Method for determining index for assessing cardiac function of subject

Abstract

The present invention relates to a method for determining an index for evaluating cardiac function of a subject on the basis of a first value and a second value of a liver hardness parameter of the subject, the first value corresponding to a value of a liver hardness parameter obtained before or immediately after performing a predetermined cardiac stimulus, and the second value corresponding to a value of a liver hardness parameter obtained immediately after performing the predetermined cardiac stimulus. The predetermined cardiac stimulus alters the cardiovascular system of the subject, and the second value corresponds to a value of a liver hardness parameter after the predetermined cardiac stimulus is performed; wherein the first value and the second value are spaced at most 6 hours.

Description

Technical Field

[0001] The present invention relates to the field of cardiac assessment. More specifically, the present invention relates to determining an index for assessing the cardiac function of a subject. Background Art

[0002] The main function of the heart is to distribute oxygenated blood and nutrients to the organs. Thus, the cardiac function of a subject represents the ability of the heart to meet the metabolic needs of the body.

[0003] Heart failure occurs when the heart cannot pump enough blood through the arteries to meet the needs of the metabolic organs and cannot receive all of the venous blood returning to the heart for oxygenation and purification. Thus, the main hemodynamic manifestation of heart failure is an increase in blood volume and pressure in the ventricles, pulmonary vessels, central veins, and peripheral veins and organs (referred to as "congestion").

[0004] The gold standard method for assessing cardiac function is right heart catheterization. This procedure is performed by puncturing the femoral vein, subclavian vein, internal jugular vein, or antecubital vein. A probe is inserted into the right atrium, then through the tricuspid valve, into the right ventricle, and finally through the pulmonary valve into the pulmonary artery. Right heart catheterization allows for the measurement of pressures in the right ventricle (e.g., right ventricular pressure or right atrial pressure) and in the pulmonary artery with high precision. However, this procedure is invasive and requires a high level of expertise on the part of the operator performing the procedure.

[0005] Therefore, there is a need to develop reliable and non-invasive techniques for assessing the cardiac function of individuals (such as those at risk or suspected or diagnosed with heart disease). Summary of the Invention

[0006] One aspect of the present invention relates to determining an index (or score) for assessing the cardiac function of a subject based on at least two liver stiffness measurements taken before and after a predetermined cardiac stimulation (also referred to as cardiac excitation). Depending on the type of predetermined excitation or stimulation, the measurements of the two liver stiffness values can be taken at intervals of a relatively short time period, approximately a few seconds or minutes, or even several hours. For certain stimulations, the time interval can even be within 1 hour, or even within 30 minutes, or even within a few minutes (e.g., within 15 minutes). In the context of the present invention, the longest time interval is within 6 hours.

[0007] In the context of various aspects of the present invention, the predetermined cardiac stimulation is typically a change in the subject's posture, the subject's physical activity, or the injection of a substance into the subject.

[0008] As is well known, there is a connection between the heart and the liver. The liver, known for its high metabolic activity, receives approximately 25% of the cardiac output. The liver generates venous blood flow through the hepatic veins and the inferior vena cava, neither of which has valves. This feature causes the filling pressure of the right heart to be directly transmitted backward to the liver. For example, acute decompensated heart failure (ADHF) increases the pressure in the right atrium, also known as central venous pressure (CVP), leading to liver congestion, and this relationship is prognostic.

[0009] In the article "Liver stiffness is directly influenced by central venous pressure" by Millonig et al. published in the Journal of Hepatology (Volume 52, Issue 2, February 2010, pp. 206-210), the authors revealed the correlation between liver stiffness measurement (LSM) and CVP in the context of ADHF.

[0010] In the article "Use of liver stiffness measurements in acute decompensated heart failure: new applications of a non-invasive technique" by Dhillon et al. published in ESC Heart Failure (July 12, 2022), the authors reported that elevated LSM can serve as an independent predictor of worsening ADHF and increased cardiac events, higher all-cause mortality, and worse postoperative outcomes after placement of a left ventricular assist device (LVAD). The article also mentioned several studies that collectively concluded that LSM significantly decreases after diuresis in patients admitted for ADHF.

[0011] In the article "Prognostic value of access-to-discharge change in integral congestion assessment for predicting adverse outcomes in patients with decompensated heart failure" by Kobalava et al. published in the Archives of Razi Institute (June 2022), the authors studied whether changes in LSM during hospitalization and at discharge in subjects hospitalized for decompensated heart failure had predictive value for adverse cardiac events occurring in these subjects during the year following discharge. To this end, the authors determined the change in LSM during hospitalization and at discharge (thus, the two measurements were usually separated by several days or weeks). The authors compared the LSM differences between patients with adverse events and those without adverse events and found a significant difference between the groups and thus a significant association between the change in LSM and the occurrence of cardiac events (p = 0.002). The authors also determined that there was a significant difference in the survival probability between patients with an LSM change higher than or equal to -44% and those with an LSM change lower than -44% (p = 0.001), thus showing that an LSM change higher than or equal to -44% has predictive value for risk prediction.

[0012] Therefore, in this article by Kobalava et al. (2022), the authors determined that the decrease in LSM during the start and end of hospitalization was an indicator of the level of cardiac congestion (or the level of reduction in cardiac congestion) associated with the treatment received. Thus, in this article, the goal was to quantify the evolution of cardiac function using the LSM values before and after hospitalization.

[0013] The object of the present invention is very different from the objects reported in the above-mentioned literature. One aspect of the present invention allows for the rapid non-invasive assessment of the cardiac function of a subject at a given moment using LSM. Thus, this is not a question of evaluating how long-term treatment measures change the congestion level of the subject. It should be understood that one aspect of the present invention can be used to evaluate the cardiac function of individuals with heart disease but without obvious symptoms of heart failure and individuals suspected of having heart disease or predisposed to heart diseases that can lead to heart failure.

[0014] In one aspect of the present invention, by utilizing the change in LSM of a subject before and after a predetermined cardiac stimulation, the cardiac function can be evaluated in a much shorter time than in the prior art (usually a few seconds or minutes to a few hours compared to several days or weeks). In other words, one aspect of the present invention relates to evaluating cardiac function in a single procedure using non-invasive tests performed at two very close intervals.

[0015] The inventors have determined and disclosed a relevant index for evaluating cardiac function, which is constructed from two LSM values before and after performing a predetermined cardiac stimulation as defined above. This is far from the teachings of the above-mentioned articles, none of which indicate that two LSM values determined within such a short time interval (and not necessarily related to the treatment of heart failure) can be used to evaluate the cardiac function of a subject.

[0016] Accordingly, one aspect of the present invention relates to a computer-implemented method for determining an index for evaluating the cardiac function of a subject, the method comprising:

[0017] obtaining a first value of the liver stiffness parameter of the subject, the first value being associated with a first time;

[0018] obtaining a second value of the liver stiffness parameter of the subject, the second value being associated with a second time that is strictly greater than the first time; and

[0019] determining the index based on the first value and the second value of the liver stiffness parameter of the subject;

[0020] wherein the first value corresponds to the value of the liver stiffness parameter obtained before or immediately after performing a predetermined cardiac stimulation that changes the cardiovascular system of the subject, and the second value corresponds to the value of the liver stiffness parameter after performing the predetermined cardiac stimulation;

[0021] wherein the difference between the second time and the first time is at most 6 hours.

[0022] In one embodiment, the difference between the second time and the first time is at most 5 hours. In another embodiment, the difference is at most 4 hours. In yet another embodiment, the difference is at most 3 hours. In one embodiment, the difference is at most 2 hours. In another embodiment, the difference is at most 1 hour. In yet another embodiment, the difference is at most 30 minutes, such as at most 15 minutes, and in one embodiment, the difference is at most 10 minutes, for example at most 5 minutes or even at most 2 minutes.

