Diagnostic and Prognostic Value of Angiography-derived IMR

Study Overview
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Brief Summary
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The importance of the microvasculature in determining clinical outcomes has been highlighted in patients with coronary artery disease (CAD). For patients with stable CAD, despite the success of percutaneous coronary intervention (PCI) in relieving a stenosis in the epicardial coronary artery, microvascular dysfunction may preclude sufficient coronary flow and myocardial perfusion, possibly leading to worse clinical outcome. With the technical development of computational fluid dynamics, angiographic derivation of index of Index of Microcirculatory Resistance (IMR) without pressure wire, hyperemic agents, or theromdilution method is available as a potential alternative for pressure wire-derived IMR. In this regard, the current study will evaluate diagnostic implication of angiography-derived IMR and its prognostic implication after PCI in patients with stable CAD.

Detailed Description
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The importance of the microvasculature in determining clinical outcomes has been highlighted in patients with coronary artery disease (CAD). For patients with stable CAD, despite the success of percutaneous coronary intervention (PCI) in relieving a stenosis in the epicardial coronary artery, microvascular dysfunction may preclude sufficient coronary flow and myocardial perfusion, possibly leading to worse clinical outcome. With the technical development of computational fluid dynamics, angiographic derivation of IMR without pressure wire, hyperemic agents, or theromdilution method is available as a potential alternative for pressure wire-derived IMR. In this regard, the current study will evaluate diagnostic implication of angiography-derived IMR and its prognostic implication after PCI in patients with stable CAD. This study cohorts consist with 3 separate cohort: first, internal diagnostic accuracy cohort, which will evaluate correlation between angiography-derived IMR and hyperemic microvascular resistance calculated using Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography (CZT-SPECT)-derived myocardial blood flow and invasively measured pressure data. For this, 53 consecutive patients with available CZT-SPECT within 3 months of measuring FFR in the left anterior descending coronary artery will be evaluated. Second: external diagnostic cohort, in which diagnostic accuracy of angiography-derived IMR will be assessed in patients with ischemia and no obstructive coronary artery disease (INOCA) and normal controls, whose results were previously published (J Nucl Cardiol. 2020 Sep 30. doi: 10.1007/s12350-020-02252-8.) Among this cohort, 45 patients with no obstructive CAD and normal CZT-SPECT perfusion imaging will be regarded as normal controls, in 35 INOCA patients, vessels with normal corresponding perfusion territory will be regarded as internal control. Third, prognosis cohort, in which 138 consecutive CAD patients received PCI with available angiograms and who were suitable for angiographic fractional flow reserve and IMR measurement will be analyzed. Primary clinical outcome will be cardiac death or congestive heart failure at 2 years from index procedure. Secondary outcome will be any myocardial infarction, ischemia-driven revascularization, definite or probable stent thrombosis, congestive heart failure admission and angina pectoris admission at 2 years from index procedure.

Official Title
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Diagnostic Value of Angiography-derived Index of Microvascular Resistance in Coronary Artery Disease Patients and Its Prognostic Implication After Percutaneous Coronary Intervention

Conditions
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Coronary Microvascular Dysfunction, Myocardial Ischemia

Intervention / Treatment
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* Device: Angiography-drived Index of Microcirculatory Resistance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CAD patients with available CZT-SPECT within 3 months of measuring FFR in the left anterior descending coronary artery (Cohort 1) INOCA patients and normal controls confirmed by CZT-SPECT and angiography (Cohort 2) Stable CAD patients received PCI (Cohort 3) analyzable angiograms at the index procedure Exclusion Criteria: Previous coronary artery bypass grafting Chronic total occlusion patients limited image quality of coronary angiography Insufficient angiographic project for TIMI frame count Severe tortuosity of target vessel No optimal projection for reconstruction

Ages Eligible for Study
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Minimum Age: 19 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 |
| --- | --- |
| Internal Diagnostic Accuracy Cohort<br>Consecutive patients with available CZT-SPECT within 3 months of measuring FFR in the left anterior descending coronary artery. In these patients, correlation between angiography-derived IMR and hyperemic microvascular resistance will be assessed. | Device: Angiography-drived Index of Microcirculatory Resistance<br>* From coronary angiographic images, angiography-derived IMR will be calculated based on mathematical calculation. Angiography-derived IMR = (hyperemic Pa x angiography-derived FFR) x (vessel length / {K x V diastole}). Hyperemic Pa will be estimated from resting Pa according to prespecified equation.<br>* Other names: CaIMR;|
| External Diagnostic Accuracy Cohort<br>Patients are subgroup of previously published study (J Nucl Cardiol. 2020 Sep 30. doi: 10.1007/s12350-020-02252-8.), INOCA patients and normal controls confirmed by CZT-SPECT and angiography will be included for the assessment of angiography-derived IMR in diagnosing microvascular dysfunction. | Device: Angiography-drived Index of Microcirculatory Resistance<br>* From coronary angiographic images, angiography-derived IMR will be calculated based on mathematical calculation. Angiography-derived IMR = (hyperemic Pa x angiography-derived FFR) x (vessel length / {K x V diastole}). Hyperemic Pa will be estimated from resting Pa according to prespecified equation.<br>* Other names: CaIMR;|
| Prognosis Cohort<br>Prognosis cohort, in which angiography-derived IMR will be measured in the target vessel after successful revascularization. Those patients have follow-up data after 2 years from index procedure. | Device: Angiography-drived Index of Microcirculatory Resistance<br>* From coronary angiographic images, angiography-derived IMR will be calculated based on mathematical calculation. Angiography-derived IMR = (hyperemic Pa x angiography-derived FFR) x (vessel length / {K x V diastole}). Hyperemic Pa will be estimated from resting Pa according to prespecified equation.<br>* Other names: CaIMR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy | Correlation between angiography-derived IMR and HMR | at the index procedure | 
| Major adverse cardiac events | Major adverse cardiac events (MACE), including cardiac death and readmission due to heart failure. | at 28 months from index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of cardiac death, readmission due to heart failure and angina | A composite of cardiac death, readmission due to heart failure and angina | at 28 months from index procedure | 
| A composite of cardiac death, readmission due to heart failure, spontaneous MI, target vessel revascularization and angina | A composite of cardiac death, readmission due to heart failure, spontaneous MI, target vessel revascularization and angina. | at 28 months from index procedure | 
| Cardiac death | Cardiac death | at 28 months from index procedure | 
| Readmission due to heart failure | Readmission due to heart failure | at 28 months from index procedure | 
| Spontaneous MI | Spontaneous MI | at 28 months from index procedure | 
| Target vessel revascularization | Target vessel revascularization | at 28 months from index procedure | 
| Readmission due to angina | Readmission due to angina | at 28 months from index procedure |