Source: https://patents.google.com/patent/ES2614272T3/en
Timestamp: 2019-11-15 11:54:31
Document Index: 244943272

Matched Legal Cases: ['art 18', 'art 18', 'art 20', 'art 20', 'art 20', 'art 20', 'art 20', 'art 18', 'art 18', 'art 20', 'art 20', 'art 20', 'art 192', 'art 194', 'art 192', 'art 192', 'art 18', 'art 20', 'art 20']

ES2614272T3 - Multiple electrode catheter assemblies for renal neuromodulation and associated systems and methods - Google Patents
Multiple electrode catheter assemblies for renal neuromodulation and associated systems and methods Download PDF
ES2614272T3
ES2614272T3 ES13715790.5T ES13715790T ES2614272T3 ES 2614272 T3 ES2614272 T3 ES 2614272T3 ES 13715790 T ES13715790 T ES 13715790T ES 2614272 T3 ES2614272 T3 ES 2614272T3
ES13715790.5T
Leonila Rivera
Sukyoung Shin
William W. CHANG
2012-05-11 Priority to US201261646218P priority Critical
2012-05-11 Priority to US201261646218P priority
2013-03-11 Application filed by Medtronic Ardian Luxembourg SARL filed Critical Medtronic Ardian Luxembourg SARL
2013-03-11 Priority to PCT/US2013/030207 priority patent/WO2013169340A1/en
2017-05-30 Publication of ES2614272T3 publication Critical patent/ES2614272T3/en
A renal neuromodulation system (10) for the treatment of a human patient, the system comprising: a procedural guide wire an elongated cylindrical body (16) having a proximal end (18) and a distal end (20), where the end distal (20) of the elongated cylindrical body (16) is configured for intravascular delivery on the procedural guidewire (66) to a patient's renal artery a preformed tubular spiral structure (50) disposed at or near the distal end (20) of the elongated cylindrical body (16), where the spiral structure (50) is configured to transform between an unexpanded configuration and an expanded configuration that tends to assume the shape of the preformed spiral structure (50) and where the spiral structure ( 50) is composed, at least in part, of multifilar braided nitinol wire; and a plurality of electrodes (24) associated with the spiral structure (50), where the elongated cylindrical body (16) and the spiral structure (50) together define a light for guide wire therethrough and where the light for wire The guide is configured to slidably receive the procedural guide wire (66) to locate the spiral structure (50) at a target treatment site within a patient's renal blood vessel and to restrict the spiral structure (50) in the non-expanded configuration, and where the procedural guide wire is configured so that the proximal movement of the procedural guide wire (66) through the light for guide wire with respect to the spiral structure (50) so that a distal end portion of the guide wire (66) is at least partially within the light for guide wire transforms the spiral structure (50) into the expanded configuration, and where the procedural guide wire (66) comprises and a distal part that has variable flexibility along it and where at least one region of the distal part of the guide wire (66) is also configured to remain within the part of the light for guide wire defined by the structure in spiral (50) when the spiral structure (50) is in the expanded configuration.
Multiple electrode catheter assemblies for renal neuromodulation and associated systems and methods.
The present technology refers, in general, to renal neuromodulation and associated systems and methods. In particular, several embodiments relate to radiofrequency (RF) ablation catheter assemblies of multiple electrodes for intravascular renal modulation and associated systems and methods.
The sympathetic nervous system (SNS) is a primarily involuntary body control system normally associated with stress responses. SNS fibers innervate tissue in almost any organ system of the human body and can affect features such as pupil diameter, intestinal motility and urinary production. Such regulation may have adaptive utility in maintaining homeostasis or preparing the body for a rapid response to environmental factors. The chronic activation of the SNS, however, is a common poorly adapted response that can drive the progression of many pathologies. Excessive activation of renal SNS in particular has been identified experimentally and in humans as a likely contributor to the complex pathophysiology of hypertension, volume overload states (such as heart failure), and progressive nephropathy. For example, radiotracer dilution has demonstrated increased renal norepinephrine ("NE") release rates in patients with essential hypertension,
Cardiorenal sympathetic nerve hyperactivity can be particularly pronounced in patients with heart failure. For example, an emanation of exaggerated NE from the heart and plasma kidneys is often found in these patients. The activation of the intensified SNS commonly characterizes both chronic and terminal nephropathy. In patients with terminal nephropathy, plasma levels of NE above the median have been shown to be predictive of cardiovascular disease and several causes of death. This is also true for patients suffering from diabetic or contrast nephropathy. The evidence suggests that sensory afferent signals originating from diseased kidneys are fundamental contributors to initiating and sustaining a high central sympathetic discharge.
The sympathetic nerves that innervate the kidneys end in the blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of renal sympathetic nerves can cause increased renin release, increased sodium reabsorption (Na +), and reduced renal blood flow. These components of neural regulation of renal function are considerably stimulated in pathologies characterized by intensified sympathetic tone and probably contribute to an increase in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation is probably a cornerstone of the loss of renal function in cardiorenal syndrome (i.e. renal dysfunction as a progressive complication of chronic heart failure). Pharmacological strategies to disrupt the consequences of renal efferent sympathetic stimulation include sympatholphic drugs that act centrally, beta blockers (designed to reduce renin release), inhibitors and blockers of the angiotensin converting enzyme receptor (designed to block the action of angiotensin II and the activation of aldosterone as a result of the release of renin), and diuretics (designed to counteract the retention of sodium and water mediated by the renal sympathetic system). These pharmacological strategies, however, have significant limitations including limited efficacy, therapeutic compliance problems, side effects, and others. Recently, intravascular devices that reduce sympathetic nerve activity by applying an energy field to a target site in the renal blood vessel (for example, by RF ablation) have been shown to reduce blood pressure in patients with treatment-resistant hypertension.
WO 2012/061161 refers to catheter devices that have multiple electrode series for renal neuromodulation and associated systems and methods. Among others, WO 2012/061161 describes a treatment device that allows a large wire to remain at least partially inserted in an elongated cylindrical body during treatment. The treatment device includes a single light in each of a tubular support structure and the elongated cylindrical body. The treatment device includes a treatment set having a plurality of energy supply elements mounted on the tubular support structure defining a single central light. In operation, the insertion of the wire grinds substantially straight through the tubular support structure straightens the tubular support structure to place the treatment assembly in a low profile delivery state.
Many aspects of the present disclosure can be better understood with reference to the following drawings. The
Components in the drawings are not necessarily to scale. Instead, it is emphasized to clearly illustrate the principles of the present disclosure. In addition, components may be shown as transparent in certain views for clarity of illustration only and not to indicate that the illustrated component is necessarily transparent.
Figure 1 is a partially schematic diagram of a neuromodulation system configured in accordance with an embodiment of the present technology.
Figure 2 illustrates the modulation of renal nerves with a multi-electrode catheter configured in accordance with an embodiment of the present technology.
Figure 3A is a side view of a distal part of a catheter having a therapeutic assembly or treatment section in a delivery state (e.g., low profile or retracted configuration) outside a patient according to an embodiment of the present technology.
Figure 3B is a perspective view of the distal part of the catheter of Figure 3A in an unfolded state (eg, expanded configuration) outside the patient.
Figure 4 is an enlarged view of a part of the treatment device of Figure 3A.
Figure 5 is a partially schematic side view of a loading tool.
Figure 6 is a conceptual diagram illustrating the sympathetic nervous system and how the brain communicates with the body through the sympathetic nervous system.
Figure 7 is an enlarged anatomical view illustrating nerves that innervate a left kidney to form a renal plexus that surrounds a left renal artery.
Figures 8A and 8B are anatomical and conceptual views, respectively, illustrating a human body that includes a brain and kidneys and efferent and afferent neural communication between the brain and the kidneys.
Figures 9A and 9B are anatomical views illustrating, respectively, an arterial vasculature and a venous vasculature of a human being.
