Coronary blood flow determination device and coronary blood flow measurement device

Abstract

Provided is a coronary blood flow measurement device capable of acquiring significant information for determination of ischemic heart disease caused by stenosis or the like in a coronary blood vessel on the basis of measurement of a blood flow (coronary blood flow) in a blood vessel (coronary blood vessel) of a heart. This coronary blood flow measurement device (10) includes: a CFR acquisition means (12) for acquiring a calculated value of coronary blood flow reserve (CFR); and a cCFR calculation means (14) for obtaining a blood pressure correction CFR (cCFR) by converting the calculated value of the coronary blood flow reserve (CFR) acquired by the CFR acquisition means into a value under a condition of an arbitrary specific value (ΔPs) of an arteriovenous pressure difference (ΔP(a-v)) by using a linear relationship between a maximum hyperemia coronary blood flow (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)).

Description

Coronary blood flow determination device and coronary blood flow measurement device

[0001] The present invention relates to a coronary blood flow measurement device capable of obtaining significant information for determining ischemic heart disease caused by stenosis or the like in the cardiovascular system based on the measurement of the blood flow (coronary blood flow) in the blood vessels (cardiovascular system) of the heart.

[0002] The cardiovascular system is the blood vessels responsible for blood circulation to the myocardium, and the coronary arteries consist of epicardial coronary arteries visible to the naked eye and microvessels visible under a microscope. When stenosis / occlusion due to arteriosclerosis or microcirculation disorder occurs in such coronary arteries and the coronary arteries cannot perform their proper functions, the amount of blood containing sufficient oxygen and nutrients cannot be supplied to the myocardium, leading to ischemic heart diseases typified by angina pectoris and myocardial infarction.

[0003] For ischemic heart diseases, examinations are required to take appropriate measures and treatments. Physiologically, the pathological conditions of such ischemic heart diseases are indicated by a decrease in the blood flow in the epicardial coronary arteries (low FFR value) or a decrease in the autoregulation function of coronary blood flow (low CFR value).

[0004] By the way, as described in the background art section of Japanese Patent Application Publication No. 2017-510412 (Patent Document 1), conventionally, calculated values such as CFR and FFR have been used as indicators for determining ischemic heart disease. However, as will be described later, it has been difficult to accurately determine ischemic heart disease using these indicators.

[0005] Also, even when ischemic heart disease is recognized based on calculated values such as CFR and FFR, it has not been possible to objectively show the degree of abnormality in each of the epicardial coronary arteries and microvessels in the coronary arteries consisting of the epicardial coronary arteries and microvessels.

[0006] Japanese Patent Application Publication No. 2017-510412

[0007] The present invention was made against the background of the circumstances described above, and includes the invention relating to improved CFR according to the first to third aspects described below, the invention relating to improved coronary blood flow rate Q according to the fourth to eighth aspects, and the invention relating to ER and MR according to the ninth to twelfth aspects. All of these inventions relate to a coronary blood flow measuring device that can obtain meaningful information for determining ischemic heart disease caused by cardiovascular stenosis, microcirculatory disorders, etc., based on the measurement of the amount of blood flow (coronary blood flow) in the blood vessels (cardiovascular system) of the heart.

[0008] The inventions relating to the first to third embodiments described below concern improved CFR. CFR, also known as "coronary flow reserve," is an index known to indicate how many times the coronary blood flow at maximum congestion can be increased compared to the resting state. A small CFR value (for example, less than 2) indicates that the function of supplying sufficient blood flow is impaired due to the presence of significant stenosis or microcirculatory impairment. However, the inventors have found that conventionally used CFR values ​​have large variations due to measurement conditions, etc., and therefore, it is difficult to accurately determine, for example, the presence or absence of ischemic heart disease. Herein, one of the objectives of the inventions relating to the first to third embodiments described below is to present a newly improved calculated CFR value that suppresses variations due to measurement conditions, etc., compared to conventionally used CFR, and enables more accurate determination of, for example, the presence or absence of ischemic heart disease.

[0009] The inventions relating to the fourth to eighth aspects described below concern improved coronary blood flow rate Q, etc. CFV can be referred to as "total coronary blood flow rate" as a sub-concept of coronary blood flow rate Q, as will be described later. That is, Q (hyp.) is the "maximum coronary blood flow rate" indicating the extent of cardiovascular coronary blood flow at maximum congestion, and CFV (hyp.) can be referred to as the "maximum total coronary blood flow rate" indicating the extent of total coronary blood flow in the entire heart at maximum congestion. However, in practice, the use of CFV (hyp.) values ​​for assessment in relation to ischemic heart disease and the like has not been actively utilized. The reason for this is thought to be that, due to differences in hemodynamics among individual patients, there are large individual differences in the obtained values, making it difficult to compare and evaluate them using the same index value (CFV (hyp.) value). In this context, the inventors have conducted extensive research to effectively utilize CFV (hyp.) values ​​in the diagnosis of ischemic heart disease and other conditions. As a result, they have discovered, from a new perspective, the possibility of using CFV (hyp.) and the like for more generalized quantitative evaluation. One of the objectives of the inventions described in the fourth to eighth aspects below is to present improved calculated values ​​of CFV and the like that enable accurate diagnosis of conditions such as ischemic heart disease.

[0010] The inventions relating to the ninth to twelfth aspects described below concern ER and MR. Both ER and MR are cardiovascular resistances; the former, ER, is called "coronary artery resistance," while the latter, MR, is called "cardiac microcirculation resistance." However, conventionally, it has not been possible to objectively and quantitatively measure ER and MR, making it difficult to determine the extent of stenosis or other abnormalities in the epicardial coronary arteries and microvessels when ischemic heart disease is observed in the cardiovascular system. Conventionally, methods have been proposed to determine the presence or absence of abnormalities in ER and MR using the aforementioned CFR and FFR values, for example, by considering statistical information. Specifically, cases where the FFR is 0.8 or higher but the CFR is less than 2.0 can generally be inferred to be cases of stenosis or other abnormalities in the MR (microvessels), suggesting that microcirculatory dysfunction is dominant. On the other hand, cases where the FFR is 0.8 or lower but the CFR is 2.0 or higher can be inferred to be cases of stenosis or other abnormalities in the ER (epidermal coronary artery), suggesting that epicardial coronary artery stenosis is dominant. However, as mentioned above, there is a large variation in CFR values ​​depending on the measurement conditions, and the FFR value is generally an estimate of the percentage increase in blood flow due to the release of stenosis, based on blood pressure measurements at the upstream and downstream sites of stenosis in the coronary arteries, and does not represent coronary blood flow itself. Therefore, the accuracy of determining the presence or absence of ER and MR abnormalities is insufficient, and it has not been possible to objectively and quantitatively determine ER and MR. Herein, as a result of the inventors' further considerations, the inventions relating to the 9th to 12th aspects described below aim to provide a new technology that can more accurately infer the presence and location of cardiovascular abnormalities by utilizing measurement values ​​that can be obtained as physical measurements.

[0011] The following describes preferred embodiments for understanding the present invention. However, each embodiment described below is illustrative and can be combined with others as appropriate. Furthermore, the multiple components described in each embodiment can be recognized and adopted as independently as possible, and can be combined with any component described in another embodiment as appropriate. Thus, the present invention is not limited to the embodiments described below, and various other embodiments can be realized.