[0023] In one embodiment, the first liver stiffness measurement and the second liver stiffness measurement are performed using the same elastography device. It should be understood that the first liver stiffness measurement and the second liver stiffness measurement can be performed using two separate elastography devices.

[0024] The inventors have determined that changes in LSM after a predefined cardiac stimulation can assess the cardiac condition of a subject, thereby determining whether the subject has any potential cardiac dysfunction or risk.

[0025] This is advantageous for very quickly (within a few minutes in some embodiments) assessing the cardiac function of a subject and does not require any invasive procedure since LSM is measured non-invasively. In particular, this index (referred to as the cardiohepatic congestion (CHC) index) can determine the hepatic congestion of an individual patient, thereby indicating impaired cardiac function.

[0026] This is a recent result not yet published by some of the inventors of the present application, which has prompted them to explore an index for assessing cardiac function based on LSM. In fact, as detailed in the unpublished EP patent application EP23305032.7 assigned to the applicant, the inventors have found that, contrary to what one might think, the stiffness of the liver region of a subject is not a constant value but varies over time. In particular, it has been found that changes in the cardiac signal over time can be detected in the liver stiffness measurement results. More specifically, the inventors have found that changes in the central venous pressure (CVP) over time can be detected in the time-domain LSM signal. Thus, since blood pressure fluctuates rapidly within seconds in the case of cardiac dysfunction, the inventors of the present invention have thought that such fluctuations should be observed in the LSM signal.

[0027] After the work of EP23305032.7, the inventors of the present invention have further determined that LSM is mainly affected by three components: a component related to fibrosis, a component related to inflammation, and a component related to congestion. In the context of the present invention, at least two liver stiffness measurements are used to establish an index for assessing the cardiac function of a subject, and the at least two measurements are performed during a short time interval (less than 6 hours). During such a time interval, the component related to fibrosis and the component related to inflammation are unlikely to change. Thus, mainly the component related to congestion causes the change from one measurement value to another after a predefined cardiac stimulation, thereby enabling the assessment of cardiac function and eliminating any possible bias associated with other variables known to affect LSM.

[0028] "Assessing cardiac function" refers to assessing the ability of the heart to meet the metabolic needs of the body. Thus, it should be understood that "assessing cardiac function" includes assessing potential cardiac dysfunction. It should be noted that the determined index can assess cardiac function and thus can potentially detect the risk of cardiac dysfunction, but does not identify what type of dysfunction. Typically, a subject with an index indicating a high risk of cardiac dysfunction will require additional tests to confirm and identify the dysfunction. In particular, the determined index can provide an indication of the level of cardiac congestion that is directly related to cardiac function.

[0029] "Subject" refers to any human or animal individual. "Liver stiffness parameter" refers to any parameter related to the liver stiffness of a subject. For example, a liver stiffness parameter can be a liver stiffness measurement result, but can also be a parameter related to other physical quantities, such as elasticity, Young's modulus, shear modulus, shear wave velocity, viscoelasticity, viscosity, or any combination biomarker derived from (or combined from) one or more of the above physical quantities.

[0030] The liver stiffness (LS) parameter value can be obtained by any elastography technique, such as transient elastography (e.g., vibration-controlled transient elastography), acoustic radiation force-based elastography, or magnetic resonance elastography.

[0031] A predefined cardiac stimulus refers to a predefined event to which the heart of a subject is subjected. Thus, a predefined cardiac stimulus is a predefined event that is specifically designed to modify and is capable of modifying certain functional characteristics of the heart, thereby causing a significant and detectable change in the liver stiffness value that can be used to determine a reliable index of cardiac function within a short period of time (i.e., up to 6 hours and, in some embodiments, up to a few minutes) to assess the cardiac condition of the subject. This is different from other cardiac stimuli caused by the subject's exercise, which may not be sufficient to determine a reliable index of cardiac function within a short period of time. These changes in functional characteristics can reveal cardiac dysfunction. The phenotypic manifestation of this dysfunction is congestion. In one or more embodiments, the patient follows instructions from a healthcare professional, such as a doctor and / or an operator of an elastography system, which is specifically constructed and arranged to determine an index of the cardiac function of the subject.

[0032] "Immediately after" a predefined cardiac stimulus means that a first time associated with a first value is greater than the time at which the predefined cardiac stimulus occurs, but is not too far apart in time. More specifically, the difference between the first time and the time at which the predefined cardiac stimulus occurs is typically on the order of a few seconds (e.g., less than 30 or 45 seconds), and may also be a few minutes, but in all cases is less than 5 minutes, and in one embodiment is less than 2 minutes.

[0033] It should be understood that the index can be a quantitative index (e.g., the index can take real values) or a type index (e.g., a risk level). Thus, the wording "calculate an index" or "determine an index" can mean calculating or determining a number, as well as determining a category or rank and / or a classification number within a category or rank.

[0034] It should be noted that, where possible, the first value corresponds to the value of the liver stiffness (LS) parameter before performing a predetermined cardiac stimulation. In particular, the first value can correspond to the liver stiffness (LS) parameter value at a moment "immediately before" performing the predetermined cardiac stimulation (i.e., within seconds to minutes before the predetermined cardiac stimulation (e.g., less than 5 minutes before the predetermined cardiac stimulation)).

[0035] However, it is not always optimal to measure the LS parameter before performing a predetermined cardiac stimulation, since, where possible, it is recommended to measure the LS parameter when the subject is in the supine position. Thus, if the predetermined cardiac stimulation is, for example, a change in posture from a standing position to a supine position, the first value can be measured "immediately" after performing the predetermined cardiac stimulation (when the subject has just lain down), and the second value can be measured at a time after the first value (e.g., several minutes later, e.g., less than 10 minutes, and in one or more embodiments less than 5 minutes).

[0036] As described above, within the short time period (0 to 6 hours) between the first and second stiffness measurements, only the liver stiffness component related to congestion may change, and the components related to fibrosis and / or inflammation remain constant. Thus, analyzing the change between the first value of the parameter LS and the second value of the parameter LS provides an indication of the congestion level of the subject and, thus, an indication of his / her cardiac function.

[0037] Thus, various aspects of the present invention can non-invasively evaluate the cardiac function of a subject (and thus detect potential dysfunctions) according to an easily implemented scheme. Additionally, it is easy to maintain the same measurement posture for the elastography step. It should be understood that various aspects of the present invention can even be used for subjects or patients with limited mobility and / or frail subjects or patients. The index can be easily interpreted within a very short time and provides information about the cardiac state of the subject.

[0038] In one or more embodiments, the first time can correspond to the time of performing the first liver stiffness measurement, and the second time can correspond to the time of performing the second liver stiffness measurement.

[0039] In one or more embodiments, the predetermined cardiac stimulation includes at least one of the following:

[0040] - a change in the posture of the subject;

[0041] - Physical exercise performed by the subject; and

[0042] - Injection of a substance that alters the hemodynamic characteristics of the subject.

[0043] In one or more embodiments where the predetermined cardiac stimulation is a change in the subject's posture, the difference between the second time and the first time can be at most 15 minutes.

[0044] For example, the change in posture can be at least one of the following:

[0045] - Changing from a standing position to a supine position, or from a supine position to a standing position;

[0046] - Changing from the Trendelenburg position to a supine position, or from a supine position to the Trendelenburg position;

[0047] - Changing from a supine position with at least one leg of the subject lowered to a supine position with at least one leg of the subject raised, or from a supine position with at least one leg of the subject raised to a supine position with at least one leg of the subject lowered; and

[0048] - Changing from the Fowler's position to a supine position, or from a supine position to the Fowler's position.

