Devices, systems and methods for determining a renal denervation treatment response index

Abstract

The present invention relates to determining a treatment response index. In order to improve and facilitate a hypertension treatment process, a device (10) for determining a treatment response index is provided, the device comprising a data input unit (12), a data processor (14) and a data output unit (16). The data input unit is configured to receive a value (18) of at least one first measurement result of a physiological parameter of a subject's renal vasculature under a first condition. And provide a value (20) of at least one second measurement result of a physiological parameter of the vasculature under a second condition. Under the second condition, a predetermined stimulus is provided, and the first condition is unstimulated or at least differently stimulated. The data processor is configured to generate a treatment response index. In an example, the data output unit is configured to classify a subject into one of at least two groups of subjects based on the treatment response index.

Description

Technical Field

[0001] The invention relates to a device for determining a treatment response index, a system for determining a treatment response index and a method for determining a treatment response index, as well as a computer program element and a computer-readable medium. Background Art

[0002] Hypertension is associated with major health risks. One of the causes of hypertension is sympathetic overdrive, which affects renal function and blood pressure regulation because it causes vasoconstriction of peripheral vessels, especially the renal arteries. Renal denervation (RDN) is a treatment option to block nerve signals and lower blood pressure in patients with resistant or uncontrolled hypertension. However, the efficacy of renal denervation varies widely between patients. Previous and ongoing trials of renal denervation have shown that responses vary widely between patients undergoing renal denervation. It has been shown that this can make the hypertension management process cumbersome. Summary of the invention

[0003] Therefore, there may be a need to improve and facilitate the hypertension management process.

[0004] The objects of the invention are solved by the subject matter of the independent claims; further embodiments are incorporated in the dependent claims. It should be noted that the aspects of the invention described below are applicable to devices, systems and methods for determining a treatment response index to classify patients who can be successfully treated, and only exemplarily describe devices, systems and methods for determining a treatment response index for renal denervation.

[0005] According to the present invention, a device for determining a renal response index is provided. The device includes a data input, a data processor and a data output. The data input is configured to provide the value of at least one first measurement result of a physiological parameter of the renal vasculature of an object under a first condition. The data input is also configured to provide the value of at least one second measurement result of a physiological parameter of the renal vasculature under a second condition. Under the second condition, a predetermined stimulus is provided, and the first condition is unstimulated or at least differently stimulated. The data processor is configured to determine a ratio between the at least one second measurement result and the at least one first measurement result. The data processor is also configured to generate a renal response index based on the determined ratio and the predetermined stimulus. The data output is configured to provide the renal response index.

[0006] The Renal Responsiveness Index provides valuable information about possible renal denervation processes. Thus, as mentioned above, the Renal Responsiveness Index supports hypertension management, since renal denervation is an example of a measure to be taken to manage hypertension. The Renal Responsiveness Index provides a convenient support to the user to make further decisions about other possible steps. The Renal Responsiveness Index provides objective data to the user in an intuitive manner.

[0007] The renal response index may also be called the renal denervation index or the renal denervation response index.

[0008] In one example, the first condition is not stimulated by an external stimulus.

[0009] In one example, the first condition is less stimulating.

[0010] In another example, different kinds of stimulation are provided under the first condition than under the second condition. Different stimulations induce different responses and thus can provide measurement data suitable for determining an index.

[0011] The term "ratio" refers to a calculated relationship of at least two values ​​of the measurement results. The term "index" refers to an indication about the likely response to renal treatment. The ratio itself may already implicitly provide information about such a response. However, in the examples, the index is a modified indication, such as a ratio applied to the calculation step to provide an intuitive and recognizable index.

[0012] In one example, a generalized index / ratio is defined for two measurements V1 and V2 as:

[0013] (a V1+b V2) / (c V1+d V2)

[0014] This allows ratios such as V1 / V2, but also allows, for example, dividing the difference between values ​​by the mean, eg a=1, b=-1, c=d=0.5.

[0015] In one example, more than two values ​​V1, V2, V3, . . . are provided.

[0016] According to an example, the data input unit is configured to receive a value of at least one first measurement data and / or a value of at least one second measurement result from at least one device of the group including an intravascular device and a non-invasive external device including an extravascular imaging device.

[0017] In one example, the data input unit is configured to receive a value of at least one first measurement data and / or a value of at least one second measurement from the intravascular device.

[0018] In another example, the data input unit is configured to receive a value of at least one first measurement data and / or a value of at least one second measurement result from the extravascular imaging device.

[0019] According to an option additionally or alternatively provided, the physiological parameter is at least one of the group consisting of vascular blood pressure, pulse wave velocity, vascular impedance, vascular blood flow, vascular blood flow velocity and vascular geometry.

[0020] According to one example, the predetermined stimulus for the second condition is provided as at least one of the group of physical manipulation, drug stimulation, and electrical stimulation.

[0021] According to an option provided additionally or alternatively, the stimulation causes a hemodynamic change. The renal response index is determined as at least one item from the group consisting of a vascular impedance change index, a renal blood flow change index, a pulse propagation change index, and a pulse reflex change index.

[0022] According to one example, the data processor is further configured to determine whether the generated renal response index is below or above a predetermined threshold, the threshold indicating possible suitability for renal denervation. In addition, the data output is configured to provide a threshold indicator. Further, the renal response index provides for stratification of individuals into at least two groups, wherein one of the groups indicates that the subject is unlikely to respond well to renal denervation therapy.

[0023] The thresholds are based on empirical data, such as data retrieved from clinical studies.

[0024] According to one example, the data input is configured to provide the values ​​of the first measurement result for the left renal artery and for the right renal artery under a first condition. The data input is also configured to provide the values ​​of the second measurement result for the left renal artery and for the right renal artery under a second condition.

[0025] In a first option, the data processor is configured to: i) determine a ratio between the second measurement and the first measurement for each of the left and right renal arteries, respectively, and generate a respective index for each of the left and right renal arteries, respectively.

[0026] In a second option provided additionally or alternatively, the data processor is configured to: ii) determine an average ratio between the second measurement and the first measurement for the left and right renal arteries and generate the index based on the average ratio.

[0027] In a third option also provided additionally or alternatively, the data processor is configured to: iii) determine an average ratio between the second measurement results and the first measurement results for the left and right renal arteries, and generate the index based on the difference between the left and right measurements divided by the average ratio.

[0028] According to the present invention, a system for determining a renal response index is also provided. The system comprises a measuring device having at least one sensor element, the sensor element being configured to measure at least one physiological parameter of a subject's renal vasculature. The system further comprises an apparatus for determining a renal response index according to one of the aforementioned examples. The system comprises a display device. The measuring device is configured to provide the value of at least one first measurement result and the value of at least one second measurement result to the classification device. The display device is configured to at least display the renal response index generated by the classification device.

[0029] According to one example, the measuring apparatus comprises an intravascular device having at least one sensor element configured to be inserted into a vascular structure of a subject and to measure at least one physiological parameter of a renal vasculature of the subject.