[0012] [i] An invention relating to improved CFR: A coronary blood flow measuring device characterized by having a CFR acquisition means for acquiring a calculated value of coronary blood flow reserve (CFR), and a cCFR calculation means for using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)) to convert the calculated value of coronary blood flow reserve (CFR) acquired by the CFR acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) to obtain a blood pressure corrected CFR (cCFR).

[0013] This embodiment proposes a new cCFR value, which is an improved version of the conventional CFR, an index known to indicate how many times the coronary blood flow at maximum congestion can be increased compared to the resting state, by applying a specific correction calculation.

[0014] In other words, microvessels, which are peripheral blood vessels of the coronary arteries, have a function (self-regulating function) that autonomously changes their resistance in response to fluctuations in the arteriovenous pressure gradient (ΔP(a-v)) to control the resting coronary blood flow (Q(rest)) to be approximately constant within the physiological range. Therefore, the coronary blood flow Q(rest) measured at rest does not have a linear relationship with the arteriovenous pressure gradient (ΔP(a-v)). On the other hand, the coronary blood flow (Q(hyp.)) measured at maximum hyperemia is measured with the autonomous resistance changes of the microvessels removed by the administration of drugs such as vasodilators, so a linear relationship is established between it and the arteriovenous pressure gradient (ΔP(a-v)), and the vascular resistance value can be calculated from the slope of the linear graph of coronary blood flow Q(hyp.) and arteriovenous pressure gradient (ΔP(a-v)). The same is true for total coronary blood flow (CFV(rest), CFV(hyp.)), which is the blood flow of the entire heart. It can be assumed that all blood pressure-related values ​​(Pa, Pv, ΔP) remain unchanged between the resting state and the state of maximum congestion.

[0015] Specifically, a schematic diagram is shown in Figure 1. In Figure 1, coronary blood flow is represented by the generalized symbol Q, taking into consideration its application to the inventions of the fourth to eighth embodiments described later. In the invention of this embodiment, this symbol Q (Q(rest), Q(hyp.)) can be understood as CFV (CFV(rest), CFV(hyp.)), which is the total coronary blood flow of the entire heart. As shown in Figure 1, in CASE #1 and CASE #2, the CFR value obtained from the measured values ​​is approximately the same as Q(hyp.) / Q(rest). However, in reality, CASE #1 has a large margin of coronary blood flow at maximum congestion compared to CASE #2. This is one example of how blood flow dynamics can differ even if the CFR value is the same, and it can be said that there are limitations to conventional determination methods.

[0016] In this embodiment, we focus on the linear relationship between total coronary blood flow (CFV) (hyp.) and the arteriovenous pressure difference (ΔP(a-v)) at maximum hyperemia, and obtain a blood pressure-corrected CFR value (cCFR value) by converting the CFR value under the condition of a predetermined arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)). By using such a cCFR value, the influence of fluctuations in the arteriovenous pressure difference (ΔP(a-v)) is reduced or avoided, enabling more accurate determination.

[0017] A second aspect of the invention relating to improved CFR is a coronary blood flow measuring device relating to the first aspect of the improved CFR, as follows: A coronary blood flow measuring device wherein the calculated value of coronary blood flow reserve (CFR) obtained by the CFR acquisition means is a calculated value obtained based on measured values ​​of coronary blood flow (Q) within the range of 80 to 120 mmHg for the arteriovenous pressure difference (ΔP(a-v)), and an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) is set to a specific value within the range of 80 to 120 mmHg.

[0018] According to this embodiment, coronary blood flow (Q(rest), Q(hyp.)) for calculating CFR is measured within a physiological range in which the resting coronary blood flow (Q(rest)) is controlled to be approximately constant by the self-regulating function of blood flow by microvessels, and an arbitrary specific value (ΔPs) of the arteriovenous pressure gradient (ΔP(a-v)) is set as an evaluation criterion within this physiological range. This makes it possible to more efficiently reduce or avoid the influence on the CFR value caused by differences in blood pressure among patients when measuring coronary blood flow (Q).

[0019] A third aspect of the invention relating to improved CFR is as follows: A coronary blood flow determination device characterized by comprising: a CFR acquisition means for acquiring a calculated value of coronary flow reserve (CFR); a cCFR calculation means for obtaining a blood pressure corrected CFR (cCFR) by converting the calculated value of coronary flow reserve (CFR) acquired by the CFR acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)); and an ischemic heart disease determination means for determining the presence or absence of ischemic heart disease using the value of the blood pressure corrected CFR (cCFR) obtained by the cCFR calculation means.

[0020] According to this embodiment, as described in the invention described in the first or second embodiment relating to the improved CFR, a blood pressure-corrected CFR (cCFR) value is used in which the influence of fluctuations in the arteriovenous pressure gradient (ΔP(a-v)) is reduced or avoided compared to the conventional CFR value. This makes it possible to make a more accurate determination of the presence and degree of ischemic heart disease.

[0021] [ii] Invention relating to improved coronary blood flow rate Q, etc. The first aspect of the invention relating to improved coronary blood flow rate Q, etc. is as follows: A coronary blood flow rate measuring device characterized by having a Q(hyp.) acquisition means for acquiring a measured value of the coronary blood flow rate (Q(hyp.)) at maximum hyperemia, and a cQ(hyp.) calculation means for using the linear relationship between the coronary blood flow rate (Q(hyp.)) at maximum hyperemia and the arteriovenous pressure difference (ΔP(a-v)) to convert the measured value of the coronary blood flow rate (Q(hyp.)) at maximum hyperemia acquired by the Q(hyp.) acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) to obtain a blood pressure corrected Q(hyp.) (cQ(hyp.)).

[0022] This embodiment proposes a new cCFV value, which is an improved version of CFV (Coronatal Flow Volume) that represents the total coronary blood flow of the entire heart, achieved through a specific correction calculation. In this specification, the coronary blood flow in any vascular site (the coronary blood flow of individual vessels such as the right coronary artery, the left anterior descending coronary artery, and the left circumflex coronary artery) is generalized and referred to as coronary blood flow: Q. To distinguish the sum of the coronary blood flows of individual cardiovascular vessels, i.e., the total blood flow of the entire heart, from this coronary blood flow: Q, it is referred to as total coronary blood flow: CFV (Coronary Flow Volume). Furthermore, the total coronary blood flow when a state of maximum congestion is artificially created using vasodilators, etc., is defined as the total coronary blood flow at maximum congestion: CFV(hyp.), and this CFV(hyp.) indicates the extent of the total blood flow of the entire heart at maximum congestion. In this embodiment, the coronary blood flow rate can be applied to, for example, the blood flow rate of a single coronary artery. Therefore, in this embodiment, the coronary blood flow rate (coronary blood flow rate applicable regardless of the location or number of coronary arteries to which it is applied), as a higher-level concept than CFV, will be represented by Q, and the description will be based on this coronary blood flow rate Q. Incidentally, the above values ​​(Q, CFV, Q(hyp.), CFV(hyp.)) can now be measured using modalities such as PET-CT.

[0023] In other words, coronary blood flow (Q(hyp.)) at maximum hyperemia decreases compared to healthy conditions when there is epicardial coronary artery stenosis or microcirculatory impairment. Therefore, it is considered significant for estimating the presence and degree of vascular stenosis, but it has not been actively utilized until now. The reason for this is thought to be that the values ​​obtained vary greatly from person to person because hemodynamics differ among individual patients, making it difficult to imagine comparing and evaluating using the same index value (Q(hyp.) value).

