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WO2025247725A1 - Stimulation prédictive et thérapie par ablation pour une dénervation rénale - Google Patents

Stimulation prédictive et thérapie par ablation pour une dénervation rénale

Info

Publication number
WO2025247725A1
WO2025247725A1 PCT/EP2025/064003 EP2025064003W WO2025247725A1 WO 2025247725 A1 WO2025247725 A1 WO 2025247725A1 EP 2025064003 W EP2025064003 W EP 2025064003W WO 2025247725 A1 WO2025247725 A1 WO 2025247725A1
Authority
WO
WIPO (PCT)
Prior art keywords
therapy
stimulation
blood vessel
electrodes
catheter
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2025/064003
Other languages
English (en)
Inventor
Gerry O. Mccaffrey
Scott R. Stanslaski
Thomas Fernando VALENZUELA
Binit PANDA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medtronic Ireland Manufacturing ULC
Original Assignee
Medtronic Ireland Manufacturing ULC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medtronic Ireland Manufacturing ULC filed Critical Medtronic Ireland Manufacturing ULC
Publication of WO2025247725A1 publication Critical patent/WO2025247725A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • A61B5/4893—Nerves

Definitions

  • This disclosure relates to systems and methods assessing placement of an ablation or sensing probe within a blood vessel. Further, aspects of the disclosure are directed to methods and systems for predicting stimulation and ablation parameters of nerves enervating a blood vessel.
  • a catheter can be configured to deliver neuromodulation (e.g., denervation) therapy to a target tissue site to modify the activity of nerves at or near the target tissue site.
  • the nerves can be, for example, sympathetic or parasympathetic nerves.
  • the sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Chronic over-activation of the SNS is a maladaptive response that can drive the progression of many disease states.
  • excessive activation of the renal SNS has been identified experimentally and in humans as a contributor to the complex pathophysiology of arrhythmias, hypertension, states of volume overload (e.g., heart failure), and progressive renal disease.
  • Percutaneous renal denervation is a minimally invasive procedure that can be used to treat hypertension and other diseases caused by over-activation of the SNS.
  • a clinician delivers energy, such as radiofrequency, ultrasound, cooling, or other energy to a treatment site within the renal vessels to reduce, and/or permanently stop the activity of nerves surrounding a blood vessel.
  • the energy delivered to the treatment site may provide various therapeutic effects through alteration of sympathetic nerve activity.
  • One aspect of the disclosure is a system for denervation of nerves of a blood vessel.
  • the system includes a first catheter configured to be navigated within a blood vessel of a patient, the catheter may include a first plurality of electrodes, and the first catheter being configured to apply stimulation and therapy to nerves adjacent the blood vessel; a second catheter configured to be navigated within the blood vessel of a patient, the second catheter may include a second plurality of electrodes, and the second catheter being configured to detect a signal emitted by nerves to which stimulation has been applied; a stimulation source in electrical communication with at least one electrode of the first plurality of electrodes and configured to output a stimulation signal to the at least one electrode of the first plurality of electrodes of the first catheter; and a computing device including a memory and a processor, the memory storing instructions that when executed, cause the processor to receive the signal detected by the second plurality of electrodes and determine an evoked compound action potential (ECAP) value based at least in part on the signal.
  • ECAP evoked compound action
  • Implementations may include one or more of the following features.
  • the system where the first catheter is configured for placement with the blood vessel and the second catheter is configured for placement within a branch of the blood vessel.
  • the memory stores instructions that, when executed, cause the processor to: cause the stimulation source to output a series of increasing magnitude stimulation signals, where the stimulation source is configured to transmit the series of increasing magnitude stimulation signals to the first plurality of electrodes to be applied to a wall of the blood vessel.
  • the memory stores instructions that, when executed, cause the processor to: determine a corresponding ECAP value for each magnitude of stimulation signal applied to the wall of the blood vessel.
  • the memory stores instructions that, when executed, cause the processor to: determine an ECAP saturation point.
  • the memory stores instructions that, when executed, cause the processor to: correlate the ECAP saturation point with a therapy power level.
  • the memory stores instructions that, when executed, cause the processor to: cause the stimulation source to cease generation of stimulation signals when no ECAP is detected after two or more different magnitudes of stimulation signal are applied to the wall of the blood vessel; and output for display in a user interface an indicator that no nerves are detected at a location of the first catheter, or that movement of the first catheter is required.
  • the system may include a therapy source in communication with the first catheter.
  • the memory stores instructions that, when executed, cause the processor to, during application of a therapy via the first electrodes, determine a change in ECAP in excess of a threshold and stops the therapy source from outputting therapy to the first plurality of electrodes.