The present technology refers to devices and systems to achieve electrically and / or thermally induced renal neuromodulation (that is, to make neural fibers that innervate the kidney inert or inactive or otherwise completely or partially of reduced function) by percutaneous transluminal intravascular access . In particular, embodiments of the present technology refer to catheters and catheter assemblies that have multiple electrode series and that are movable between a supply or low profile state (for example, a generally straight form) and an unfolded state (by example, a generally radially expanded helical shape). The electrodes or energy supply elements comprising the series of multiple electrodes are configured to supply energy for example, electrical energy, RF energy, pulsed electrical energy, thermal energy) to a renal artery after they have been advanced to it by means of a catheter along a percutaneous transluminal trajectory (for example, a perforation of the femoral artery, an iliac artery and the aorta, a radial artery or other suitable intravascular trajectory). The catheter or catheter assembly that carries the series of multiple electrodes is sized and shaped so that the electrodes or energy supply elements contact an inner wall of the renal artery when the catheter is in the unfolded state (for example, helical ) inside the renal artery. In addition, the helical shape of the deployed part of the catheter that carries the series allows blood to flow through the helix, which is expected to help prevent occlusion of the renal artery during activation of the energy supply element. In addition, the blood flow in and around the series can cool the associated energy supply elements and / or surrounding tissue. In some embodiments, cooling the energy supply elements allows the supply of higher power levels at lower temperatures than can be achieved without refrigeration. This feature is expected to help create deeper and / or larger lesions during therapy, reduce the temperature of the intimal surface, and / or allow longer activation times with reduced risk of overheating during treatment.
The invention is defined by the system of claim 1.
Specific details of the technology are described below with reference to Figures 1-9B. Although many of the embodiments are described below with respect to devices, systems and methods for intravascular modulation of renal nerves using multiple electrode series, other applications and other embodiments
In addition to those described in this document, they are within the scope of the technology. Additionally, several other embodiments of the technology may have different configurations, components or procedures than those described herein. One skilled in the art, therefore, will therefore understand that the technology may have other embodiments with additional elements, or the technology may have other embodiments without several of the features shown and described below with reference to Figures 1-9B.
As used herein, the terms "distal" and "proximal" define a position or direction with respect to the treating practitioner or control device of the practitioner (eg, a handle assembly). "Distal" or "distally" are a position distant from or in a direction away from the physician or the physician's control device. "Proximal" and "proximally" are a position near or in a direction towards the physician or the physician's control device.
Renal neuromodulation is partial or complete disability or other effective alteration of nerves that innervate the kidneys. In particular, renal neuromodulation comprises inhibiting, reducing and / or blocking neural communication along neural fibers (i.e., efferent and / or afferent nerve fibers) that innervate the kidneys. Such incapacitation can be long-term (for example, permanent or for periods of months, years or decades) or short-lived (for example, for periods of minutes, hours, days or weeks). Renal neuromodulation is expected to effectively treat several weather conditions characterized by increased global sympathetic activity and, in particular, conditions associated with central sympathetic overstimulation such as hypertension, heart failure, acute myocardial infarction, metabolic smdrome, insulin resistance, diabetes, hypertrophy. left ventricular, chronic and terminal nephropathy, inappropriate fluid retention in heart failure, cardiorenal smdrome, osteoporosis, and sudden death. The reduction of afferent neural signals contributes to the systematic reduction of sympathetic tone / impulse, and renal neuromodulation is expected to be useful in the treatment of various conditions associated with hyperfunction or systemic sympathetic hyperactivity. Renal neuromodulation can potentially benefit various organs and body structures innervated by sympathetic nerves.
Various techniques can be used to partially or completely disable neural pathways, such as those that innervate the kidney. The deliberate application of energy (eg, electrical energy, thermal energy) to the tissue by one or more energy supply elements may induce one or more desired thermal heating effects in localized regions of the renal artery and adjacent regions of the renal plexus, that are intimately within or adjacent to the adventitia of the renal artery. The deliberate application of the effects of thermal warming can achieve neuromodulation throughout all or part of the renal plexus.
The effects of thermal heating may include both thermal ablation and alteration or non-ablative thermal damage (for example, by sustained heating and / or resistive heating). The desired thermal heating effects may include raising the temperature of target neural fibers above a desired threshold to achieve non-ablative thermal alteration, or above a higher temperature to achieve ablative thermal alteration. For example, the target temperatures may be above body temperature (for example, about 37 ° C) but less than about 45 ° C for non-ablative thermal alteration, or the target temperature may be about 45 ° C or higher for Ablative thermal alteration.
More specifically, exposure to thermal energy (heat) that exceeds a body temperature of approximately 37 ° C, but below a temperature of approximately 45 ° C, can induce thermal alteration by moderate heating of the target neural fibers or vascular structures which perfuse the target fibers. In cases where vascular structures are affected, the target neural fibers are denied perfusion, resulting in necrosis of the neural tissue. For example, this can induce non-ablative thermal alteration in the fibers or structures. Exposure to heat above a temperature of approximately 45 ° C, or above approximately 60 ° C, can induce thermal alteration by substantial heating of the fibers or structures. For example, such higher temperatures may thermally remove the target neural fibers or vascular structures, in some patients, it may be desirable to achieve temperatures that thermally remove the target neural fibers or vascular structures, but that are less than about 90 ° C , or less than about 85 ° C, or less than about 80 ° C, and / or less than about 75 ° C. Regardless of the type of heat exposure used to induce thermal neuromodulation, a reduction in renal sympathetic nerve activity (ANSR) is expected.
II Selected embodiments of neuromodulation systems
Figure 1 illustrates a renal neuromodulation system 10 ("system 10") configured in accordance with an embodiment of the present technology. The system 10 includes an intravascular catheter 12 operatively coupled to an energy source or energy generator 26 (for example, an RF energy generator). The catheter 12 may include an elongated cylindrical body 16 having a proximal part 18, a handle 34 in a proximal region
of the proximal part 18, and a distal part 20. The catheter 12 may also include a therapeutic set or treatment section 21 (shown schematically) in the distal part 20 (for example, fixed to the distal part 20, which defines a section of the distal part 20, etc.). As explained in more detail below, the set
Therapeutic 21 may include a support structure 22 and a series of two or more delivery elements of
energy 24 (eg, electrodes) configured to be delivered to a renal blood vessel (for example, a renal artery) in a low profile configuration. Upon delivery to the target treatment site within the renal blood vessel, the therapeutic set 21 is further configured to be deployed to an expanded state (for example, a generally spiral / helical configuration) to supply energy at the treatment site. and provide electrically and / or thermally therapeutically effective renal neuromodulation.
Alternatively, the deployed state may be non-helical, provided that the deployed state supplies the
energizes the treatment site. The therapeutic set 21 can be transformed between the delivery and deployment states using self-expansion.
The proximal end of the therapeutic assembly 21 is carried by or is fixed to the distal part 20 of the elongated cylindrical body 16. A distal end of the therapeutic assembly 21 may terminate the catheter 12 with, for example, a traumatic tip 40. In some embodiments, the distal end of the therapeutic set 21 can also be configured to engage another element of the system 10 or catheter 12. For example, the distal end of the therapeutic set 21 can define a passage for receiving a gma wire (not shown) for supply of the device of treatment using techniques on the wire (“OTW”) or fast exchange (“RX”). Additional details regarding these provisions are described below.
The catheter 12 can be electrically coupled to the power source 26 via a cable 28, and the power source 26 (e.g., an RF power generator) can be configured to produce a mode and magnitude of energy selected for supply to the site of treatment by means of the power supply elements 24. As described in more detail below, feed wires (not shown) can extend along the elongated cylindrical body 16 or through a light in the cylindrical body 16 the elements of individual energy supply 24 and transmitting the treatment energy to the energy supply elements 24. In some embodiments, each energy supply element 24 includes its own supply wire. In other embodiments, however, two or more energy supply elements 24 may be electrically coupled to the same supply wire. A control mechanism 32, such as a remote pedal or handheld control device, may be connected to the power source 26 to allow the practitioner to start, terminate and, optionally, adjust various operational features of the power source 26, including, but not limited to, power supply. The remote control device (not shown) may be positioned in a sterile field and operatively coupled to the power supply elements 24, and may be configured to enable the practitioner to selectively activate and deactivate the energy supply elements 24. In other embodiments, the remote control device may be incorporated in the handle assembly 34.