[0024] In this context, the inventors have conducted extensive research to effectively utilize the value of coronary artery blood flow (Q(hyp.)) at maximum congestion, and have discovered, from a new perspective, the possibility of using the Q(hyp.) value for quantitative evaluation. Specifically, they have found that the variability of the Q(hyp.) value among patients is mainly due to (i) variability caused by differences in the arteriovenous pressure difference (ΔP(a-v)) at the time of measurement, and (ii) variability caused by differences in the patient's physique. Therefore, they have found that the usefulness of the Q(hyp.) value can be improved by mitigating or eliminating these (i) and (ii) with appropriate corrections as needed.

[0025] Furthermore, according to the above embodiment, by focusing on the linear relationship between coronary blood flow rate (Q(hyp.)) at maximum hyperemia and the arteriovenous pressure difference (ΔP(a-v)), and utilizing this characteristic, a blood pressure-corrected Q(hyp.) value (cQ(hyp.) value) is obtained by converting the coronary blood flow rate (Q(hyp.)) at maximum hyperemia under the condition of a predetermined arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)). With such a cQ(hyp.) value, the influence due to differences in the arteriovenous pressure difference (ΔP(hyp.)) at the time of measurement is reduced or avoided.

[0026] Therefore, the blood pressure corrected Q(hyp.) (cQ(hyp.)) values ​​obtained by this embodiment can be used, for example, as a significant quantitative evaluation index for estimating the presence or degree of vascular stenosis. Furthermore, it can be used, for example, when determining FFR, which has been conventionally used together with CFR in the diagnosis of coronary artery blood flow disease, using the directly measured coronary blood flow ratio rather than indirect measurement by the intracoronary pressure ratio.

[0027] A second aspect of the invention relating to improved coronary blood flow rate Q, etc., is as follows: A coronary blood flow rate measuring device characterized by having a Q(hyp.) acquisition means for acquiring a measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)), and a body surface area correction Q(hyp.) calculation means for calculating a body surface area correction Q(hyp.) which corrects the body surface area by correcting the measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)) acquired by the Q(hyp.) acquisition means using the body size values ​​of the target patient.

[0028] According to this embodiment, the value of coronary blood flow (Q(hyp.)) at maximum congestion is examined in relation to the patient's body size, and a standardized body surface area corrected Q(hyp.) is obtained by applying a correction for differences in body size. With such a body surface area corrected Q(hyp.) value, the influence due to differences in body size among patients is reduced or avoided.

[0029] Therefore, the body surface area corrected Q (hyp.) value obtained by this embodiment can be used as a significant quantitative evaluation index for estimating, for example, the presence or degree of vascular stenosis. Furthermore, it can be used, for example, when determining FFR, which has been conventionally used together with CFR in the diagnosis of coronary artery blood flow disease, using a directly measured coronary blood flow ratio rather than an indirect measurement using the intracoronary pressure ratio.

[0030] A third aspect of the invention relating to improved coronary blood flow rate Q, etc., is as follows: A means for acquiring a measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)); a means for calculating a blood pressure corrected Q(hyp.) by using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)), and converting the measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)) acquired by the Q(hyp.) acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)); A coronary blood flow measuring device characterized by having a calculation means for calculating at least one value of a body surface area corrected Q(hyp.) or a blood pressure / body surface area corrected Q(hyp.) by correcting the measured value of the maximum hypertensive coronary blood flow (Q(hyp.)) obtained by the Q(hyp.) acquisition means or the blood pressure corrected Q(hyp.) (cQ(hyp.)) obtained by the cQ(hyp.) calculation means, using the body size values ​​of the target patient.

[0031] According to this embodiment, a blood pressure / body surface area corrected Q(hyp.) can be obtained in which the influence of differences in arteriovenous pressure gradient (ΔP(a-v)) at the time of measurement and the influence of differences in patient body size are both reduced or avoided in the value of coronary blood flow rate (Q(hyp.)) at maximum congestion.

[0032] Therefore, the blood pressure / body surface area corrected Q(hyp.) value obtained by this embodiment can be used for determining coronary artery blood flow diseases, etc.

[0033] A fourth aspect of the invention relating to improved coronary blood flow rate Q, etc., is as follows: A means for acquiring a measured value of total coronary blood flow rate (CFV(hyp.)) at maximum hyperemia; and a blood pressure-corrected total coronary blood flow rate (cCFV(hyp.)) at maximum hyperemia, obtained by converting the measured value of total coronary blood flow rate (CFV(hyp.)) acquired by the CFV(hyp.) acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)), using the linear relationship between total coronary blood flow rate (CFV(hyp.)) at maximum hyperemia and arteriovenous pressure difference (ΔP(a-v)); A coronary blood flow determination device characterized by having an ischemic heart disease determination means that determines the presence or absence of ischemic heart disease using at least one value from the following: the measured value of the total coronary blood flow at maximum congestion (CFV(hyp.)) obtained by the CFV(hyp.) acquisition means, or the surface area corrected CFV(hyp.) or the blood pressure / surface area corrected total coronary blood flow index at maximum congestion (cCFI) obtained by correcting the blood pressure corrected total coronary blood flow at maximum congestion (cCFV(hyp.)) using the body size values ​​of the target patient.

[0034] According to this embodiment, as described in the inventions described in the first to third embodiments relating to the improved coronary blood flow rate Q, the value of the improved CFV(hyp.) ("cCFV(hyp.)" and / or "body surface area corrected CFV(hyp.) or blood pressure / body surface area corrected total coronary blood flow index at maximum congestion (cCFI)") is used for the total coronary blood flow rate (in this embodiment, coronary blood flow rate throughout the heart) CFV(hyp.) at maximum congestion, in which at least one of the effects due to differences in arteriovenous pressure gradient (ΔP(a-v)) at the time of measurement and the effects due to differences in the patient's physique is reduced or avoided. This makes it possible to make an accurate determination of the presence and degree of ischemic heart disease.

[0035] A fifth aspect of the invention relating to improved coronary blood flow rate Q, etc., is a coronary blood flow measuring device relating to the fourth aspect relating to the improved coronary blood flow rate Q, and is as follows: It comprises a CFR acquisition means for acquiring a calculated value of coronary flow reserve (CFR), and a cCFR calculation means for using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)) to convert the calculated value of coronary blood flow reserve (CFR) acquired by the CFR acquisition means into a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) to obtain a blood pressure corrected CFR (cCFR). Coronary blood flow determination device in which the ischemic heart disease determination means determines the presence or absence of ischemic heart disease using, in addition to at least one value of the blood pressure-corrected total coronary blood flow at maximum congestion (cCFV(hyp.)), the body surface area-corrected CFV(hyp.), or the blood pressure / body surface area-corrected total coronary blood flow index at maximum congestion (cCFI), the value of the blood pressure-corrected CFR (cCFR) obtained by the cCFR calculation means.

[0036] In this embodiment, in addition to the value of the improved CFV (hyp.) ("cCFV (hyp.)" and / or "body surface area corrected CFV (hyp.) or blood pressure / body surface area corrected total coronary blood flow index at maximum congestion (cCFI)") described in the fourth embodiment of the invention relating to improved coronary blood flow Q, etc., it becomes possible to determine ischemic heart disease with greater accuracy by also considering the value of the blood pressure corrected CFR (cCFR) described in the third embodiment of the invention relating to improved CFR. [iii] Invention relating to ER and MR The first embodiment of the invention relating to ER and MR is as follows. A coronary blood flow determination device characterized by comprising: a measurement data set acquisition means for acquiring measured values ​​of total coronary blood flow (CFV(hyp.)), aortic pressure (Pa), and coronary sinus pressure (Pv) at the same time; a ΔP(a-v) acquisition means for acquiring a calculated value of the arteriovenous pressure difference (ΔP(a-v)); and a determination value calculation means for calculating coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as cardiovascular resistance using the measured values ​​and calculated values ​​acquired by the measurement data set acquisition means and the ΔP(a-v) acquisition means, thereby determining the coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as determination values ​​for ischemic heart disease.