  • the therapy and stimulation signals are simultaneously applied to a wall of the blood vessel via the first plurality of electrodes.
  • the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, an ultrasound therapy, a cryogenic therapy, or a chemical therapy. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer- accessible medium.
  • Another aspect includes a method of performing a therapeutic procedure.
  • the method includes applying a stimulation signal to a blood vessel wall via at least one of a first plurality of electrodes on a distal portion of a first catheter located within the blood vessel; receiving a signal emitted from nerves adjacent the blood vessel via at least one of a second plurality of electrodes on a distal portion of a second catheter located within a branch of the blood vessel, and determining an evoked compound action potential (ECAP) value based on the received signal.
  • ECAP evoked compound action potential
  • Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods.
  • Implementations may include one or more of the following features.
  • the method may include: causing a stimulation source to output a series of increasing magnitude stimulation signals, where the stimulation source is configured to transmit the series of increasing magnitude stimulation signals to the first plurality of electrodes and applied to a wall of the blood vessel.
  • the method may include: determining corresponding ECAP values for each magnitude of stimulation signal applied to the wall of the blood vessel.
  • the method may include: ceasing generation of stimulation signals when no ECAP is detected after two or more different magnitudes of stimulation signal are applied to the wall of the blood vessel; and displaying in a user interface an indicator that no nerves are detected at the location of the first catheter, or that movement of the first catheter is required.
  • the method may include: determining an ECAP saturation point.
  • the method may include: correlating the ECAP saturation point with a therapy power level.
  • the method may include: generating a therapy at a therapy source; transmitting the therapy to at least one of the first or second catheters; and applying the therapy to the wall of the blood vessel.
  • the method may include: detecting, during application of therapy, a change in ECAP in excess of a threshold; and stopping the therapy source from outputting therapy.
  • a further aspect of the disclosure is a system including a catheter configured to be navigated within a blood vessel of a patient, the catheter may include a first plurality of electrodes and a second plurality of electrodes, where the first plurality of electrodes are configured to deliver stimulation and therapy to nerves adjacent the blood vessel, and where the second plurality of electrodes are configured to detect a signal emitted by nerves to which stimulation is applied via at least one electrode of the first plurality of electrodes; a stimulation source in electrical communication with the at least one electrode of the first plurality of electrodes and configured to output a stimulation signal to the at least one electrode of the first plurality of electrodes; and a computing device including a memory and a processor, where the memory stores instructions that when executed, cause the processor to receive the signal detected by the second plurality of electrodes and determine an evoked compound action potential (ECAP) value based at least in part on the signal.
  • ECAP evoked compound action potential
  • Implementations may include one or more of the following features.
  • the system where the first plurality of electrodes is configured for placement with the blood vessel and the second plurality of electrodes is configured for placement within a branch of the blood vessel.
  • the system may include a therapy source in communication with a therapy delivery device coupled to the catheter.
  • the therapy delivery device may include the first plurality of electrodes.
  • the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, an ultrasound therapy, a cryogenic therapy, or a chemical therapy.
  • Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium.
  • a system and method for denervation of nerves of a blood vessel including a first catheter configured for navigation within a blood vessel of a patient, the catheter having a first plurality of electrodes for applying stimulation and therapy to nerves adjacent the blood vessel, a second catheter configured for navigation within the blood vessel of a patient, the second catheter having a second plurality of electrodes for detecting a signal emitted by nerves to which stimulation has been applied, a stimulation source in electrical communication with the first plurality of electrodes and configured to output a stimulation signal to the first plurality of electrodes of the first catheter, and a computing device including a memory and a processor, the memory storing instructions that when executed, cause the processor to receive the signal detected by the second plurality of electrodes and determine an evoked compound action potential (ECAP) value.
  • ECAP evoked compound action potential
  • FIG. l is a schematic diagram of a therapy system provided in accordance with some examples of the disclosure.
  • FIG. 2 is a schematic view of a workstation of the therapy system of FIG. 1;
  • FIG. 3 is a perspective view of a therapeutic or sensing device of the therapy system of FIG. 1 advanced within a portion of the patient’s anatomy and in a deployed condition in accordance with some examples of the disclosure;
  • FIG. 4 is a perspective view of two therapeutic of sensing devices of the therapy system of FIG. 1 advanced within a blood vessel and a branch of that blood vessel in accordance with the disclosure;
  • FIG. 4B depicts a method of detecting and denervating nerves in accordance with the disclosure
  • FIGS. 5 A and 5B depict a method of detecting and denervating nerves in accordance with the disclosure
  • FIG. 6 is a graphical representation of the method of FIGS. 5A and 5B in accordance with the disclosure.
  • FIG. 7 is a cross-sectional view of a blood vessel receiving therapy in accordance with the disclosure.
