Application of regadenoson in echocardiography

Abstract

The invention relates to application of regadenoson in preparation of a medicine for detecting heart ischemic diseases in echocardiography. Preferably, the echocardiogram is selected from one or more of a load echocardiogram, a cardiac angiography echocardiogram, a transthoracic Doppler echocardiogram and a two-dimensional spot tracking echocardiogram. Preferably, the cardiac ischemic diseases are selected from one or more of non-obstructive cardiac ischemic diseases and obstructive cardiac ischemic diseases. By applying the medicine provided by the invention, the diagnosis of diseases of patients has good accuracy, sensitivity, specificity and safety.

Description

[0001] The present invention claims priority of the prior application entitled “Application of Reganosen in Echocardiography” and application number 202410400391.X filed on April 3, 2024. The contents of the above-mentioned prior application are incorporated into this text by introduction. Technical Field

[0002] The present invention relates to the field of biomedicine, and in particular to the application of Reganosane in echocardiography. Background Art

[0003] Ischemic heart disease is a common cardiovascular disease with a high mortality rate. Causes of ischemic heart disease include coronary artery blockage or lesions, or coronary artery microvascular dysfunction, etc.

[0004] Heart disease can be detected and identified through cardiac imaging methods. For example, coronary angiography (CAG) is considered the "gold standard" for diagnosing coronary heart disease. However, clinical findings show that the accuracy of diagnosing heart disease only through indicators such as the degree of coronary artery stenosis in coronary angiography is limited because there is no clear correspondence between whether the coronary artery is stenotic and whether the heart is ischemic. Clinically, coronary heart disease is usually diagnosed when the coronary artery stenosis is ≥70% detected by CAG, and interventional surgery is required. Patients with stenosis but no myocardial ischemia are ignored, resulting in over-medicalization. At the same time, myocardial ischemia is not examined for patients without stenosis, delaying the treatment of patients with myocardial ischemia without stenosis. Studies in the past 20 years have shown that coronary microvascular dysfunction (CMD) and coronary artery spasm (CAS) are important mechanisms leading to myocardial ischemia. However, since it is currently impossible to directly evaluate the coronary microvasculature, the symptoms caused by its dysfunction are often mistaken for non-cardiac factors, leading to misdiagnosis and insufficient treatment. Clinically, this disease with ischemic chest pain symptoms and objective evidence of myocardial ischemia, but no obstructive coronary artery stenosis found by CAG is defined as ischemic non-obstructive coronary artery disease (INOCA). Therefore, choosing appropriate cardiac imaging methods to detect whether the patient has cardiac ischemia is conducive to a more complete understanding of the patient's heart condition, especially timely detection of INOCA and early treatment.

[0005] Generally, in the process of detecting ischemic heart disease, it is often necessary to compare the blood flow at rest with the blood flow during cardiac exercise. However, many patients are unable to exercise due to physical reasons or the exercise load is difficult to reach the expected goal. Drug stress test is an effective supplementary method. Therefore, during the test, it is beneficial to use drugs that increase the patient's blood flow in the short term but do not cause peripheral vasodilation. Commonly used coronary vasodilators are adenosine (such as Adenoscan), which binds to subtypes A1 and A 2A , A 2B The effect is produced by interaction with the adenosine receptor family of A3, among which A 2A Receptors play an important role in regulating myocardial oxygen consumption and coronary blood flow. 2A Side effects caused by interactions with other receptors, such as reduced cardiac conductivity caused by binding to the A1 receptor and bronchial constriction caused by binding to the A3 receptor, limit the clinical use of adenosine. On the other hand, in order to obtain imaging data that can evaluate cardiac function, its short half-life requires continuous and large-scale drug administration to patients in clinical practice. This increases the probability of side effects in patients when using adenosine for echocardiography testing. At the same time, these side effects and other factors will have an uncontrollable impact on the test results, reducing the accuracy and sensitivity of the test results.

