will be measured by thermodilution method with pressure wire and arterial physiological detector which are produced by St. Jude Medical. IMR = Pd ∙Tmn<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy | To compare diagnostic accuracy of caIMR for coronary microvascular dysfunction with IMR as control. | Through study completion, an average of 7 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity, specificity, positive predictive value, and negative predictive value | To compare the diagnostic performance between caIMR and IMR in the patient level, with IMR as the reference standard. | Through study completion, an average of 7 months. | 
| ROC curve, and AUC | Using IMR as reference standard, draw the ROC curve of caIMR. The definition of ischemia is IMR≥25. | Through study completion, an average of 7 months. | 
| Diagnostic performance on the vessel level | The diagnostic features of caIMR compared with IMR on the vessel level. | Through study completion, an average of 7 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodynamics, Computational fluid dynamics, Index of microcirculatory resistance, Fractional flow reserve, Angiography-derived IMR