[0049] "Supine position" refers to the position where the subject lies on their back (face and torso upward). In the supine position, the subject's legs can be lowered or raised (or one leg can be lowered while the other leg is raised). Thus, in one or more embodiments, the change in posture can include raising a leg that was originally lowered or lowering a leg that was originally raised.

[0050] It is desirable to measure the LS measurement results when the subject is in a lying position. Thus, in one or more embodiments, the first and second values can be measured when the subject is in a supine position, the Trendelenburg position, or a position where at least one leg of the subject is raised.

[0051] When the predetermined cardiac stimulation is:

[0052] - Changing from the Trendelenburg position to a supine position, or from a supine position to the Trendelenburg position, or

[0053] - Changing from a supine position with at least one leg of the subject lowered to a supine position with at least one leg of the subject raised, or from a supine position with at least one leg of the subject raised to a supine position with at least one leg of the subject lowered, or

[0054] - Changing from the Fowler's position to the supine position or from the supine position to the Fowler's position, or

[0055] - Changing from the supine position to the standing position,

[0056] The first value corresponds to the value of the liver stiffness parameter before performing a predetermined cardiac stimulation. In fact, for such a postural change, the subject is in the lying position before performing the predetermined cardiac stimulation, that is, in the preferred position for measuring LSM.

[0057] When the predetermined cardiac stimulation is changing from the standing position to the supine position, the first value corresponds to the value of the liver stiffness parameter obtained immediately after performing the predetermined cardiac stimulation (e.g., within 30 seconds after performing the predetermined cardiac stimulation, in one embodiment, within 15 seconds after performing the predetermined cardiac stimulation).

[0058] In various embodiments, the predetermined cardiac stimulation may include a predetermined physical exercise.

[0059] The predetermined physical exercise may include a series of "typical" fitness or gym exercises (jumping, squats, lunges, crunches, burpees, etc.), brisk walking, running on a treadmill, etc.

[0060] In these embodiments, the first value corresponds to the value of the liver stiffness parameter before performing the predetermined cardiac stimulation. For example, the first value can be measured for a patient lying in the supine position.

[0061] For example, when the predetermined cardiac stimulation includes a predetermined physical exercise, the difference between the second time and the first time can be between 0 minutes and 30 minutes.

[0062] As a supplement, the predetermined cardiac stimulation may also include the administration of an inotropic substance, a vasoconstrictive substance or a vasodilatory substance.

[0063] In this case, the difference between the second time and the first time can be between 0 and 4 hours, for example, up to 4 hours.

[0064] In one or more embodiments, the predetermined cardiac stimulation may include injecting a substance that changes the hemodynamic characteristics of the subject, and the predetermined cardiac stimulation is equivalent to a fluid-induced predetermined cardiac stimulation or hemodialysis.

[0065] The injected substance is generally a substance specifically designed to change the hemodynamic characteristics of the subject, thereby causing a significant and detectable change in the liver stiffness value that can determine a reliable index of cardiac function within a short time (i.e., up to 6 hours, and in some embodiments up to a few minutes), so as to evaluate cardiac function.

[0066] Fluid-induced cardiac stimulation is equivalent to injecting fluid, such as a crystal (such as a saline solution) or a colloid, into the bloodstream of a subject over a short period of time (e.g., less than 45 minutes).

[0067] Depending on the type of injected substance, the difference between the second time and the first time can vary significantly. For example, the predetermined cardiac stimulation can be the injection of dopamine or dobutamine or both, and in this way, the response of the heart can be detected very quickly (e.g., within 10 seconds or 15 seconds). In such an example, the difference between the second time and the first time can be less than 1 minute.

[0068] For other substances, the difference can be greater, such as several hours. In one embodiment, the difference is less than 3 hours (for certain cases, even between 3 hours and 6 hours is acceptable).

[0069] In one or more embodiments, the exponent can be a function of the difference between the first value and the second value.

[0070] In one or more embodiments, the exponent can be further calculated based on the first time and the second time.

[0071] In one or more embodiments, the method further comprises:

[0072] - obtaining a set of at least one additional value of the liver stiffness parameter of the subject, each additional value being associated with a time between the first time and the second time;

[0073] wherein the exponent is further determined based on the set of at least one additional value.

[0074] In these embodiments, the exponent is determined based on more than two LS parameter values. This can track the evolution of the LS parameter values over time, such as checking whether the LS parameter has stabilized (or conversely, determining whether the LS parameter has not stabilized, e.g., due to its continued increase), and / or estimating the time when the LS parameter reaches stability, and / or determining the rate of increase or decrease of the change.

[0075] In one or more embodiments, the set of at least one additional value can include n - 2 values LSM2,..., LSM n-1 , where n is an integer greater than or equal to 3, and the exponent can be the following function:

[0076]

[0077] where LSM1 represents the first value of the liver stiffness parameter, and LSM n represents the second value of the liver stiffness parameter,

[0078] where is a real coefficient, for example:

[0079] 。

[0080] In one or more embodiments, the method further comprises: receiving information related to selecting a predetermined cardiac stimulation from a plurality of predetermined cardiac stimulations.

[0081] In these embodiments, the method further comprises: determining a second time associated with a second liver stiffness measurement upon receiving information related to the selection of the predetermined cardiac stimulation.

[0082] Another aspect of the present invention relates to an apparatus for determining an index for evaluating the cardiac function of a subject, the apparatus comprising a calculation module configured to perform the method according to any one of the foregoing embodiments.

[0083] In one or more embodiments, the calculation module is further configured to determine a cardiac condition based on the calculated index and at least one threshold;

[0084] wherein, the apparatus further comprises a display screen configured to display an indicator related to the determined cardiac condition.

[0085] This cardiac condition represents the risk level of cardiac dysfunction of the subject. For example, the cardiac condition can be a categorical variable, which can be labeled as "normal", "below normal", or "abnormal".

[0086] For example, by comparing the determined index with a plurality of predetermined numerical ranges, the label of the cardiac condition can be determined. As a non-limiting example, in one or more embodiments, when the determined index value is within a first predetermined numerical range, the cardiac condition of the subject is considered "normal"; when the determined index value is within a second predetermined numerical range, the cardiac condition of the subject is considered "below normal"; and when the determined index value is within a third predetermined numerical range, the cardiac condition of the subject is considered "abnormal". It should be understood that in other embodiments, more or fewer predetermined numerical ranges can also be used to classify and characterize the determined index.

[0087] In one or more embodiments, a plurality of predetermined numerical ranges of the index can be constructed based on existing liver stiffness measurement values, and these numerical values, numerical differences, or numerical combinations are expected to characterize the cardiac condition.

[0088] In one or more embodiments, multiple predetermined numerical ranges of an index can also be constructed based on available physiological data obtained from various subjects or patients and indicative of various cardiac conditions. Examples of physiological data can include one or more data obtained through pulse measurement, blood pressure measurement, echocardiogram, electrocardiogram, right heart catheterization measurement, stress test, magnetic resonance imaging, and cardiac computed tomography measurement.

[0089] In addition, the display screen can also be configured to display the calculated index either alone or together with the determined cardiac condition.

[0090] For example, the display screen can be configured to display a visual indicator associated with the determined index to estimate the cardiac function (or cardiac condition) of the subject.

[0091] In one or more embodiments, the calculation module can further be configured to obtain at least one piece of information related to the following parameters: the fibrosis parameter of the subject; the biological parameter of the subject; and the anthropometric parameter of the subject;

[0092] And the calculation module can be configured to determine at least one threshold and / or cardiac condition based on the obtained information.

[0093] "Anthropometric parameter" refers to any parameter related to the dimensional characteristics of the subject.