[0037] This embodiment makes it possible to objectively and quantitatively indicate the degree of vascular resistance present in the epicardial coronary arteries and microvessels, which constitute the cardiovascular system, by presenting a new indicator of cardiovascular abnormalities such as ischemic heart disease.

[0038] In particular, this embodiment enables the determination of ischemic heart disease based on calculated values ​​of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) by theoretical calculation using various measurement values ​​such as total coronary blood flow (CFV), aortic pressure (Pa), and coronary sinus pressure (Pv), which can be directly measured in the patient.

[0039] Therefore, when there is stenosis or other obstruction in the cardiovascular system, it becomes possible to objectively and quantitatively determine, for example, the location of such obstruction—whether it is in the epicardial coronary arteries or microvessels—and the degree of such obstruction, using calculated numerical values.

[0040] A second aspect of the invention relating to ER and MR is a coronary blood flow measuring device relating to the first aspect relating to ER and MR, and is as follows: A coronary blood flow determination device that includes the following relational expressions (i) and (ii) as relational expressions in the determination value calculation means: [Relational expression (i)] A relational expression that includes coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as the total cardiovascular resistance (TCR (hyp.)) of the cardiovascular system at maximum hyperemia [Relational expression (ii)] A relational expression between coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) for the calculated value of arteriovenous pressure difference (ΔP(a-v))

[0041] According to this embodiment, by acquiring measured and calculated values ​​for the cardiovascular system at maximum congestion, it becomes possible to efficiently determine coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) by utilizing the relationship between the coronary arteriovenous pressure gradient, vascular resistance, and blood flow in the cardiovascular system, while eliminating the influence of variable microvascular resistance (MR) by removing autonomous resistance changes in microvessels.

[0042] A third aspect of the invention related to ER and MR is a coronary blood flow measurement device according to the first or second aspect related to the ER and MR, as follows. The measurement data set acquisition means acquires a measurement value at rest in addition to the measurement value at maximum hyperemia. The determination value calculation means calculates using a relational expression including a coronary artery resistance (ER), a myocardial microcirculation resistance (MR), and a cardiac variable microvascular resistance (MRvariable) as the vascular resistance of the cardiovascular system, thereby obtaining the cardiac variable microvascular resistance (MRvariable) as a determination value in addition to the coronary artery resistance (ER) and the myocardial microcirculation resistance (MR).

[0043] According to this aspect, by obtaining measurement values and calculated values for the cardiovascular system at rest in addition to the cardiovascular system at maximum hyperemia, not only the coronary artery resistance (ER) and the myocardial microcirculation resistance (MR), but also the cardiac variable microvascular resistance (MRvariable), which is a variable resistance in the microvasculature, can be efficiently obtained by utilizing the relationship between the coronary venous pressure difference, vascular resistance, and blood flow in the cardiovascular system.

[0044] And since the value of the cardiac variable microvascular resistance (MRvariable) is a resistance component responsible for the self-regulation function of blood flow, the presence or absence of circulatory disorders can be evaluated by itself. That is, in patients with a healthy self-regulation function of blood flow, MRvariable at rest is high. Patients with coronary artery disease or coronary microcirculation disease, or patients with both, have a low MRvariable at rest.

[0045] A fourth aspect of the invention related to ER and MR is as follows. An ER, MR acquisition means for acquiring respective calculated values of coronary artery resistance (ER) and cardiac microcirculation resistance (MR) as the vascular resistance of the total cardiovascular system, and based on the values of the coronary artery resistance (ER) and the cardiac microcirculation resistance (MR) acquired by the ER, MR acquisition means, when a high value is recognized only in the coronary artery resistance (ER), it is determined as coronary artery disease (CAD), when a high value is recognized only in the cardiac microcirculation resistance (MR), it is determined as coronary microcirculation disease (CMD), and when high values are recognized in both the coronary artery resistance (ER) and the cardiac microcirculation resistance (MR), it is determined as both diseases of coronary artery disease (CAD) and coronary microcirculation disease (CMD). A coronary blood flow determination device having a determination means.

[0046] According to this aspect, as described in the inventions according to the first to third aspects related to ER and MR, based on the calculated values of the coronary artery resistance (ER) and the cardiac microcirculation resistance (MR), it becomes possible to objectively and quantitatively determine the location and degree of stenosis or the like in the cardiovascular system.

[0047] According to the invention related to improved CFR, it is possible to obtain a blood pressure-corrected CFR (cCFR) with improved accuracy for the coronary flow reserve (CFR) as an index indicating how many times the coronary blood flow of the entire heart at maximum hyperemia can be increased compared to that at rest. Therefore, by using the value of such blood pressure-corrected CFR (cCFR), it is also possible to more accurately determine, for example, the presence or absence of ischemic heart disease.

[0048] According to the invention related to improved CFV or the like, regarding the values of the coronary blood flow (Q(hyp.), CFV(hyp.)) at maximum hyperemia, it is possible to reduce or even eliminate at least one of the influence due to the difference in the arteriovenous pressure difference (ΔP(a-v)) at the time of measurement and the influence due to the difference in the physique of the patient. Therefore, the corrected value obtained for the coronary blood flow (Q(hyp.), CFV(hyp.)) can also be assumed to be used, for example, as a quantitative evaluation index useful for estimating the presence or absence and degree of ischemic heart disease.

[0049] According to the invention relating to ER and MR, coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) can be determined by theoretical calculation using various measurement values ​​such as total coronary blood flow (CFV), aortic pressure (Pa), and coronary sinus pressure (Pv), which can be directly measured in the patient, as well as global FFR, which can be obtained by directly measuring or by other diagnostic devices including simulation devices. Therefore, for example, it becomes possible to objectively and quantitatively determine the location of cardiovascular stenosis, such as whether it is in the epicardial coronary arteries or microvessels, and the degree of such stenosis, based on the determined values ​​of each resistance (ER, MR).

[0050] This is a graph showing the relationship between arteriovenous pressure difference (ΔP(a-v)) and coronary blood flow rate (Q) to explain the present invention. This is a schematic diagram illustrating an example of a coronary blood flow measurement device according to the present invention. This is a graph corresponding to Figure 1 to explain the inventions relating to improved CFR and improved CFV, etc. This is a graph and model diagram to explain the inventions relating to ER and MR. This is a judgment flowchart to explain an example of the determination of ischemic heart disease based on the inventions relating to ER and MR.

[0051] Embodiments of the present invention will be described below with reference to the drawings and other drawings. First, a list of definitions for abbreviations and symbols used in this specification is shown in Tables 1 to 3 below.

[0052]

[0053]

[0054]

[0055] First, Figure 2 shows an overview of an example of a coronary blood flow measurement device according to the present invention. This coronary blood flow measurement device 10 includes a measuring device 12 for acquiring measurement values ​​of the patient's basic biological information, and a calculation processing device 14 for acquiring judgment values, etc., for determining the patient's cardiovascular condition based on the measurement values ​​of the biological information.