[0030] In one example, the intravascular device is a catheter or guidewire having a sensor in the tip (ie, distal end) region.

[0031] According to one example, the system further comprises a stimulation unit, which is configured to provide electrical stimulation and / or provide drug stimulation via drug supply. In one alternative, the stimulation unit is integrated with the measuring device.

[0032] According to one example, the system further comprises an ablation unit configured to provide kidney ablation. In one alternative, the ablation unit is integrated with the measuring device.

[0033] According to the present invention, a method for determining a renal response index is also provided. The method comprises the following steps:

[0034] a1) Providing at least one first measurement of a physiological parameter of the renal vasculature of a subject under a first condition.

[0035] c1) providing at least one second measurement of a physiological parameter of the renal vasculature under a second condition.

[0036] wherein, under the second condition, a predetermined stimulation is provided, and under the first condition, the renal vasculature of the subject is not stimulated or at least stimulated differently than under the second condition;

[0037] d) determining a ratio between the at least one second measurement result and the at least one first measurement result, and generating a renal response index based on the determined ratio and a predetermined stimulus; and

[0038] e) providing a Renal Response Index, and / or providing a classification of the subjects into at least two groups, said classification being based on said Renal Response Index.

[0039] According to one aspect, the response to one or more specific actions is measured and quantified and set relative to a baseline index to provide an indication of the subject's physiological fitness for possible further treatment suitability.

[0040] According to one aspect, renal vascular parameters are used as an index of renal denervation. In order to provide an assessment method, one or more physiological parameters related to the renal vascular structure (i.e., the vasculature) are measured. At least two measurements are provided, at least one of which relates to a stimulated condition and at least another relates to a non-stimulated or less or differently stimulated condition. These two values ​​can then be used to calculate an index. The index can then provide some objective assessment of whether a particular subject is likely to respond to renal denervation.

[0041] According to one aspect, a system and intravascular device having sensors are provided to measure and display physiological parameters (eg, pulse wave velocity and / or resistance / impedance) in one or both renal blood vessels.

[0042] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Exemplary embodiments of the present invention will be described below with reference to the accompanying drawings:

[0044] Figure 1 An example of an apparatus for determining a renal responsiveness index is schematically shown.

[0045] Figure 2 An example of a system for determining a renal responsiveness index is shown.

[0046] Figure 3 Shows Figure 2 Another example of a system.

[0047] FIG. 4 a shows the basic steps of an example of a method for determining a renal responsiveness index.

[0048] FIG. 4b shows another example of this method.

[0049] FIG. 4c shows another example of this method.

[0050] Fig. 5a schematically shows elements of another example of a setup for determining a renal responsiveness index.

[0051] FIG. 5 b schematically shows a flow chart of data collection and processing of the example of FIG. 5 a .

[0052] FIG. 6 a schematically shows elements of another example.

[0053] FIG. 6 b schematically shows a flow chart of the example of FIG. 6 a .

[0054] Figure 7 Elements of yet another example are schematically shown.

[0055] Figure 8 Elements of another example are schematically shown.

[0056] Fig. 9 Elements of another example are schematically shown.

[0057] Fig.10 Elements of another example are schematically shown. DETAILED DESCRIPTION

[0058] Specific embodiments will now be described in more detail with reference to the accompanying drawings. In the following description, the same reference numerals are used for the same elements even in different drawings. The content defined in the description, such as detailed construction and elements, is provided to help fully understand the exemplary embodiments. Moreover, well-known functions or structures are not described in detail because they would obscure the embodiments with unnecessary details. Moreover, expressions such as "at least one", when preceding a list of elements, modify the entire list of elements and do not modify the individual elements of the list.

[0059] The term "subject" may also be referred to as an individual. A "subject" may also be referred to as a patient, but it should be noted that the term does not indicate whether the subject actually has any disease.

[0060] Figure 1An example of an apparatus 10 for determining a renal response index is schematically shown, comprising a data input 12, a data processor 14, and a data output 16. The data input 12 is configured to receive a value 18 of at least one first measurement of a physiological parameter of the renal vasculature of a subject under a first condition. The data input 12 is also configured to receive a value 20 of at least one second measurement of a physiological parameter of the renal vasculature under a second condition. Under the second condition, a predetermined stimulus is provided, and the first condition is unstimulated or at least differently stimulated. The data processor 14 is configured to determine a ratio between the at least one second measurement and the at least one first measurement. The data processor 14 is also configured to generate a renal response index 22 based on the determined ratio and the predetermined stimulus. The data output 22 is configured to provide the renal response index.

[0061] The box 24 indicated with a dashed line illustrates that the device 10 for determining a renal responsiveness index may be provided as a structural entity, for example in a housing, or as several components.

[0062] Optionally, the data output 16 is configured to provide for classification of the subjects into at least two groups based on the determined renal responsiveness index.

[0063] The device for determining a renal responsiveness index may also be referred to as a "classification device for determining a renal responsiveness index".

[0064] The index is the subject's renal response index, ie, an index of whether and how the subject responds to renal denervation.

[0065] The data input unit 12 may also be referred to as a data input unit or an input unit. The data processor 14 may also be referred to as a data processing unit or a processing unit. The data output unit 16 may also be referred to as a data output unit or an output unit.

[0066] The first and second measurements are done under different conditions. The first condition is the so-called normal condition, in which the subject is under minimal external influences and any possible stimulation is kept to a minimum. The second condition is provided as a so-called special condition, in which the subject is influenced in such a way that a stimulus is provided that may induce a different physiological behavior and thus a different physiological parameter. The (possible) stimuli are predetermined to allow a comparison of the obtained measurements.

[0067] In one example, the first condition is a non-stimulating condition and the second condition is stimulating.

[0068] In another example, the first condition is a stimulating condition and the second condition is a non-stimulating condition.

[0069] In another example, the first condition is a stimulation condition having a first stimulus, and the second condition is a stimulation condition having a second stimulus, but the second stimulus is greater than the first stimulus.

[0070] In another example, the first condition is a stimulation condition with a first stimulus, and the second condition is a stimulation condition with a second stimulus, but the first stimulus is greater than the second stimulus.

[0071] In another example, in one of the first condition and the second condition, a primary predetermined stimulus is provided, and in the other of the first condition and the second condition, a secondary stimulus is provided, wherein the primary predetermined stimulus is different from the secondary stimulus.The stimulation involves a stimulatory effect on the renal vasculature.

[0072] In another example, a plurality of stimuli that are different from each other are provided, and relative changes due to the different stimuli are considered.

[0073] In one example, the stimulation is provided as stimulation of the renal vasculature.

[0074] In another example, stimulation is provided as stimulation of other parts of the subject that causes an effect on the renal vasculature, but without directly stimulating the renal vasculature.

[0075] The first and second measurement results are provided sequentially, for example the second conditional scenario directly follows the first conditional scenario and vice versa, ie the first conditional scenario can also directly follow the second conditional scenario. The term "directly" refers to a very small time span provided therebetween.

[0076] In one example, the time span between two measurements may for example be necessary for preparing the stimulation, ie the application of a stimulation, such as a physical activity or the provision of a drug or some other treatment, or a combination thereof.

