A catheter for transvascular stimulation and denervation of parts of the autonomic nervous system of the human body, particularly for transvascular stimulation of the renal nerves or stimulation of the carotid body.

Abstract

The present invention essentially comprises a catheter that enables both nerve stimulation for mapping purposes in one or more regions of the autonomic nervous system around an artery, and denervation of the mapped one or more regions when those mapped regions are considered targets.

Description

Technical Field

[0001] The present invention relates to a catheter for transvascular stimulation and denervation of a part of the autonomic nervous system of the human body.

[0002] In this specification and in the context of the present invention, the "autonomous nervous system" means the nerves that control visceral functions but do not manage the voluntary mechanisms of the human body, and thus is distinguished from the somatic system that is involved in the relationship between the body and the outside world. This autonomous nervous system essentially innervates the viscera, and the sensory neurons of this system transmit information regarding visceral functions to the central nervous system. This autonomous nervous system is usually classified into three different categories: the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system.

[0003] In this specification and in the context of the present invention, "blood vessel" means a vein or an artery.

[0004] The present invention aims, first and foremost, to propose a simple and effective transvascular stimulation solution for transvascular stimulation and especially for denervation related thereto, particularly with a view to rapid diagnosis and / or mapping in the nerve area, especially in the context of surgical or percutaneous intervention.

[0005] The present invention is described by way of example for use in renal nerve stimulation applications, but is applicable to any other use for the stimulation of a part of the autonomic nervous system of the human body. In particular, the present invention is also applicable to the nerve stimulation of the carotid body. [[ID=..]]

Background Art

[0006] Renal sympathetic denervation by catheter is considered to be a promising method for treating mainly hypertension, but also conditions / dysfunctions such as heart failure, cardiac arrhythmias, diabetes, and pulmonary arterial hypertension.

[0007] In particular, high blood pressure constitutes a major health problem worldwide and is associated with a significantly increased risk of heart attack and stroke.

[0008] While most patients agree to long-term treatment with medications that are effective in managing their hypertension, the majority do not adhere to their treatment, particularly due to potential side effects and / or the inability of the medication to achieve blood pressure targets despite the maximum tolerated dose. In some cases, hypertension is resistant to drug treatment.

[0009] Therefore, several novel therapeutic strategies based on the use of medical devices that help control blood pressure by regulating the sympathetic nervous system have recently been developed.

[0010] Of these, renal sympathetic denervation is the most extensively studied.

[0011] Renal denervation is a technique that involves stimulating the surface of afferent and efferent nerves located around the renal artery by using an electrode catheter connected to a radio frequency generator, a multi-electrode catheter connected to an ultrasound generator, or a catheter with a needle attached distally for injecting an alcohol-based liquid preparation.

[0012] One of the main challenges of this denervation technique is the lack of markers along the renal artery to pinpoint the exact location of the nerve to be destroyed, making it impossible to determine the area to be treated in order to optimize the effectiveness of the denervation procedure.

[0013] Initial studies of renal artery denervation using catheters and radiofrequency generators for resistant hypertension have not shown consistent clinical efficacy. This is widely attributed primarily to procedural factors that limited the assessment of the completeness of the denervation achieved.

[0014] According to the authors of the following reference [1], the difficulty in predicting renal denervation and the controversy surrounding the paradigm of renal denervation as a treatment for hypertension are largely due to the lack of means to evaluate the denervation during the procedure, i.e., the lack of measurable criteria to confirm the success of the procedure.

[0015] Some authors, The aorticorenal ganglia can be identified by a transvascular approach using high-frequency unipolar electrical stimulation at 10 Hz and 25 mA current to the inferior vena cava, aorta, or its branches. Stimulation of the radial ganglion of the aorta induces arterial constriction and a resulting increase in blood pressure. Renal denervation inhibits the activation of afferent renal nerves, resulting in the elimination of renovascular responses to stimulation of the radial ganglion of the aorta. This indicates that.

