Catheter for the transvascular stimulation and denervation of part of the autonomic nervous system of a human body, in particular for transvascular stimulation of the renal nerve or stimulation of the carotid body

Abstract

The invention relates to a catheter for the transvascular stimulation and denervation of part of the autonomic nervous system of a human body, in particular for transvascular stimulation of the renal nerve or stimulation of the carotid body. The invention essentially consists of a catheter, which allows both nerve stimulation of the one or more regions of the autonomic nervous system around an artery, for mapping purposes, and denervation of the one or more mapped regions, if they are considered targets.

Description

[0001] Description

[0002] Title: Catheter for transvascular stimulation and denervation of a part of an autonomic nervous system of a human body, in particular transvascular renal nerve stimulation or stimulation of the carotid glomus.

[0003] Technical field

[0004] The present invention relates to a catheter for transvascular stimulation and denervation of a portion of an autonomic nervous system of a human body.

[0005] By "autonomic nervous system" is meant here and within the scope of the invention, the nervous system which directs the internal organic functions, and does not manage the voluntary mechanisms of the human body and is thus distinguished from the somatic system which concerns the body's relations with the outside world. The autonomic nervous system essentially innervates the internal organs and its sensory neurons of this system carry information from visceral functions to the central nervous system. Three categories are usually distinguished in the autonomic nervous system: the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system.

[0006] By "blood vessel" is meant here and within the scope of the invention, a vein or an artery.

[0007] The invention aims firstly to propose a simple and effective solution for both trans-vascular stimulation, particularly for rapid diagnosis and / or for the purpose of mapping a nerve region, particularly with a view to a surgical or percutaneous intervention, particularly afferent denervation.

[0008] Although described with reference to an application of renal nerve stimulation, the invention applies to any other application of stimulation of a part of the autonomic nervous system of the human body. In particular, the invention also applies to nerve stimulation of the carotid glomus.

[0009] Prior art

[0010] Renal sympathetic denervation by catheter appears promising for treating pathologies / deficiencies that are primarily hypertension, but also heart failure, cardiac arrhythmias, diabetes, and pulmonary arterial hypertension.

[0011] In particular, hypertension is a major health problem worldwide associated with a significantly increased risk of heart attacks and strokes.

[0012] Although the majority of patients agree to be treated long-term with effective medications to treat their hypertension, a large proportion of them remain non-compliant, particularly due to possible side effects and / or the inability of the medication to achieve blood pressure targets despite maximally tolerated regimens. In some cases, high blood pressure is refractory to drug treatments.

[0013] Thus, several new treatment strategies based on the implementation of medical devices have recently been developed to help control blood pressure by modulating the sympathetic nervous system.

[0014] Among these, renal sympathetic denervation has been the most studied.

[0015] Renal denervation is a technique consisting of performing superficial stimulation of the afferent and efferent nerves located around the renal arteries, either using an electrode catheter connected to a radiofrequency generator, or using a multi-electrode catheter connected to an ultrasound generator, or using a catheter equipped at its distal end with needles for injecting an alcohol-based liquid product.

[0016] One of the major challenges of this denervation technique is the lack of landmarks along the renal arteries identifying the exact location of the part of the nerves to be destroyed and thus determining the areas to be treated to optimize the effectiveness of the denervation treatment.

[0017] Early trials of transcatheter renal artery denervation for resistant hypertension using a radiofrequency generator did not show consistent clinical efficacy, widely considered to be primarily due to procedural factors that limited the assessment of the completeness of denervation achieved.

[0018] According to the authors of [1], the difficulty of predicting renal denervation and the controversy surrounding the paradigm of renal denervation as an antihypertensive treatment owe much to the absence of means of evaluating the act during the procedure, that is to say, of a measurable criterion to confirm the success of the procedure.

[0019] Authors have shown that:

[0020] - the aortic co-renal ganglia can be localized transvascularly with high-frequency unipolar electrical stimulation, at 10Hz under a current of 25mA of the inferior vena cava or the aorta, or its branches,

[0021] - stimulation of the aorticorenal ganglia induces arterial vasoconstriction and a concomitant increase in blood pressure,

[0022] - renal denervation blocks activation of the afferent renal nerve and subsequently abolishes renovascular responses to stimulation of the aorticorenal ganglia.