[0077] In one example, the index is based on two quasi-static measurements.

[0078] In another example, the index is to determine the response time and / or transition time, so that the "time span" is relevant.

[0079] The determination of the physiological parameters is an objective measurement. The index derived from this data is also an objective assessment, because in the example, the renal response index is based on clinical data. As an example, physiological parameters are collected for multiple cases and the corresponding results of renal denervation treatment are evaluated to identify a threshold for the renal response index. The threshold can also be provided in the form of a range. For example, a range that has been shown to cause specific positive (or negative) results of renal denervation can be identified. In another example, a range can be defined in which it is not possible to clearly assign to one of the two groups, and further steps are recommended for reliable assessment.

[0080] The Renal Responsiveness Index provides an objective assessment of the subject's condition in terms of possible treatment approaches to the renal innervation. The Renal Responsiveness Index thus supports the physician's treatment decisions. The Renal Responsiveness Index provides a relationship between statistical data and current conditions, as shown by objective measurements of physiological parameters. Of course, the index is based on empirical data and has been validated by clinical studies.

[0081] The index, for example provided in the form of a threshold value or a threshold range, provides information on whether a subject undergoing a renal denervation procedure will show positive effects of such renal denervation procedure.

[0082] In one example, the renal responsiveness index relates to the suitability of a corresponding subject for renal denervation surgery.

[0083] In an example, the data input unit 12 is configured to receive a value of at least one first measurement data and / or a value of at least one second measurement result from a device (not shown in detail) of at least one of the group comprising an intravascular device and a non-invasive external device comprising an extravascular imaging device. The physiological parameter is at least one of vascular blood pressure, pulse wave velocity, vascular impedance, vascular blood flow, vascular blood flow velocity and vascular geometry.

[0084] Note that the data input unit 12 is configured to receive data, ie values, from a device such as an intravascular device or an extravascular imaging device, provided as a selection. Note that the type of physiological parameter is also provided as a selection, ie additionally or alternatively.

[0085] In one example, vascular impedance is referred to as flow resistance. Flow resistance is related to downstream resistance. Note that this does not relate to the resistance in the vessel where the measurement is made.

[0086] In one example, the first and second measurements relate to the same physiological parameter.

[0087] In another example, the first and second measurements relate to different physiological parameters.

[0088] The predetermined stimulation for the second condition is provided as at least one of the group of physical manipulation, drug stimulation, and electrical stimulation.

[0089] The stimulation induces hemodynamic changes, and the renal response index is determined as at least one of the group consisting of a vascular impedance change index, a renal blood flow change index, a pulse propagation change index, and a pulse reflex change index.

[0090] The predetermined stimulus for the second condition is in a group of predetermined stimuli for the second condition, provided as a selection.

[0091] Stimulation causing hemodynamic changes, and the renal response index being determined as at least one of the group consisting of a vascular impedance change index, a renal blood flow change index, a pulse propagation change index, and a pulse reflex change index, is also provided as an option.

[0092] The vascular impedance change index may also be called the resistance change index, the pulse propagation change index may also be called the propagation index, and the pulse reflection change index may also be called the reflection index.

[0093] In one example, a combination of these indices is provided to determine the renal response index.

[0094] The data processor 14 may be further configured to determine whether the generated renal response index is below or above a predetermined threshold value indicating possible suitability for renal denervation. The data output 16 is configured to provide a threshold indicator. The renal response index provides for stratification of individuals into at least two groups, wherein one of the groups indicates that the subject is less likely to respond well to renal denervation therapy, i.e., into one group that responds better to renal denervation therapy than the other group.

[0095] In the example, provided as an option, the data output 16 is configured to provide the value of the at least one first measurement result and / or the value of the at least one second measurement result.

[0096] In the example, as the dashed line in Figure 1 , the data input 12 is configured to receive another value 26 of another first measurement of another physiological parameter of the renal vasculature of the subject under the first condition. The data input 12 is also configured to receive another value 28 of another second measurement of another physiological parameter of the renal vasculature under the second condition. The data processor 14 is configured to determine a ratio between the another second measurement and the another first measurement. The data processor 14 is also configured to generate the renal response index based on the determined ratio between the at least one second measurement and the at least one first measurement, the determined ratio between the another second measurement and the another first measurement, and the predetermined stimulus.

[0097] In one example, each measurement delivers an index.Multiple measurements / stimuli can determine the index based on a predetermined index (measured under different conditions).

[0098] In the example, shown as an option, a display 30 is provided which is configured to show the renal response index.The display 30 may be provided as an integrated display unit.

[0099] In another example, the display 30 is configured to display a value of at least one first measurement result and / or a value of at least one second measurement result.

[0100] In an example not further shown, the data input 12 is configured to provide the values ​​of the first measurement for the left renal artery and for the right renal artery under a first condition. The data input 12 is also configured to provide the values ​​of the second measurement for the left renal artery and for the right renal artery under a second condition.

[0101] In one option, the data processor 14 is configured to: i) determine a ratio between the second measurement and the first measurement for each of the left and right renal arteries, respectively, and generate a respective index for each of the left and right renal arteries separately.

[0102] Additionally or alternatively, the data processor 14 is configured to ii) determine an average ratio between the second measurement and the first measurement for the left and right renal arteries and generate the index based on the average ratio.

[0103] Additionally or alternatively, the data processor 14 is configured to iii) determine an average ratio between the second measurement and the first measurement for the left and right renal arteries.The data processor 14 is further configured to generate the index based on a difference between the left and right measurements divided by the average ratio.

[0104] In one example, based on the results, both renal vessels were treated with a similar renal denervation procedure.

[0105] In another example, the renal vessels are treated with different renal denervation procedures depending on the results.

[0106] In another example, only one of the renal vessels is treated with a renal denervation procedure based on the results.

[0107] Figure 2An example of a system 50 for determining a renal response index is shown. The system 50 comprises a measuring device 52 having at least one sensor element 54, the sensor element being configured to measure at least one physiological parameter of the renal vasculature of a subject. The system 50 further comprises an apparatus 10 for determining a renal response index according to one of the aforementioned examples. The system 50 further comprises a display device 56. The measuring device 52 is configured to provide the value of at least one first measurement result and the value of at least one second measurement result to the classification device. The display device 56 is configured to at least display the renal response index generated by the classification device.

[0108] Figure 3 An option is shown, in which the measuring apparatus 52 comprises an intravascular device 58 having at least one sensor element 60 which is configured to be inserted into a vascular structure of a subject and to measure at least one physiological parameter of the renal vasculature of the subject.

[0109] In another option, not shown in detail, the measuring device 52 comprises an extravascular imaging device configured to measure at least one physiological parameter of the renal vasculature of the subject by imaging.

[0110] In one option, Figure 2 As shown, the system 50 further comprises a stimulation unit 62, which is configured to provide electrical stimulation and / or provide drug stimulation through drug supply. The stimulation unit 62 can be integrated with a measuring device (not shown). As stimulation, one or more stimuli can be provided.