  • FIG. 8 depicts a method of detecting and denervating nerves in accordance with the disclosure.
  • FIG. 9 depicts a graphical representation of the method of FIG. 8 in accordance with the disclosure.
  • This disclosure describes therapeutic systems and methods and particularly ablation systems and methods for denervation or neuromodulation of nerves such as the sympathetic, or parasympathetic, nerves. Some aspects of the disclosure are directed to ablation and denervation of unmyelinated nerve fibers in and around blood vessels or other luminal tissues. In particular, this disclosure is directed to systems and methods that provide pre-procedure and intra-procedure feedback on nerve recruitment, ablation power settings, and/or therapeutic efficacy.
  • the ablation energy may be desirable to ensure that when ablation energy is applied, the ablation energy reaches all or substantially all nerves enervating the blood vessel.
  • Application of stimulation energy to evoke a nervous system response which may be detectable based on hemodynamic or vessel dimension responses (e.g., vasoconstriction, increase in blood pressure, increase in vessel stiffness, reduced blood flow, increased vascular resistance, etc.) has been suggested as a method of identifying locations for placement of an ablation catheter for application of therapy. These changes in response to stimulation may be observed using imaging, pulse-wave velocity, or through the use of pressure and/or flow sensors within the blood vessel.
  • a stimulation catheter is placed within a blood vessel to be denervated and used to apply stimulation energy to the wall of the blood vessel (e.g., the renal artery).
  • a sensing catheter is placed within a branch of the blood vessel (e.g., branches of the renal artery).
  • Stimulation is applied to the blood vessel at multiple magnitudes (e.g., at every 5 mA between 10 and 30 mA).
  • An evoked compound action potential (ECAP) at each stimulation magnitude is detected by the sensing catheter.
  • the sensed responding ECAP does not increase in amplitude compared to the prior level of stimulation (e.g., an ECAP saturation point).
  • the ECAP saturation point may be correlated to a power level for the application of therapy to the nerves of the blood vessel and/or a time for application of the therapy.
  • a stimulation signal, at the saturation point can be applied to the wall of the blood vessel using the stimulation catheter to confirm the efficacy of the therapy.
  • the stimulation catheter may be repositioned such that multiple sites within the blood vessel may be stimulated to identify a location(s) with the nerves present.
  • stimulation can be swept through stimulation signal magnitudes (e.g., from 5 mA to 40 mA) to identify a magnitude of stimulation signal at which no increased ECAP is observed as compared to the prior magnitude of stimulation signal (e.g., an ECAP saturation point).
  • a higher stimulation magnitude may capture nerves more distant from the electrode(s) delivering the stimulation signal.
  • the stimulation magnitude at which no increase in ECAP is detected may be a proxy for nerve depth.
  • a power level and/or duration for therapy may be based on the magnitude of the stimulation signal at which no further ECAP increase is observed.
  • This power level or therapy duration is calibrated to achieve a denervation of the nerves located a distance from the blood vessel wall inner surface associated with the saturation point. This power level or therapy duration can then be utilized during the denervation procedure.
  • a stimulation signal at the saturation point can be applied after completion of the denervation procedure to confirm efficacy of the denervation based on whether nerve activity is sensed.
  • ECAP saturation point therapy can be applied simultaneously with the stimulation.
  • a change in ECAP e.g., a reduction in ECAP
  • this may indicate that the nerves being stimulated have been successfully denervated and thus incapable of evoking the ECAP response to the stimulation.
  • the therapy may be stopped.
  • Still a further aspect of the disclosure assesses the ECAP response to stimulation during therapy delivery.
  • the power e.g., amplitude
  • the therapy e.g., amplitude
  • a stimulation signal is applied at a first magnitude for a first duration. If at the conclusion of the first duration of application of the stimulation signal an ECAP response is detected, both the therapy power level and the stimulation signal magnitude level are increased. This process is repeated until an ECAP saturation point is detected. Following detection of the ECAP saturation point, the therapy power level associated with the detected ECAP saturation point is maintained until denervation is completed.
  • a stimulation signal at the ECAP saturation point magnitude may be applied to confirm the efficacy of the denervation.
  • the nerves being stimulated may be too distant from the therapy delivery element to be successfully denervated at that location.
  • These nerves which are being stimulated to produce the ECAP response may be, for example, late arriving nerves, i.e., nerves that approach the blood vessel wall distal of the location of the therapy delivery element.
  • the catheter applying the ablation energy may be repositioned within the blood vessel, e.g., within a blood vessel branch and application of another ablation to ablate nerves (e.g., additional nerves) enervating the blood vessel and its branches.