[0056] The coronary blood flow measurement device 10 shown in Figure 2 is merely an example of its general structure, and its specific configuration is not limited. For example, the measurement device 12 illustrated in Figure 1 is equipped with a measurement catheter that approaches the patient's cardiovascular system, and this catheter is capable of measuring coronary blood flow, coronary artery pressure, coronary sinus pressure, etc. However, devices that acquire various measurement values ​​using X-rays, magnetic fields, ultrasound, etc., can also be used, and if necessary, measurement devices that measure the patient's biological information such as weight and height can also be appropriately used. Furthermore, the arithmetic processing device 14 does not need to be a dedicated device; for example, it can be configured by using the hardware of a general-purpose computer device to execute software for specific arithmetic processing. The arithmetic processing device 14 includes an input means for inputting various numerical values ​​for calculation, an arithmetic means for executing predetermined arithmetic processing based on the input numerical values, a determination means for executing determination processing according to predetermined conditions based on the calculated values ​​obtained by the arithmetic processing, and an output means for outputting calculated values, determination results, etc. Input methods may include manual input or voice input, or they may include wired or wireless communication between the measuring device 12 and the processing unit 14 to automatically input the measured values ​​acquired by the measuring device 12. Output methods may include monitor display means, printing means, or transmission means for external transmission via wireless or wired connection.

[0057] In such a coronary blood flow measuring device 10, the measurement and determination of the cardiovascular state of a patient, including the measurement of coronary blood flow, is performed by the following operations or processes such as measurements and calculations.

[0058] First, the measuring device 12 acquires various biological measurements for a specific patient. These measurements include resting coronary blood flow (Q(rest)), maximal coronary blood flow (Q(hyp.)), aortic pressure (Pa), and coronary sinus pressure (Pv). The patient's height, weight, and global FFR value are also acquired.

[0059] Generally, FFR values ​​are determined by measuring the coronary artery pressure at maximum congestion in the proximal and peripheral sides of a specific coronary artery suspected of having a stenotic lesion, for example, using a catheter equipped with a pressure sensor. However, in this embodiment, we adopt FFR (global FFR), which targets the coronary blood flow of the entire heart. This global FFR is a composite of the FFRs of the three main epicardial coronary arteries (left anterior descending artery, left circumflex artery, and right coronary artery), and is known to indicate the degree of stenosis in the entire epicardial coronary artery. Here, as will be described later, it will be treated the same as a measured value as one of the values ​​input to the processing unit 14 as biological information used in calculations to determine ER, MR, etc. Incidentally, global FFR can be determined by non-invasive blood flow measurement methods such as PET-CT or by simulation from the patient's cardiovascular CT data. Alternatively, the FFR of the three main epicardial coronary arteries can be invasively measured using a catheter equipped with a general pressure sensor, and the FFR values ​​of each of the three vessels can be added together according to their respective ratios to determine the FFR value.

[0060] Next, based on these measurements, the processing unit 14 calculates and obtains corrected coronary blood flow rate and judgment information such as ER and MR.

[0061] [i] Obtaining improved CFR As already explained with reference to Figure 1, coronary flow reserve (CFR) is a value defined by the following formula and can be calculated from the resting coronary blood flow rate (Q(rest)) and the coronary blood flow rate at maximum hyperemia (Q(hyp.)), both of which are measured values.

[0062] CFR=Q(hyp.) / Q(rest)

[0063] However, since the arteriovenous pressure gradient (ΔP(a-v)) at the time of measurement is not constant, as can be seen from Figure 1, even if the coronary flow reserve (CFR) is the same for different patients (for example, CFR = 2.5), if the arteriovenous pressure gradient (ΔP(a-v)) at the time of measurement is different (for example, ΔP = 80 and ΔP = 120), they cannot be evaluated equally.

[0064] Therefore, by performing a correction calculation according to the following formula, the blood pressure corrected CFR (cCFR) can be obtained by converting the arteriovenous pressure difference (ΔP(a-v)) to a value under the condition of an arbitrary specific value (ΔPs) common to all of them. This calculation is performed by the arithmetic processing unit 14.

[0065] cCFR=CFR×ΔPs / ΔP(av)

[0066] The specific pressure gradient (ΔPs) is a predetermined value and can be appropriately set within the range in which the self-regulating function of blood flow due to autonomous resistance changes by microvessels is exerted (for example, within the range of ΔP = 80 to 120). Specifically, if such a specific pressure gradient (ΔPs) is set to 100, the above formula becomes as follows: cCFR = CFR × 100 / ΔP(a - v)

[0067] The blood pressure-corrected CFR (cCFR) obtained using the above calculation formula can be understood as converting each CFR value (Q(hyp.) / Q(rest)) shown in Figure 1 to an evaluation value under the condition of a common arbitrary specific value (ΔPs = 100) of the arteriovenous pressure gradient (ΔP(a-v)), as shown in Figure 3. Therefore, by using such a blood pressure-corrected CFR (cCFR), it becomes possible to evaluate even measurements taken under different arteriovenous pressure gradients (ΔP(a-v)) under the same conditions, and to accurately evaluate or determine the cardiovascular state based on CFR.

[0068] [ii] Acquisition of improved coronary blood flow Q, etc. (1) Blood pressure corrected CFV (hyp.), blood pressure corrected Q (hyp.) As already explained, the value of coronary blood flow (CFV (hyp.), Q (hyp.)) at maximum hyperemia is affected by the arteriovenous pressure difference (ΔP) at the time of measurement, just like the coronary flow reserve (CFR) mentioned above. As can be seen from Figure 1, even if the coronary blood flow (CFV (hyp.), Q (hyp.)) at maximum hyperemia is the same for different patients, they cannot be evaluated equally if the arteriovenous pressure difference (ΔP (a-v)) at the time of measurement is different.

[0069] Therefore, by performing a correction calculation according to the following formula, the blood pressure-corrected coronary blood flow rate (cCFV(hyp.), cQ(hyp.)) can be obtained by converting the arteriovenous pressure difference (ΔP(a-v)) to a value under the condition of an arbitrary specific value (ΔPs) common to all of them. This calculation is performed by the arithmetic processing unit 14.

[0070] cCFV(hyp.)=CFV(hyp.)×ΔPs / ΔP(av)

[0071] cQ(hyp.)=Q(hyp.)×ΔPs / ΔP(av)

[0072] Note that the arbitrary specific value (ΔPs) of the arteriovenous pressure gradient (ΔP(a-v)) is a specific value predetermined within the physiological range, similar to the blood pressure-corrected coronary flow reserve (cCFR) mentioned above. For example, if the specific pressure gradient (ΔPs) is set to 100, the above formulas become as follows: cCFV(hyp.) = CFV(hyp.) × 100 / ΔP(a-v) cQ(hyp.) = Q(hyp.) × 100 / ΔP(a-v)

[0073] The blood pressure-corrected CFV(hyp.)(cCFV(hyp.)) and blood pressure-corrected Q(hyp.)(cQ(hyp.)) obtained using the above calculation formula can be understood as being converted to evaluation values ​​under the condition of a common arbitrary value (ΔPs = 100) of the arteriovenous pressure gradient (ΔP(a-v)). Therefore, by using such blood pressure-corrected CFV(hyp.)(cCFV(hyp.)) and blood pressure-corrected Q(hyp.)(cQ(hyp.)), it becomes possible to calculate coronary blood flow values ​​under the same conditions even if the measurements are taken under different arteriovenous pressure gradients (ΔP(a-v)).