[0111] Alternatively, the stimulation unit is integrated with the intravascular device.

[0112] In another alternative, the stimulation unit is provided as a separate device.

[0113] In one example, the drug supply is provided by a device such as an infusion set or an inhalation device.

[0114] In another example, the medication supply is provided by a staff member, such as in the form of a substance that is applied to a subject.

[0115] In one option, Figure 2 As shown, the system 50 further includes an ablation unit 64 configured to provide renal ablation. The ablation unit 64 may be integrated with a measurement device (not shown).

[0116] In one option, the ablation unit is integrated with the intravascular device.

[0117] In another option, the ablation unit is provided as a separate device.

[0118] In yet another option, the system includes both a stimulation unit and an ablation unit. In one example, the stimulation unit and the ablation unit are each provided as a separate unit. In another example, one of the stimulation unit and the ablation unit is provided as a separate unit, and the other of the stimulation unit and the ablation unit is provided as an integrated unit. In addition, the stimulation unit and the ablation unit are each provided as an integrated unit.

[0119] In another option not shown in detail, the system 50 is configured to provide an initial renal response index before the ablation procedure and to provide a further renal response index after at least a first portion of the ablation procedure. A success index is provided based on a ratio of the further renal response index to the initial renal response index.

[0120] FIG. 4 a shows basic steps of an example of a method 100 for determining a renal responsiveness index, which comprises the following steps.

[0121] In a first step 102 , also referred to as step a1 ), at least one first measurement of a physiological parameter of the renal vasculature of a subject under a first condition is provided.

[0122] In a second step 104, also referred to as step c1), at least one second measurement result of a physiological parameter of the renal vessel under a second condition is provided. Under the second condition, a predetermined stimulation is provided. The first condition is non-stimulating or at least differently stimulating.

[0123] In a third step 106, also referred to as step d), a renal response index is generated based on the at least one first measurement and the at least one second measurement. In an exemplary embodiment, a ratio between the at least one second measurement and the at least one first measurement is determined, and the renal response index is generated based on the determined ratio and the predetermined stimulus.

[0124] In a fourth step 108, also referred to as step e), a renal response index is provided and / or a classification of the subjects into at least two groups is provided.

[0125] The method for determining the renal responsiveness index may also be referred to as a "classification method for determining the renal responsiveness index".

[0126] The first measurement and the second measurement are performed in a sequential manner. In an example, the first measurement is performed before the second measurement. In another example, the second measurement is performed before the first measurement.

[0127] The non-stimulating, less stimulating, or differently stimulating condition may also be referred to as the subject's baseline condition.

[0128] Fig. 4b shows another example of the method 100, wherein between step a1) and step c1), a step b) of stimulating 110 the renal vasculature by at least one of physical manipulation, drug stimulation and electrical stimulation is further provided.

[0129] Fig. 4c shows another example of the method 100, wherein a step a2) of displaying 112 the value of at least one first measurement result is also provided. Additionally or alternatively, a step c2) of displaying 114 the value of at least one second measurement result is provided.

[0130] In another option provided additionally or alternatively, there is also provided a step f) of indicating 116 whether the generated renal response index is below or above a predetermined threshold value indicating the possible suitability of renal denervation.

[0131] In an example not further shown, another value of another first measurement of another physiological parameter of a renal blood vessel of a subject under a first condition is provided; and another value of another second measurement of another physiological parameter of a renal blood vessel under a second condition is also provided. A ratio between another second measurement result and another first measurement result is determined. The renal response index is generated based on the determined ratio between the at least one second measurement result and the at least one first measurement result, the determined ratio between the another second measurement result and the another first measurement result, and the predetermined stimulus.

[0132] In an example not further shown, a first measurement result under a first condition is provided for the left renal artery and the right renal artery; and a second measurement result is provided for the left renal artery and the right renal artery under a second condition. A ratio between the second measurement result and the first measurement result is determined for each of the left renal artery and the right renal artery, respectively, and a corresponding index is generated for each of the left renal artery and the right renal artery, respectively.

[0133] Additionally or alternatively, an average ratio between the second measurement and the first measurement of the left and right renal arteries is determined, and the index is generated based on the average ratio.

[0134] In one option, the results for both renal arteries are displayed separately, ie, the left index and the right index, and the average result, ie, the common index, is also displayed.

[0135] One measure of vascular health is pulse wave velocity (PWV). Pulse wave velocity is defined as the speed at which pressure / flow pulses propagate from the aorta to any peripheral vessels; the stiffer the vessel, the faster the PWV. In one example, to determine PWV, the arrival time of the heart pulse wave is measured at two different locations (e.g., the carotid artery and the femoral artery), and the difference between the arrival times is measured. By measuring or approximating the distance between the two locations, the PWV can be estimated.

[0136] As mentioned previously, sympathetic overactivation may cause peripheral and renal arterial vasoconstriction. Vasoconstriction increases vascular stiffness and should therefore be associated with a “locally” increased pulse wave velocity. The pulse wave velocity in the renal arteries of patients with resistant hypertension may be high; exceeding 20 m / s, which makes it difficult to determine the pulse wave velocity in the relatively short renal arteries (2 to 6 cm).

[0137] Clinical data suggest that certain physiological parameters, such as pressure / blood velocity (pulse wave velocity) in the renal artery and blood flow resistance in the preconditioning of the intrarenal vasculature, can be used to predict the outcome of renal denervation.

[0138] In one example, renal artery resistance and pulse wave velocity measured in the vessel are used during renal denervation to: 1.) predict responders prior to renal denervation therapy, and 2.) assess the success of renal denervation ablation.

[0139] Because there are no "normal" or standard values ​​for pulse wave velocity (or any other renal hemodynamic parameter) in the renal arteries, it is difficult to determine the values ​​associated with sympathetic overactivation. In one example, the sympathetic nerves and therefore the hemodynamic properties of the kidneys and renal arteries can be altered by drugs or other stimulation. Because patients who are suitable for renal denervation have sympathetic overactivation, stimulation of the sympathetic nerves in these patients should have limited effects on renal hemodynamics because they are already in a state of overactivity. Therefore, the information contained in the changes in renal hemodynamics at baseline and after sympathetic nerve stimulation can distinguish between those patients who are already in a state of sympathetic overactivation (who may respond to a renal denervation response) and those who are not in a state of sympathetic overactivation (who may not respond).

[0140] Furthermore, hemodynamic parameters may differ between the left and right kidneys, and treatment decisions based on measurements in only one renal artery may be inappropriate. Measurements in both renal arteries may indicate left-right asymmetry in hemodynamic parameters, which may require modification of treatment decisions.

[0141] Physiological parameters (e.g., pressure, flow, pulse wave velocity, or resistance) show variability, especially when measured in two different renal vessels or over a longer time frame. Each measurement performed by minimally invasive methods in a given renal vessel may give a different measurement, making a single measurement of pulse wave velocity or resistance in a single renal artery difficult to interpret.