[0094] This information can more precisely interpret the LS parameter value while considering characteristics specific to the subject that may affect the LS parameter value.

[0095] In one or more embodiments, the above device can be an elastography device. Thus, in these embodiments, the determination of the index is performed by the elastography device.

[0096] In these embodiments, the display screen is also configured to display multiple optional predetermined cardiac stimulations.

[0097] Alternatively, the determination of the index can be performed by a separate device connected to or in communication with the elastography device (for receiving the LS parameter value).

[0098] On the other hand, there is provided a computer program product including a non-transitory computer-readable medium having a computer program including program instructions. The computer program can be loaded into a data processing unit, and is adapted to cause the data processing unit to execute the above method when the computer program runs on the data processing unit.

[0099] Other features and benefits of the methods and devices disclosed herein will become apparent from the following description of non-limiting embodiments and with reference to the accompanying drawings. Description of the Drawings

[0100] In the drawings, various aspects of the present invention are shown by way of example and not limitation, where like reference numerals denote like elements, and wherein:

[0101] Figure 1 is a flowchart depicting an embodiment of the present invention;

[0102] Figure 2 shows an example of a computing module configured to implement a method for determining an index for evaluating the cardiac function of a subject;

[0103] Figure 3 shows an example of an apparatus for determining an index for evaluating the cardiac function of a subject in one embodiment of the present invention;

[0104] Figure 4 shows an example of an apparatus for determining an index for evaluating the cardiac function of a subject in another embodiment of the present invention. Detailed Description of the Invention

[0105] Figure 1 is a flowchart depicting an embodiment of the present invention. As detailed below, Figure 1 the steps of can be performed by a computing module or processing circuit integrated in, connected to, or communicating with an elastography device.

[0106] In a first step 110, a first value of the liver stiffness (LS) parameter of a subject is obtained. This first value LSM1 is associated with a first time t1.

[0107] In step 120, a second value of the LS parameter of the subject is obtained. This second value LSM2 is associated with a second time t2, where the second time t2 is strictly greater than t1: t 2> t1.

[0108] Elastography is performed using an elastography device to carry out a first liver stiffness measurement and a second liver stiffness measurement. For example, the first liver stiffness measurement and the second liver stiffness measurement can be performed by transient elastography (such as vibration-controlled transient elastography), acoustic radiation force-based elastography, or magnetic resonance elastography.

[0109] In one or more embodiments, the elastography device may include a measurement probe, a processing circuit, and one or more non-transitory memories encoded with instructions to perform the various functions, steps, programs, or actions of the methods and devices or device elements disclosed herein.

[0110] In one or more embodiments, the elastography device may further include a display and a graphical user interface. The display and the graphical user interface may be controlled by the processing circuitry to cause the graphical user interface to display visual information to prompt an operator of the elastography device to perform a first liver stiffness measurement and a second liver stiffness measurement at a predetermined time. The graphical user interface of the elastography device may also be configured to prompt the operator to initiate one or more predetermined cardiac stimulations on a subject / patient being examined. For example, in one or more embodiments, the graphical user interface of the elastography device may be configured to display a drop-down menu that includes a plurality of selectable predetermined cardiac stimulations to be performed on the subject / patient being examined. In one or more embodiments of the present invention, each of the selectable predetermined cardiac stimulations to be performed on the subject / patient is associated with a specific first time t1 and / or a second time t2 at which the first liver stiffness measurement and / or the second liver stiffness measurement should be performed. The specific first time t1 and / or the second time t2 associated with the selectable predetermined cardiac stimulation may be automatically adjusted based on additional parameters input by the operator of the elastography device into the elastography device. As a non-limiting example, the additional parameters may include the age, height, weight, body mass index (BMI), body surface area (BSA), fat mass index, waist circumference, presence or absence of sarcopenia, frailty index or score, right ventricular or left ventricular ejection score, right atrial or left atrial diameter or volume, inferior vena cava diameter, circulating BNP (B-type natriuretic peptide), and / or pro-BNP.

[0111] In one or more embodiments of the present invention, the liver stiffness measurement may be triggered automatically or manually. In one or more embodiments of the present invention, selecting a predetermined cardiac stimulation via the graphical user interface may trigger a routine executed by the processing circuitry that prompts an operator of the elastography device to a) perform a first liver stiffness measurement at a first time t1, b) initiate a predetermined cardiac stimulation, and c) perform a second liver stiffness measurement at a second time t2. For example, in one or more embodiments, the processing circuitry of the elastography device may cause the display and the graphical user interface to display visual information to indicate to the operator to a) perform a first liver stiffness measurement at a first time t1, b) initiate a predetermined cardiac stimulation, and c) perform a second liver stiffness measurement at a second time t2. Alternatively or additionally, in one or more embodiments, the processing circuitry of the elastography device may control and cause a speaker of the elastography device or a speaker of a remote device communicatively coupled to the elastography device to indicate to the operator of the elastography device to a) perform a first liver stiffness measurement at a first time t1, b) initiate a predetermined cardiac stimulation, and c) perform a second liver stiffness measurement at a second time t2.

[0112] As described above, it should be understood that the b) predetermined cardiac stimulation may be initiated before a) performing the first liver stiffness measurement at the first time t1.

[0113] It should be noted that in the above example, the display and the graphical user interface (GUI) are integrated in the elastography device. This is not mandatory. In an alternative, an external device (i.e., external to the elastography device) may include a display and a GUI to display visual information to prompt an operator to perform a first liver stiffness measurement and a second liver stiffness measurement on the elastography device at a predetermined time, and to prompt the operator to initiate one or more predetermined cardiac stimulations on the subject / patient under examination. The external device may also include a user interface for receiving the measurement values obtained from performing the measurements (e.g., the operator may input these values using the keyboard or touch screen of the external device).

[0114] Return reference Figure 1 , the first value obtained in step 110 corresponds to the measured value of the LS parameter obtained before the individual receives a predetermined cardiac stimulation that changes his / her cardiovascular system or the measured value of the LS parameter obtained immediately after receiving the predetermined cardiac stimulation. "Immediately after" means that the first value is associated with a time between T and where T is the time when the predetermined cardiac stimulation occurs or ends. Typically on the order of a few seconds, it may also be a few minutes, but in all cases less than 5 minutes and in one embodiment less than 2 minutes. Thus, the first time t1 associated with the first value LSM1 satisfies, for example, or .

[0115] The predetermined cardiac stimulation corresponds to a predetermined event that has an impact on the cardiovascular system of the subject, such as but not limited to changes in heart rate, changes in blood volume in the ventricles, changes in muscle activity, changes in blood fluidity, etc. Generally, the predetermined cardiac stimulation may be at least one of the following:

[0116] - The subject changes posture (raising at least one leg, moving from a raised posture to a lying position, etc.);

[0117] - The subject performs physical activity (e.g., performing low-intensity to high-intensity exercise within a few minutes); and

[0118] - Injecting a substance (vasodilator, vasoconstrictor, saline solution, inotropic solution, etc.) into the subject that changes the hemodynamic characteristics of the subject.

[0119] The above examples may be combined. For example, the predetermined cardiac stimulation may include physical activity and injecting a substance that changes the hemodynamic characteristics of the subject.

[0120] The change in posture changes the blood volume in the heart chambers, which can have a direct impact on possible congestion in a subject with cardiac dysfunction. For example, the change in posture may be at least one of the following:

[0121] - Changing from a standing position to a supine position, or from a supine position to a standing position;

[0122] - Changing from the Trendelenburg position to a supine position, or from a supine position to the Trendelenburg position;

[0123] - Changing from a supine position with at least one leg of the subject lowered to a supine position with at least one leg of the subject raised, or from a supine position with at least one leg of the subject raised to a supine position with at least one leg of the subject lowered; and

[0124] - Changing from the Fowler's position to a supine position, or from a supine position to the Fowler's position.