[0006] REGADENOSON (313348-27-5) is a known 2A Receptor agonists have the advantages of fewer side effects and longer half-life compared to vasodilators such as adenosine. For example, the document "Robert C. Hendel et al, Journal of the American College of Cardiology, Vol. 46, No. 11, 2005: 2069-75" mentioned that Reganosane has the advantages of good patient tolerance, fewer side effects, less impact on blood pressure, and simpler administration compared to adenosine and dipyridamole.

[0007] In addition, some clinical studies have shown that Reganosin has a stable application performance compared with adenosine in patients with mild to moderate asthma and moderate to severe COPD, such as "Janet Wei, et al, Cardiovasc Disord Med. 2019; 2019:.doi:10.31487 / j.cdm.2019.01.01." The literature mentioned that adenosine is the default vasodilator, and if the patient has a history of asthma, Reganosin is used. It can also be seen from the above literature that Reganosin is a suitable vasodilator, and it is meaningful to study the detection effect of Reganosin in the sub-field of nuclear medicine imaging to improve the accuracy of disease diagnosis. Summary of the invention

[0008] In view of this, the present invention provides a method for detecting cardiac ischemic diseases using Reganosine in echocardiography, which has better safety and patient compliance than adenosine when used in echocardiography, and has good accuracy and sensitivity for diagnosing cardiac ischemic diseases compared to adenosine.

[0009] The present invention provides the following technical solutions:

[0010] The use of Reganosin in the preparation of drugs for detecting cardiac ischemic diseases in echocardiography.

[0011] Preferably, the echocardiogram is selected from one or more of stress echocardiogram, myocardial contrast echocardiogram, transthoracic Doppler echocardiogram, and two-dimensional speckle tracking echocardiogram.

[0012] Preferably, the ischemic heart disease is selected from non-obstructive ischemic heart disease and / or obstructive ischemic heart disease.

[0013] Preferably, the ischemic heart disease is selected from non-obstructive ischemic heart disease.

[0014] Preferably, the non-obstructive cardiac ischemic disease is selected from one or more of ischemia with non-obstructive coronary artery disease, coronary microvascular dysfunction, non-coronary obstructive coronary heart disease, chronic coronary syndrome, non-coronary obstructive myocardial ischemia or coronary microvascular dysfunction myocardial ischemia.

[0015] Preferably, the ischemic heart disease is selected from obstructive ischemic heart disease.

[0016] Preferably, the obstructive ischemic heart disease is selected from one or more of coronary artery obstructive myocardial ischemia and coronary artery obstructive coronary heart disease.

[0017] Preferably, the concentration of Reganosane in the drug is 0.01-0.2 mg / mL, preferably 0.08 mg / mL.

[0018] Through the above technical solution, the present invention has the following beneficial technical effects:

[0019] 1. The use of Reganosin during the patient testing process has few side effects and high safety, thereby reducing inaccurate test results caused by factors such as uncontrollable emergencies of the patient's physiological state and improving the sensitivity and accuracy of the test;

[0020] 2. Reganosine can detect various cardiac function indicators of patients in echocardiography, and has better clinical diagnostic accuracy and sensitivity than adenosine;

[0021] 3. Reganosant is widely used as a vasodilator in echocardiography and can be used to diagnose various types of cardiac ischemic diseases, especially non-obstructive cardiac ischemic diseases that cannot be diagnosed by CAG;

[0022] The test results of Reganosin in echocardiography have been proven to have important clinical guidance significance through experiments, and can guide clinical graded medication and therapeutic intervention measures. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 : Schematic diagram of experimental process one and experimental process two of the present invention.

[0024] Figure 2 : Three schematic diagrams of the experimental process of the present invention. DETAILED DESCRIPTION

[0025] In the following description, a large number of specific details are provided to provide a more thorough understanding of the present invention. However, it is apparent to those skilled in the art that the present invention can be implemented without one or more of these details. In other examples, in order to avoid confusion with the present invention, some technical features well known in the art are not described.

[0026] The implementation of the present invention is described in detail below in conjunction with the definitions of terms:

[0027] The present invention provides the use of Reganosane in preparing a medicine for detecting cardiac ischemic diseases in echocardiography.

[0028] IRegano

[0029] Regadenoson (313348-27-5) of the present invention is an A 2A Receptor agonists have fewer side effects and a longer half-life (33-108 minutes) and can be used as coronary vasodilators.