[0016] The following reference [2] mentions electrical stimulation with a current of 10 mA, a pulse width of 5 ms, and a frequency of 20 Hz, and similar observations have been made.

[0017] Regarding these, the authors of the following document [3] state the name "ConfidenHT 商標The authors use a commercially available multi-electrode catheter, which has a distal end that unfolds into an ellipsoidal shape with four branches when a button on the handle is pressed, with each branch supporting one electrode. This catheter is highly invasive because its diameter is quite large, approximately 2.67 mm (8 French). The authors mention the possibility of nerve mapping using such a catheter, but this has not yet been demonstrated, considering that the unfolded shape cannot move freely within the artery and cannot easily reach other nerve sites. Furthermore, it is not easy to position this catheter in place.

[0018] Therefore, the devices proposed to date are considered too invasive and are not necessarily reliable and / or easy to use for accurate renal artery mapping. [Overview of the Initiative] [Problems that the invention aims to solve]

[0019] Therefore, there is a need to improve the devices for renal nerve stimulation and afferent denervation in order to overcome the above-mentioned shortcomings.

[0020] More generally, there is a need for a medical device that allows for the stimulation of certain nerves in the autonomic nervous system, particularly for the purpose of mapping or checking the effects of denervation, and for non-invasive purposes, and for a medical device for afferent denervation, that is simple, rapid, and effective.

[0021] The objective of this invention is to satisfy this need at least partially. [Means for solving the problem]

[0022] To achieve this objective, the present invention provides a catheter for transvascular stimulation and denervation of a portion of the autonomic nervous system of the human body, An electrically insulating tubular deployer sheath for introduction into the tubular sheath of an introducer or guide catheter, the electrically insulating tubular deployer sheath intended to be introduced into the blood vessels of the human body; An elongate deployer element having at least one electrical-conduction line, the distal end of which comprises a plurality of electrical contact points, optionally a plurality of piezoelectric actuators, and optionally a plurality of needles, an electrically conductive deployable structure. The structure is in the form of an elongated element mounted within the tubular unfolding sheath so as to be able to slide between a folded position and an unfolded position within the tubular unfolding sheath, where the structure is compressed in the folded position and unfolded in the unfolded position, where the structure is unfolded and electrical stimulation is performed to map the peripheral region of the blood vessel by electrically stimulating a portion of the autonomic nervous system around the peripheral region by passing an electric current through an external electrical pulse generator connected to the conductive wire, where then, in the unfolded position, electrical denervation or ultrasonic denervation, which is performed by the piezoelectric actuator, or injection of alcohol into the needle, the elongated unfolding element Regarding the above-mentioned catheter, which is equipped with the following:

[0023] Advantageously, once electrical or ultrasonic denervation is performed, the structure is designed to remain in the deployed position in order to perform electrical stimulation for checking the denervation.

[0024] According to a first advantageous embodiment variant, the structure is formed by an expandable metallic mesh of tubular shape in the deployed position, and at least some of the wire intersections of the plurality thereof define a plurality of electrical contact points provided with piezoelectric actuators as required.

[0025] According to a second advantageous embodiment variant, the structure is formed by a set of curved and mutually independent metal arms, the set of metal arms being connected to the conductive wire at their bases and defining a shape exhibiting umbrella-type rotational symmetry at their deployed end positions, and some of the arms of the arms define a plurality of electrical contact points provided with piezoelectric actuators as required.

[0026] According to this second variant, the wire and the arm are hollow, and at least a part of the free end of the arm tapers to form a plurality of alcohol injection needles. This enables denervation to be performed by injecting alcohol.

[0027] Preferably, the diameter of the wire of the mesh or the diameter of the arm of the umbrella is 40 to 200 micrometers.

[0028] The number of electrical contact points per peripheral region can be at least two, preferably at least four, preferably at least six, preferably at least eight.

[0029] Advantageously, the structure has an outer diameter of 3 to 9 mm in its deployed position.