[0142] In one example, multiple measurements are taken at different times, in different locations, in different renal arteries, before, during, or after various stimulations and combined into a composite index value. The index is less susceptible to natural variations than single measurements. The index facilitates treatment decisions, for example, by defining a threshold above which treatment may be recommended.

[0143] Well-defined manipulations such as pharmacological stimulation, physical manipulation, and / or electrical stimulation of the sympathetic nervous system would enable better stratification to distinguish sympathetic-related hypertension from other renal diseases.

[0144] Sympathetic hyperactivity, increased venous pressure, changes in vascular structure (e.g. stenosis), swelling of the kidney (e.g. hydronephrosis) can cause changes in PWV or resistance / impedance. The last two mentioned may also affect only one kidney.

[0145] All of these factors may alter hemodynamic parameters for these multiple reasons, and thus manipulation-based analysis may allow for better stratification.

[0146] In one example, measures of total vascular resistance include renal vascular geometry, renal perfusion, and venous blood pressure.

[0147] The measure of total vascular resistance includes arterial stiffness, renal perfusion, and venous flow. Through the previously mentioned maneuvers, the influence of sympathetic nerve activity and arterial stiffness can be determined. The calculated index will be specific to the decision regarding the renal denervation treatment.

[0148] Using a device with at least one sensor for pulse wave velocity or measuring the internal resistance / impedance of a vessel, multiple measurements can be recorded. If only a single measurement is performed, the system will acquire and record that measurement. A value representing the measurement is displayed on the system.

[0149] When a second measurement is recorded in a bilateral / contralateral vessel, the second value will be displayed and a value representing the average of the two measurements will also be displayed.

[0150] The same steps can be repeated before / after and during physical manipulation or other sympathetic stimulation to assess the effects on the hemodynamic parameters pressure, pulse wave velocity, and impedance.

[0151] The same procedure can be repeated at a later stage after treatment to assess the effectiveness of the treatment and to compare the values ​​of the measurements before and after treatment in a single vessel or in two vessels.

[0152] In one example, it is provided:

[0153] An intravascular guidewire or catheter having at least one sensor element that measures pressure, flow, electrical impedance and / or geometry of a blood vessel.

[0154] Stimulation devices that use physical manipulation and / or drug stimulation and / or electrical stimulation to provide stimulation to the kidneys, renal arteries, or nervous system.

[0155] A system that records a measurement using a device sensing element in a first renal artery; and records another measurement when one or more stimulation devices stimulate the renal artery; and displays the results of the first renal artery on the system, along with a threshold or indicator as to whether the patient is a candidate for renal denervation.

[0156] As optional elements, provided are:

[0157] A system determines an index describing a property of a first renal blood vessel based on measurements recorded by the device; and displays the index on the system, along with a threshold or indicator as to whether the patient is a candidate for renal denervation.

[0158] A system that records another measurement of a second contralateral renal artery without stimulation; and records a further measurement when stimulated by one or more stimulation devices, the measurement determining an index in the second renal vessel based on the measurement recorded by the device; and displays the results for the second kidney and an average based on both (left and right) measurements on the system; and determines an index of the measurements in two opposing vessels with and without stimulation by the stimulation device.

[0159] Repeat the above measurements and index calculations to determine the system for successful ablation.

[0160] An intravascular device as described above, wherein a stimulation unit (eg for electrical stimulation) is integrated therein.

[0161] An intravascular device as described above, wherein an ablation unit for renal denervation is integrated therein.

[0162] An intravascular device as described above, wherein a stimulation unit (eg, for electrical stimulation) and an ablation unit for renal denervation are integrated.

[0163] In one example, a system is provided that can be used to test for the possibility of renal denervation response (RND) by measuring renal pulse waves and / or physiological responses to stimulation of the sympathetic nervous system.

[0164] The proposed stimulation is delivered by stimulation devices. These stimulation devices may be at least one of the following techniques: a) physical manipulation, and / or b) drug stimulation, and / or c) electrical stimulation.

[0165] This stimulus can be a specific vasodilator (dopamine, nitrates, adenosine, etc.), a neuromodulatory drug of the nerves (anesthetic / temporary sympathetic blocking drugs or sympathetic stimulants), or a handgrip performed / administered before or during the measurement, or any other stimulus that affects the sympathetic response.

[0166] Physical maneuvers can be compression maneuvers that block the peripheral vascular system and venous blood flow, or respiratory maneuvers that block central venous pressure and intraperitoneal pressure (eg Müller maneuver, Valsalva maneuver), which serve as a regulated pressure on the kidneys and renal vessels.

[0167] In one example, the response before / after and during stimulation is measured by arterial physiology (pressure, pulse wave velocity, resistance, flow, vascular geometry or a combination), particularly in the renal artery. An index derived from these measurements is then used to stratify patients into at least two groups; one of which represents patients who are unlikely to respond well to treatment.

[0168] Composite hemodynamic index

[0169] An index of stimulation-induced hemodynamic changes will be determined based on measurements before / after and during stimulation. Measurements will be made at one, two and / or multiple locations in the renal vasculature.

[0170] The measurement will be made with or without gating on other physiological parameters. A typical gating is the measurement synchronized with the ECG of the beating heart. This allows measurements to be made during periods of no reflection or at maximum or minimum values ​​of the physiological parameters.

[0171] In the following example, the setup for taking measurements before / after and during stimulation is described in detail.

[0172] Through these examples, the indices of hemodynamic changes caused by different stimuli will be determined.

[0173] The composite hemodynamic index determined was:

[0174] Vascular resistance change index;

[0175] Renal flow showed an index of change;

[0176] Pulse Spread Index; and

[0177] Pulse reflex index.

[0178] In determining the index, drug-induced stimulation, electrical stimulation, physical manipulation or a combination of different stimuli may be applied. When the term stimulation is used hereinafter, the stimulation may be a single stimulation or a combination of multiple stimuli.

[0179] In an example, the pulse propagation index is provided as a pulse propagation change index.

[0180] In an example, the pulse reflection index is provided as a pulse reflection variation index.

[0181] For each index, a cut-off value will be defined that describes whether a patient will benefit from renal denervation treatment.

[0182] Vascular resistance index To determine the effect of arterial stiffness of the renal arteries, the vascular resistance change index was determined as the ratio of vascular resistance (R = perfusion pressure / flow) during stimulation relative to a reference value determined without stimulation:

[0183] Vascular resistance change index = R stim / R ref

[0184] For various stimuli:

[0185] Vascular resistance change index = R( stim_1+stim_2+…+stim_n ) / R ref

[0186] In one example, to determine the effect of sympathetic nerve activity on renal vascular resistance, a vascular resistance change index is determined as the ratio of vascular resistance (R = perfusion pressure / flow) during stimulation relative to a reference value determined in the absence of stimulation.

[0187] If the determined index value is below a certain threshold, the patient is likely to be a renal denervation responder. The value depends on the type and dose of the stimulus. The quantitative values ​​are given only as examples for a specific stimulus.