[0030] In a specific embodiment, the Reganosane of the present invention is Reganosane injection.

[0031] In a specific embodiment, the concentration of the reganoxan of the present invention in the drug is 0.01-2 mg / mL, 0.02-1.5 mg / mL, or 0.05-1 mg / mL.

[0032] II Echocardiography

[0033] The drug prepared by using the reganoxan of the present invention plays a role in echocardiography. The echocardiography of the present invention can be one or more of stress echocardiography (SE), myocardial contrast echocardiography (MCE), transthoracic Doppler echocardiography (TTDE), and two-dimensional speckle tracking echocardiography (2D-STE).

[0034] The above detection methods can provide comprehensive information on various cardiac function indicators of patients, including anatomical information, ventricular wall motion information, ventricular function parameters and hemodynamic data.

[0035] In one embodiment, the echocardiogram of the present invention is a pharmacological stress echocardiogram.

[0036] In one embodiment, Reganosant is injected into the patient within 2-30 seconds, 5-20 seconds, 8-12 seconds, or 10 seconds before the start of the stress test of the stress echocardiogram.

[0037] In one embodiment, 0.1-20 mL, 1-10 mL, 3-7 mL or 5 ml of Reganosant is injected into the patient within 2-30 seconds, 5-20 seconds, 8-12 seconds or 10 seconds before the start of the stress test of the stress echocardiogram.

[0038] In one embodiment, the stress test of stress echocardiography lasts for 5-60min, 10-50min, 20-40min, 25-35min or about 30min. In one embodiment, dynamic images of the patient are collected by stress echocardiography, including resting echocardiogram before drug administration and stress echocardiogram images after drug administration.

[0039] In one embodiment, the patient's ventricular wall motion, blood flow, ventricular contractility, etc. are obtained through image analysis.

[0040] III Ischemic heart disease

[0041] The ischemic heart disease of the present invention is a heart disease caused by myocardial ischemia and hypoxia due to changes in cardiac circulation.

[0042] In one embodiment, the cardiac ischemic disease of the present invention is selected from at least one of coronary heart disease, coronary artery disease, angina pectoris, myocardial infarction, myocardial infarction, vasospasm, vascular microcirculatory dysfunction, myocardial ischemia, and chronic ischemic heart disease.

[0043] In one embodiment, the cardiac ischemic disease of the present invention particularly refers to a cardiac ischemic disease caused by non-coronary artery stenosis.

[0044] In one embodiment, the cardiac ischemic disease of the present invention can also be selected from one or more of coronary artery obstructive myocardial ischemia and coronary artery obstructive coronary heart disease.

[0045] In one embodiment, the cardiac ischemic disease of the present invention is selected from one or more of ischemia with non-obstructive coronary artery disease (INOCA), coronary microvascular dysfunction (CMD), chronic coronary syndrome, non-coronary obstructive coronary heart disease, non-coronary obstructive myocardial ischemia or coronary microvascular dysfunction myocardial ischemia.

[0046] Hereinafter, the present invention will be further described in detail by way of examples.

[0047] Purpose of the test

[0048] Through clinical trials targeting unspecified populations, we validated the efficacy of Reganosin in detecting cardiac ischemia by echocardiography. The accuracy, sensitivity, specificity and safety of sexually transmitted diseases.

[0049] Experimental drugs

[0050] The test group was Reganosan Injection: Nanjing Ruike Health Biopharmaceutical Co., Ltd., with a specification of 5mL:0.4mg and a storage condition of a closed environment not exceeding 25°C.

[0051] The control group was adenosine injection: Penglai Nuokang Pharmaceutical Co., Ltd., with a specification of 30mL:90mg and a storage condition of a closed environment at 10-30℃.

[0052] Test process

[0053] The test flow diagram of the present invention is as follows Figure 1 Disease diagnosis and testing methods: coronary angiography (CAG), stress echocardiography (SE) and myocardial perfusion imaging (MPI).