  • ablate nerves e.g., additional nerves
  • RF radiofrequency
  • the methods and systems described herein may employ any of the therapy modalities described herein including without limitation monopolar or bipolar RF, microwave, ultrasound, chemical, cryogenic and other already developed or yet to be developed therapy modalities. Further, combinations of these therapies may be applied without departing from the scope of the disclosure.
  • the following description focuses on navigation to and application of therapy to the renal artery to denervate sympathetic or, in certain embodiments, parasympathetic, nerves in, around, and proximate the renal arteries.
  • the present disclosure is not so limited.
  • the devices, systems, and techniques described herein may be used in conjunction with neuromodulation (e.g., denervation) performed from within any suitable anatomical lumen that has nerves adjacent to the anatomical lumen.
  • Example anatomical lumens include the celiac trunk and its branches (including the common hepatic artery and its branches (including the gastroduodenal artery and its branches, the right gastric artery and its branches, and the proper hepatic artery and its branches), the left gastric artery and its branches, and the splenic artery and its branches), the superior mesenteric artery and its branches, the gonadal artery and its branches, the inferior mesenteric artery and its branches, and the like.
  • the celiac trunk and its branches including the common hepatic artery and its branches (including the gastroduodenal artery and its branches, the right gastric artery and its branches, and the proper hepatic artery and its branches), the left gastric artery and its branches, and the
  • the disclosure primarily describes neuromodulation (e.g., denervation) from within one or more arteries
  • the devices, systems, and techniques of the disclosure also may be applied to neuromodulation from within one or more veins, such as a renal vein and its branches, a hepatic vein and its branches, an intercostal vein and its branches, or the like.
  • the devices, systems, and techniques described herein may be used to perform neuromodulation (e.g., denervation) from within two or more anatomical lumens, e.g., in the renal arteries and the common hepatic artery, or any other combination of two or more anatomical lumens, either simultaneously or sequentially.
  • the systems, devices, and methods described herein may be useful in conjunction with neuromodulation (e.g., denervation) within a body lumen other than a vessel, for extravascular neuromodulation and/or for use in conjunction with therapies other than neuromodulation.
  • neuromodulation e.g., denervation
  • the therapeutic devices described herein may also be placed laparoscopically placed in or near one or more of the above-identified blood vessels, or another luminal tissue without departing from the scope of the present disclosure.
  • one or more of the embodiments described herein may be performed via external placement of one or more therapeutic device to achieve the desired neuromodulation methodologies described herein.
  • FIG. 1 illustrates a therapy system provided in accordance with the present disclosure and generally identified by reference numeral 10.
  • therapy system 10 may be used in connection with a C-arm imaging system or other imaging station (e.g., computed tomography, cone beam computed tomography, magnetic resonance imaging, ultrasound imaging, etc.), which may facilitate navigation of a therapeutic device 50 to a desired location within the patient’s anatomy (e.g., the patient’s renal artery), application of denervation therapy to the tissue proximate the renal artery to denervate sympathetic nerves within the tissue, and monitoring of one or more parameter, such as impedance, for use in evaluating the denervation therapy.
  • a C-arm imaging system or other imaging station e.g., computed tomography, cone beam computed tomography, magnetic resonance imaging, ultrasound imaging, etc.
  • a therapeutic device 50 e.g., a desired location within the patient’s anatomy (e.g., the patient’s renal artery), application of denervation therapy
  • the therapy system 10 includes a workstation 20 and a therapeutic device 50 operably coupled to the workstation 20.
  • the therapy system may be used with an imaging device 70, which may be operably coupled to a display 72.
  • the patient “P” is shown lying on an operating table 12 with the therapeutic device 50 inserted through a portion of the patient’s femoral artery, although it is contemplated that the therapeutic device 50 may be inserted into any suitable portion of the patient’s vascular network that is in fluid communication with a desired blood vessel for therapy.
  • the therapy system 10 may employ any suitable number of therapeutic devices 50.
  • the therapeutic devices 50 may employ the same or different therapy modalities and be operably coupled to the workstation 20. Further, the therapeutic device 50 may employ a guidewire (now shown) or a guide catheter 58 (FIG. 3) without departing from the scope of the disclosure.
  • the workstation 20 includes a computer 22, a therapy source 24 (e.g., one or more of an RF generator, a microwave generator, an ultrasound generator, a cryogenic medium source, a chemical source, etc.) operably coupled to the computer 22, and a stimulation source 24a (configured for generation of stimulation signals, e.g., ultrasound, electrical, RF, etc.).
  • a therapy source 24 e.g., one or more of an RF generator, a microwave generator, an ultrasound generator, a cryogenic medium source, a chemical source, etc.
  • a stimulation source 24a configured for generation of stimulation signals, e.g., ultrasound, electrical, RF, etc.