[0030] The present invention also relates to a stimulation and denervation kit, An introducer or guide catheter having at least one tubular introducer sheath for introduction into the blood vessels of the human body, The above-described stimulating and denervating catheter is designed to introduce the introducer or guide catheter into the introducer sheath. The above-mentioned stimulation and denervation kit is equipped with the above-mentioned features.

[0031] The present invention also provides a method for stimulating and denervating a portion of a patient's autonomic nervous system, and, if necessary, performing surgical intervention. i / Insertion of a guide catheter or introducer into the femoral artery or radial artery of the human body; ii / Introducing a catheter for transvascular stimulation and denervation, where the catheter is: An electrically insulating tubular deployment sheath, An elongated unfolding element having at least one conductive wire, wherein its distal end is in the form of a conductive unfoldable structure comprising a plurality of electrical contact points, optionally a plurality of piezoelectric actuators, and optionally a plurality of needles, and It is equipped with; iii / Sliding the elongated element in the tubular unfolding sheath between a folded position and an unfolded position within the tubular unfolding sheath, wherein the structure is compressed in the folded position and unfolded in the unfolded position, so that at least some of the electrical contact points of the plurality of electrical contact points, and optionally at least some of the piezoelectric actuators of the plurality of piezoelectric actuators, and optionally at least some of the needles of the plurality of needles, in contact with at least one peripheral region of the blood vessel; iv / By applying an electric current through an external electrical pulse generator connected to the conductive wire, a portion of the autonomic nervous system around the peripheral region is electrically stimulated to map the peripheral region, and then, at the deployed location, electrical denervation is performed by the piezoelectric actuator, or, if necessary, ultrasonic denervation, or alcohol is injected into the needle; v / If necessary, apply current using an external electrical pulse generator connected to the conductive wire. iv / Check the denervated peripheral region by electrically stimulating one or more denervated areas in step iv / . The above method includes the following steps.

[0032] Accordingly, the present invention comprises a catheter that enables both nerve stimulation for mapping purposes in one or more regions of the autonomic nervous system around an artery, and denervation of the mapped one or more regions when those mapped regions are considered targets.

[0033] In other words, with the same catheter remaining in place, the distal structure of the catheter is deployed to map at least one nerve region, and subsequently, if the mapping indicates that denervation is necessary, denervation is performed, and, advantageously, the denervation is checked, or the completeness of the denervation is checked.

[0034] This nerve stimulation is transvascular (arterial or venous) renal stimulation of a region of the sympathetic nervous system that may generate arterial hypertension. Therefore, it is possible to completely identify one or more nerve regions to be denervated in order to reduce or eliminate hypertension. This stimulation also allows for verification of the effects of previously performed denervation.

[0035] By performing rapid stimulation, temporary arterial hypotension and / or bradycardia (reduced cardiac function) can be observed. This allows for the prediction of bradycardia or arterial hypotension before carotid artery repair, and therefore, the administration of medication to avoid this risk.

[0036] The guide catheter or introducer of the stimulation kit according to the present invention may be perfectly conventional for the vascular anatomical structure around the nerve area to be diagnosed and sequentially denervated.

[0037] In both mapping and post-denervation examination, the required intensity of nerve stimulation (unipolar stimulation is preferable) is low. Typically, the strength of the supplied alternating current can range from 10 to 25 mA at a frequency of 200 to 2000 times / minute (10 to 20 Hz) for approximately 10 to 60 seconds.

[0038] Denervation by high frequency, ultrasonic generation by a piezoelectric actuator, current supplied by a conductive wire, or injection of alcohol is performed instantaneously and reliably once mapping is performed, because the catheter according to the present invention does not move. As a result, one or more peripheral regions to be denervated can be accurately identified.

[0039] The entire kit is easy to handle because it only requires a mechanical sliding motion: inserting one of the catheters according to the present invention into a guide catheter or introducer that has been previously introduced into an artery, and then inserting one of the elongated elements into the deployment sheath to deploy the structure.