[0023] Publication [2], which mentions electrical stimulation at 20 Hz with 5 ms pulses under a current of 10 mA, makes a similar observation.

[0024] The authors of the publication [3] use a multi-electrode catheter marketed under the name "ConfidenHT™" with a distal end that deploys in the form of an ellipsoid with four branches, each supporting an electrode, by pressing a button on a handle. This catheter is very invasive because its diameter is large, around 2.67 mm (8 French) and if the authors mention the possibility of nerve mapping with such a catheter, this remains to be demonstrated given the deployed shape which cannot be truly moved within the artery to at least easily reach other nerve sites. The placement of this catheter is also not easy to achieve.

[0025] Thus, the devices proposed to date can be considered too invasive and are not necessarily reliable in guaranteeing mapping of a renal artery and / or not easy to implement.

[0026] There is therefore a need to improve renal nerve stimulation and afferent denervation devices, in order to overcome the above drawbacks.

[0027] More generally, there is a need for a medical device that allows nerve stimulation of a part of the autonomic nervous system to be carried out, which is simple, rapid and effective, in particular for the purposes of mapping or monitoring the effectiveness of denervation, and non-invasive, and for a medical device for related denervation. The aim of the invention is to meet this need at least in part.

[0028] Statement of the invention

[0029] To this end, the invention relates to a catheter for transvascular stimulation and denervation of a part of an autonomic nervous system of a human body comprising:

[0030] - an electrically insulating tubular deployment sheath intended to be introduced into a tubular sheath of an introducer or guide catheter, itself intended to be introduced into a blood vessel of the human body;

[0031] - an elongated deployment element comprising at least one electrical conduction line whose distal end is in the form of a deployable, electrically conductive structure, comprising a plurality of electrical contact points and, where appropriate, a plurality of piezoelectric actuators and, where appropriate, a plurality of needles,the elongate element being slidably mounted in the tubular deployment sheath between a folded position inside the tubular deployment sheath in which the structure is compressed and a deployed position in which the structure is deployed with at least part of the contact points and, where appropriate, the piezoelectric actuators and, where appropriate, the needles in contact with at least one peripheral zone of the blood vessel to electrically stimulate the part of the autonomic nervous system around the peripheral zone by sending an electric current by means of an external electrical pulse generator and connected to the electrical conduction line, so as to carry out electrical stimulation for mapping the peripheral zone followed by electrical denervation or, where appropriate, denervation by ultrasound produced by the piezoelectric actuators or by injecting alcohol into the needles, in said deployed position.,

[0032] Advantageously, the structure is adapted to remain in said deployed position, once the electrical or ultrasound denervation has been carried out, so as to carry out electrical stimulation to control the denervation.

[0033] According to a first advantageous embodiment variant, the structure is constituted by an expandable metal mesh of tubular shape in a deployed position of which at least a part of the wire crossings define the plurality of electrical contact points and where appropriate provided with piezoelectric actuators. According to a second advantageous embodiment variant, the structure is constituted by an assembly of curved metal branches independent of each other, connected at their base to the electrical conduction line, which delimit an axisymmetrical shape of umbrella type, in their extreme deployed position, with a portion of at least a part of the branches defining the plurality of electrical contact points and where appropriate provided with piezoelectric actuators.

[0034] According to this second variant, the line and the branches are hollow with at least part of the free end of the latter being pointed to form a plurality of alcohol injection needles. Thus, denervation can be carried out by injection of alcohol.

[0035] Preferably, the diameter of the wires of the mesh or the branches of the umbrella is between 40 and 200 microns.

[0036] The number of electrical contact points per peripheral zone may be equal to at least two, preferably at least four, preferably at least six, preferably at least eight.

[0037] Advantageously, the structure has, in its deployed position, an external diameter of between 3 and 9 mm.