  • the computer 22, therapy source 24, and/or stimulation source 24a are integrated in a single component and may be referred to as a generator, controller, or console.
  • the computer 22 is coupled to a display 26 that is configured to display one or more user interfaces 28.
  • the computer 22 may be a desktop computer or a tower configuration with display 26 or may include a laptop computer or other computing device.
  • the computer 22 includes a processor 30 which executes software stored in a memory 32.
  • the memory 32 may store one or more applications 34 and/or algorithms 44 to be executed by the processor 30.
  • a network interface 36 enables the workstation 20 to communicate with a variety of other devices and systems via the internet.
  • the network interface 36 may connect the workstation 20 to the Internet via a wired or wireless connection. Additionally, or alternatively, the communication may be via an ad hoc Bluetooth® or wireless network enabling communication with a wide- area network (WAN) and/or a local area network (LAN).
  • WAN wide- area network
  • LAN local area network
  • the network interface 36 may connect to the Internet via one or more gateways, routers, and network address translation (NAT) devices.
  • the network interface 36 may communicate with a cloud storage system 38, in which further data, image data, and/or videos may be stored.
  • the cloud storage system 38 may be remote from or on the premises of the hospital such as in a control or hospital information technology room. It is envisioned that the cloud storage system 38 could also serve as a host for more robust analysis of acquired images (e.g., fluoroscopic, computed tomography (CT), magnetic resonance imaging (MRI), cone-beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or reinforcement data for analysis and/or comparison).
  • CT computed tomography
  • MRI magnetic resonance imaging
  • CBCT cone-beam computed tomography
  • An input module 40 receives inputs from an input device such as a keyboard, a mouse, voice commands, an energy source controller (e.g., a foot pedal or handheld remote-control device) that enables the clinician to initiate, terminate, and optionally, adjust various operational characteristics of the therapy source 24 and/or stimulation source 24a, including, but not limited to, therapy or stimulation delivery, amongst others.
  • An output module 42 connects the processor 30 and the memory 32 to a variety of output devices such as the display 26.
  • the display 26 may be a touchscreen display.
  • the therapy source 24 may be configured to generate and/or output one or more of RF energy (monopolar or bipolar), microwave energy, ultrasound energy, cryogenic energy, or chemical ablation medium via semi-automated or automated control algorithm 44 stored on the memory 32 and/or under the control of a clinician.
  • RF energy monopolar or bipolar
  • microwave energy microwave energy
  • ultrasound energy ultrasound energy
  • cryogenic energy or chemical ablation medium
  • chemical ablation medium via semi-automated or automated control algorithm 44 stored on the memory 32 and/or under the control of a clinician.
  • the therapy source 24 may be configured to produce a selected mode of energy and/or therapy for delivery to the treatment site via the therapeutic device 50, as will be described in further detail hereinbelow.
  • the therapy source 24 may be configured to sense voltage and current (e.g., in the case of RF or other electrical energy) applied to target tissue via the therapeutic device 50.
  • one or more sensors on the therapeutic device 50 may monitor the temperature of the target tissue or tissue proximate the target tissue, and/or a portion of the therapeutic device 50.
  • an application 34 on the computer 22 may be configured to calculate an impedance of the tissue through which therapeutic energy is transmitted to provide an indication of the status of the tissue.
  • the computer 22 may be configured to output the status to the display 26 on one or more user interfaces 28 to provide a clinician with both intraprocedural and post-procedural feedback regarding the therapy.
  • the stimulation source 24a outputs a non- therapeutic signal to elicit an ECAP efferent response from the nerves in or near the location of the therapeutic device 50.
  • the stimulation signal may be a current injection signal where a voltage is monitored for safety or a voltage injection signal.
  • the stimulation source 24a generates a low frequency stimulation signal.
  • the low frequency stimulation signal may for example have a frequency of between about 5 Hz and about 1 kHz, optionally between about 10 Hz and 700Hz, between about 50Hz and 500 Hz, between about 100 Hz and 500 Hz, or between about 200 and 400 Hz.
  • the signal has a pulse width of between about 3 and about 10 ms, optionally between about 5 and 8 ms, or about 7 ms.
  • the signal has a current of between about 5 and about 50 mA, optionally between about 10 and 45 mA, optionally between about 15 and 34 mA, between about 20 and 35 mA, or about 30 mA.
  • the signal has a voltage of between 1 and 100 V, optionally between about 10 and 50 V, between about 20 and 40V, or about 30V or between about 25 and 75 V, between about 35 and 60 V, or about 50V.
  • the stimulation signal from the stimulation source 24a may be a monophasic or a biphasic waveform.