[0125] This is not restrictive. It should be understood that other posture changes may also be possible. In the above examples, one of the starting or ending postures is the supine position because this is the recommended position for measuring the LSM of the subject, but it can also be other postures.

[0126] The predetermined cardiac stimulation may also include physical activities performed by the subject. In this case, the patient is required to perform one or more series of exercises, which can be changed from low intensity to high intensity and last for several seconds or minutes. For example, the predetermined cardiac stimulation can be a standard cardiac stress test, but the patient can also be made to perform less strenuous physical activities.

[0127] As described above, the physical activity can be combined with the injection of a substance to increase the inotropic stimulation of the heart. The substance can be dobutamine or other inotropic solutions, saline solutions, vasoconstrictor solutions or vasodilator solutions. The vasoconstrictor or vasodilator can be, for example, an arterial vasoconstrictor or vasodilator, a venous vasoconstrictor or vasodilator, or a pulmonary artery vasodilator.

[0128] The physical activity can be replaced by an inotropic intravenous drug stimulation. Therefore, the predetermined cardiac stimulation can only include injecting a substance into the patient. The substance can be a saline solution, an inotropic solution, a vasoconstrictor solution or a vasodilator solution. The predetermined cardiac stimulation can also be a fluid-induced stimulation (injecting fluid, such as a crystal (such as a saline solution) or a colloid, within a short period of time (e.g., within 45 minutes)) or hemodialysis.

[0129] When the predetermined cardiac stimulation includes injecting a substance into the subject, it should be noted that the aim is to rapidly change the cardiac characteristics, rather than to evaluate the long-term (e.g., over several days) effect of the treatment on heart diseases.

[0130] The second value corresponds to the measured value of the LS parameter after a predetermined cardiac stimulation has been performed and in particular after a first liver stiffness measurement has been performed.The second value is associated with a second time t2 which is strictly greater than the first time t1: t2>t1.

[0131] Depending on the embodiment, the second value corresponds to a LSM measurement value a few seconds to a few minutes or even a few hours after performing the predetermined cardiac stimulation.

[0132] Where possible, the first value corresponds to the value of the LS parameter before the predetermined cardiac stimulation was performed. However, this is not always optimal, for example when the predetermined cardiac stimulation is "subject moves from standing position to lying position", because it is not recommended to measure the LS of a standing subject. Therefore, in this last example, the subject remains in a standing position for a while and then he may be asked to lie down. The first value of LS is measured just after he lies down, while the second value of LS is measured a few minutes later.

[0133] In any case, in the context of the present invention, the difference between the second time and the first time comprises up to 6 hours, for example:

[0134] 0<t2-t1<6 hours.

[0135] The LS parameter may be any parameter related to the LS of the subject.

[0136] In one or more embodiments, the LS parameter corresponds to a single value of the LS measurement (LSM). For example, each value of the LSM i (in ) can be compared with the corresponding time t i The LSM performed on the subjects corresponds to that of the subjects.

[0137] In an alternative embodiment, a sequence of J LS measurements may be used. Calculate LS parameters LSM i , J is an integer strictly greater than 1. For example, when the operator triggers a measurement, the measurement sequence can be acquired with a predefined frequency (for example, from 4 measurements per second to 1 measurement per k seconds, where k is an integer between 1 and 5, depending on the elastic imaging technology used). The LS parameter can be derived by any statistical parameter determined from the measurement sequence. Typically, the LS parameter may correspond to the mean or median of the measurement sequence, but other statistical parameters may also be used. The parameter may also be a combination of several statistical parameters, such as a combination of at least one position parameter (mean, median, quantile, minimum, maximum, etc.), and finally combined with at least one dispersion parameter (standard deviation, coefficient of variation, etc.). With the value LSM i The associated time t iIt may be the time to trigger a series of measurements (corresponding to the time of obtaining the first measurement result, with a final delay of a predefined offset), but there may also be other implementations. For example, the time can be defined as the time of obtaining the last measurement result in the measurement sequence, or the average time between the first measurement and the last measurement in the measurement sequence.

[0138] In other implementations, the elastography device is configured to obtain a signal LSM(t) representing the change of LSM over time, as described in EP patent application number EP23305032.7. In these implementations, the LS parameter can be a function of the maximum value, minimum value, average value, standard deviation, and / or percentage of the obtained signal LSM(t). For example, it can be based on the signal LSM(t) measured during a time interval (e.g., the average value or amplitude of the LSM signal during the time interval ) to determine each value LSM of the LS parameter i ( ). For example, the time t i associated with this value LSM i can correspond to or (with a final delay of a predefined offset), corresponding to the average time of , or any other time related to the time interval .

[0139] Now some examples of predefined cardiac stimulation are provided to illustrate one or more embodiments of the present invention. These examples are not restrictive.

[0140] In the first example, the predefined cardiac stimulation corresponds to a postural change from a standing position to a supine position. Since it is not recommended to perform LS measurement in the standing position, the first value LSM1 of the LS parameter can be associated with the time t1 immediately after the postural change (i.e., when the patient is lying down). For example, the first value LSM1 can be measured within 5 to 90 seconds after the postural change. The second value LSM2 of the LS parameter can be associated with the time t2 within 1 to 5 minutes after t1.

[0141] In this first example, it is expected that the difference between the second value and the first value is lower in healthy subjects and higher in patients with cardiac dysfunction or heart failure.

[0142] ​In a second example, the predefined cardiac stimulus corresponds to a change in posture from a supine position to a Trendelenburg position. The first value LSM1 can be measured in the supine position (i.e., before the posture change, e.g., 1 to 15 minutes before the posture change). The second value LSM2 is measured immediately after the posture change, i.e., just after the subject is in the Trendelenburg position (e.g., within 5 minutes after the posture change).

[0143] In both of these examples, the predefined cardiac stimulus is a change in posture, typically lasting for a few seconds.

[0144] In a third example, the predefined cardiac stimulus corresponds to physical exercise experienced by the subject. For example, the physical exercise can include a series of movements such as squats, lunges, crunches, burpees, etc., or any combination of these movements. In this example, the predefined cardiac stimulus (i.e., the physical exercise) can typically last from a few minutes to several tens of minutes, e.g., between 5 minutes and 30 minutes. The first value LSM1 can be measured in the supine position before the physical exercise. The second value LSM2 can be measured in the supine position after the physical exercise (e.g., within 15 minutes after the physical exercise ends).

[0145] In a fourth example, the predefined cardiac stimulus corresponds to a dialysis procedure. In this example, the predefined cardiac stimulus typically lasts for several hours, e.g., 3 to 5 hours. The first value LSM1 can be measured in the supine position before the dialysis begins. The second value LSM2 can be measured in the supine position after the dialysis ends (e.g., within 15 minutes after the dialysis ends).

[0146] In a fifth example, the predefined cardiac stimulus corresponds to a fluid-induced stimulus, i.e., injecting a substance into the patient's blood. The substance can be, for example, a saline solution, a vasodilator or vasoconstrictor substance, or an inotropic substance. In this example, the predefined cardiac stimulus can last from a few minutes to several hours, e.g., 1 minute to 3 hours. The first value LSM1 can be measured in the supine position before the substance injection begins. The second value LSM2 can be measured in the supine position after the substance injection ends (e.g., within 15 minutes after the injection ends).