[0038] The invention also relates to a stimulation and denervation assembly, comprising:

[0039] - an introducer or guide catheter comprising at least one tubular introduction sheath, intended to be introduced into a blood vessel of the human body;

[0040] - a stimulation and denervation catheter as described above, adapted to be introduced into the insertion sheath of the introducer or guide catheter.

[0041] The invention also relates to a method for nerve stimulation and denervation of a part of the autonomic nervous system of a patient and, where appropriate, surgical intervention, comprising the following steps: i / introduction of a guide catheter or an introducer into a femoral or radial artery of a human body; ii / introduction of a trans-vascular stimulation and denervation catheter comprising:

[0042] - an electrically insulating tubular deployment sheath, - an elongated deployment element comprising at least one electrical conduction line, the distal end of which is in the form of an electrically conductive deployable structure, comprising a plurality of electrical contact points and, where appropriate, a plurality of piezoelectric actuators and, where appropriate, a plurality of needles, iii / sliding the elongated element in the tubular deployment sheath from a folded position inside the tubular deployment sheath in which the structure is compressed to a deployed position in which the structure is deployed with at least some of the contact points and, where appropriate, the piezoelectric actuators and, where appropriate, the needles in contact with at least one peripheral zone of the blood vessel,iv / electrical stimulation of the part of the autonomic nervous system around the peripheral zone by sending an electrical current by means of an external electrical pulse generator and connected to the electrical conduction line, so as to carry out an electrical stimulation of mapping of the peripheral zone followed by an electrical denervation or, where appropriate, a denervation by ultrasound produced by the piezoelectric actuators or by injection of alcohol into the needles, in said deployed position. v / where appropriate, electrical stimulation of one or more peripheral zones denervated according to step iv / by sending an electrical current by means of an external electrical pulse generator and connected to the electrical conduction line so as to carry out a control of the denervation carried out.,

[0043] Thus, the invention consists of a catheter, which allows both nerve stimulation of the area(s) of the autonomic nervous system around an artery, for mapping purposes and denervation of the mapped area(s), if considered as targets.

[0044] In other words, with the same catheter remaining in place and with its distal structure deployed, it is possible to map at least one nerve area, followed by denervation if the mapping has revealed its necessity, and advantageously control or completeness of the denervation.

[0045] This nerve stimulation is a transvascular renal stimulation (artery or vein) of the areas of the sympathetic system likely to generate high blood pressure. This allows us to perfectly identify the nerve area(s) to be denervated in order to reduce or eliminate high blood pressure. This stimulation also allows us to verify the effectiveness of the denervation carried out previously.

[0046] By performing rapid pacing, temporary hypotension and / or bradycardia (slow heart rate) may be observed. This allows bradycardia or hypotension to be predicted prior to a carotid angioplasty procedure and therefore to be anticipated and drugs administered to avoid this pitfall.

[0047] The guide catheter or introducer of the stimulation assembly according to the invention can be completely conventional for the anatomy of the blood vessel around the nerve area to be diagnosed and subsequently denervated.

[0048] The intensity of nerve stimulation, which is advantageously unipolar stimulation, is required, both for mapping and post-denervation monitoring. Typically, the intensity of the delivered alternating current can range from 10 to 25 mA for approximately 10 to 60 seconds, at a frequency ranging from 200 to 2000 / min (10 to 20 Hz).

[0049] Denervation performed by radiofrequency or by generation of ultrasound by piezoelectric actuators using the current supplied by the electrical conduction line or by the injection of alcohol is performed instantly and reliably since the catheter according to the invention is not moved once the mapping has been carried out. Thus, the peripheral area(s) to be denervated are precisely located.

[0050] The handling of all the components of the assembly is simple since only mechanical sliding actions are necessary, on the one hand of the catheter according to the invention in a guide or introducer catheter previously introduced into an artery, and on the other hand of the elongated element in the deployment sheath so as to deploy the structure.