[0040] Depending on the shape and / or dimensions of the distal structure to be deployed, a catheter according to the present invention can be placed in the guide catheter or introducer to perform mapping, denervation, and, if necessary, integrity checks for the entire renal nerve section of an individual, or the catheter can be slightly slid, preferably by pulling the catheter outward, and thus advanced continuously one or more regions at a time.

[0041] The electrical pulse generator can be connected by a connector or permanently fixed to a catheter according to the present invention. An easy-to-operate HMI control interface can be envisioned, for example, a simple button for changing the control mode, such as a button for switching from an electrical stimulation current to a current for generating high-frequency waves or a button for driving a piezoelectric element to generate ultrasound for a denervation process.

[0042] In summary, there are many advantages to transvascular nerve stimulation kits for diagnostic purposes, but the following points are among them: It is a medical device that is easy to install, and in particular, it is equipped with an additional catheter that is easy to install and use; To enable highly reliable transvascular nerve stimulation (which allows for very accurate mapping of one or more nerve regions of the patient's autonomic nervous system) and subsequent denervation intervention in the same device, and preferably to allow verification (checking of completeness) of the intervention's effects during and after the intervention; It must be possible to implement it in any existing guide catheter; The possibility of using thinner, less invasive catheters, typically having a diameter of 6 French rather than 8 French like conventional devices, is particularly relevant for use in the pre-surgical stage.

[0043] Further advantages and features will become clearer by reading the detailed description, which is non-limiting and refers to the attached drawings. [Brief explanation of the drawing]

[0044] [Figure 1] Figure 1 is a schematic diagram illustrating the use of a renal nerve stimulation kit according to the present invention, which includes a guide catheter into which a catheter for both stimulation and denervation is introduced, and the guide catheter is directly introduced into the peripheral artery of the patient. [Figure 2] Figure 2 shows a modified example of the first embodiment of the deployable distal structure of a catheter according to the present invention, which is in the form of a mesh having multiple intersections that define contact points with blood vessels facing the renal artery in the deployed position. [Figure 3] Figure 3 is a perspective view of a modified example of a first embodiment of the deployable distal structure of a catheter according to the present invention, which is in the form of a set of arms that define the point of contact with a blood vessel facing the renal artery in the deployed position. [Modes for carrying out the invention]

[0045] In the following specification and throughout this application, the terms “distal” and “proximal” are used to refer to the patient’s body in which renal nerve stimulation, followed by denervation intervention, is performed. Accordingly, the distal end of the elongated electrically conductive element of the catheter according to the present invention is the end that is located furthest in the patient’s body between nerve stimulation for diagnosis and subsequent denervation.

[0046] It should be noted that various elements are not necessarily shown to actual size. Figure 1 shows a stimulation and denervation kit according to the present invention. Guide catheter 1 is inserted into the femoral artery.

[0047] Such a guide catheter 1 can be small in diameter. The guide catheter 1 conforms to existing standards for peripheral intravascular catheters. The catheter 1 is equipped with a flushing device 10 with stopcocks for flushing the inside of the catheter 1 with a suitable flushing fluid or for injecting a contrast agent, and is commonly referred to as a “valve” or “Y-piece”.

[0048] The stimulating and denervating catheter 2 according to the present invention is introduced into the sheath of the guide catheter 1. The length of the catheter 2 is typically 180 to 300 cm.

[0049] This catheter 2 is first introduced into the tubular sheath of the guide catheter 1 and is equipped with an electrically insulating tubular deployable sheath 3.

[0050] An elongated deployment element 4 is installed inside the tubular deployment sheath 3, which has a sliding function.

[0051] The elongated element 4 comprises at least one conductive wire, the distal end 42 of which is in the form of a conductive, deployable structure comprising a plurality of electrical contact points 420, a plurality of piezoelectric actuators as desired, and a plurality of needles as desired.

[0052] The proximal end 41 of the conductive wire is electrically connected to an external electrical pulse generator 5.

[0053] Before any stimulus is initiated, the elongated element 4 is in a folded position within the tubular unfolding sheath 3 in which the structure 42 is compressed.