[0074] Furthermore, when evaluating the cardiovascular system using the calculated value of the total coronary blood flow of the heart, and determining, for example, the presence or degree of ischemic heart disease, it becomes possible to evaluate or determine with high accuracy by using the blood pressure-corrected CFV(hyp.)(cCFV(hyp.)) obtained by the above calculation formula. The presence or degree of ischemic heart disease can be determined by setting a normal range for the blood pressure-corrected CFV(hyp.)(cCFV(hyp.)) using, for example, a statistical method, and then performing a comparative calculation that relatively evaluates the calculated value and deviation from that normal range. In addition, the processing of such comparative calculations and other determinations is performed by the determination means of the calculation processing unit 14.

[0075] (2) Surface area corrected CFV (hyp.), Surface area corrected Q (hyp.) Furthermore, the values ​​of coronary blood flow at maximum congestion (CFV (hyp.), Q (hyp.)) differ from the coronary flow reserve (CFR) mentioned above, which is obtained as a comparative value with the resting value in the same patient, as the values ​​of coronary blood flow at maximum congestion are obtained as measured values ​​under a single condition (at maximum congestion). Both represent the absolute value of blood flow and are presumed to correlate with differences in body size among patients. In particular, the inventors have found that the values ​​of coronary blood flow at maximum congestion (CFV (hyp.), Q (hyp.)) differ depending on the patient's body size, and therefore, when evaluating the cardiovascular state based on such values ​​(CFV (hyp.), Q (hyp.)), it is effective to make appropriate corrections according to the patient's body size.

[0076] Furthermore, we found that, for example, body surface area (BSA) is a suitable value to represent differences in patient body size.

[0077] According to these findings, by performing a correction calculation on the coronary blood flow rate (CFV(hyp.), Q(hyp.)) at maximum congestion according to the following formula, it is possible to obtain body surface area corrected CFV(hyp.) and body surface area corrected Q(hyp.) by converting them to values ​​under equivalent body size conditions. This calculation is performed by the arithmetic processing unit 14.

[0078] Body surface area correction CFV (hyp.) = CFV (hyp.) / BSA

[0079] Body surface area correction Q(hyp.)=Q(hyp.) / BSA

[0080] Furthermore, the body surface area (BSA) can be a value (including an approximate value) obtained by various known means, including calculations such as the Dupoir formula shown in [Equation 1] below.

[0081] The surface area-corrected CFV(hyp.) and Q(hyp.) obtained using the above calculation formulas can be understood as conversions of the measured coronary blood flow rate (CFV(hyp.), Q(hyp.)) at maximum congestion to evaluation values ​​under predetermined body size conditions. Therefore, by using these surface area-corrected CFV(hyp.) and Q(hyp.), it becomes possible to calculate the coronary blood flow rate under the same body size conditions even if the measurements are from patients with different body sizes.

[0082] Furthermore, when evaluating the cardiovascular system using the calculated value of the total coronary blood flow of the heart, and determining, for example, the presence or degree of ischemic heart disease, it becomes possible to evaluate or determine with high accuracy by using the body surface area corrected CFV (hyp.) obtained by the above calculation formula. The presence or degree of ischemic heart disease can be determined by setting a normal range for the body surface area corrected CFV (hyp.) using, for example, a statistical method, and then performing a comparative calculation that relatively evaluates the value and deviation of the calculated value based on that normal range. In addition, the processing of such comparative calculations and other determinations is performed by the determination means of the calculation processing unit 14.

[0083] (3) Blood pressure and body surface area corrected CFV (hyp.), Blood pressure and body surface area corrected Q (hyp.) When evaluating the cardiovascular system using the calculated value of the total coronary blood flow of the heart, for example, when determining the presence or degree of ischemic heart disease, it is possible to use at least one of the blood pressure corrected total coronary blood flow (cCFV (hyp.)) described in column (1) above and the body surface area corrected CFV (hyp.) described in column (2) above. It is also possible to perform the determination using the blood pressure corrected total coronary blood flow (cCFV (hyp.)) and the determination using the body surface area corrected CFV (hyp.) separately and evaluate each separately.

[0084] In this context, it is possible to correct the measured total coronary volume (CFV(hyp.)) at maximum congestion by applying both blood pressure correction and body surface area correction. For example, a blood pressure and body surface area corrected total coronary volume index at maximum congestion (cCFI) can be calculated by applying both blood pressure correction and body surface area correction based on the following formula. This cCFI can then be used to evaluate the patient's cardiovascular system and, for example, determine the presence and severity of ischemic heart disease.

[0085] cCFI=cCFV / BSA

[0086] Furthermore, the determination of the presence and severity of ischemic heart disease using the calculated value of the blood pressure / body surface area corrected total coronary blood flow index (cCFI) can be performed by comparative calculation, similar to the case using body surface area corrected CFV (hyp.), by setting a normal range using, for example, statistical methods, and relatively evaluating the calculated value and deviation from that normal range. In addition, the determination process using such comparative calculations is performed by the determination means of the arithmetic processing unit 14.

[0087] [iii] Acquisition of ER, MR, etc. First, Figure 4 shows a model representation of the relationship between blood flow and arteriovenous pressure difference for the entire cardiovascular system of the heart. Note that the hypothetical maximum hyperemia shown in Figure 4 is assumed to be the blood flow of a normal vessel without stenosis in the epicardial coronary arteries.

[0088] In this case, at maximum hyperemia, with variable microvascular resistance (MRvariable) excluded, the total coronary volume (CFV(hyp.)) at maximum hyperemia is approximately proportional to the arteriovenous pressure gradient (ΔP(a-v)), and the slope of the linear graph of coronary volume CFV(hyp.) and arteriovenous pressure gradient (ΔP(a-v)) corresponds to the total cardiovascular resistance (TCR(hyp.)), which is the sum of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR). Thus, the following relations (i) and (ii) can be obtained as relational equations that include coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as cardiovascular resistance.

[0089] [Relationship (i)] A relationship that includes coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as the total cardiovascular resistance (TCR (hyp.)) at maximum hyperemia. [Relationship (ii)] A relationship between the calculated value of arteriovenous pressure gradient (ΔP(a-v)) and coronary artery resistance (ER) and cardiac microcirculatory resistance (MR).

[0090] The above relations (i) and (ii) can be specifically described as follows: [Relationship (i)] TCR(hyp.) = ER + MR = ΔP(a - v) × 1000 / CFV(hyp.) However, in the above formula, the unit of CFV(hyp.) is mmHg・min / mL, but the unit of TCR(hyp.) is the same as that used for pulmonary artery resistance, [Wood] (mmHg・min / L). [Relationship (ii)] globalFFR = MR / (ER + MR)

[0091] Substituting the above relation (i) into (ER + MR) in relation (ii) yields the following equations: globalFFR = MR / TCR (hyp.) MR = globalFFR × TCR (hyp.) ER = (1 - globalFFR) × TCR (hyp.)

[0092] The TCR (hyp.) used to calculate MR and ER in each of the above equations can be calculated from the above relation (i) using the following formula: TCR (hyp.) = ΔP(a-v) × 1000 / CFV(hyp.)

[0093] Therefore, according to the calculation process described above, the values ​​of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) can be determined based on each measured value.