[0051] Depending on the shape and / or dimensions of the distal structure to be deployed, the catheter according to the invention can either be left in place in the guide catheter or the introducer to map, denervate, and if necessary, complete an entire renal nerve portion of an individual, or it can be slid slightly, preferably by withdrawing it outwards and thus proceeding successively zone(s) by zone(s). The electrical pulse generator can be connected by connectors or permanently fixed to the catheter according to the invention. It is possible to envisage an easy-to-handle HMI control interface such as a simple button to change the control mode and, for example, to switch from an electrical stimulation current to an electrical current to generate radio frequencies or to actuate the piezoelectrics in order to produce ultrasound for the denervation step.

[0052] In summary, the advantages of a transvascular nerve stimulation set for diagnostic purposes are numerous, including:

[0053] - a medical device that is easy to install, including an additional catheter that is easy to install and use;

[0054] - the same object which successively allows reliable transvascular nerve stimulation, which allows very precise mapping of the nerve zone(s) of a patient's autonomic nervous system and a denervation intervention and preferably to verify the effectiveness of the intervention during and after it (completeness),

[0055] - possibility of implementation on any existing guide catheter;

[0056] - possibility of using a smaller, less invasive catheter, typically 6 French in diameter and not 8 French as in state-of-the-art devices, especially before a possible surgical procedure.

[0057] Other advantages and characteristics will become more apparent upon reading the detailed description, given for illustrative and non-limiting purposes, with reference to the following figures.

[0058] Brief description of the drawings

[0059] [Fig 1] Figure 1 is a schematic view illustrating the use of a renal nerve stimulation assembly according to the invention with a guide catheter into which is introduced both a stimulation and denervation catheter according to the invention, the guide catheter being introduced directly into a peripheral artery of a patient.

[0060] [Fig 2] Figure 2 shows a first variant embodiment of the deployable distal structure of a catheter according to the invention, in the form of a grid with multiple crossing points which, in its deployed position, define the points of contact with the blood vessel opposite a renal artery. [Fig 3] Figure 3 is a perspective view of a first variant embodiment of the deployable distal structure of a catheter according to the invention, in the form of an assembly of branches which, in its deployed position, define the points of contact with the blood vessel opposite a renal artery.

[0061] Detailed description

[0062] In the following description and throughout the present application, the terms "distal" and "proximal" are used with reference to the body of a patient for whom renal nerve stimulation followed by denervation intervention is to be performed. Thus, the distal end of the electrically conductive elongated element of the catheter according to the invention is the end located furthest inside the patient during nerve stimulation for diagnosis followed by denervation.

[0063] Please note that the various elements are not necessarily represented to scale.

[0064] Figure 1 shows a stimulation and denervation assembly according to the invention.

[0065] A guide catheter 1 is introduced into a femoral artery.

[0066] Such a guide catheter 1 may be of small diameter. It complies with the standards for existing peripheral intravascular catheters. The catheter 1 may include a tap-type flushing device 10, commonly referred to as a “valve” or “Y,” for flushing the interior of the catheter 1 with a suitable flushing liquid or for injecting contrast medium.

[0067] A stimulation and denervation catheter 2 according to the invention is introduced into the sheath of the guide catheter 1. The length of this catheter 2 is typically between 180 and 300 cm.

[0068] This catheter 2 firstly comprises an electrically insulating tubular deployment sheath 3, introduced into the tubular sheath of the guide catheter 1.

[0069] An elongated deployment element 4 is slidably mounted in the tubular deployment sheath 3.

[0070] This elongated element 4 comprises at least one electrical conduction line whose distal end 42 is in the form of a deployable, electrically conductive structure, comprising a plurality of electrical contact points 420 and, where appropriate, a plurality of piezoelectric actuators and, where appropriate, a plurality of needles.

[0071] The proximal end 41 of the electrical conduction line is electrically connected to an external electrical pulse generator 5.

[0072] Before any stimulation begins, the elongate member 4 is in a folded position inside the tubular deployment sheath 3 in which the structure 42 is compressed.

[0073] Once the elongated element has slid opposite a portion of the renal artery to be denervated, the structure 42 is deployed with, in this deployed position, at least part of the contact points 420 and, where appropriate, piezoelectric actuators and, where appropriate, needles in contact with at least one peripheral zone of the blood vessel to electrically stimulate the part of the autonomic nervous system around the peripheral zone by sending an electric current.