[0054] Efficacy indicators

[0055] After obtaining the diagnostic results of stress echocardiography and myocardial perfusion imaging (MPI, using single-photon computed tomography, i.e., SPECT) for Reganosine injection / adenosine injection, the accuracy, sensitivity, and specificity of the test results of the two drugs can be calculated according to the four-cell table shown in Table 1:

[0056] Table 1

[0057]

[0058] When the MPI result is positive and the SE diagnosis result is also positive, the “case” is determined to be a true positive;

[0059] When the MPI result is negative and the SE diagnosis result is positive, the “case” is judged to be a false positive;

[0060] When the MPI result is positive and the SE diagnosis result is negative, this “case” is judged to be a false negative;

[0061] When the MPI result is negative and the SE diagnosis result is negative, this “case” is determined to be a true negative.

[0062] Calculation formula:

[0063] Accuracy = (a+d) / (a+b+c+d);

[0064] Sensitivity = a / (a+c);

[0065] Specificity = d / (b+d).

[0066] Example 1 Screening of test subjects

[0067] The inclusion criteria for the subjects were as follows: aged 18 to 75 years old, regardless of gender; patients with clinically confirmed or suspected coronary heart disease, typical or definite angina attacks, or stable chest pain symptoms.

[0068] Example 2 Clinical trial process 1

[0069] This study adopted a multicenter, randomized, double-crossover design.

[0070] After the patients passed the screening examination, they were randomly divided into the Reganosin injection-adenosine injection group (RA group) or the adenosine injection-Reganosin injection group (AR group). After the previous stage of administration, they entered the next stage of administration after a washout period. If the subjects had completed coronary angiography (CAG) before the first administration, they did not need to repeat stage 3.

[0071] The dosing regimen is as follows:

[0072] Table 2

[0073]

[0074] in:

[0075] Dosage and administration of Reganoxan: Inject 0.4 mg / 5 mL into a peripheral vein within 10 seconds, followed by immediate flushing of the line with 5 mL of normal saline.

[0076] Adenosine dosage: infusion dose 140μg / kg / min, medication time 6min, total dose 0.84mg / kg. It needs to be calculated according to each patient's weight and infused using a microinjection pump.

[0077] 1. Pre-drug inspection

[0078] The subjects' routine physiological conditions and medical history were observed and evaluated within 14 days before the first administration to ensure that their physical condition was suitable for completing this experiment.

[0079] 2. Study Visits

[0080] This study conducted approximately 4 research visits in total, and the specific process was as follows.

[0081] Phase 1

[0082] The subjects were randomly divided into groups after fasting for 4 hours before the stress test.

[0083] Vital sign detection: Vital signs (body temperature, blood pressure, heart rate, respiratory rate) were measured within 30 minutes before drug administration (reganosine for the RA group and adenosine for the AR group) and 30 minutes after the start of SE loading. Blood pressure and heart rate were checked 3 minutes, 6 minutes, and 10 minutes after the start of loading drug administration.

[0084] Check 12-ECG: Check 12-ECG within 30 minutes before drug administration and 3 minutes, 6 minutes, 10 minutes, and 30 minutes after the start of loading.

[0085] During the trial, continuous electrocardiogram monitoring was performed and stress echocardiography images were collected (including resting echocardiography before drug administration and stress echocardiography after drug administration).

[0086] Phase 2

[0087] After a 1-day washout period and safety check, the second dosing cycle began. The dosing and testing methods were the same as in phase 1, with adenosine administered to the RA group and reganoxan administered to the AR group.

[0088] Stage 3 Coronary Angiography Tests

[0089] Coronary angiography was performed according to the subjects' conditions.

[0090] Phase 4 Trial End-of-Trial Review

[0091] After the trial, the subjects were subjected to the following examinations: urine pregnancy / blood pregnancy test, vital signs, physical examination, 12-ECG, and the subjects' adverse events and concomitant medications were recorded.