  • a biphasic wave form a leading phase of each successive pulse of the biphasic waveform is switched or otherwise inverted.
  • a biphasic waveform having an initial pulse with an anodal leading phase and a cathodal trailing phase is followed by a second pulse with a cathodal leading phase and an anodal trailing phase which will be followed by a third pulse returning to an anodal leading phase and a cathodal trailing phase, and so on.
  • a biphasic waveform having an initial pulse with a cathodal leading phase and an anodal trailing phase may be followed by a second pulse with an anodal leading phase and a cathodal trailing phase which will be followed by a third pulse returning to a cathodal leading phase and an anodal trailing phase.
  • the leading phase of each pulse of the biphasic waveform may be alternated for the duration of the application of neurostimulation to the target tissue.
  • the stimulation source 24a generates a biphasic waveform at an energy level that is less the therapeutic (i.e., denervation energy) generated by the therapy source 24 such that the stimulation generated by the stimulation source 24a does not denervate the target tissue.
  • the stimulation signal may include a series of pulses with each pulse having a leading cathodal phase and a trailing anodal phase.
  • the stimulation signal may be applied between pairs of electrodes for a duration (e.g., between 10 and 60 seconds). At the conclusion of the duration the phases can be switched such that the stimulation signal has a leading anodal phase and a trailing cathodal phase.
  • the stimulation signal is applied with the leading anodal phase for a second duration (which may be the same or different from the first duration, 10 -60 seconds). At the conclusion of the second duration, again the leading phase of the stimulation signal may be switched back to the original stimulation signal where necessary or appropriate for the application.
  • FIG. 3 depicts one embodiment of a therapeutic device 50 in accordance with the disclosure.
  • the therapeutic device 50 includes an elongated shaft 52 having a handle (not shown) disposed on a proximal end portion of the elongated shaft 52.
  • the therapeutic device 50 includes an energy delivery assembly 54 on a distal portion of the elongate shaft 52 at which electrodes 56 are located.
  • the elongated shaft 52 of the therapeutic device 50 is configured to be advanced over a guide wire (not shown) within a portion of the patient’s vasculature, such as a femoral artery or other suitable portion of patient’s vascular network that is in fluid communication with the patient’s renal artery.
  • the energy delivery assembly 54 is configured to be transformed from an initial, undeployed configuration having a generally linear profile, to a second, deployed or expanded configuration, where the energy delivery assembly 54 forms a generally spiral and/or helical configuration for delivering energy to a site for application of therapeutic energy or application of stimulation signals at the treatment site.
  • the energy delivery assembly 54 when in the second, expanded configuration, is pressed against or otherwise contacts the walls of the patient’s vasculature tissue.
  • the energy delivery assembly 54 may be deployed in other configurations without departing from the scope of the present disclosure.
  • the therapeutic device 50 may be configurable, for example, using one or more pull wires (not shown) to adjust the configuration to promote contact between the electrodes 56 and the wall of the renal artery.
  • the therapeutic device 50 may be capable of being placed in one, two, three, four, or more different configurations depending upon the design needs of the therapeutic device 50 or the location at which therapy is to be applied.
  • the energy delivery assembly 54 and electrodes 56 may be formed on an exterior of an inflatable balloon, and expandable basket, a lasso, or a pigtail catheter to achieve the placement of the electrodes 56 in contact with the blood vessel wall without departing from the scope of the disclosure.
  • a single therapeutic devices 50 may be employed.
  • the elongated shaft 52 may be configured to be received within a portion of a guide catheter or guide sheath (such as a 6F guide catheter) 58 that is utilized to navigate the therapeutic device 50 to a desired location.
  • a guide catheter or guide sheath such as a 6F guide catheter
  • the guide catheter 58 is inserted into an access point such as the femoral artery, or another arterial or venous access site to gain access to the vascular system.
  • the guide catheter 58 is advanced to the desired location, for example to cannulate a renal artery.
  • a guide wire (not shown) is advanced through the guide catheter 58 and to a location where therapy is to be applied (i.e., beyond a distal end of the guide catheter 58) and into the desired blood vessel (e.g., the renal artery).
  • the therapeutic device 50 is then advanced over the guide wire beyond the end of the guide catheter 58 exposing the electrodes 56 at the location where the therapy is to be applied.
  • the guide wire is then retracted within the therapeutic device 50 and the guide catheter 58. Retraction of the guide wire within the therapeutic device 50 causes the energy delivery assembly 54 of the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (as shown in FIG. 3) with the electrodes 56 contacting the wall of the blood vessel.
  • the guide catheter 58 may be retracted relative to the therapeutic device 50 to achieve a desired placement of the electrodes 56 in contact with the blood vessel wall.