[0094] Furthermore, in addition to the total coronary volume at peak congestion (CFV(hyp.)) mentioned above, by using the resting total coronary volume (CFV(rest)) at the same arteriovenous pressure gradient (ΔP(a-v)) as a measured value, variable microvascular resistance (MRvariable) can be calculated. The following [relationship iii] holds between the resting total coronary volume (CFV(rest)), total cardiovascular resistance (TCR(rest) = ER + MRvariable + MR), and arteriovenous pressure gradient (ΔP(a-v)).

[0095] [Relational expression (iii)] ΔP(av)=(ER+MRvariable+MR)×CFV(rest)

[0096] Furthermore, as can be seen from Figure 4, the variable microvascular resistance (MRvariable) can be expressed using coronary artery resistance (ER) and microcirculatory resistance (MR) as follows: [Equation 2] MRvariable = (ER + MRvariable + MR) - (ER + MR)

[0097] Substituting the aforementioned TCR(hyp.) relation and the above relation (iii) into [Equation 2], we obtain the following [Equation 3]: [Equation 3] MRvariable = (ΔP(a-v) × 1000 / CFV(rest)) - TCR(hyp.)

[0098] Therefore, using this calculation process, in addition to coronary artery resistance (ER) and cardiac microcirculatory resistance (MR), the value of variable cardiac microvascular resistance (MRvariable) can also be determined based on each measurement value.

[0099] The coronary artery resistance (ER), cardiac microcirculatory resistance (MR), and cardiac variable microvascular resistance (MRvariable) values ​​obtained by calculation from each measurement can then be used, for example, as quantitative evaluation values ​​representing the magnitude of each vascular resistance.

[0100] Furthermore, since the value of variable cardiac microvascular resistance (MRvariable) is a resistance component responsible for the self-regulation of blood flow, it can be used to assess the presence or absence of circulatory disorders. In other words, in patients with healthy self-regulation of blood flow, the resting MRvariable is high. In patients with coronary artery disease, coronary microcirculatory disease, or both, the resting MRvariable is low.

[0101] Furthermore, when using these calculated values ​​of coronary artery resistance (ER), cardiac microcirculatory resistance (MR), and cardiac variable microvascular resistance (MRvariable) to determine (including evaluation, etc.) whether vascular resistance is normal or abnormal, similar to the case using the body surface area corrected CFV (hyp.) mentioned above, a range of normal values ​​can be set using, for example, statistical methods, and the calculated values ​​and deviations can be evaluated relatively based on these normal values ​​through comparative calculations. In addition, the processing of such comparative calculations, etc., is performed by the determination means of the arithmetic processing unit 14.

[0102] (4) Flowchart for determining ischemic heart disease using each calculated value An example of the processing flow in the determination means that determines ischemic heart disease using each calculated value obtained in accordance with the descriptions in sections (1) to (3) above is shown in Figure 5.

[0103] First, in step S1, it is determined whether or not the patient's cardiovascular system is suspected to have ischemic heart disease. Specifically, this can be done by appropriately using the calculated values ​​cCFR, cCFV, and cCFI obtained through "[i] Acquisition of improved CFR" and "[ii] Acquisition of improved CFV, etc." and determining whether or not these calculated values ​​are within the normal range using pre-set evaluation criteria (which can be set, for example, by statistical methods as described above).

[0104] If the calculation value in step S1 is determined to be within the normal range, the process proceeds to step S2, where it is determined that there is no suspicion of ischemic heart disease, and the judgment process ends by outputting the judgment result as necessary.

[0105] On the other hand, if the result of the judgment process in step S1 is determined to be outside the normal range, the process proceeds to step S3 and then to step S4, with ischemic heart disease suspected.

[0106] Step S4 can be performed by using the calculated values ​​of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) obtained through the "[iii] Acquisition of ER, MR, etc." and determining whether these calculated values ​​are within the normal range based on a predetermined evaluation criterion (which can be set, for example, by statistical methods as described above).

[0107] If the judgment process in step S4 determines that only the calculated value of coronary artery resistance (ER) exceeds the normal range, the process proceeds to step S5, where coronary artery disease (CAD) is determined, this determination result is output, and the process terminates.

[0108] On the other hand, if the judgment process in step S4 determines that only the calculated value of cardiac microcirculatory resistance (MR) exceeds the normal range, the process proceeds to step S6, where coronary microcirculatory disease (CMD) is determined, this determination result is output, and the process terminates.

[0109] Furthermore, if the judgment process in step S4 determines that both the calculated values ​​of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) are above the normal range, the process proceeds to step S7, where it is determined that both coronary artery disease (CAD) and coronary microcirculatory disease (CMD) are present, and this determination result is output before the process terminates.

[0110] Incidentally, as examples of the judgment process described above, the following shows the application examples for a normal patient (Case #1), a patient with coronary artery disease (CAD) (Case #2), a patient with coronary microcirculation disease (CMD) (Case #3), and a patient with both coronary artery disease (CAD) and coronary microcirculation disease (CMD) (Case #4).

[0111] First, the measured values ​​for each patient in cases #1 to #4 are shown in Tables 4 to 7 below.

[0112]

[0113]

[0114]

[0115]

[0116] Next, for each patient in cases #1 to #4, the calculated values ​​were determined as described above, and the results of determining whether ischemic heart disease was suspected based on these calculated values ​​are shown in [Table 8] and [Table 9] below.

[0117]

[0118]

[0119] The results shown in Tables 8 and 9 above demonstrate that the determination of ischemic heart disease based on the calculated values ​​according to the present invention is significant. Regarding the calculated values ​​in Tables 8 and 9, the criteria for the normal range should be determined by statistical methods as described above. For example, the normal value for coronary flow reserve (CFR) is 2 to 5, the normal value for blood pressure-corrected coronary flow reserve (cCFR) is 2 to 5, and the normal values ​​for coronary artery resistance (ER), cardiac microcirculatory resistance (MR), and total cardiovascular resistance at maximum hyperemia (TCR (hyp.)) can all be considered to be 400 Woods or less.

[0120] Although the present invention has been described in detail above, it should not be interpreted restrictively by the above-mentioned specific descriptions, and it can be implemented in various forms with modifications, changes, and improvements based on the knowledge of those skilled in the art. Furthermore, it goes without saying that such embodiments are all included within the scope of the present invention, as long as they do not depart from the spirit of the present invention.

[0121] For example, the [relationship formula (ii)] exemplified in the section "[iii] Acquisition of ER, MR, etc." above was defined as assuming that the total coronary volume at maximum congestion (CFV (hyp.)) is proportional to the arteriovenous pressure gradient (ΔP (a - v)) and inversely proportional to cardiovascular resistance (ER + MR). However, any relationship formula between total coronary volume at maximum congestion (CFV (hyp.)), arteriovenous pressure gradient (ΔP (a - v)), and cardiovascular resistance (ER + MR) is acceptable. Such a relationship formula could be one obtained based on, for example, fluid dynamics theory or a relationship formula obtained using statistical methods.

[0122] Furthermore, when determining ischemic heart disease and other conditions, it is not necessary to consider all of the calculated values ​​exemplified in the above embodiment; at least one calculated value can be selectively adopted as appropriate. For example, if blood pressure-corrected coronary flow reserve (cCFR) or variable microvascular resistance (MRvariable) are not considered, there is no need to calculate those values.

[0123] Furthermore, in the section "[ii] Acquisition of Improved CFV, etc." above, "(2) Body Surface Area Corrected CFV (hyp.), Body Surface Area Corrected Q (hyp.)", body surface area (BSA) values ​​were used as a value representing the difference in patient body size, but this is not limited to this value. For example, values ​​based on weight, etc., may be used, allowing for some error.