[0188] Stimulation can be accomplished by different pharmacological agents and at different drug doses. For all drugs, they generally interact with receptors as neurotransmitters, but in different ways. Some drugs interact primarily with Alpha receptors, others with Beta receptors, and some with both. From a hemodynamic point of view, some drugs are vasoactive (dilate or constrict arteries), while others are cardioactive (increase cardiac output and systemic blood pressure). All types of drugs change blood pressure, renal blood flow and renal pulse wave velocity. For each, a dedicated index and corresponding thresholds will be defined.

[0189] Sympathetic overactivation causes peripheral vasoconstriction. Thus, in the kidneys, this reduces renal blood flow due to renal artery constriction. Renal sympathetic overactivation can be considered a renovascular disorder that impedes renal blood flow. Vasodilation stimulates increased flow and vice versa, requiring lower perfusion pressures to achieve comparable renal blood volumes.

[0190] An example of drug stimulation via sympathostimulatory drugs (e.g., epinephrine) is provided: a value less than 1.2 is recommended to suggest renal denervation treatment.

[0191] In a similar manner, values ​​above 0.8 may be considered recommended for renal denervation therapy when sympathetic blocking drugs such as phentolamine are used.

[0192] The threshold value is just an example and may also be set differently.

[0193] Renal blood flow change index : This index determines the effect of a stimulus or combination of stimuli on flow rate (specified as the change in renal minute volume).

[0194] The renal flow index was determined as the ratio of renal flow during stimulation (or stimulations) relative to a reference value determined in the absence of stimulation:

[0195] Renal flow index = F stim / F ref

[0196] For various stimuli:

[0197] Renal flow index = F( stim_1+stim_2+…+stim_n ) / F ref

[0198] If the value of the determined index is above a certain threshold, the patient is a candidate for effective renal denervation therapy.

[0199] When sympathostimulatory drugs (sympathomimetics, such as epinephrine) are used, a value above 0.8 may be considered to suggest renal denervation.

[0200] In a similar manner, values ​​above 1.2 may be considered recommended for renal denervation therapy when sympathetic blocking drugs such as phentolamine are used.

[0201] The threshold value is just an example and may also be set differently.

[0202] Pulse Spread Index : This index determines the effect of a stimulus or a combination of stimuli on the propagation of the pulse in the renal artery. This index determines the change in the pulse wave velocity.

[0203] The pulse spread index was determined as the ratio of renal flow during stimulation (or stimulations) relative to a reference value determined in the absence of stimulation:

[0204] Pulse Wave Index = PVW STIM / PVW REF

[0205] For various stimuli:

[0206] Pulse Wavelength Index = PWV( stim 1+stim_2+…+stim_n ) / P( ref )

[0207] Vasoconstriction is associated with stiffening of the vessel walls. Therefore, the pulsatile motion of the pressure wave of blood through the vessels is expected to be faster. In patients who are suitable for renal denervation, the increase in stiffness and therefore the increase in pulse wave velocity after additional sympathetic stimulation is expected to be not as great, so that the ratio is only slightly above 1. In patients who do not have hypertension caused by sympathetic overactivation, sympathetic stimulating drugs (such as epinephrine) will cause vasoconstriction and thus PVW. (stim) and a larger increase in the pulse propagation index.

[0208] When sympathostimulatory drugs (sympathomimetics, such as epinephrine) are used, a value lower than 1.2 may be considered to suggest renal denervation.

[0209] In a similar manner, sympatholytic drugs (eg, phentolamine) may be used in the opposite manner. When sympatholytic drugs are used, a value above 0.8 may be considered to suggest renal denervation.

[0210] If the value of the determined index is above a certain threshold, the patient is a candidate for effective renal denervation therapy.

[0211] The threshold value is just an example and may also be set differently.

[0212] Pulse reflex index: This index determines the effect of a stimulus or a combination of stimuli on the pulse reflection at the renal vascular bed measured in the renal artery. This index determines the change in pulse rise time and the attenuation of pulse amplitude.

[0213] Due to the short length of the renal artery, the pulse transmission time is shorter than the pulse rise time in the renal artery. Therefore, the pulse reflection index is determined in the time domain by the change in rise time and pulse shape.

[0214] The pulse reflex index is determined as the ratio of renal flow during stimulation (or stimulations) relative to a reference value determined in the absence of stimulation:

[0215] Pulse reflex index = P 上升时间(stim) / P 上升时间(ref)

[0216] For various stimuli:

[0217] Pulse reflection index = P 上升时间(stim 1+stim_2+…+stim_n ) / P 上升时间(ref)

[0218] When sympathostimulatory drugs are used, a value lower than 1.2 may be considered to suggest renal denervation.

[0219] In a similar manner, sympatholytic drugs (eg, phentolamine) may be used in the opposite manner. When sympatholytic drugs are used, a value above 0.8 may be considered to suggest renal denervation.

[0220] If the value of the determined index is above a certain threshold, the patient is a candidate for effective renal denervation therapy.

[0221] A schematic diagram and flow chart of another example are shown in Figures 5a and 5b. This example includes an intravascular device (elongated member) having at least one pulse wave velocity sensor element that records the pulse wave velocity in the renal artery. After this measurement is completed, a stimulation technique is used to stimulate the renal system. Preferably, the stimulation technique is integrated into the same intravascular device, such as a catheter with a drug delivery lumen. During stimulation, the intravascular device records the PWV. stim The processing unit processes the raw measurement result into two values, which represent the pulse wave velocity at rest and during stimulation. For example, the two recordings are synchronized with the ECG, and the pulse wave velocity values ​​of the two different states are determined by averaging a plurality of cycles. The display unit displays the result together with an indicator as to whether the patient is suitable for renal denervation.

[0222] FIG. 5 a schematically shows the elements, and FIG. 5 b schematically shows a flow chart of data acquisition and processing of the example of FIG. 5 a .

[0223] The first box indicates a subject 210 with kidneys 212, and a smaller box indicates a nervous system 214. Another box above the kidneys 212 indicates a renal artery 216. A measuring device 218 is indicated to provide data from the renal artery 216. The measuring device 218 is shown partially inserted into the vasculature of the subject 210. A data acquisition / recording unit 220 is at least data-connected to the measuring device 218. The data acquisition / recording unit 220 is at least data-connected to a processing unit 222. A console / display 224 is connected to the processing unit 222. The processing unit 222 is also connected to one or more stimulation units 226 that can act on the nervous system 214, one or more kidneys 212, and / or the renal artery 216.

[0224] In the flow chart, a first condition 252 results in a first measurement 254, a second condition 256 results in a second measurement 258, and an nth condition 260 results in an nth measurement 262. The measurements 254, 258, 262 are subjected to signal processing 264. Next, a display of the measure is provided 266. Furthermore, explanations and recommendations 268 are provided.

[0225] A schematic diagram and a flow chart of another example are shown in Figures 6a and 6b. This example is similar to the above example, except that two (or more) measurements are further compressed into a single index value. The index value can be used in conjunction with a threshold to guide treatment decisions. The index can be calculated by the ratio of the two measurements or another predefined algorithm. Optionally, the index calculation can be determined by a series of measurements performed at different stimulation levels and / or time points.