[0054] When the elongated element is slid to face the portion of the renal artery to be denervated, the structure 42 is deployed, and in this deployed position, at least a portion of the contact point 420, optionally at least a portion of the piezoelectric actuator, and optionally at least a portion of the needle are in contact with at least one peripheral region of the blood vessel, thereby electrically stimulating a portion of the autonomic nervous system around the peripheral region by supplying an electric current.

[0055] Therefore, at the deployed position, electrical stimulation is performed to map the peripheral region of the sympathetic nervous system S through the renal artery AR, and subsequently, denervation is performed by electrical denervation, or ultrasonic denervation if necessary, or by injecting alcohol into the needle, provided by the piezoelectric actuator.

[0056] Figure 2 shows the structure 42 in the deployed position as a tubular expandable metal mesh, where at least a portion of the wire intersection 420 defines the plurality of electrical contact points, which are optionally equipped with piezoelectric actuators.

[0057] This modification allows the entire process of mapping, denervating, and checking for integrity to be performed over a substantial length of the nervous system S, particularly over multiple peripheral regions Z1, Z2, and Z3, without moving the catheter 2.

[0058] Figure 3 shows a set of curved, independent metal arms 422 as the structure 42, which are connected at their bases to the conductive wire and define a shape exhibiting umbrella-like rotational symmetry.

[0059] Therefore, at their deployed end positions, at least a portion of the arm 422 defines the plurality of electrical contact points 420, and a piezoelectric actuator is provided.

[0060] This modification allows for more precise identification of the surrounding area to be denervated, but it is preferable to slide the catheter 2 by withdrawing it within the guide catheter 1.

[0061] The conductive wire and branch are hollow, and at least a portion of the free end of the branch is pointed to form multiple alcohol injection needles, thereby enabling denervation without generating high-frequency and / or ultrasonic waves.

[0062] The following describes the method of renal nerve stimulation, denervation, and checking, or checking completeness, performed using the aforementioned kit.

[0063] This method is applicable when the practitioner diagnoses the renal artery, subsequently denervates it, and preferably verifies or checks the integrity of one or more denervated areas.

[0064] Process i / : The practitioner proceeds to introduce the guide catheter 1 into the femoral artery of human body C.

[0065] Process ii / : Next, the practitioner inserts the catheter 2 into the introducer sheath of the guide catheter 1 until the distal end 42 is correctly positioned within the renal artery AR to be diagnosed and denervated.

[0066] Step iii / : The practitioner slides the elongated element 4 from a folded position to an unfolded position within the tubular unfolding sheath 3. The structure 42 is then unfolded, and at least some of the contact points of the plurality of contact points, and optionally at least some of the piezoelectric actuators of the plurality of piezoelectric actuators, and optionally at least some of the needles, into contact with at least one peripheral region Z1, Z2, or Z3 of the blood vessel (Figure 2 or Figure 3).

[0067] Process iv / :Direct unipolar stimulation is applied to the elongated element 4. More specifically, this elongated element conducts current in unipolar mode. The current supplied by the generator 5 may be approximately 15mA to 25mA per minute, with a pulse frequency of 200 to 2000 times / minute (10 to 20Hz).

[0068] Next, the response to this stimulus is measured for each region of the nervous system S facing the area in contact with various contact points 420. Thus, the peripheral region is mapped.

[0069] Next, one or more regions identified as highly responsive to stimulation are subjected to electrical denervation by the piezoelectric actuator or, if necessary, ultrasonic denervation at the deployed position, or to the injection of alcohol into the needle.

[0070] Process v / : In step iv / , electrical stimulation of one or more peripheral regions that have been denervated is performed by supplying current from the generator 5 to check the denervation that has been performed.

[0071] The present invention is not limited to the examples described herein, and in particular, it is possible to combine the features of the illustrated examples in modified forms not shown.

[0072] Other modifications and improvements can be provided without departing from the scope of the present invention.