The energy source or energy generator 26 may be configured to supply the treatment energy by means of an automated control algorithm 30 and / or under the control of a physician. For example, the power source 26 may include computer devices (for example, personal computers, server computers, tablets, etc.) that have processing circuits (for example, a microprocessor) that are configured to execute stored instructions related to the algorithm of control 30. In addition, the processing circuits may be configured to execute one or more evaluation / feedback algorithms 31, which may be communicated to the practitioner. For example, the power source 26 may include a monitor or display 33 and / or associated features that are configured to provide visual, audio or other indications of power levels, sensor data and / or other feedback. The power source 26 may also be configured to communicate feedback and other information to another device, such as a monitor in a catheterization laboratory.
The power supply elements 24 can be configured to supply power independently (i.e., they can be used monopolarly), simultaneously, selectively or sequentially, and / or can supply power between any desired combination of the elements (i.e., they can be used bipolar way). In monopolar embodiments, a neutral or dispersive electrode 38 may be electrically connected to the energy generator 26 and fixed to the outside of the patient (for example, as shown in Figure 2). In addition, the practitioner may optionally select which energy supply element or elements 24 are used for power supply to form one or more highly personalized lesions within the renal artery that have various shapes or patterns. In yet other embodiments, the system 10 may be configured to provide other suitable forms of treatment energy, such as a combination of monopolar and bipolar electric fields.
In several embodiments, the power source 26 may include a radio frequency identification (RFID) evaluation module (not shown) mounted on or near one or more ports on the power source 26 and configured to read and write wirelessly on one or more RFID tags (not shown) on the
catheter 12. In a particular embodiment, for example, catheter 12 may include an RFID tag housed inside or otherwise attached to the connecting part of the cable 28 that is coupled to the power source 26. The RFID tag may include, for example, an antenna and an RFID chip to process signals, send / receive RF signals, and store data in a memory. Suitable RFID tags include, for example, MB89R 118 RFID tags available from Fujitsu Limited of Tokyo, Japan. The memory portion of the RFID tag may include a plurality of blocks allocated for different types of data. For example, a first memory block may include a validation identifier (for example, a unique identifier associated with the specific type of catheter and generated from the unique ID of the RFID tag using an encryption algorithm), and a The second memory block may be assigned as a catheter use counter that can be read and then written by the RFID module carried by the power source 26 after the use of the catheter. In other embodiments, the RFID tag may include additional memory blocks allocated for additional catheter use counters (for example, to allow catheter 12 to use a specific limited number of times) and / or other information associated with the catheter. 12 (for example, lot number, customer number, catheter model, totalized data, etc.).
The RFID evaluation module carried by the power source 26 may include an antenna and a processing circuit that are used together to communicate with one or more parts of the power source 26 and read / write wirelessly on one or more RFID tags in its vicinity (for example, when the cable 28 that includes an RFID tag is attached to the power source 26). Suitable RFID evaluation modules include, for example, a TRF7960A evaluation module available from Texas Instruments Incorporated of Dallas, Texas.
In operation, the RFID evaluation module is configured to read information from the RFID tag (carried by cable 28 or other suitable part of catheter 12), and to communicate the information to a power source software 26 to validate the fixed catheter 12 (for example, validate that catheter 12 is compatible with energy source 26), read the number of previous uses associated with particular catheter 12 and / or write on the RFID tag to indicate the use of the catheter. In various embodiments, the power source 26 may be configured to disable the power supply to catheter 12 when predefined conditions of the RFID tag are not met. For example, when each catheter 12 is connected to the power source 26, the RFID evaluation module can read a unique anti-counterfeit number in an encrypted format from the RFID tag, decrypt the number, and then authenticate the number and the catheter data format for recognized catheters (for example, catheters that are compatible with particular energy source 26, anti-counterfeit catheters, etc.). In various embodiments, the RFID tag may include one or more identifiers that correspond to a specific type of catheter, and the RFID evaluation module may transmit this information to a main controller of the power source 26, which can adjust the configuration. (for example, the control algorithm 30) of the power source 26 at the desired operating parameters / characteristics (eg, power levels, display modes, etc.) associated with the specific catheter. In addition, if the RFID evaluation module identifies catheter 12 as forgery or is unable to otherwise identify catheter 12, the power source 26 can automatically disable the use of catheter 12 (for example, exclude the power supply) .
Once catheter 12 has been identified, the RFID evaluation module can read the memory address spaces of the RFID tag to determine if catheter 12 was previously connected to a generator (i.e., was previously used). In certain embodiments, the RFID tag may limit catheter 12 to a single use, but in other embodiments the RFID tag may be configured to allow more than one use (eg, 2 uses, 5 uses, 10 uses, etc.). ). If the RFID evaluation module recognizes that catheter 12 has been written (ie used) more than a predetermined limit of use, the RFID module can communicate with power source 26 to disable the supply of energy to catheter 12 In certain embodiments, the RFID evaluation module may be configured to interpret all catheter connections to a power source within a predefined period of time (for example, 5 hours, 10 hours, 24 hours, 30 hours, etc. .) as a single connection (ie a single use), and allow catheter 12 to be used multiple times within the predefined period of time. After catheter 12 has been detected, recognized, and considered as a "new connection" (for example, not used more than the predefined limit), the RFID evaluation module can write on the RFID tag (for example, the time and date of use of the system and / or other information) to indicate that catheter 12 has been used. In other embodiments, the RFID evaluation module and / or the RFID tag may have different features and / or different configurations.
The system 10 may also include one or more sensors (not shown) located next to or within the power supply elements 24. For example, the system 10 may include temperature sensors (eg, thermocouple, thermistor, etc.), impedance sensors, pressure sensors, optical sensors, flow sensors and / or other suitable sensors connected to one or more supply wires (not shown) that transmit signals from the sensors and / or transport energy to the energy supply elements 24. Figure 2 (with additional reference to Figure 1) illustrates the modulation of renal nerves with an embodiment of the system 10. Catheter 12 provides access to the renal PR plexus through an intravascular path T, such as an access site percutaneous in the femoral artery (illustrated), brachial, radial or axillary to a treatment site
target within a respective renal artery AR. As illustrated, a section of the proximal part 18 of the cylindrical body 16 is exposed externally of the patient. By manipulating the proximal part 18 of the cylindrical body 16 from outside the intravascular path T, the physician can advance the cylindrical body 16 through the sometimes tortuous intravascular path T and remotely manipulate the distal part 20 of the cylindrical body 16. In In the embodiment illustrated in Figure 2, the therapeutic assembly 21 is delivered intravascularly to the treatment site using a wire 66 in an OTW technique. As previously indicated, the distal end of the therapeutic assembly 21 can define a light or passage to receive the large wire 66 for supply of the catheter 12 using OTW or RX techniques. At the treatment site, the coarse wire 66 can be extracted or removed at least partially axially, and the therapeutic assembly 21 can be transformed or otherwise moved to a deployed arrangement for supplying energy at the treatment site. Additional details regarding these arrangements are described below with reference to Figures 3A and 3B. The grna wire 66 may comprise any suitable medical grano wire sized to fit slidably within the light. In a particular embodiment, for example, the wire 66 may have a diameter of 0.356 mm (0.014 inches). This document also describes that the therapeutic set 21 can be supplied to the treatment site within a large sheath (not shown) with or without using the large wire 66. When the therapeutic set 21 is in the target site, the large sheath it can be extracted or retracted at least partially and the therapeutic assembly 21 can be transformed to the deployed arrangement. Additional details regarding this type of configuration are described below. In this document it is further described that the cylindrical body 16 can be addressable, in turn, so that the therapeutic assembly 21 can be delivered to the treatment site without the help of the large wire 66 and / or the large sheath.
Image-guided, for example, computed tomography (CT), fluoroscopy, intravascular ultrasound (USIV), optical coherence tomography (TCO), intracardiac echocardiography (EIC), or other appropriate guiding modality, or combinations thereof, may used to aid placement and manipulation by the practitioner of the therapeutic set 21. For example, a fluoroscopy system (for example, including a flat panel, x-ray, or c-arc detector) can be rotated to visualize and accurately identify the target treatment site. In other embodiments, the treatment site can be determined using USIV, TCO and / or other suitable mapping modalities that can correlate the target treatment site with an identifiable anatomical structure (e.g., a medullary feature) and / or a ruler radiopaque (for example, placed under or over the patient) before supplying catheter 12. In addition, in some embodiments, image-guided components (eg, USIV, TCO) can be integrated with catheter 12 and / or run in parallel to catheter 12 to provide image guidance during the placement of the therapeutic set 21. For example, the image-guided components (eg, USIV or TCO) can be coupled to at least one of the therapeutic set 21 (e.g., proximal to therapeutic arms 25) to provide three-dimensional images of the vasculature next to the target site to facilitate placement or deployment of the whole mul multiple electrodes inside the target renal blood vessel.