  • the guide wire is not required, and the placement described herein above may be achieved without the use of the guide wire (e.g., with only a guide catheter).
  • the elongated shaft 52 of the therapeutic device 50 may include an aperture (not shown) at a distal end thereof and configured to slidably receive the guidewire over which the therapeutic device 50, either alone or in combination with the guide catheter 58, are advanced.
  • the guidewire is utilized to guide the therapeutic device 50 to the target tissue using over-the-wire (OTW) or rapid exchange (RX) techniques, at which point the guide wire may be partially or fully removed from the therapeutic device 50, enabling the therapeutic device 50 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (FIG. 3).
  • OW over-the-wire
  • RX rapid exchange
  • the therapeutic device 50 may transition from the first, undeployed configuration to the second, deployed configuration automatically (e.g., via a shape memory alloy, etc.) or manually (e.g., via pull wires, guide wire manipulation, etc. that is controlled by the clinician).
  • a pressure sensor 60 may be incorporated into the guide sheath 58 or the shaft elongated 52 for detection of physiological parameters of the patient.
  • the physiological parameter is blood pressure though other parameters may be detected without departing from the scope of the disclosure.
  • the electrodes 56 are disposed in spaced relation to one another along a length of the therapeutic device 50 forming the energy delivery assembly 54. As will be appreciated, these electrodes 56 are in communication with the therapy source 24 and the stimulation source 24a. The electrodes 56 may deliver therapy and/or stimulation independently of one another, simultaneously, selectively, or sequentially. The electrodes 56 may be in electrical communication with a ground pad (not shown) placed on the patient’s skin and electrically connected to the generator and/or stimulator to enable the application of monopolar RF energy for therapy. Additionally or alternatively, therapy and/or stimulation energy may be applied between any desired combination of the electrodes 56, without requiring the use of a ground pad (e.g., bipolar stimulation or therapy).
  • a ground pad e.g., bipolar stimulation or therapy
  • FIG. 4 is a schematic representation of a blood vessel 100 and blood vessel branches 102 in accordance with an aspect of the disclosure.
  • a proximal therapeutic device 50 is placed in the blood vessel 100 (e.g., the renal artery) and a distal therapeutic device 50 is placed in a branch blood vessel (e.g., a renal artery branch) 102.
  • the electrodes 56 of the proximal therapeutic device 50 emits the stimulation signals 104 that impact the nerves 106.
  • the stimulation signals 104 elicit an ECAP response 108 from the nerves that is detected by the electrodes 56 of the distal therapeutic device 50.
  • the detected ECAP response is transmitted to the computing device 20 and analyzed application 34 to generate one or more indicators displayed in a user interface 28 on a display 26, in accordance with the disclosure.
  • a single therapeutic device 50 may incorporate the electrodes 56 of both therapeutic devices 50 shown in FIG. 4.
  • the elongated shaft 52 has two energy delivery assemblies 54, one proximal and one distal each with one or more electrodes 56. Both energy delivery assemblies may be capable of applying stimulation, applying therapy, and detecting ECAP without departing from the scope of the disclosure.
  • the therapeutic device may have just a single energy delivery assembly and one or more of the electrodes 56 can be configured to apply the stimulation signal, one or more of the electrodes 56 may be configured to sense the ECAP, and one or more of the electrodes 56 may be configured to apply therapy.
  • any given electrode 56 may perform more than one of apply stimulation, sense ECAP, and apply therapy without departing from the scope of the disclosure.
  • a method of assessment of the placement of the proximal therapeutic device 50 to achieve an efficacious therapy and the undertaking of the therapy may be undertaken in accordance with method 150 outlined in FIG. 4B.
  • a stimulation signal is applied via the electrodes 56 of for example the proximal therapeutic device 50 (or a proximal set of electrodes 56 where both proximal and distal electrodes 56 are on a single therapeutic device 50).
  • signals emitted from nerves are received by the electrodes 56 of the distal therapeutic device 50 (or a distal set of electrodes 56 where both proximal and distal electrodes 56 are on a single therapeutic device 50).
  • an evoked compound action potential is determined.
  • ECAP evoked compound action potential
  • a further method in accordance with the disclosure is depicted in connection with method 200 of FIGS 5 A and 5B.
  • a stimulation signal generated by the stimulation source 24a is applied via the electrodes 56 of the proximal therapeutic device 50 to the wall of the blood vessel (e.g., the renal artery).
  • a determination is made whether ECAP is detected via the electrodes 56 on the distal therapeutic device 50 in the blood vessel branch. If ECAP is detected, at step 206 the ECAP is recorded, and the stimulation magnitude is increased at step 208. If no ECAP is detected at step 204, the method proceeds directly to step 208. At step 210 the stimulation is applied at the increased magnitude.