[0092] Example 3 Clinical trial process 2

[0093] Since SPECT stress myocardial perfusion imaging is of excellent value in diagnosing ischemic heart disease and has a guiding role, as recorded in the literature (Zhang Yuan, Ren Xiaohui, Gu Chao. [J]. Hainan Medicine, 2021, 32(20): 2667-2670.). Therefore, during the test process of Example 2 above, when the results of Reganosin injection and adenosine injection SE are inconsistent, Reganosin injection drug stress myocardial perfusion imaging (MPI) is added to detect cardiac blood flow, that is, SPECT examination. Using the SPECT examination results as the standard, the accuracy, sensitivity and specificity of Reganosin SE and adenosine SE in diagnosing myocardial ischemia are evaluated.

[0094] Experimental drug: the aforementioned Reganosin injection.

[0095] Test process:

[0096] After the subjects underwent routine vital sign testing, a drug loading test was performed: 5 ml of injection (containing 0.4 mg of Reganosant) was quickly injected into the patient's vein (about 10 seconds), and the patient was immediately flushed with 5 ml of normal saline after the injection.

[0097] Then, the imaging agent 99Tcm-MIBI was immediately injected intravenously from another intravenous channel of the patient. The patient was then given routine ECG monitoring. Myocardial tomography was performed 60 to 90 minutes after the injection of the imaging agent, and images were collected.

[0098] Example 4 Test results of Example 2 and Example 3

[0099] The sample size of this study consisted of 24 cases, including 15 males and 9 females, with an average age of 56 years.

[0100] Positive criteria for stress echocardiography in diagnosing cardiac ischemic disease may include any of the following (in Table 3, if at least one of the following conditions occurs in the regorafenib group or adenosine group, it is "+"):

[0101] ① New abnormal motion of ≥2 adjacent ventricular wall segments during stress testing, i.e., decreased motion, absent motion, or paradoxical motion;

[0102] ② During the stress test, the abnormal degree of ventricular wall motion shown by resting echocardiography increases, that is, the originally weakened segment becomes motionless or paradoxical after load, and the originally motionless segment becomes paradoxical after load;

[0103] ③ Left ventricular global longitudinal strain (LVGLS) or ejection fraction decreased or did not increase compared with the baseline state;

[0104] ④Coronary blood flow reserve (CFVR) <2.5;

[0105] ⑤Left ventricular contractility reserve (LVCR) ≤ 1.1;

[0106] ⑥ Other clinically significant manifestations of myocardial ischemia.

[0107] The positive criteria for CAG detection of coronary heart disease: stenosis of the left or right coronary artery main branches (right coronary artery, left anterior descending artery, left circumflex artery, left main trunk) or their first-level branches is ≥50%, which is judged as positive coronary angiography, and the results in Table 3 show "+".

[0108] Positive criteria for MPI examination of myocardial ischemia: drug stress MPI shows sparse or defective radioactivity distribution in one or more segments of the left ventricle in two or more consecutive levels, indicating a positive result. The results in Table 3 show "+".

[0109] The results of this experiment are shown in the following table.

[0110] Table 3

[0111] serial number Reganosin(R)SE Results Adenosine (A) SE results CAG Results MPI Results 1 + - + + 2 + - + - 3 + + - / 4 + - + + 5 + NA (off) - / 6 + + - / 7 + + - / 8 + - - + 9 + - + + 10 + + - / 11 + + - / 12 + - - + 13 + + + / 14 - - + / 15 + + + / 16 + + + / 17 + + + / 18 - + + - 19 + + + / 20 + + + / 21 + + + / 22 - - + / 23 - + + + 24 - - - /

[0112] Note: “+” represents positive, “-” represents negative, and “ / ” represents not tested.

[0113] The accuracy, sensitivity and specificity of reganosine and adenosine for diagnosing myocardial ischemia were calculated according to the above formulas. The results are shown in Table 4 below:

[0114] Table 4

[0115] sample accuracy Sensitivity Specificity Regano 91％ 94％ 80％ Adenosine 74％ 72％ 80％