The deliberate application of energy from the energy supply elements 24 can then be applied to target tissue to induce one or more desired neuromodulatory effects in localized regions of the renal artery and adjacent regions of the PR renal plexus, which are arranged within of, adjacent to, or in close proximity to the adventitia of the renal artery AR. The deliberate application of energy can achieve neuromodulation throughout all or at least a part of the PR renal plexus. The neuromodulatory effects are, in general, depending on, at least in part, the power, the time, the contact between the energy supply elements 24 (Figure 1) and the vessel wall, and the blood flow through the glass. Neuromodulatory effects may include denervation, thermal ablation, and / or non-ablative thermal damage or alteration (for example, by sustained heating and / or resistive heating). The desired thermal heating effects may include raising the temperature of target neural fibers above a desired threshold to achieve non-ablative thermal alteration, or above a higher temperature to achieve ablative thermal alteration. For example, the target temperature may be above body temperature (for example, approximately 37 ° C) but be less than approximately 45 ° C for non-ablative thermal disturbance, or the target temperature may be approximately 45 ° C or higher for ablative thermal alteration. The desired effects of non-thermal neuromodulation may include altering the electrical signals transmitted in a nerve.
Figure 3A is a side view of the distal part 20 of the catheter 12 and the therapeutic assembly or treatment section 21 in a delivery state (e.g., low profile or retracted configuration) outside a patient, and Figure 3B it is a perspective view of the therapeutic set 21 in an unfolded state (eg, expanded configuration) outside the patient. As previously described, catheter 12 may be configured for OTW delivery from an access site where the wire grinds 66 (Figure 2) is initially inserted to a treatment site (for example, within a renal artery) , and catheter 12 is installed on the wire. As described in more detail below, a large wire can be inserted into or at least partially removed from the distal portion 20 to transform the therapeutic assembly 21 between the delivery state (Figure 3A) and the unfolded state (Figure 3B). As shown in Figure 3A, a thick wire (not shown) extending through at least a portion of the length of catheter 12 is configured to straighten a preformed spiral / helical control member 50 (schematically shown in lmeas
discontinuous) of the catheter 12 during delivery, and the gma wire can be slidly removed or moved at least partially with respect to the distal part 20 to allow the therapeutic assembly 21 to transform to the unfolded state (Figure 3B).
As best seen in Figure 3A, the therapeutic assembly 21 includes multiple (eg, four, five, etc.) energy supply elements 24 carried by the support structure 22. In this embodiment, the structure The support tube 22 comprises a flexible tube 42 and the pre-formed control member 50 within the tube 42. The flexible tube 42 may be composed of a polymeric material such as polyamide, polyimide, amide-polyether block copolymer sold under the trademark PEBAX , polyethylene terephthalate (PET), polypropylene, polycarbonate-based thermoplastic polyurethane, aliphatic marketed under the trademark CARbOtHANE, or a polyether ether ketone (PEEK) polymer that provides the desired flexibility. In other embodiments, however, tube 42 may be composed of other suitable materials.
As mentioned above, it is further described that the preformed control member 50 can be used to provide a spiral / helical shape to the relatively flexible distal portion 20 of the catheter 12. As seen best in Figure 3B , for example, the control member 50 is a tubular structure comprising a nitinol multifilar braided wire with a light therethrough and sold under the trademark HELICAL HOLLOW STRAND (HHS), and commercially available from Fort Wayne Metals of Fort Wayne, Indiana. The tubular control member 50 may be formed from various different types of materials, may be arranged in a single or double layer configuration, and may be manufactured with a tension, compression, torque and selected direction of passage. The HHS material, for example, can be cut using a laser, electric shock machining (EDM), electrochemical grinding (ECG), or other suitable means to achieve a desired length and geometry of the finished component. For example, as best seen in Figure 3B, the control member 50 in the present embodiment has a preset spiral / helical configuration that defines the deployed state of the therapeutic assembly 21 so that the delivery elements of energy 24 of the therapeutic set 21 are displaced from each other (for example, displaced both angularly and longitudinally with respect to a longitudinal axis of the renal artery) and can be positioned in stable position with a wall of the renal artery (Figure 2) for treatment . For clarification purposes, the pre-established helical shape of the therapeutic set 21 in its deployed state can be defined by dimensions (for example, diameter and pitch of the propeller) that are different from the dimensions (for example, diameter and pitch of the propeller) of the HHS itself. In other words, the control member that forms a multifilar hollow tube 50 is, in turn, preset in a helical shape.
It is expected that forming control member 50 of one or more multi-stranded stranded wires of nitinol or other similar materials eliminates the need for any one or more additional reinforcing wires or structures within the support structure 22 to provide a desired level of support. and rigidity to the therapeutic set 21. This feature is expected to reduce the number of manufacturing processes required to form catheter 12 and reduce the number of materials required for the device. Another feature of the therapeutic assembly 21 is that the control member 50 and the inner wall of the tube 42 are in minimal contact and there is little or no space between the control member 50 and the tube 42 (as seen from the best way in figure 4). In one embodiment, for example, the tube 42 can be expanded before assembly, so that the application of hot air to the tube 42 during the manufacturing process can contract the tube on the control member 50, as will be understood by the experts in the matter of ordinary use of contractile tube materials. It is expected that this feature will inhibit or eliminate wrinkles or folds that could occur in the tube 42 as the therapeutic assembly 21 is transformed from the relatively straight supply state to the deployed, generally helical state.
In other embodiments, the control member 50 and / or other components of the support structure 22 may be composed of different materials and / or have a different arrangement. For example, the control member 50 may be formed from other suitable memory materials (eg, wire or tubes of nickel titanium (nitinol), in addition to HHS, shape memory polymers, electroactive polymers) that they are preformed or preformed in the desired deployed state. Alternatively, the control member 50 may be formed from multiple materials, such as a compound of one or more polymers and metals.
The series of energy supply elements 24 may include different series of band electrodes separated along the support structure 22 and attached to the tube 42 using an adhesive. Band or tubular electrodes may be used in some embodiments, for example, since they usually have lower power requirements for ablation compared to disk or flat electrodes. In other embodiments, however, disk electrodes or planes are also suitable. In yet another embodiment, electrodes having a spiral or coil shape can be used. In some embodiments, the energy supply elements 24 may be equidistant, along the length of the support structure 22. The energy supply elements 24 may be formed from any suitable metal material (eg, gold , platinum and platinum and iridium alloy, etc.). In other embodiments, however, the number, arrangement and / or composition of the energy supply elements 24 may vary.
Figure 4 is an enlarged view of a part of catheter 12 of Figure 3A. With reference to Figures 1 and 4 together, each energy supply element or electrode 24 is electrically connected to the energy source 26 (Figure 1) by means of a conductor or two-wire wire 44 that extends through a tube light 42 Each power supply element 24 can be welded or otherwise electrically coupled to its power supply wire 44, and each wire 44 can extend through the tube 42 and the elongated cylindrical body 16 (Figure 1) for the entire length of the cylindrical body, so that a proximal end thereof is coupled to the power source 26 (Figure 1). As indicated above, the tube 42 is configured to fit tightly against the control member 50 and the wires 44 to minimize the space between an internal part of the tube 42 and the components positioned therein to help prevent the formation of wrinkles in the therapeutic set 21 during deployment. In some embodiments, the catheter 12 may also include an insulating layer (eg, a PET layer or other suitable material) on the control member 50 to electrically isolate, in addition, the material (eg, HHS) of the control member 50 of the wires 44.