[0073] In the illustrated example, the guide catheter or inserter is introduced through the femoral artery, i.e., the femoral artery located in the groin, but it may also be introduced through the radial artery, i.e., the radial artery in one of the patient's wrists.

[0074] An introducer can be used instead of a guide catheter.

[0075] List of References JPEG2026524813000002.jpg71170

Claims

1. A catheter (2) for transvascular stimulation and denervation of a part of the autonomic nervous system of the human body, An electrically insulating tubular deployable sheath (3) for introduction into a tubular sheath of an introducer or guide catheter, the electrically insulating tubular deployable sheath (3) intended to be introduced into the blood vessels of the human body; An elongated unfolding element (4) having at least one conductive wire, the distal end (42) of which is in the form of a conductive unfoldable structure comprising a plurality of electrical contact points (420), optionally a plurality of piezoelectric actuators, optionally a plurality of needles, wherein the elongated element is mounted in the tubular unfolding sheath so as to be able to slide between a folded position and an unfolded position within the tubular unfolding sheath, where the structure is compressed in the folded position and unfolded in the unfolded position, where at least some of the plurality of electrical contact points, and optionally the plurality of piezoelectric actuators, are unfolded. The elongated unfolding element (4) has at least some of the piezoelectric actuators of several piezoelectric actuators, and optionally at least some of the needles of the plurality of needles, in contact with at least one of the peripheral regions of the blood vessel, and an electric current is passed through it by an external electric pulse generator connected to the conductive wire, thereby electrically stimulating a portion of the autonomic nervous system around the peripheral region (Z1, Z2, Z3) to perform electrical stimulation for mapping the peripheral region, and thereafter, at the unfolded position, electrical denervation is performed by the piezoelectric actuators, or optionally ultrasonic denervation, or alcohol is injected into the needles. The catheter (2) is equipped with the following.

2. A catheter (2) for stimulation and denervation according to claim 1, comprising an electrical pulse generator (5) electrically connected to a conductive wire and permanently or detachably attached thereto, in particular by a connector.

3. A catheter for stimulation and denervation according to claim 1 or 2, wherein, once electrical or ultrasonic denervation has been performed, the structure is designed to remain in the deployed and positioned position in order to perform electrical stimulation to check the denervation.

4. A catheter for stimulation and denervation according to any one of claims 1 to 3, wherein the structure is formed of a tubular, expandable metal mesh in an unfolded position, and at least some of the wire intersections thereof define a plurality of electrical contact points, which are optionally equipped with piezoelectric actuators.

5. A catheter (2) for stimulation and denervation according to any one of claims 1 to 3, wherein the structure is formed by a set of curved, mutually independent metal arms (422), the set of metal arms (422) connected at their bases to the conductive wires and defining an umbrella-shaped rotationally symmetrical form at their extended end positions, and some of the arms define a plurality of electrical contact points, which are optionally equipped with piezoelectric actuators.

6. A catheter (2) for stimulation and denervation according to claim 5, wherein the line and the arm are hollow, and at least a portion of the free end of the arm is pointed to form a plurality of alcohol injection needles.

7. A catheter for stimulation and denervation according to any one of claims 4 to 6, wherein the diameter of the wires of the mesh or the diameter of the arms of the umbrella is 40 to 200 micrometers.

8. A catheter (2) for stimulation and denervation according to any one of claims 1 to 7, wherein the number of electrical contact points per peripheral region is at least 2, preferably at least 4, preferably at least 6, and preferably at least 8.

9. A catheter (2) for stimulation and denervation according to any one of claims 1 to 8, wherein the structure has an outer diameter of 3 to 9 mm in its deployed position.

10. A stimulant and denervation kit, An introducer or guide catheter (1) having at least one tubular introducer sheath for introduction into the blood vessels of the human body; A catheter for stimulation and denervation according to any one of claims 1 to 9, which is designed to introduce the introducer or the guide catheter into the introducer sheath. The stimulation and denervation kit comprising the above-mentioned equipment.

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