[0116] Example 5 Clinical trial process three

[0117] This experiment was set up to further verify the effect of Reganosin and adenosine in the diagnosis of non-obstructive cardiac ischemic diseases by echocardiography. This study adopted a multicenter, randomized, double-crossover design. The experimental process included clinical trial process one and Reganosin injection drug stress myocardial perfusion imaging (MPI) to detect cardiac blood flow, that is, SPECT examination. Taking the MPI results as the standard, the accuracy of Reganosin SE and adenosine SE results in diagnosing cardiac ischemic diseases, especially non-obstructive cardiac ischemic diseases, was evaluated. The experimental drugs and experimental process were the same as clinical trial process two. First, samples with negative CAG results and positive MPI results in the study samples were screened out. Among them, negative CAG indicated that the patient's coronary artery did not have obvious stenosis, and the MPI results were positive at the same time, indicating that the patient had a problem of cardiac ischemia. Such patients are likely to suffer from non-obstructive cardiac ischemic diseases. The echocardiograms of such samples were analyzed in more detail, and the differences in the test results of Reganosin and adenosine (the specific positive indicator types detected) were compared to determine the effectiveness and sensitivity of Reganosin and adenosine in the diagnosis of non-obstructive cardiac ischemic diseases by stress echocardiography. The higher the proportion of positive tests that can be detected, the better the effectiveness; and the more positive indicator types that can be detected, the higher the sensitivity.

[0118] The sample size of this study was 98 cases, including 59 males and 39 females, with an average age of 55. A total of 20 groups of samples with negative CAG results and positive MPI results were selected, and the results are shown in Table 5 below.

[0119] Table 5

[0120]

[0121] Based on the above results, the effectiveness and sensitivity of Reganosin and adenosine for the diagnosis of non-obstructive ischemic heart disease are calculated. Among them, "effectiveness" corresponds to the proportion of positive test results, and in the effective samples (at least one drug detected positive), "sensitivity" corresponds to the proportion of more positive indicators detected for the same patient compared to another drug. For example, patient 15 was tested positive for Reganosin but adenosine was not, and Reganosin had better effectiveness for the test of this patient; for another example, patient 17 was tested three positive indicators by Reganosin but adenosine was only detected two, and Reganosin had better sensitivity for this patient. The results of patients 1-20 in Table 5 are summarized as shown in Table 6 below.

[0122] Table 6

[0123] sample Effectiveness Sensitivity Regano 60％ 33.3％ Adenosine 50％ 25％

[0124] Example 6 Safety Test

[0125] During the aforementioned clinical trials, adverse reactions in patients were evaluated according to the following criteria:

[0126] Grade 1: Mild; asymptomatic or mild; only clinical or diagnostic observations; no treatment required.

[0127] Grade 2: Moderate; minor, local or noninvasive treatment required; age-appropriate limitation in instrumental activities of daily living.

[0128] Grade 3: Severe or medically significant but not immediately life-threatening; resulting in hospitalization or prolonged hospitalization; causing disability; limiting self-care activities of daily living.

[0129] The test results are shown in Table 7 below.

[0130] Table 7

[0131] level Related to R (incidence) Related to A (incidence) Level 1 17 / 24(70.8％) 16 / 24(66.7％) Level 2 1 / 24(4.2％) 2 / 24(8.3％) Level 3 - 1 / 24(4.2％) total 18 / 24(75.0％) 19 / 24(79.2％)

[0132] Among the 24 cases in this study, there were 18 adverse reactions related to Reganosant, of which 17 were grade 1 and 1 was grade 2; there were 19 adverse reactions related to adenosine, of which 16 were grade 1, 2 were grade 2, and 1 was grade 3. The incidence of adverse reactions to Reganosant was 75.0%; the incidence of adverse reactions to adenosine was 79.2%.

[0133] Result analysis:

[0134] From the clinical trial process one and two, it can be seen that the results of Table 3 and Table 4 show that when the CAG result is "+", the SE result is "+" accounting for 66.7%, indicating that the patient has coronary artery stenosis and ischemia; when the CAG result is "+", the SE result is "-" accounting for 33.3%, indicating that the patient has coronary artery stenosis but no myocardial ischemia; when the CAG result is "-", the SE result is "+" accounting for 87.5%, indicating that the patient has no coronary artery stenosis, but myocardial ischemia. It can be seen that the results of diagnosing heart disease based solely on CAG results cannot fully reflect the patient's heart condition, especially whether the patient suffers from ischemic heart disease.