As best seen in Figure 4, each power supply element 24 may include tapered end portions 24a (eg, chamfers) configured to provide an obtuse angle between an outer surface of the tube 42 and an outer surface of the corresponding power supply element 24. It is expected that the smooth angle transition provided by tapered end portions 24a will help prevent a large sheath or charging tool from clogging or capturing the edges of the custom power supply elements 24 that the large cover or loading tool is moved over the length of the therapeutic set 21 (figures 3A and 3B) during the advance and withdrawal. In other embodiments, the extent of tapered portions 24a over the power supply elements 24 may vary. In some embodiments, tapered end portions 24a comprise chamfers formed from adhesive material at either end of the corresponding power supply elements 24. In other embodiments, however, tapered end portions 24a may be formed from the same material. that the tube 42 (for example, formed in one piece with the tube 42 or formed separately and fixed to both ends of corresponding energy supply elements 24). In addition, tapered portions 24a are an optional feature that may not be included in some embodiments.
Referring again to Figures 3A and 3B, the therapeutic assembly 21 includes the traumatic flexible curved tip 40 at a distal end of the assembly 21. The curved tip 40 is configured to provide a distal opening 41 for the large wire 66 (Figure 2 ) that moves the large wire away from the wall of the renal artery when the therapeutic set 21 is in the pre-established deployed configuration. This feature is expected to facilitate the alignment of the helical therapeutic assembly 21 in the renal blood vessel as it expands, while also reducing the risk of damaging the blood vessel wall when the distal tip of the wire is advanced from the opening. 41. The curvature of the tip 40 can be modified depending on the particular dimensions / configuration of the therapeutic set 21. As seen in the best way in Figure 3B, for example, in the illustrated embodiment, the tip 40 is curved so which is outside the preset spiral / helical axis defined by the control member 50. In other embodiments, however, the tip 40 may have a different curvature. In some embodiments, the tip 40 may also comprise one or more radiopaque markers 52 and / or one or more sensors (not shown). The tip 40 can be fixed to the distal end of the support structure 22 by means of adhesive, crimping, molding on model part or other suitable techniques.
The flexible curved tip 40 may be made of a polymeric material (for example, polyether-amide block copolymer sold under the trademark PEBAx), a thermoplastic polyether-urethane material (sold under the trademarks ELASTHANE or PELLETHANE), or other suitable materials that have the desired properties, including a selected durometer. As indicated above, the tip 40 is configured to provide an opening for the large wire 66, and it is desirable that the tip itself maintain a desired shape / configuration during operation. Accordingly, in some embodiments, one or more additional materials may be added to the tip material to help improve the retention of the tip shape, in a particular embodiment, for example, about 5 to 30 percent by weight of Siloxane can be mixed with the tip material (for example, thermoplastic polyether urethane material), and an electron beam or gamma irradiation can be used to induce crosslinking of the materials. In other embodiments, the tip 40 may be formed from different materials and / or have a different arrangement.
In operation (and with reference to Figures 2, 3A and 3B), after placing the therapeutic set 21 in the desired location within the patient's renal artery AR, the therapeutic set 21 can be transformed from its delivery state to its state deployed or layout deployed. The transformation can be initiated using a device component arrangement, as described herein with respect to the particular embodiments and their various modes of deployment. The therapeutic assembly 21 can be deployed by retracting the large wire 66 until a distal tip of the large wire 66 is generally aligned with the tip 40 of the catheter 12. The large wire 66 has a variable stiffness or flexibility along its length to provide a greater flexibility distally. When the variable-shaped flexible wire 66 is partially retracted, as described above, the preset helical shape of the
control 50 provides a recovery force sufficiently to overcome the straightening force provided by the most distal part of the wire gma 66, so that the therapeutic assembly 21 can be deployed to its helical configuration. Furthermore, since the flexible distal part of the gma 66 wire remains within the therapeutic assembly 21 in the unfolded state, the gma 66 wire can grant additional structural integrity to the helically shaped part during the treatment. This feature is expected to help mitigate or reduce problems associated with keeping the therapeutic set 21 in place during treatment (for example, help with vasoconstriction).
This document further describes that the gma 66 wire can have a stiffness profile that allows the distal part of the gma 66 wire to remain extended from the opening 41 while still allowing the therapeutic assembly 21 to be transformed to its deployed configuration. The gma 66 wire can be completely removed from the therapeutic set 21 (for example, a more distal terminal part of the gma 66 wire is proximal to the therapeutic set 21) to allow for transformation, while a more distal part of the gma 66 wire remains inside the body cylindrical 16. The gma 66 wire can be completely removed from the cylindrical body 16. In any of the previous examples, the practitioner can extract the gma 66 wire sufficiently to observe the transformation of the therapeutic assembly 21 to the deployed configuration and / or until an image X-ray show that the distal tip of the GMA 66 wire is in a desired location with respect to the therapeutic assembly 21 (for example, generally aligned with the tip 40, completely removed from the therapeutic assembly 21, etc.). In some embodiments, the extraction extension for the GMA 66 wire may be based, at least in part, on the discretion of the practitioner with respect to the selected GMA wire and the extraction extension necessary to achieve deployment.
After treatment, the therapeutic assembly 21 can be transformed back to the low profile delivery configuration by advancing the gma 66 wire axially with respect to the therapeutic set 21. In one embodiment, for example, the gma 66 wire can be advanced to that the distal tip of the gma 66 wire is generally aligned with the tip 40, and then the catheter 12 can be pulled back over the stationary gma wire 66. In other embodiments, however, the most distal part of the wire can be advanced gma 66 to a different location with respect to the therapeutic set 21 to achieve the transformation of the therapeutic set 21 back to the low profile arrangement.
The embodiments of the catheter systems described above include a procedural gma wire to guide the catheter to the treatment site and also to restrict the therapeutic set or treatment section in a low profile delivery state. In further embodiments, catheter systems configured in accordance with the present technology may also include an external loading tool that can be arranged and retracted on the therapeutic set to further assist with the transformation of the therapeutic set between delivery and deployed configurations.
Figure 5, for example, is a partially schematic side view of a loading tool 190. The loading tool 190 is a tubular structure configured to move slidably along an outer surface of the cylindrical body 16 and the therapeutic assembly 21 (for purposes of illustration, the therapeutic set 21 and associated features are shown in broken lines). The loading tool 190 has a size and rigidity suitable for maintaining the therapeutic assembly 21 in the low profile configuration for the evacuation of the gma 66 wire (Figure 2), that is, insertion of the proximal end of the gma 66 wire into the opening distal 41. In the illustrated example, the loading tool 190 may include a tapered part 192 to help facilitate the advance of the sheath over the therapeutic assembly 21 and associated energy supply elements 24. In some examples, a distal part 194 of the charging tool 190 may also include rounded and smooth inner and outer edges 195 to help rest the inner wall of the charging tool on the power supply elements 24 during the progress of the charging tool with respect to the assembly Therapeutic 21. The loading tool 190 may be composed of high density polyethylene (HDPE) or other suitable materials having a strength and lub desired wealth. In other examples, the loading tool 190 may be composed of two or more different materials. In one example, for example, the larger diameter section of the distal loading tool 190 of the tapered part 192 may be composed of HDPE, while the smaller diameter section of the proximal loading tool 190 of the tapered part 192 may be composed of linear low density polyethylene (LLDPE). In other additional examples, the loading tool 190 may be composed of different materials and / or have a different arrangement.
In some examples, loading tool 190 may be used together with catheter 12 while catheter 12 is external to the patient before treatment, and then removed from catheter 12 before catheter 12 is inserted into the patient. More specifically, as described above, the loading tool 190 can be used to keep the therapeutic assembly 21 in the low profile configuration, while the gma wire is evacuated (moving from a distal end to a proximal end of the catheter 12) . The loading tool 190 can then be removed from the catheter 12, and the therapeutic assembly 21 can be restricted in the delivery configuration with the gma wire support. In another example, the loading tool 190 may remain
installed on the catheter 12 after the evacuation of the gma wire, but the length of the catheter 12 can slide down to a proximal part 18 of the catheter 12 near the handle 34 (Figure 1). In this way, the loading tool 190 remains with the catheter 12, but does not interfere during the treatment.