[0074] It is thus possible to carry out electrical stimulation of the peripheral zone of the sympathetic nervous system S through the renal artery AR followed by electrical denervation or, if necessary, denervation by ultrasound produced by the piezoelectric actuators or by injection of alcohol into the needles, in the said deployed position.

[0075] Figure 2 shows, as structure 42, in its deployed position, an expandable metal mesh of tubular shape of which at least a part of the crossings of wires 420 define the plurality of electrical contact points and where appropriate provided with piezoelectric actuators.

[0076] This variant makes it possible to carry out all the stages of mapping, denervation and completion over a significant portion of the nervous system S, in particular several peripheral zones Z1, Z2, Z3, without having to move the catheter 2.

[0077] Figure 3 shows, as structure 42, an assembly of curved and independent metal branches 422, connected at their base to the electrical conduction line, which delimit an axisymmetric umbrella-type shape.

[0078] Thus, in their extreme deployed position, a portion of at least one part of the branches 422 defining the plurality of electrical contact points 420 and where appropriate provided with piezoelectric actuators. This variant can allow finer discrimination of the peripheral zones to be denervated, but requires sliding, preferably by withdrawal of the catheter 2 into the guide catheter 1.

[0079] It is possible to provide that the electrical conduction line and the branches are hollow with at least a portion of the free end of the latter at a point to form a plurality of alcohol injection needles in order to carry out denervation without having to generate radio frequencies and / or ultrasounds.

[0080] The method of renal nerve stimulation, denervation, and control or completeness implemented by the previously described assembly is now described.

[0081] This method is applied when a practitioner wishes to make a diagnosis of the renal artery followed by denervation and preferably a verification or completeness of one or more denervated areas.

[0082] Step i / : a practitioner then introduces the guide catheter 1 into a femoral artery of a human body C.

[0083] Step ii / : the practitioner then introduces the catheter 2 into the introduction sheath of the guide catheter 1, until ensuring that the distal end 42 is well positioned in the renal artery AR to be diagnosed and denervated.

[0084] Step iii / : The practitioner iii / slides the elongated element 4 in the tubular deployment sheath 3 from a folded position to a deployed position. The structure 42 is then deployed with at least part of the contact points and, where appropriate, piezoelectric actuators and, where appropriate, needles in contact with at least one peripheral zone Z1, Z2 or Z3 of the blood vessel (figure 2 or 3).

[0085] Step iv / : Direct unipolar stimulation is performed on the elongated element 4. More precisely, this elongated element conducts current in unipolar mode. The current delivered by the generator 5 can be of the order of 15mA to 25mA with a pulse frequency between 200 and 2000 / min (10 to 20 Hz) for 1 min.

[0086] The response to this stimulation is then measured for each area of ​​the nervous system S with respect to the area in contact with the various contact points 420. Thus, the mapping of the peripheral areas is carried out. For the area(s) identified as responding significantly to the stimulation, an electrical denervation is then carried out or, where appropriate, a denervation by ultrasound produced by the piezoelectric actuators or by injection of alcohol into the needles, in said deployed position.

[0087] Step v / : electrical stimulation of one or more peripheral areas denervated according to step iv / is carried out by sending an electric current using the generator 5 so as to carry out a check of the denervation carried out.

[0088] The invention is not limited to the examples which have just been described; one can in particular combine characteristics of the examples illustrated within non-illustrated variants.

[0089] Other variations and improvements may be provided without departing from the scope of the invention.

[0090] If in the illustrated examples the introduction of the guide or introducer catheter is done via the femoral route, that is to say in the femoral artery at the level of the groin, it can also be done via the radial route, that is to say in the radial artery at the level of the patient's wrist.

[0091] Instead of a guide catheter, an introducer can be used.