[0135] Through the auxiliary examination of Reganoshen echocardiography, patients can be classified: if the SE result and CAG result are both "+", it indicates that the patient has coronary artery stenosis accompanied by ischemia and needs intervention. In the case of CAG result "+", if the degree of stenosis is low (stenosis ≤ 70%) and the SE result is "-", no intervention is required. If the degree of stenosis is high (stenosis ≥ 70%), direct intervention will be performed in the past clinically, but after adopting the method of the present invention, if the SE result is "-", such patients may not necessarily need interventional treatment, and need to be comprehensively judged based on the severity of symptoms, degree of stenosis, location of stenosis, blood indicators, other examination indicators, etc. Treatment methods; conversely, if the CAG result is "-", the clinic may not think that the patient has heart disease and needs intervention in the past, but according to the method of the present invention, if the patient's SE result is "+", it means that the patient has ischemic heart disease of non-coronary artery obstruction type, and further examinations may be required, such as coronary artery spasm stimulation test and / or microvascular function test, and appropriate intervention will be given according to the examination results.

[0136] From the clinical trial process three, as shown in Tables 5 and 6, for samples to be diagnosed as non-obstructive ischemic heart disease, the overall results of the effectiveness and sensitivity of Reganosant are better than those of adenosine, indicating that Reganosant is of great significance for the clinical diagnosis of SE in non-obstructive ischemic heart disease.

[0137] From the safety test, as shown in Table 7, compared with adenosine, the incidence and degree of adverse reactions of Reganosin are lower, and it has better safety of use. In terms of clinical use time, Reganosin is given once, the examination time is short, and patients have better compliance. The above-mentioned adverse reactions to adenosine, especially serious adverse reactions, are likely to be one of the reasons for the decrease in the accuracy and sensitivity of the test results.

[0138] It can be seen that the method of the present invention is suitable for diagnosing ischemic heart diseases, especially for diagnosing ischemic heart diseases of non-coronary artery obstruction type, and can provide more accurate treatment for patients with heart diseases in clinical practice. Furthermore, from the comparison of efficacy index results, it can be seen that compared with adenosine, Reganosine has higher detection accuracy, sensitivity and specificity.

[0139] In addition, for clinical use, the stress test of Reganosin stress echocardiography lasts about 30 minutes; the stress test of adenosine stress echocardiography lasts about 60 minutes; and the MPI test lasts about 2 days. Since most tertiary hospitals are overcrowded with patients, a one-time simple administration of Reganosin is conducive to controlling the examination time and is friendly to the examination departments with crowded patients.

[0140] In the above embodiments, all technical solutions under the concept of the present invention belong to the protection scope of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications without departing from the principle of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. The use of Reganosin in the preparation of drugs for detecting cardiac ischemic diseases in echocardiography.

2. The use according to claim 1, wherein the echocardiogram is selected from one or more of stress echocardiogram, myocardial contrast echocardiogram, transthoracic Doppler echocardiogram, and two-dimensional speckle tracking echocardiogram.

3. The use according to any one of claims 1-2, wherein the ischemic heart disease is non-obstructive ischemic heart disease.

4. The use according to claim 3, wherein the non-obstructive heart ischemic disease is selected from one or more of ischemia with non-obstructive coronary artery disease, coronary microvascular dysfunction, non-coronary obstructive coronary heart disease, chronic coronary syndrome, non-coronary obstructive myocardial ischemia or coronary microvascular dysfunction myocardial ischemia.

5. The use according to any one of claims 1-2, wherein the ischemic heart disease is obstructive ischemic heart disease.

6. The use according to claim 5, wherein the obstructive heart ischemic disease is selected from one or more of coronary artery obstructive myocardial ischemia and coronary artery obstructive coronary heart disease.

7. According to the use according to any one of claims 1-2, the Reganosin is an injection, and preferably the concentration of Reganosin in the drug is 0.01-2 mg / mL.

8. According to the concentration of claim 7, the concentration of Reganoxan in the drug is 0.05-1 mg / mL, preferably 0.08 mg / mL.

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