In still other examples, however, the loading tool 190 may remain at or near the distal part 20 (Figure 1) of the catheter 12 during treatment. For example, a physician may keep the loading tool 190 at or near the distal part 20 of the catheter 12 and then insert the loading tool 190 into a hemostasis valve (not shown) connected to a gma catheter (not shown). Depending on a profile of the loading tool 190 and an internal diameter of the hemostasis valve, the practitioner may be able to insert approximately 2 to 4 cm of the loading tool 190 into the hemostasis valve. An advantage of this approach is that the therapeutic set 21 (Figures 3A and 3B) is additionally protected as the catheter 12 is advanced through the hemostasis valve, and the physician is expected to feel little or no friction between the catheter 12 and the hemostasis valve. In other examples, however, the loading tool 190 may have a different arrangement with respect to the hemostasis valve and / or the other components of the system 10 (Figure 1) during operation.
III. Relevant anatomy and physiology
The following description provides more details regarding the relevant anatoirna and physiology of the patient. This section aims to supplement and expand the previous description regarding the relevant anatoirna and physiology, and provide additional context regarding the disclosed technology and the therapeutic benefits associated with renal neuromodulation. For example, as previously mentioned, several properties of the renal vasculature can form the design of treatment devices and associated methods to achieve renal neuromodulation, and impose specific design requirements for said devices. Specific design requirements may include accessing the renal artery, ureter or renal pelvic anatoirna, facilitating stable contact between a therapeutic element of a treatment device and a luminal surface or wall and / or effectively modulating the renal nerves using the therapeutic element .
The SNS is a branch of the autonomic nervous system along with the enteric nervous system and the parasympathetic nervous system. It is always active at the basal level (called sympathetic tone) and becomes more active during periods of stress. Like other parts of the nervous system, the sympathetic nervous system works through a series of interconnected neurons. Sympathetic neurons are often considered part of the peripheral nervous system (SNP), although many are within the central nervous system (CNS). The sympathetic neurons of the spinal cord (which is part of the CNS) communicate with the peripheral sympathetic neurons through a series of sympathetic ganglia. Within the ganglia, sympathetic spinal cord neurons bind to peripheral sympathetic neurons through synapses. Sympathetic spinal cord neurons are therefore called presynaptic (or preganglionic) neurons, while peripheral sympathetic neurons are called postsynaptic (or postganglionic) neurons.
In synapses within sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds to and activates nicotmic acetylcholine receptors in postganglionic neurons, in response to this stimulus, postganglionic neurons primarily release norepinephrine (norepinephrine). Prolonged activation may trigger adrenaline release from the adrenal medulla.
Once released, norepinephrine and epinephrine bind to adrenergic receptors in peripheral tissues. Adrenergic receptor binding causes a neuronal and hormonal response. Physiological manifestations include dilated pupils, increased heart rate, occasional vomiting, and increased blood pressure. There is also increased sweating due to the union of cholinergic receptors of the sudonpary glands.
The sympathetic nervous system is responsible for positively and negatively regulating many homeostatic mechanisms in living organisms. The fibers coming from the SNS extend through tissues in almost every organ system, providing at least some regulatory function to characteristics as diverse as the pupil diameter, intestinal motility and urinary production. This response is also known as the sympathetic-adrenal response of the organism, since the preganglionic synthetic fibers that terminate in the adrenal medulla (but also all other sympathetic fibers) secrete acetylcholine, which activates the secretion of adrenaline (epinephrine) and to a lesser extent norepinephrine (norepinephrine). Therefore, this response that acts mainly on the cardiovascular system is directly mediated by impulses transmitted through the sympathetic nervous system and indirectly by catecholamines secreted from the adrenal medulla.
Science normally considers the SNS an automatic regulation system, that is, one that works without the intervention of conscious thought. Some evolutionary theorists suggest that the sympathetic nervous system
It worked in early organisms to maintain survival, since the sympathetic nervous system is responsible for preparing the body for action. An example of this preparation is in the moments before getting up, in which the sympathetic discharge increases spontaneously in preparation for action.
1 The nice chain
As shown in Figure 6, the SNS provides a network of nerves that allows the brain to communicate with the body. The sympathetic nerves originate within the spine, toward the center of the spinal cord in the column of intermediate lateral cells (or lateral horn), beginning in the first thoracic segment of the spinal cord and are believed to extend to the second or third lumbar segments. Since its cells begin in the thoracic and lumbar regions of the spinal cord, the SNS is said to have a thoracolumbar discharge. The axons of these nerves leave the spinal cord through the anterior radius / root. They pass near the medullary (sensory) ganglion, where they enter the anterior branches of the medullary nerves. However, unlike somatic innervation, they quickly separate through white branch connectors that connect to the paravertebral ganglia (which are close to the spine) or prevertebral (which are close to the aortic bifurcation) that extend to along the spine.
In order to reach the target organs and glands, axons must travel long distances in the body, and, to achieve this, many axons transmit their message to a second cell through synaptic transmission. The ends of the axons join through a space, the synapse, to the dendrites of the second cell. The first cell (the presynaptic cell) involves a neurotransmitter through the synaptic cleft where it activates the second cell (the postsynaptic cell). The message is then transported to the final destination.
In the SNS and other components of the peripheral nervous system, these synapses are established at sites called ganglia. The cell that sends its fiber is called a preganglionic cell, while the cell whose fiber leaves the ganglion is called a postganglionic cell. As previously mentioned, the preganglionic cells of the SNS are located between the first thoracic segment (T1) and the third lumbar segments (L3) of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.
The nodes include not only the sympathetic trunks but also the cervical ganglia (upper, middle and lower), which send sympathetic nerve fibers to organs of the head and thorax, and the celiac and mesenteric ganglia (which send sympathetic fibers to the intestine).
2. Kidney nerves
As shown in Figure 7, the kidney's neural system includes the renal plexus, which is closely associated with the renal artery. The renal plexus is an autonomic plexus that surrounds the renal artery and is embedded within the adventitia of the renal artery. The renal plexus extends along the renal artery until it reaches the substance of the kidney. The fibers that contribute to the renal plexus arise from the celiac ganglion, the superior mesenteric ganglion, the aorticorrenal ganglion and the aortic plexus. The renal plexus, also called the renal nerve, is mainly composed of sympathetic components. There is (or at least very little) parasympathetic neural activity of the kidney.
The preganglionic neuronal cell bodies are located in the column of interlateral cells of the spinal cord. The preganglionic axons pass through the paravertebral ganglia (they do not establish synapses) until they become the minor splanchnic nerve, the minimal splanchnic nerve, first lumbar splanchnic nerve, second lumbar splanchnic nerve, and move to the celiac ganglion, the superior mesenteric ganglion , and the aorticorrenal ganglion. Postganglionic neuronal cell bodies leave the celiac ganglion, the superior mesenteric ganglion, and the aorticorrenal ganglion to the renal plexus and are distributed to the renal vasculature.
The messages move through the SNS in a bidirectional flow. Efferent messages can trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system can accelerate heart rate, widen the bronchial ducts, decrease motility (movement) of the large intestine, constrict blood vessels, increase peristalsis in the esophagus, cause pupil dilation, piloerection (skin of hen) and perspiration (sweating), and raise blood pressure. Afferent messages carry signals from various organs and sensory receptors in the body to other organs and, particularly, the brain.
Hypertension, heart failure and chronic kidney disease are a few of many pathologies that result from chronic activation of the SNS, especially the renal sympathetic nervous system. The chronic activation of the SNS is a poorly adapted response that drives the progression of these pathologies. The pharmaceutical treatment of
Renin-angiotensin-aldosterone system (SRAA) has been a long, but somewhat ineffective, approach to reducing the hyperfunction of the SNS.
As mentioned above, the renal sympathetic nervous system has been identified as a fundamental contributor to the complex pathophysiology of hypertension, volume overload states (such as heart failure), and progressive nephropathy, both experimentally and in beings. humans. Studies using radiotracer dilution methodology based on measuring the release of norepinephrine from the kidneys to the plasma revealed increased rates of excessive release of renal norepinephrine (NE) in patients with essential hypertension, particularly in young hypertensive subjects, which along with excessive release of NE increased from the heart, it is consistent with the hemodynamic profile normally observed in early hypertension and characterized by an increase in heart rate, cardiac output, and renovascular resistance. It is now known that essential hypertension is commonly neurogenic, often accompanied by a pronounced hyperfunction of the sympathetic nervous system.