[0226] FIG. 6 a schematically shows the elements, and FIG. 6 b schematically shows a flow chart of data acquisition and processing of the example of FIG. 6 a .

[0227] FIG6a shows similar features to FIG5a. The first frame indicates a subject 310 having (one or more) kidneys 312, a nervous system 314, and a renal artery 316. A measuring device 318 connected to a data acquisition / recording unit 320 is also provided, which is connected to a processing unit 322. A console / display 324 is also provided. One or more stimulation units 326 can act on the patient 310. As described above, an index 328 is shown.

[0228] In the flow chart, the first condition 352 is used for the first measurement 354, the second condition 356 is used for the second measurement 358, the nth condition 360 is used for the nth measurement 362, and the measurements 354, 358, 362 are signal processed 364. Next, a display of the measure 366 is provided, but followed by a calculation of the index 367. In addition, as described above, an interpretation and recommendation 368 is provided.

[0229] exist Figure 7 A schematic diagram of another example is shown in , which is similar to the two examples of Figures 5a / 5b and 6a / 6b above, but differs in that the drug delivery device is used to test the sympathetic and hemodynamic responses to drug-induced changes in neuromodulation and vascular properties by measuring renal pulse waves and pressure, flow and impedance.

[0230] Figure 7 These elements are shown schematically. The corresponding flow chart is not shown.

[0231] A subject 410 is shown having kidney(s) 412, a nervous system 414 and a renal artery 416. A measuring device 418 is provided which is connected to a data acquisition / recording unit 420 which is connected to a processing unit 422 and a console / display 424 which can display an index 428. As a stimulation unit, a drug delivery unit 426 is provided.

[0232] exist Figure 8 5a / 5b and 6a / 6b, except that the stimulation of the energy delivery device is applied in the renal tissue, respectively, in the renal vessels. The energy can be, for example, electrical energy, thermal energy, light energy or ultrasound energy.

[0233] Figure 8 These elements are shown schematically. The corresponding flow chart is not shown.

[0234] A subject 510 is shown having a kidney(s) 512, a nervous system 514 and a renal artery 516. A measuring device 518 is provided which is connected to a data acquisition / recording unit 520 which is connected to a processing unit 522 and a console / display 524 which can display an index 528. As a stimulation unit, a stimulator in the form of an energy delivery device 526 is provided.

[0235] exist Fig. 9 A schematic diagram of another example is shown in . This example is similar to the two examples of Figures 5a / 5b and 6a / 6b above, except that the stimulation is in the form of a physical manipulation or activity, such as a handgrip or other body movement of the patient.

[0236] Fig. 9These elements are shown schematically. The corresponding flow chart is not shown.

[0237] A subject 610 is shown with kidney(s) 612, nervous system 614 and renal artery 616. A measuring device 618 is provided which is connected to a data acquisition / recording unit 620 which is connected to a processing unit 622 and a console / display 624 which can display an index 628. As a stimulation unit, a physical stimulus 626 in the form of a handgrip is provided.

[0238] exist Fig.10 Another example is shown in FIG. This example is similar to the above five examples (FIG. 5a / 5b, FIG. 6a / 6b, Figure 7 , Figure 8 and Fig. 9 ) except that measurements are taken in both the left and right kidneys to determine the response difference index of the two kidneys. The likelihood of a response is assessed based on the measurement results of each of the two kidneys (at least one measurement for each kidney). The processing unit will determine and display information for both kidneys and give treatment guidance based on this information, which may include: treating both renal arteries, treating only the right renal artery, treating only the left renal artery, and not treating.

[0239] Fig.10 These elements are shown schematically. The corresponding flow chart is not shown.

[0240] A subject 710 is shown with a nervous system 714 and a renal artery 716. A measurement device 718 is provided connected to a data acquisition / recording unit 620, which is connected to a processing unit 722 and a console / display 724. A stimulation unit 726 is also provided. The subject is shown with a right kidney 714. R and left kidney 714 L , and right renal artery 716 R and left renal artery 716 L The console / display 724 shows the right kidney index 728 R and left kidney index 728 L .

[0241] In another example not shown, a system similar to the systems described in the six examples above is provided, wherein a stimulation unit (eg, for electrical stimulation) is integrated into an intravascular device.

[0242] In another example not shown, a system similar to the one described in the above examples is provided, wherein an ablation unit for renal denervation is integrated in an intravascular device.

[0243] In another example not shown, a system similar to the one described in the above examples is provided, wherein a stimulation unit (eg for electrical stimulation) and an ablation unit for renal denervation are integrated.

[0244] In another example not shown, a system similar to the one described in the above example is provided, wherein measurements may be repeated after (partial) ablation of the nerve and wherein the processing unit will provide a measure of treatment success to help the interventionalist decide whether to stop or continue the treatment.

[0245] In another example, not shown, a system similar to the previous example is provided, except that the measurement device is positioned in a non-renal artery that is also affected by sympathetic overexcitation. Examples of such arteries are, for example, the tibial artery, the femoropopliteal artery, the brachial artery, and the radial / ulnar artery. Thus, the hemodynamic measurements are measured in the non-renal artery, and the measured indices are then used to determine whether the subject is a candidate for effective denervation therapy.

[0246] In a further exemplary embodiment of the present invention, a computer program or a computer program element is provided, characterized in that it is adapted to perform the method steps of the method according to one of the preceding examples on a suitable system.

[0247] Therefore, the computer program element can be stored on a computer unit or distributed on more than one computer unit, which can also be a part of an embodiment of the present invention. The computing unit can be suitable for executing the steps of the above method or causing the execution of the steps of the above method. In addition, it can be suitable for operating the parts of the above device. The computing unit can be suitable for automatically operating and / or executing the user's command. The computer program can be loaded into the working memory of a data processor. Therefore, a data processor can be equipped to implement the method of the present invention.

[0248] Aspects of the present invention may be implemented in a computer program product, which may be a collection of computer program instructions stored on a computer-readable storage device that may be executed by a computer. The instructions of the present invention may be any interpretable or executable code mechanism, including but not limited to scripts, interpretable programs, dynamic link libraries (DLLs), or Java classes. The instructions may be provided as a complete executable program, a partial executable program, as a modification (e.g., an update) to an existing program, or as an extension (e.g., a plug-in) to an existing program. Furthermore, portions of the processing of the present invention may be distributed across multiple computers or processors.

[0249] As described above, a processing unit, such as a controller, implements a control method. The controller can be implemented in a variety of ways using software and / or hardware to perform the various functions required. A processor is an example of a controller that uses one or more microprocessors that can be programmed using software (e.g., microcode) to perform the required functions. However, a controller can be implemented with or without a processor, and can also be implemented as a combination of dedicated hardware for performing some functions and a processor (e.g., one or more programmed microprocessors and associated circuits) for performing other functions.

[0250] Examples of controller components that may be used in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field programmable gate arrays (FPGAs).