[0092] List of cited references

[0093] [1]: Pierre C. Qian et al « Transvascular Pacing of Aorticorenal Ganglia Provides a stable Procedural Endpoint for Renal Artery Denervation », Cardiovascular Interventions VOL. 12, NO. 12, 2019, by the American College of Cardiology Foundation.

[0094] [2]: Masaomi Chinushi, et al. « Blood Pressure and Autonomic Responses to Electrical Stimulation of the Renal Arterial Nerves Before and After Ablation of the Renal Artery » Hypertension. 2013; 61 :450-456. http: / / hyper.ahajournals.org

[0095] [3]: Konstantinos P. Tsioufis et al. « Safety and performance of diagnostic electrical mapping of renal nerves in hypertensive patients » EuroIntervention 2018;14: el334-el342 publié en ligne Septembre 2018. DOI: 10.4244 / EIJ-D-18-00536

Claims

Claims 1. Catheter (2) for transvascular stimulation and denervation of a part of an autonomic nervous system of a human body comprising: - an electrically insulating tubular deployment sheath (3) intended to be introduced into a tubular sheath of an introducer or guide catheter, itself intended to be introduced into a blood vessel of the human body; - an elongated deployment element (4) comprising at least one electrical conduction line whose distal end (42) is in the form of a deployable, electrically conductive structure comprising a plurality of electrical contact points (420) and, where appropriate, a plurality of piezoelectric actuators and, where appropriate, a plurality of needles, the elongated element being slidably mounted in the tubular deployment sheath between a folded position inside the tubular deployment sheath in which the structure is compressed and a deployed position in which the structure is deployed with at least a portion of the contact points and, where appropriate, the piezoelectric actuators and, where appropriate, the needles in contact with at least one peripheral zone of the blood vessel to electrically stimulate the portion of the autonomic nervous system around the peripheral zone (Z1, Z2,Z3) by sending an electric current by means of an external electric pulse generator and connected to the electric conduction line, so as to carry out an electric stimulation of mapping of the peripheral zone followed by an electric denervation or where appropriate a denervation by ultrasound produced by the piezoelectric actuators or by injection of alcohol into the needles, in said deployed position., 2. Stimulation and denervation catheter (2) according to claim 1, comprising an electrical pulse generator (5), electrically connected to the electrical conduction line, and fixed to the latter in a permanent or removable manner, in particular by means of a connector.

3. Stimulation and denervation catheter (2) according to claim 1 or 2, the structure being adapted to remain in said deployed position, once the electrical or ultrasound denervation has been carried out, so as to carry out electrical stimulation to control the denervation.

4. Stimulation and denervation catheter (2) according to one of the preceding claims, the structure being constituted by an expandable metal mesh of tubular shape in a deployed position of which at least part of the wire crossings define the plurality of electrical contact points and where appropriate provided with piezoelectric actuators.

5. Stimulation and denervation catheter (2) according to one of claims 1 to 3, the structure being constituted by an assembly of curved and mutually independent metal branches (422), connected at their base to the electrical conduction line, which delimit an axisymmetrical umbrella-type shape, in their extreme deployed position, with a portion of at least one part of the branches defining the plurality of electrical contact points and where appropriate provided with piezoelectric actuators.

6. Stimulation and denervation catheter (2) according to claim 5, the line and the branches being hollow with at least part of the free end of the latter being pointed to form a plurality of alcohol injection needles.

7. Stimulation and denervation catheter (2) according to one of claims 4 to 6, the diameter of the wires of the mesh or of the branches of the umbrella being between 40 and 200 microns.

8. Stimulation and denervation catheter (2) according to one of the preceding claims, the number of electrical contact points per peripheral zone being equal to at least two, preferably at least four, preferably at least six, preferably at least eight.

9. Stimulation and denervation catheter (2) according to one of the preceding claims, the structure having, in its deployed position, an external diameter of between 3 and 9 mm.

10. Stimulation and denervation set, including: - an introducer or guide catheter (1) comprising at least one tubular introduction sheath, intended to be introduced into a blood vessel of the human body; - a stimulation and denervation catheter (2) according to one of the preceding claims, adapted to be introduced into the introduction sheath of the introducer or the guide catheter.

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