The activation of sympathetic cardiorenal nerve activity is even more pronounced in heart failure, as demonstrated by an exaggerated increase in the emanation of NE from the heart and kidneys to plasma in this group of patients. In line with this notion is the recent demonstration of a strong negative predictive value of renal sympathetic activation on mortality from different causes and heart transplantation in patients with congestive heart failure, which is independent of global sympathetic activity, the filtration rate glomerular, and the left ventricular ejection fraction. These findings support the notion that treatment regimens that are designed to reduce sympathetic renal stimulation have the potential to improve survival in patients with heart failure.
Both chronic and terminal nephropathy are characterized by intensified sympathetic nerve activation. In patients with terminal nephropathy, plasma levels of norepinephrine above the median have been shown to be predictive of both death from different causes and death as a result of cardiovascular disease. This is also true for patients suffering from diabetic or contrast nephropathy. There is convincing evidence to suggest that sensory afferent signals originating from diseased kidneys are fundamental contributors to initiating and sustaining high central sympathetic discharge in this group of patients; This facilitates the appearance of the well-known adverse consequences of chronic sympathetic hyperfunction, such as hypertension, left ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes and metabolic smdrome.
i. Renal sympathetic efferent activity
The nerves sympathetic to the kidneys end in the blood vessels, the juxtaglomerular apparatus and the renal tubules. Stimulation of renal sympathetic nerves causes an increase in renin release, an increase in sodium reabsorption (Na +) and a reduction in renal blood flow. These components of the neural regulation of renal function are considerably stimulated in pathologies characterized by intensified sympathetic tone and clearly contribute to the increase in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation is probably a cornerstone of the loss of renal function in cardiorenal syndrome, which is a renal dysfunction as a progressive complication of chronic heart failure, with a climactic development that normally fluctuates with the patient's condition and treatment. Pharmacological strategies to disrupt the consequences of renal efferent sympathetic stimulation include sympatholytic drugs that act centrally, beta blockers (designed to reduce renin release), inhibitors and angiotensin converting enzyme receptor blockers (designed to block the action of angiotensin II and the activation of aldosterone as a result of the release of renin), and diuretics (designed to counteract the retention of sodium and water mediated by the renal sympathetic system). However, current pharmacological strategies have significant limitations including limited efficacy, therapeutic compliance problems, side effects and others.
ii. Renal sensory afferent nerve activity
The kidneys communicate with integral structures in the central nervous system through renal sensory afferent nerves. Several forms of "renal injury" can induce the activation of sensory afferent signals. For example, renal ischemia, reduction of systolic volume or renal blood flow, or an abundance of adenosine can trigger the activation of afferent neural communication. As shown in Figures 8A and 8B, this afferent communication could be from the kidney to the brain or it could be from one kidney to the other kidney (through the central nervous system). These afferent signals are integrated centrally and can result in an increase in sympathetic discharge. This sympathetic impulse is directed towards the kidneys, thus activating the SRAA and inducing an increase in renin secretion, sodium retention, fluid volume retention and vasoconstriction. Central sympathetic hyperfunction also affects other organs and body structures that have sympathetic nerves such as the heart and peripheral vasculature, giving as
The adverse effects of sympathetic activation have been described, several aspects of which also contribute to the increase in blood pressure.
Physiology, therefore, suggests that (i) tissue modulation with efferent sympathetic nerves will reduce inappropriate renin release, sodium retention, and reduction of renal blood flow, and that (ii) nerve tissue modulation Afferent sensory will reduce the systematic contribution to hypertension and other pathologies associated with increased central sympathetic tone through its direct effect on the posterior hypothalamus as well as the contralateral kidney. In addition to the central hypotensive effects of afferent renal neuromodulation, a desirable reduction of central sympathetic discharge to various other organs such as the heart and vasculature is anticipated.
B. Additional clinical benefits of renal neuromodulation
As provided above, renal neuromodulation is likely to be valuable in the treatment of various weather conditions characterized by an increase in global and particularly renal sympathetic activity, such as hypertension, metabolic syndrome, insulin resistance, diabetes, ventricular hypertrophy. left, chronic terminal nephroparia, inappropriate fluid retention in heart failure, cardiorenal smdrome and sudden death. Since the reduction of afferent neural signals contributes to the systematic reduction of sympathetic tone / impulse, renal neuromodulation could also be useful in the treatment of other conditions associated with systematic sympathetic hyperactivity. Therefore, renal neuromodulation can also benefit other organs and body structures that have sympathetic nerves, including those identified in Figure 6.
According to the present technology, neuromodulation, a left and / or right renal plexus PR, which is closely associated with a left and / or right renal artery, can be achieved through intravascular access. As Figure 9A shows, blood moved by contractions of the heart is transported from the left ventricle of the heart through the aorta. The aorta descends through the thorax and branches into the left and right renal arteries. Below the renal arteries, the aorta bifurcates into the left and right iliac arteries. The left and right iliac arteries descend, respectively, through the left and right branches and join the left and right femoral arteries.
As Figure 9B shows, blood accumulates in the veins and returns to the heart, through the femoral veins inside the iliac veins and into the inferior vena cava. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava rises to transport blood into the right atrium of the heart. From the right atrium, blood is pumped through the right vent inside the lungs, where it is oxygenated. From the lungs, oxygenated blood is transported into the left atrium. From the left atrium, oxygenated blood is transported by the left ventricle back to the aorta.
As provided herein, the femoral artery can be accessed and cannulated at the base of the femoral triangle just below the midpoint of the inguinal ligament. A catheter can be inserted percutaneously into the femoral artery through this access site, it can be passed through the iliac artery and the aorta, and placed in the left or right renal artery. This includes an intravascular trajectory that offers minimally invasive access to a respective renal artery and / or other renal blood vessels.
The wrist region, upper arm and shoulder provide other locations for catheter introduction into the arterial system. For example, catheterization of the radial, brachial or axillary artery can be used in select cases. Catheters introduced through these access points can be passed through the subclavian artery on the left side (or through the subclavian and brachiocephalic arteries on the right side), through the aortic arch, below the descending aorta and into the renal arteries using a standard angiographic technique.
Since neuromodulation of a left and / or right renal plexus can be achieved in accordance with the present technology through intravascular access, properties and characteristics of the renal vasculature may impose limitations on and / or shape the design of devices, systems and methods for achieve said renal neuromodulation. Some of these properties and characteristics may vary between the population of patients and / or within a time between specific patients, as well as in response to pathologies, such as hypertension, chronic kidney disease, vascular disease, terminal kidney disease, insulin resistance, diabetes, metabolic smdrome, etc. These properties and characteristics, as explained herein, may have relevance in the efficacy of the procedure and the specific design of the intravascular device. Properties of
interests may include, for example, material / mechanical, spatial, fluid dynamics / hemodynamic and / or thermodynamic properties.
As described above, a catheter can be advanced percutaneously into the left or right renal artery through a minimally invasive intravascular path. However, minimally invasive renal arterial access can be challenging, for example, since compared to some other arteries that are routinely accessed using catheters, the renal arteries are often extremely tortuous, can be of diameter relatively small, and / or can be of relatively short length. In addition, renal arterial atherosclerosis is common in many patients, particularly those with cardiovascular disease. Renal arterial anatoirna can also vary significantly from one patient to another, which further complicates the minimally invasive access. A significant interpatient variation can be observed, for example, in relative tortuosity, diameter, length, and / or atherosclerotic plaque burden, as well as in the exit angle at which a renal artery branches from the aorta. Apparatus, systems and methods to achieve renal neuromodulation through intravascular access must take into account these and other aspects of the renal arterial anatomy and its variation between the population of patients when access to a renal artery is minimally invasive.
In addition to complicating renal arterial access, specificities of the renal anatomy also complicate the establishment of stable contact between neuromodulatory devices and a luminal surface or wall of a renal artery. When the neuromodulator apparatus includes an energy supply element, such as an electrode, a coherent positioning and an appropriate contact force applied by the energy supply element to the vessel wall may be important for predictability. However, navigation is normally impeded by the narrow space within a renal artery, as well as the tortuosity of the artery. In addition, establishing consistent contact can be complicated by patient movement, breathing, and / or the cardiac cycle. These factors, for example, can cause significant movement of the renal artery with respect to the aorta, and the cardiac cycle may temporarily distend the renal artery (that is, cause the artery wall to throb).