[0124] Furthermore, each calculated value based on the present invention can be used in conjunction with other evaluation values ​​as needed when determining ischemic heart disease, and can also be used appropriately for purposes other than determining ischemic heart disease, such as understanding the cardiovascular condition of a patient, and is not limited to any particular use.

[0125] 10 Coronary blood flow measurement device 12 Measurement device 14 Calculation processing device

Claims

1. A coronary blood flow determination device characterized by comprising: a measurement data set acquisition means for acquiring measured values ​​of total coronary blood flow (CFV(hyp.)), aortic pressure (Pa), and coronary sinus pressure (Pv) at the same time; a ΔP(a-v) acquisition means for acquiring a calculated value of the arteriovenous pressure difference (ΔP(a-v)); and a determination value calculation means for calculating the coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as cardiovascular resistance using the measured values ​​and calculated values ​​acquired by the measurement data set acquisition means and the ΔP(a-v) acquisition means, thereby determining the coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as determination values ​​for ischemic heart disease.

2. The coronary blood flow determination device according to claim 1, wherein the relational expression in the determination value calculation means includes the following relational expressions (i) and (ii): [Relational expression (i)] A relational expression including coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as the total cardiovascular resistance (TCR (hyp.)) of the cardiovascular system at maximum hyperemia [Relational expression (ii)] A relational expression between coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) for the calculated value of arteriovenous pressure difference (ΔP(a-v)) 3. The coronary blood flow determination device according to claim 1 or 2, wherein the measurement data set acquisition means acquires measurement values ​​at rest in addition to measurement values ​​at maximum congestion, and the determination value calculation means calculates the coronary artery resistance (ER) and the cardiac microcirculatory resistance (MR) as cardiovascular vascular resistance, in addition to the cardiac variable microvascular resistance (MRvariable), using a relational expression, thereby determining the coronary artery resistance (ER) and the cardiac microcirculatory resistance (MRvariable) as determination values.

4. A coronary blood flow determination device comprising: an ER and MR acquisition means for acquiring calculated values ​​of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) as total cardiovascular vascular resistance; and a determination means for determining, based on the values ​​of coronary artery resistance (ER) and cardiac microcirculatory resistance (MR) acquired by the ER and MR acquisition means, that if a high value is observed only in the coronary artery resistance (ER), it is determined to be coronary artery disease (CAD); if a high value is observed only in the cardiac microcirculatory resistance (MR), it is determined to be coronary microcirculatory disease (CMD); and if high values ​​are observed in both the coronary artery resistance (ER) and cardiac microcirculatory resistance (MR), it is determined to be both coronary artery disease (CAD) and coronary microcirculatory disease (CMD).

5. A coronary blood flow measuring device characterized by comprising: a CFR acquisition means for acquiring a calculated value of coronary flow reserve (CFR); and a cCFR calculation means for using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)) to convert the calculated value of coronary blood flow reserve (CFR) acquired by the CFR acquisition means into a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) to obtain a blood pressure corrected CFR (cCFR).

6. The coronary flow rate measuring device according to claim 5, wherein the calculated value of coronary flow reserve (CFR) obtained by the CFR acquisition means is a calculated value obtained based on measured values ​​of coronary flow rate (Q) within the range of 80 to 120 mmHg for the arteriovenous pressure difference (ΔP(a-v)), and an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) is set to a specific value within the range of 80 to 120 mmHg.

7. A coronary blood flow determination device comprising: a CFR acquisition means for acquiring a calculated value of coronary flow reserve (CFR); a cCFR calculation means for obtaining a blood pressure corrected CFR (cCFR) by converting the calculated value of coronary flow reserve (CFR) acquired by the CFR acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)); and an ischemic heart disease determination means for determining the presence or absence of ischemic heart disease using the value of the blood pressure corrected CFR (cCFR) obtained by the cCFR calculation means.

8. A coronary blood flow measuring device characterized by comprising: a Q(hyp.) acquisition means for acquiring a measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)); and a cQ(hyp.) calculation means for using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)) to convert the measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)) acquired by the Q(hyp.) acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)) to determine a blood pressure corrected Q(hyp.) (cQ(hyp.)).

9. A coronary blood flow measuring device characterized by comprising: a Q(hyp.) acquisition means for acquiring a measured value of the maximum coronary blood flow rate (Q(hyp.)) at peak hyperemia; and a body surface area correction Q(hyp.) calculation means for calculating a body surface area correction Q(hyp.) by correcting the measured value of the maximum coronary blood flow rate (Q(hyp.)) at peak hyperemia acquired by the Q(hyp.) acquisition means using the body size values ​​of the target patient.

10. A means for obtaining a measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)), and a means for calculating a blood pressure corrected Q(hyp.) by using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)), and converting the measured value of the coronary blood flow rate at maximum hyperemia (Q(hyp.)) obtained by the Q(hyp.) acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)), A coronary blood flow measuring device characterized by having a calculation means for calculating at least one value of a body surface area corrected Q(hyp.) or a blood pressure / body surface area corrected Q(hyp.) by correcting the measured value of the maximum hypertensive coronary blood flow (Q(hyp.)) obtained by the Q(hyp.) acquisition means or the blood pressure corrected Q(hyp.) (cQ(hyp.)) obtained by the cQ(hyp.) calculation means, using the body size values ​​of the target patient.

11. A CFV (hyp.) acquisition means for acquiring a measured value of the total coronary blood flow rate (CFV (hyp.)) at maximum hyperemia, and a blood pressure-corrected total coronary blood flow rate (cCFV (hyp.)) obtained by converting the measured value of the total coronary blood flow rate (CFV (hyp.)) acquired by the CFV (hyp.) acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP (a-v)), using the linear relationship between the total coronary blood flow rate (CFV (hyp.)) at maximum hyperemia and the arteriovenous pressure difference (ΔP (a-v)), A coronary blood flow determination device characterized by having an ischemic heart disease determination means that determines the presence or absence of ischemic heart disease using at least one value from the following: the measured value of the total coronary blood flow at maximum congestion (CFV(hyp.)) obtained by the CFV(hyp.) acquisition means, or the surface area corrected CFV(hyp.) or the blood pressure / surface area corrected total coronary blood flow index at maximum congestion (cCFI) obtained by correcting the blood pressure corrected total coronary blood flow at maximum congestion (cCFV(hyp.)) using the body size values ​​of the target patient.

12. The system includes a CFR acquisition means for acquiring a calculated value of coronary flow reserve (CFR), and a cCFR calculation means for calculating blood pressure-corrected CFR (cCFR) by using the linear relationship between the coronary blood flow rate at maximum hyperemia (Q(hyp.)) and the arteriovenous pressure difference (ΔP(a-v)), and converting the calculated value of coronary flow reserve (CFR) acquired by the CFR acquisition means to a value under the condition of an arbitrary specific value (ΔPs) of the arteriovenous pressure difference (ΔP(a-v)). The coronary blood flow determination device according to claim 11, wherein the ischemic heart disease determination means determines the presence or absence of ischemic heart disease using, in addition to at least one value of the blood pressure-corrected total coronary blood flow at maximum congestion (cCFV(hyp.)), the body surface area-corrected CFV(hyp.), or the blood pressure / body surface area-corrected total coronary blood flow index at maximum congestion (cCFI), the value of the blood pressure-corrected CFR (cCFR) obtained by the cCFR calculation means.

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