[0147] Referring again to Figure 1 , in step 130, an index (referred to as the cardiohepatic congestion index CHCI (or CHC index)) for evaluating the cardiac function of the subject is calculated or determined based on a function of the first value and the second value of the LSM parameter: 。In one or more embodiments, the processing circuitry of the elastography device determines the index. Alternatively, the processing circuitry of a remote electronic terminal or a remote server in communication with the elastography device is used to determine the index. In the latter embodiment, the remote electronic terminal or the remote server may communicate with the elastography device via a wired link or a wireless link. According to an embodiment, the CHC index may take on real or integer values. For example, the CHC index may take on any real value, or a real value strictly greater than 0, or a real value between -1 and 1 or between 0 and 1. In an embodiment, the CHC index may be a categorical (or "qualitative") variable (e.g., a risk level or severity level of cardiac dysfunction).

[0148] In some embodiments, the higher the index value, the greater the risk that the subject has cardiac dysfunction. Conversely, the closer the index is to 0, the lower the risk that the subject has cardiac dysfunction, and thus the heart function is "normal".

[0149] It should be understood that the CHC index may be defined such that a value close to 0 corresponds to a high risk of cardiac dysfunction and a high index value corresponds to a low risk of cardiac dysfunction.

[0150] The CHC index reflects the change in the LS parameter caused by a predetermined cardiac stimulus that may cause or relieve cardiac congestion.

[0151] In an embodiment, the CHC index is the difference between a second value of the LS parameter and a first value of the LS parameter as a function of:

[0152]

[0153] where 。

[0154] For example, the CHC index may be defined as:

[0155] 。

[0156] In this example, the CHC index represents the change in the LS parameter caused by a predetermined cardiac stimulus.

[0157] The index may also be divided by a reference value homogeneous with the modulus to make it dimensionless, e.g.:

[0158] 。

[0159] In an alternative or supplementary embodiment to the previous embodiments, the CHC index may be further calculated based on times t1, t2 associated with values LSM1, LSM2 of the LS parameter: 。

[0160] For example, the CHC index can correspond to the rate of change of the LS parameter (or a function thereof) and is defined as follows:

[0161] .

[0162] Other forms of functions can also be used to define the CHC index. For example, the CHC index can be in the form of a logical equation, such as:

[0163]

[0164] where β is a real coefficient.

[0165] The time T at which the predetermined cardiac stimulation occurs can also be used to calculate the CHC index: .

[0166] In all the examples provided above, the absolute value of the formula can be taken to obtain a positive index. Additionally, all the above formulas can be multiplied by a constant coefficient, thereby reducing the possible values to values within a certain range. This coefficient can also be directly or inversely proportional to the baseline LS value (e.g., a value of the LS parameter) to compensate for the influence of baseline liver fibrosis on the change in LSM before and after the execution of the predetermined cardiac stimulation.

[0167] Referring again to Figure 1 , in optional step 140, at least one additional value related to the subject can be obtained. Note that step 140 can be performed before steps 110, 120, and / or 130, or in parallel with these steps.

[0168] One additional value can be, for example, the fibrosis parameter of the subject, such as the baseline fibrosis value of the subject. In particular, this additional value can be the baseline value of the LS parameter. For example, when the subject has significant fibrosis, even in the absence of congestion, the daily (or "normal") value of the subject's LSM is relatively high. The baseline value of the LS parameter can be the LS parameter value determined after the subject has lain down for a sufficient length of time (e.g., from several minutes to dozens of minutes, such as 15 minutes), so that the LSM value is stable. Such a baseline value provides a reference for determining how the heart adapts to the predetermined cardiac stimulation.

[0169] Alternatively or additionally, one additional value can be the biological or anthropometric parameter of the subject. For example, the additional value includes at least one blood biomarker (biological parameter). The anthropometric parameter can be, for example, body mass index (BMI), body surface area (BSA), height, weight, age, waist circumference, fat mass index, presence or absence of sarcopenia, right ventricular or left ventricular ejection score, inferior vena cava diameter, circulating BNP or pro-BNP, etc.

[0170] As described above, in the case of measuring the baseline LS, this value can be used to determine the CHC index (in this case, step 140 is performed between steps 130). This value can also be used to interpret the CHC index value, as detailed below. In fact, the fibrosis level of the subject and certain biological or anthropometric parameters may affect the average value of the subject's LS parameters, or the degree to which a predetermined cardiac stimulation affects the LS parameter value. Therefore, in order to avoid interpretive biases associated with confounding factors, these parameters can be considered to correct or analyze the CHC index value.

[0171] When using at least one additional value to interpret the CHC index (but not calculate the CHC index), step 140 can be performed after (or before) step 130.

[0172] In optional step 150, at least one threshold can be obtained. The at least one threshold can be received by a computing module or processing circuit (e.g., in the case of a predefined threshold) or determined. The at least one threshold obtained in step 150 can define a risk level of cardiac dysfunction, and thus the risk level of the subject can be determined (in step 160) based on the CHC index value of the subject and the at least one threshold.

[0173] In one or more embodiments, the at least one threshold can be equal to at least one predefined value. For example, when the CHC index corresponds to the absolute value of the difference between a second value and a first value of the LS parameter (i.e., CHCI = |LSM2 - LSM1|), two predefined thresholds can be received: Th1 and Th2. If CHCI ≤ Th1, the subject is considered to be at "low risk", if Th2 ≤ CHCI ≤ Th1, the subject is considered to be at medium risk, and if CHCI > Th2, the subject is considered to be at high risk. For example, Th1 = 2 kPa and Th2 = 20 kPa. It should be understood that other values can also be used, and multiple levels other than 3 levels can also be defined.

[0174] In embodiments where the threshold is predefined and received by the computing module, step 150 can be performed before 110, 120, 130, and / or 140, or in parallel with one or more of these steps.

[0175] In the above example, the threshold is the same for all subjects. Alternatively, the predetermined threshold may depend on other characteristics, such as the average degree or average value of fibrosis of the subject, or the subject's BMI (Body Mass Index) / weight / height / body fat index / sarcopenia / etc. In such an embodiment, the threshold for one subject may vary from another subject according to their characteristics. These characteristics may correspond to fibrosis parameters, biological parameters, and / or anthropometric parameters of the subject. For example, these characteristics may correspond to all or part of the parameters received in step 140.

[0176] In an embodiment, in step 150, the calculation module may thus determine the threshold based on the additional value received in step 140. In these embodiments, step 150 must be performed after step 140.

[0177] In other embodiments, the threshold is not a predefined value, and the calculation module is configured to determine the threshold based on a reference value and the additional value received in step 140. In these embodiments, step 150 must also be performed after step 140.

[0178] In some of the above embodiments, the additional value received in step 140 is considered to determine the threshold for comparison with the CHC index, so as to evaluate (step 160) the risk level of the subject. This can avoid the deviation caused by the parameters related to the LS parameter value of the subject (e.g., the fibrosis, biological, or anthropometric parameters of the subject).

[0179] Alternatively, this "correction" can be performed at the level of the CHC index itself rather than at the level of the threshold. Thus, in an alternative embodiment, a "corrected" value of the CHC index is determined based on the value determined in step 130 and the additional value received in step 140. To determine (step 160) the risk level of the subject, the corrected CHC index can be compared with the threshold obtained in step 150, which is the same for all subjects.

[0180] As described above, in optional step 160, the risk level can be determined based on the CHC index determined in step 130, the threshold obtained in step 150, and the additional value obtained in step 140. The risk level represents the risk that the subject has cardiac dysfunction. Therefore, it represents the cardiac function of the subject. For example, a "high risk" level can detect potential cardiac dysfunction, while a "low risk" level reflects normal cardiac function.

[0181] When the CHC index is a categorical variable, step 150 can be omitted, and the CHC index determined in step 130 and the additional value obtained in step 140 can be used to determine the new risk level in step 160.

[0182] Finally, in step 170, the CHC index and / or the risk level can be displayed on a display device controlled by the calculation module.