After accessing a renal artery to facilitate stable contact between the neuromodulator apparatus and a luminal surface of the artery, nerves in and around the adventitia of the artery can be safely modulated by the neuromodulator apparatus. Effectively applying thermal treatment from within a renal artery is not trivial, given the potential thermal complications associated with such treatment. For example, the minimum and mean renal artery are highly vulnerable to thermal injury. As described in more detail below, the thickness of the minimum-half that separates the light from the vessel from its adventitia means that the target renal nerves may be multiple millimeters away from the luminal surface of the artery. Sufficient energy can be supplied to the target renal nerves to modulate the target renal nerves without overcooling or overheating the vessel wall to the extent that the wall freezes, dries, or is potentially otherwise affected to an undesired extent. A potential thermal complication associated with excessive warming is the formation of a thrombus from coagulant blood that flows through the artery. Therefore, the complex mechanical and thermodynamic conditions of fluids present in the renal artery during treatment, particularly those that may affect the dynamics of heat transfer at the treatment site, may be important for applying energy from within the artery. renal.
The neuromodulator apparatus may be configured to allow the adjustable placement and repositioning of the energy supply element within the renal artery, since the location of the treatment may also affect the chemical efficacy. For example, it may be tempting to apply a complete circumferential treatment from within the renal artery, since the renal nerves may be circumferentially separated around a renal artery. In some situations, a complete circle lesion that probably results from continuous circumferential treatment may potentially be related to renal artery stenosis. Therefore, the formation of more complex lesions along a longitudinal dimension of the renal artery and / or repositioning of the neuromodulator apparatus in multiple treatment locations may be desirable. It should be noted, however, that a benefit of creating a circumferential ablation may exceed the potential for renal artery stenosis or the risk may be mitigated with certain embodiments or in certain patients and creating a circumferential ablation could be an objective. Additionally, the variable positioning and repositioning of the neuromodulator apparatus may prove useful in circumstances where the renal artery is particularly tortuous or where there are proximal branched vessels that leave the main vessel of the renal artery, making treatment in certain locations challenging.
Blood flow through a renal artery may be temporarily occluded for a short period with minimal complications or no complications. However, occlusion for a significant amount of time can be avoided in some cases to reduce the likelihood of kidney injury such as ischemia. It may be beneficial to avoid occlusion completely or, if the occlusion is beneficial for the performance, limit the duration of the occlusion, for example, 2-5 minutes.
Based on the challenges described above of (1) intervention in the renal artery, (2) consistent and stable placement of the treatment element against the vessel wall, (3) effective application of treatment by the vessel wall, (4) place and potentially relocate the treatment apparatus to allow multiple treatment locations, and (5) avoid or limit the duration of blood flow occlusion, various independent and renal vasculature-dependent properties that may be of interest include, for example, (a ) vessel diameter, vessel length, minimum-average thickness, coefficient of friction and tortuosity; (b) distensibility, stiffness and modulus of elasticity of the vessel wall; (c) velocity of maximum systolic blood flow, telediastolic, as well as the mean maximum systolic-diastolic blood flow rate, and mean / maximum volumetric blood flow; (d) specific calorific capacity of blood and / or vessel wall, thermal conductivity of blood and / or vessel wall, and / or thermal convectivity of blood flow past a treatment site in the vessel wall and / or heat transfer by radiation; (e) movement of the renal artery with respect to the aorta induced by breathing, patient movement, and / or pulsatility of the blood flow; and (f) the angle of departure of a renal artery from the aorta. These properties will be described in more detail with respect to the renal arteries. However, depending on the devices, systems and methods used to achieve renal neuromodulation, these renal artery properties can also guide and / or restrict design features.
As indicated above, an apparatus positioned within a renal artery can adapt to the geometry of the artery. The diameter of the renal artery vessel, Dar, is usually in a range of approximately 2-10 mm, with the majority of the patient population having a Dar of approximately 4 mm to approximately 8 mm and an average of approximately 6 mm. The length of the renal artery vessel, Lar, between its orifice at the junction of the aorta / renal artery at its distal ramifications, is generally in a range of approximately 5-70 mm, and a significant part of the patient population is in a range of approximately 20-50 mm. Since the target renal plexus is embedded within the adventitia of the renal artery, the composite photima-media thickness, GIM, (i.e., the radial outward distance from the luminal surface of the artery to the adventitia containing target neural structures ) is also notable and is generally in a range of approximately 0.5-2.5 mm, with an average of approximately 1.5 mm. Although some depth of treatment may be important to reach the target neural fibers, the treatment can be prevented from becoming too deep (for example,> 5 mm from the internal stop of the renal artery) to avoid non-target tissue and anatomical structures such as renal vein
An additional property of the renal artery that may be of interest is the degree of renal movement with respect to the aorta, induced by breathing and / or the pulsatility of the blood flow. The kidney of a patient, which located at the distal end of the renal artery, can move up to 10.2 cm (4 inches) cranially with respiratory displacement. This can give a significant movement to the renal artery that connects the aorta and the kidney, thus requiring the neuromodulator apparatus a unique balance of stiffness and flexibility to maintain contact between the heat treatment element and the vessel wall during cycles of breathing. In addition, the angle of departure between the renal artery and the aorta can vary significantly between patients, and they can also vary dynamically within a patient, for example, due to kidney movement. The departure angle can generally be in a range of approximately 30 ° -135 °.
1. A renal neuromodulation system (10) for the treatment of a human patient, the system comprising: a procedural gma wire
an elongated cylindrical body (16) having a proximal end (18) and a distal end (20), where the distal end (20) of the elongated cylindrical body (16) is configured for intravascular delivery on the procedural gma wire (66) to a patient's renal artery
a preformed tubular spiral structure (50) arranged at or near the distal end (20) of the elongated cylindrical body (16), where the spiral structure (50) is configured to transform between an unexpanded configuration and an expanded configuration that tends to assume the shape of the preformed spiral structure (50) and where the spiral structure (50) is composed, at least in part, of multifilar braided nitinol wire;
a plurality of electrodes (24) associated with the spiral structure (50),
where the elongated cylindrical body (16) and the spiral structure (50) together define a light for gma wire through it
and where the gma wire light is configured to slidably receive the procedural gma wire (66) to locate the spiral structure (50) at a target treatment site within a patient's blood-vessels and to restrict the structure in spiral (50) in the unexpanded configuration,
and where the procedural gma wire is configured so that the proximal movement of the procedural gma wire (66) through the light for gma wire with respect to the spiral structure (50) so that a distal end portion of the gma wire ( 66) this at least partially within the gma wire light transforms the spiral structure (50) into the expanded configuration, and
where the procedural gma wire (66) comprises a distal part that has variable flexibility along it and where at least one region of the distal part of the gma wire (66) is configured to remain within the light part for gma wire defined by the spiral structure (50) when the spiral structure (50) is in the expanded configuration.
2. The system (10) of claim 1, further comprising a flexible tube (42) that covers and is in close contact with the spiral structure (50).
3. The system (10) of claim 2, wherein the plurality electrodes (24) are attached to the flexible tube (42) using an adhesive material.
4. The system (10) of claim 1, wherein the plurality electrodes (24) are composed of gold.
5. The system (10) of claim 1, wherein the plurality electrodes (24) are individually connectable to an energy source (26) external to the patient, and where the energy source (26) is capable of individually controlling the energy supplied to each electrode (24) during therapy.
ES13715790.5T 2012-05-11 2013-03-11 Multiple electrode catheter assemblies for renal neuromodulation and associated systems and methods Active ES2614272T3 (en)
US201261646218P true 2012-05-11 2012-05-11
US201261646218P 2012-05-11
PCT/US2013/030207 WO2013169340A1 (en) 2012-05-11 2013-03-11 Multi-electrode catheter assemblies for renal neuromodulation and associated systems and methods
ES2614272T3 true ES2614272T3 (en) 2017-05-30
ID=48087687
ES13715790.5T Active ES2614272T3 (en) 2012-05-11 2013-03-11 Multiple electrode catheter assemblies for renal neuromodulation and associated systems and methods
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