A Validation Study of Nitroglycerin Induced Acute Drop of Pd/Pa (NTG-Pd/Pa) in Clinical Practice

Study Overview
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Brief Summary
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Hyperemia with adenosine was an elemental process in FFR examination. Adenosine injection will induce some discomfort, and increase cost expenditure. Nitroglycerine will induce an acute drop of Pd/Pa, and this lowest Pd/Pa was determined as NTG-Pd/Pa. NTG-Pd/Pa has a linear relationship with FFR value and has a good diagnostic accuracy to predict FFR≤0.80 in our recent study. There is only one prospective study report on the relationship between NTG-Pd/Pa and FFR. In this study, we aim to evaluate the safety of NTG-Pd/Pa, the repeatability and dose-response of this novel index. Furthermore, we will investigate the diagnostic accuracy of NTG-Pd/Pa, with FFR≤0.8 and Resting full-cycle ratio≤0.89 as ischemic threshold respectively.

Detailed Description
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Fractional flow reserve (FFR) is defined as the ratio of mean distal pressure (distal to the target lesion, Pd）to mean proximal pressure (aortic pressure, Pa) in the coronary artery(Pd/Pa) while the maximal hyperemic flow is achieved. Nowadays, FFR-guided PCI is highly recommended for the assessment of physiologic ischemia in intermediate coronary lesions. However, hyperemia with adenosine was an elemental process in FFR examination. Adenosine injection will induce some discomfort, and increase cost expenditure. Based on the clinical and physiologic outcome study, a lot of non-hyperemic indexes had been proposed, and adenosine injection could be waived. Whereas, these novel physiologic indexes are limited to the proprietary software of each vendor, curtailing clinical application. Intracoronary nitroglycerin injection was needed before each FFR assessment. Nitroglycerine will induce an acute drop of Pd/Pa, and this lowest Pd/Pa was determined as NTG-Pd/Pa. NTG-Pd/Pa has a linear relationship with FFR value and has a good diagnostic accuracy to predict FFR≤0.80 in our recent study. There is only one prospective study report on the relationship between NTG-Pd/Pa and FFR. In this study, we aim to evaluate the safety of NTG-Pd/Pa, the repeatability and dose-response of this novel index. Furthermore, we will investigate the diagnostic accuracy of NTG-Pd/Pa, with FFR≤0.8 and Resting full-cycle ratio≤0.89 as ischemic threshold respectively.

Official Title
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A Validation Study of Nitroglycerin Induced Acute Drop of Pd/Pa (NTG-Pd/Pa) in Clinical Practice

Conditions
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Hypotension Symptomatic, Ischemic Heart Disease

Intervention / Treatment
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* Diagnostic Test: Nitroglycerine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for FFR examination Exclusion Criteria: Hypersensitivity to adenosine or nitroglycerine Severe Valvular aortic stenosis Resting heart rate less than 50 beats per minutes Systolic blood pressure less than 100 mmHg or diastolic blood pressure less than 40 mmHg exposure to PDE-5 inhibitors within 48 hours. Recent intracranial hemorrhage or brain injury

Ages Eligible for Study
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Minimum Age: 21 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 |
| --- | --- |
| Repeatability group 1<br>The patient with systolic blood pressure above 120 mmHg, who will receive a repeatability test with 200mcg, then another 100 mcg nitroglycerine injection, with a time interval of 3 minutes apart. | Diagnostic Test: Nitroglycerine<br>* We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.<br>|
| Repeatability group 2<br>The patient with systolic blood pressure above 120 mmHg, who will receive a repeatability test with 200mcg, then another 200 mcg nitroglycerine injection, with a time interval of 3 minutes apart. | Diagnostic Test: Nitroglycerine<br>* We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.<br>|
| Repeatability group 3<br>The patient with systolic blood pressure above 120 mmHg, who will receive a repeatability test with 200mcg, then another 300 mcg nitroglycerine injection, with a time interval of 3 minutes apart. | Diagnostic Test: Nitroglycerine<br>* We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.<br>|
| pressure-recommended doses of NTG<br>The patient with systolic blood pressure above 100 mmHg, who will receive the nitroglycerine injection with the dose of recommendation, adjusted according to the blood pressure. | Diagnostic Test: Nitroglycerine<br>* We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The repeatability and dose response of NTG-Pd/Pa | Comparing the difference of NTG-Pd/Pa value after various dosage of nitroglycerine injection in the same coronary lesion | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac event | MACE including target lesion failure, target vessel failure, target vessel-related myocardial infarction, and cardiac death | 2 years | 
| Diagnostic accuracy of NTG-Pd/Pa 1 | Investigate the diagnostic accuracy of NTG-Pd/Pa, with FFR≤0.8 as ischemic threshold | 30 minutes | 
| Diagnostic accuracy of NTG-Pd/Pa 2 | Investigate the diagnostic accuracy of NTG-Pd/Pa, with RFR≤0.89 as ischemic threshold | 30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NTG-Pd/Pa, Fractional flow reserve, adenosine