[0183] Even though the method has been described by taking the calculation of the CHC index based on two values of the LS parameter as an example, Figure 1 it should be noted that the present invention is not limited to this case. For example, instead of Figure 2 steps 110 and 120, a set of N values LSM1,..., LSM N of the LS parameter can be obtained, where N is an integer strictly greater than 2. Each value LSM i can be associated with a corresponding time t i , where:

[0184] t1 < t2 <... < t N-1 < t N .

[0185] At least one value LSM i corresponds to the value of the LS parameter obtained before the execution of a predetermined cardiac stimulation (as defined above) or immediately after the execution of a predetermined cardiac stimulation, and at least one value LSM i corresponds to the value of the LS parameter after the execution of a predetermined cardiac stimulation. The difference between the last time t N and the first time t1 is less than 6 hours: 0 < t N - t1 < 6 hours.

[0186] This corresponds to generalizing the case in Figure 1 where N = 2.

[0187] Obtaining the LS additional value can track the evolution of LSM over time and thus determine whether the LSM value is stable "normally" (i.e., as expected for a subject without cardiac dysfunction). In particular, based on this set of measurements, one or more slopes or time constants representing the stable rate of the liver stiffness of the patient can be determined. The CHC index can be determined by these slopes or time constants. The more the number of LS parameter values, the more precisely the evolution of LSM can be determined.

[0188] In one or more embodiments, the CHC index CHCI can be calculated as a function of the first value and the second value of the LSM parameter: .

[0189] For example, the CHC index may have the following form:

[0190]

[0191] where is a set of real-valued weights.

[0192] To eliminate the influence of components other than congestion (especially components related to fibrosis and inflammation), the weights can be chosen as:

[0193] .

[0194] As described above, the CHC index can be further calculated based on the times t1,..., t N associated with the LS parameter values LSM1,..., LSM N :

[0195] .

[0196] In an embodiment, when a series of values LSM1, LSM2,..., LSM N of the LS parameter are obtained, several CHC index values can be calculated and the variation of the CHC index values over time can be analyzed. In fact, for certain predefined cardiac stimulations, especially for predefined cardiac stimulations including physical activity or injection of a substance into the blood, an increase followed by stabilization of the "before / after" difference (absolute value) is expected.

[0197] For example, a series of values , k = 2,..., N, can be determined, where LSM1 is the LS parameter value obtained before or immediately after performing a predefined cardiac stimulation, and LSM k (k = 2,..., N) is a set of LS parameter values after performing the predefined cardiac stimulation (and after the time associated with LSM1).

[0198] In this example, the variation of the CHC index values over time can be analyzed to monitor an increase, decrease, or stabilization of the index, which can provide an indication of the health status of the subject. In fact, after performing a predefined cardiac stimulation, the heart may take several minutes to adapt, so the LSM may take several minutes to normalize. Thus, the evolution of the CHC index over time and / or the evolution of the LS parameter values over time can provide information about the way the heart adapts after performing a predefined cardiac stimulation, and thus provide information about the severity of a potential cardiac dysfunction.

[0199] In one or more embodiments, the processing circuitry may be configured to determine and output a “continuous” signal representative of the LSM over time, e.g., where the frequency of measuring the LS parameter value is greater than 4 times per second, e.g., between 10 and 20 measurements per second. Known functions may be utilized to adjust the signal, e.g., using polynomial adjustment or exponential adjustment (or “regression”), e.g., using the least squares adjustment method.

[0200] In the case of exponential adjustment, the LSM may be approximated using the following function:

[0201]

[0202] where τ is a time constant representative of the stable rate of the LSM value.

[0203] In another example, the CHC index may be a classification value for representing the severity level of potential cardiac dysfunction determined based on a series of values {LSM1, LSM2, …, LSM N} (more specifically, based on the evolution of the LS parameter value over time). For example, the CHC index may take one of the following levels: “normal” if the LS parameter value remains stable or decreases over time, “moderately severe” if the LS parameter value increases and then decreases over time, “severe” if the LS parameter value increases and then stabilizes, and “very severe” if the LS parameter value continues to increase.

[0204] It should be noted that the above different levels may also be determined based on the change of the quantitative CHC index over time rather than the change of the LS parameter value over time.

[0205] Figure 2 An example of a computing module or processing circuitry configured to implement a method for determining an index for evaluating the cardiac function of a subject in an embodiment of the present invention.

[0206] In this embodiment, the computing module or processing circuitry 200 may form at least a part of a computer and includes a non-transitory memory 201 to store program instructions loadable into a circuitry 202 (e.g., a microelectronic circuitry or circuit system), and when the program instructions are executed by the circuitry 202, the program instructions are adapted to cause the circuitry 202 to perform one or more steps of the apparatus functions or methods described herein.

[0207] The memory 201 may also store data and useful information for performing the method steps described herein. For example, the circuitry 202 may be:

[0208] - A processor or processing unit adapted to interpret instructions in a computer language, the processor or processing unit may include or be associated or attached to a memory including the instructions, or

[0209] - A combination of a processor / processing unit and a memory, the processor or processing unit being adapted to interpret instructions in a computer language, the memory including the instructions, or

[0210] - An electronic card, in which steps of the present invention are described within a silicon chip, or

[0211] - A programmable electronic chip, such as an FPGA chip (Field Programmable Gate Array).

[0212] The computing module or processing circuit 200 further includes an input interface 203 for receiving LS parameter values, as well as additional values and predefined thresholds, and an output interface 204 for providing at least a calculated value of the CHC index (and ultimately determining the risk level of cardiac dysfunction of the subject under test).

[0213] Optionally, the computer circuit 202 can be connected to a screen and can be configured to control the screen and the graphical user interface such that the graphical user interface displays predetermined information, such as a visual representation of the calculated value of the CHC index and / or the determined risk level of cardiac dysfunction of the subject under test, and / or visual information indicating to the operator of the elastography device to perform one or more steps of the method described herein. The computer circuit 202 can also be configured to control the screen and the graphical user interface such that the graphical user interface displays additional information, such as but not limited to elasticity values, hardness measurement results, a measurement ready signal indicating that the probe is properly abutted against the skin of the subject / patient, and / or elastography information and / or patient information, such as the age, weight, and / or height of the patient. Additionally, in one or more embodiments, the computer circuit 202 can also be configured to control a speaker of the elastography device or a speaker of a remote device communicating with the elastography device to emit audible sounds, such as but not limited to sound instructions indicating to the operator of the elastography device to perform one or more steps of the method described herein.

[0214] Figure 3 An example of a device for determining an index for evaluating the cardiac function of a subject under test according to an embodiment of the present invention.

[0215] In this example, the computing module or processing circuit 200 is integrated into the elastography device 300. The elastography device 300 can use any known elastography technique, such as transient elastography, such as vibration controlled transient elastography (VCTE), shear wave elastography (SWE), or acoustic radiation force impulse (ARFI) elastography, or any other type of elastography, such as magnetic resonance elastography (MRE).

[0216] When the elastography device 300 uses ultrasonic elastography technology, the elastography device 300 may include a central unit 302 and an elastography probe 320. The elastography probe 320 is provided with an ultrasonic transducer 322, and the ultrasonic transducer 322 is configured to transmit and receive ultrasonic waves. The elastography probe 320 is connected to the central unit 302 of the elastography device 300 via a wired link or a wireless link. When the elastography device 300 is configured to perform transient elastography, the probe 320 is further configured to transmit transient low-frequency mechanical pulses.

[0217] The elastography device 300 may further include a human-machine interface (HMI) 301 to receive at least one additional value related to, for example, the subject under test ( Figure 1 step 140).