[0251] This exemplary embodiment of the invention covers both a computer program that right from the beginning uses the invention and a computer program that by means of an update turns an existing program into a program that uses the invention.

[0252] Furthermore, the computer program element may be able to provide all necessary steps to implement the procedures of an exemplary embodiment of the method as described above.

[0253] According to another exemplary embodiment of the present invention, a computer readable medium, such as a CD-ROM, is provided, wherein the computer readable medium has a computer program element stored thereon, the computer program element being described in the previous section. The computer program may be stored and / or distributed on a suitable medium, such as an optical storage medium or a solid-state medium provided with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.

[0254] However, the computer program may also be provided over a network like the World Wide Web and may be downloaded from such a network into the working memory of a data processor. According to a further exemplary embodiment of the invention, a medium for making a computer program element available for downloading is provided, the computer program element being arranged to perform one of the previously described embodiments of the invention.

[0255] It must be noted that embodiments of the present invention are described with reference to different subject matters. In particular, some embodiments are described with reference to method claims, while other embodiments are described with reference to device claims. However, it can be concluded by a person skilled in the art from the above and following descriptions that, unless otherwise indicated, any combination of features relating to different subject matters, in addition to any combination of features belonging to the same type of subject matter, is also considered to be disclosed by the present application. However, all features can be combined to provide synergistic effects that exceed the simple sum of the features.

[0256] Although the present invention has been illustrated and described in detail in the drawings and the foregoing description, such illustration and description should be considered illustrative or exemplary rather than restrictive. The present invention is not limited to the disclosed embodiments. Other variations of the disclosed embodiments can be understood and implemented by those skilled in the art in practicing the claimed invention by studying the drawings, the disclosure, and the dependent claims.

[0257] In the claims, the word "comprising" does not exclude other elements or steps, and the word "a" or "an" does not exclude a plurality. A single processor or other unit may perform the functions of several items recited in the claims. Although specific measures are recited in mutually different dependent claims, this does not indicate that a collection of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. An apparatus (10) for determining a renal denervation treatment response index, comprising: Data input unit (12); Data processor (14); as well as Data output unit (16); wherein the data input is configured to: receive at least one first measurement result (18) of a physiological parameter of a subject's renal vasculature under a first condition; and receive at least one second measurement result (20) of the physiological parameter of the renal vasculature under a second condition; wherein under the second condition a predetermined stimulation is provided and the first condition is unstimulated or at least differently stimulated; wherein the data processor is configured to generate a renal denervation treatment response index based on a ratio between the at least one second measurement result and the at least one first measurement result and the predetermined stimulus; and Wherein, the data output unit is configured to provide the renal denervation treatment response index (22).

2. The device according to claim 1, wherein: The data output is configured to classify the subject into one of at least two groups based on the renal denervation treatment response index, the classification being related to the suitability of the subject for renal denervation therapy.

3. The device according to claim 1 or 2, wherein: The data input unit is configured to receive the at least one first measurement result and / or the at least one second measurement result from a device of at least one of the group consisting of an intravascular device and an extravascular imaging device; and The physiological parameter is at least one item selected from the group consisting of blood pressure, pulse wave velocity, vascular impedance, blood flow, blood flow velocity and vascular geometry.

4. The device according to any one of claims 1 to 2, wherein: The predetermined stimulus for the second condition is provided as at least one of the following group: physical manipulation; Drug stimulation; and Electrical stimulation; and wherein the stimulation induces hemodynamic changes, and the renal denervation treatment response index is determined as at least one of the following groups: Vascular impedance change index; Blood flow change index; Pulse Propagation Alteration Index; and Pulse reflex change index.

5. The device according to any one of claims 1 to 2, wherein: The data processor is further configured to determine whether the generated renal denervation treatment response index is below or above a predetermined threshold, the threshold being associated with an indication of the subject's likely suitability for renal denervation therapy.

6. The device according to any one of claims 1 to 2, wherein: The data input is configured to: receive another first measurement result (26) of another physiological parameter of the subject's renal vasculature under the first condition; and receive another second measurement result (28) of the another physiological parameter of the renal vasculature under the second condition; and Wherein, the data processor is configured to generate the renal denervation treatment response index based on a determined ratio between the at least one second measurement result and the at least one first measurement result and a determined ratio between the another second measurement result and the another first measurement result.

7. The device according to claim 1, wherein: The data input section is configured to: receive the first measurement results for the left renal artery and for the right renal artery under the first condition; and receive the second measurement results for the left renal artery and for the right renal artery under the second condition; and Wherein, the data processor is configured as follows: i) determining a ratio between the second measurement result and the first measurement result for each of the left renal artery and the right renal artery, respectively; and generating a respective index for each of the left renal artery and the right renal artery, respectively; and / or ii) determining an average ratio between the second measurement and the first measurement for the left and right renal arteries; and generating the index based on the average ratio; and / or iii) determining an average ratio between the second measurement and the first measurement for the left and right renal arteries; and generating the index based on a difference between the left and right measurements divided by the average ratio.

8. A system (50) for determining a renal denervation treatment response index, the system comprising: a measurement device (52) configured to provide at least one first measurement and at least one second measurement of a physiological parameter of a subject's renal vasculature; The device (10) according to one of the preceding claims, A display device (56) is configured to display at least the renal denervation treatment response index generated by the data processor.

9. The system according to claim 8, wherein: The measuring apparatus comprises an intravascular device (58) having at least one sensor element (60) configured to be inserted into a vascular structure of a renal vasculature of the subject.

10. The system according to claim 8 or 9, comprising a stimulation unit (62) configured to provide electrical stimulation and / or to provide drug stimulation by drug supply; in, The stimulation unit is integrated with the measuring device.

11. The system according to any one of claims 8 to 9, comprising: an ablation unit (64) configured to provide renal denervation therapy by ablation; and Wherein, the ablation unit is integrated with the measuring device.

12. The system according to claim 11, wherein: The system is configured to provide an initial renal denervation treatment response index prior to the renal denervation therapy; and provide another renal denervation treatment response index after at least a first portion of the renal denervation therapy; and wherein a success index is provided based on a ratio of the further renal denervation treatment response index to the initial renal denervation treatment response index.

13. A method (100) for determining a renal denervation treatment response index, the method comprising the steps of: a1) providing (102) at least one first measurement of a physiological parameter of the renal vasculature of a subject under a first condition; c1) providing (104) at least one second measurement of the physiological parameter of the renal vasculature under a second condition; wherein, in the second condition, a predetermined stimulus is provided, and the first condition is unstimulated or at least differently stimulated; d) generating (106) a renal denervation treatment response index based on a ratio between the at least one second measurement and the at least one first measurement and the predetermined stimulus; and e) providing (108) the renal denervation treatment response index and / or classifying the subject into one of at least two groups based on the renal denervation treatment response index, the classification being related to the suitability of the subject for renal denervation therapy.

14. A computer program element for controlling an apparatus as claimed in one of claims 1 to 7 or a system as claimed in one of claims 8 to 12, the computer program element being adapted to perform the steps of the method according to claim 13 when run by a processing unit of the apparatus.

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