[0218] The elastography device 300 may include a screen 310 for displaying information related to the patient via a graphical user interface 311, such as one or more elastography measurement results, and the CHC index calculated by the calculation module and / or the determined risk level of cardiac dysfunction. The screen 310 and the graphical user interface 311 may be controlled by the calculation module or the processing circuit 200 or by a separate processing circuit of the elastography device 300 that communicates with the calculation module or the processing circuit 200.

[0219] In Figure 3 the example, the calculation module or the processing circuit 200 for implementing the calculation of the CHC index may be a dedicated module or circuit, or the same module as the calculation module or the processing circuit for determining the LSM value.

[0220] It should be noted that Figure 3 all or part of the components in

[0221] Figure 4 represents an example of a device for determining an index for evaluating the cardiac function of a subject under test in another embodiment of the present invention.

[0222] Unlike Figure 3 the elastography device of Figure 4The calculation module or processing circuit 200 is located outside the elastography device 400. In this embodiment, the calculation module or processing circuit 200 is connected to the elastography device 300 via a wired link or a wireless link 330 (such as Wi-Fi, Bluetooth®, ZigBee, etc.) to receive the LS parameter values (determined by the elastography device 300) from the elastography device 300. The calculation module or processing circuit 200 is configured to calculate the CHC index values (and ultimately calculate the risk level of cardiac dysfunction) and transmit these values to the elastography device 300, for example, to a single internal module or processing circuit of the elastography device 300. Then, the elastography device 300 can display these values on the screen 310. In this embodiment, a single internal module or processing circuit of the elastography device 300 can be used to control the display 310 and the graphical user interface 311 of the elastography device 300. Alternatively, the calculation module or processing circuit 200 can be integrated into a device that is separate from the elastography device and has its own display or screen and graphical user interface (e.g., a user device such as a smart phone or a tablet computer) to display the above information.

[0223] In Figure 3 or Figure 4 embodiments, the graphical user interface 311 of the screen 310 can also display instructions for guiding the operator through the procedure (e.g., "Place the subject in a supine position", "Trigger the first measurement", "Lift the subject's left leg", "Trigger the second measurement"). The elastography devices 300, 400 can also include a speaker 340 to issue instructions to guide the operator through the procedure.

[0224] For example, in one or more embodiments, the display screen 310 and the graphical user interface 311 can be controlled by the calculation module or processing circuit 200 or by the main processor or main control circuit of the elastography devices 300, 400 to display a drop-down menu including a plurality of optional predetermined cardiac stimulations to be performed by the subject. In one or more embodiments of the present invention, each of the optional predetermined cardiac stimulations to be performed by the subject is associated with a specific first time t1 and / or a second time t2 at which the first liver stiffness measurement and / or the second liver stiffness measurement should be performed. In one or more embodiments of the present invention, selecting a predetermined cardiac stimulation via the graphical user interface triggers the operator of the elastography devices 300, 400 to perform the following processes or procedures: a) perform the first liver stiffness measurement at the first time t1, b) initiate the predetermined cardiac stimulation, and c) perform the second liver stiffness measurement at the second time t2. In one or more embodiments of the present invention, the graphical user interface is configured to display a visual indicator representing the determined cardiac function index based on the liver stiffness values of the first and second measurements to provide an indication of the cardiac condition of the subject.

[0225] In Figure 3 or Figure 4 In embodiments, the CHC index value and / or the risk level can be transmitted to a separate external device, such as a medical device for monitoring vital signs.

[0226] When interpreting this specification and its associated claims, expressions such as "comprising", "including", "incorporating", "containing", "is" and "has" should be interpreted in a non-exclusive manner, i.e., as allowing the presence of other items or components not specifically defined.

[0227] Those skilled in the art will readily understand that various parameters disclosed in the specification can be modified and various disclosed embodiments can be combined without departing from the scope of the present invention.

Claims

1. A computer-implemented method for determining an index for evaluating the cardiac function of a subject, the method comprising: Obtaining a first value of the liver stiffness parameter of the subject, the first value being associated with a first time; Obtaining a second value of the liver stiffness parameter of the subject, the second value being associated with a second time that is strictly greater than the first time; And Determining the index based on the first value and the second value of the liver stiffness parameter of the subject; Wherein the first value corresponds to the value of the liver stiffness parameter before performing a predetermined cardiac stimulation or the value of the liver stiffness parameter obtained immediately after performing the predetermined cardiac stimulation, the predetermined cardiac stimulation changes the cardiovascular system of the subject, and the second value corresponds to the value of the liver stiffness parameter after performing the predetermined cardiac stimulation; Wherein the difference between the second time and the first time is at most 6 hours.

2. The method according to claim 1, wherein the predetermined cardiac stimulation comprises at least one of the following: A change in the posture of the subject; Physical exercise performed by the subject; and Injecting a substance that changes the hemodynamic characteristics of the subject.

3. The method according to claim 2, wherein the predetermined cardiac stimulation is a change in the posture of the subject, and the difference between the second time and the first time is at most 15 minutes.

4. The method according to claim 3, wherein the change in posture is at least one of the following: Changing from a standing position to a supine position, or from a supine position to a standing position; Changing from the Trendelenburg position to a supine position, or changing from a supine position to the Trendelenburg position; Changing from a supine position with at least one leg of the subject lowered to a supine position with at least one leg of the subject raised, or changing from a supine position with at least one leg of the subject raised to a supine position with at least one leg of the subject lowered; and Changing from the Fowler's position to a supine position, or from a supine position to the Fowler's position.

5. The method according to claim 2, wherein the predetermined cardiac stimulation comprises a predetermined physical exercise.

6. The method according to claim 5, wherein the predetermined cardiac stimulation further comprises administering a myogenic substance, a vasoconstrictive substance, or a vasodilatory substance.

7. The method according to claim 2, wherein the predetermined cardiac stimulation comprises injecting a substance that changes the hemodynamic characteristics of the subject, and the predetermined cardiac stimulation corresponds to a fluid-induced predetermined cardiac stimulation or hemodialysis.

8. The method according to any one of the preceding claims, wherein the index is a function of the difference between the first value and the second value.

9. The method according to any one of the preceding claims, wherein the index is further determined based on the first time and the second time.

10. The method according to any one of the preceding claims, further comprising: Obtaining a set of at least one additional value of the liver stiffness parameter of the subject, each additional value being associated with a time between the first time and the second time; The index is also determined based on the set of the at least one additional value.

11. The method according to claim 10, wherein the set of at least one additional value comprises n - 2 values LSM2, …, LSM n-1 , where n is an integer greater than or equal to 3, and wherein the exponent is the following function: Among them, LSM1 represents the first value of the liver stiffness parameter, and LSM2 represents the second value of the liver stiffness parameter. Among them, are real coefficients, for example: 。 12. An apparatus for determining an index for evaluating the cardiac function of a subject, the apparatus including a calculation module configured to perform the method according to any one of the preceding claims.

13. The apparatus according to claim 12, wherein the calculation module is further configured to determine a cardiac condition based on the determined index and at least one threshold; wherein the apparatus further includes a display screen configured to display an indicator related to the determined cardiac condition.

14. The apparatus according to claim 13, wherein the calculation module is further configured to obtain at least one piece of information related to the following parameters: the fibrosis parameter of the subject; the biological parameter of the subject; and the anthropometric parameter of the subject; and wherein the calculation module is configured to determine the at least one threshold and / or the cardiac condition based on the obtained information.

15. The apparatus according to any one of claims 12 to 14, the apparatus being an elastography device.

16. A non-transitory computer-readable storage medium having stored thereon a computer program including program instructions, the computer program being loadable into a data processing unit and, when run by the data processing unit, being adapted to cause the data processing unit to perform the method according to any one of claims 1 to 11.

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