  • the ECAP at the second magnitude is recorded at step 216.
  • step 238 the power level (or duration) of therapy is set based on the third magnitude of stimulation.
  • step 240 the power level (or duration) of therapy is set based on the fourth magnitude of stimulation.
  • step 242 FIG. 5B
  • the stimulation continues to be applied. As the nerves being stimulated are successfully denervated, the ECAP response to that stimulation will decrease, as depicted in FIG. 6. As will be appreciated, and with reference to FIG. 6 the nerves closest to the blood vessel wall will be treated first, while those more distant from the blood vessel wall and the electrodes 56 through which the therapy is applied require more therapy (e.g., higher power therapy or longer duration application).
  • a determination is made whether a change (decrease) in ECAP in excess of a threshold has been detected. If yes, the application of therapy is stopped at step 246 and an indicator is displayed of a successful therapy at step 248.
  • step 250 a determination is made whether the therapy has timed-out, if not the method returns to step 242 and the therapy application continues. If, however, the therapy has timed-out the method moves to step 252 where an indicator is displayed that therapy is required in the branch blood vessel.
  • therapy is applied at the set power level in the blood vessel branch.
  • the therapy in the blood vessel branch may be applied via the electrodes 56 on the distal therapeutic device 50.
  • the proximal therapeutic device 50 may be advanced into the blood vessel branch and therapy can be applied via its electrodes 56.
  • a stimulation signal may be applied to the walls of the blood vessel branch at step 256.
  • Nervous responses to stimulation e.g., vasoconstriction, changes in blood pressure, and others
  • the method can return to step 246 where an indicator of successful therapy may be displayed. If a nervous response is detected at step 258, the method progresses to step 260 where an indicator is displayed of an incomplete therapy.
  • step 242 simultaneous application of therapy
  • step 242 simultaneous application of therapy
  • step 242 stimulation at the saturation point and monitoring the ECAP
  • the disclosure is not so limited and the method may employ alternating application of therapy and stimulation until a drop in observed ECAP as a result of the stimulation in excess of a threshold is observed. If insufficient change in ECAP is observed, then the indicator of the need to apply therapy to the blood vessel branch (step 252) and steps 254 through 260 are undertaken.
  • the workstation 2 may include or be associated with one or more filters (e.g., bandpass filters and others) and other electronics to allow for the ECAP to be accurately measured and to eliminate noise associated with the application of the therapy (e.g., during RF ablation delivery).
  • filters e.g., bandpass filters and others
  • FIG. 6 is a graphic representation 300 of assessment of placement and application of therapy to a successful denervation as described above in connection with method 200.
  • the stimulation is increased step wise during a stimulation phase 302 to assess the power level required for therapy.
  • the saturation point 304 is 30 mA of stimulation, after which increases in stimulation do not result in further recruitment of nerves at the location of the therapeutic device 50 within the patient. Once the saturation point is identified, this is correlated with a power level (or duration) of a therapy and a therapy phase 306 is commenced.
  • the ECAP response is observed and as the therapy successfully ablated nerves, the ECAP response detected by electrodes 56 of the distal therapeutic device 50 begins to decrease in magnitude, shown graphically at point 308.
  • the ECAP response decreases beyond a threshold, shown graphically at point 310, the application of therapy is stopped.
  • FIG. 7 depicts a schematic representation of a denervation site 400 in accordance with the disclosure.
  • cross-section of a blood vessel 100 has an electrode 56 against a wall of the blood vessel 100.
  • a series of stimulation limit lines 402 depict the limit of stimulation signals effective a stimulation of a nerves between the stimulation line 402 and the electrode 56, for a given stimulation magnitudes (e.g., 5, 10, 20 mA).
  • Each stimulation limit line 402 is associated with a stimulation and ablation zone 404, meaning that application of a therapy at a power level (or duration) associated with a given stimulation magnitude, is intended to treat (e.g., denervate) nerves within the ablation zone.
  • a total ablation area 406 is defined.
  • the total ablation area encompasses all of the ablation zones 404, including the 20 mA ablation zone.
  • 20 mA represents the saturation point of stimulation as described hereinabove with respect to method 200 and is used to set the power level of the therapy.
  • an ablation area for the 10 mA stimulation line would incorporate the ablation zone 404 of the 5 mA stimulation line and the 10 mA stimulation line.
  • a further aspect of the disclosure is directed method 500 depicted in FIG. 8 and graphically represented in FIG. 9.
  • the application of therapy is commenced and follows a typical ramp up phase at step 502.
  • phase 602 shows graphically in FIG. 9 as phase 602
  • an initial stimulation is applied at step 504, depicted in FIG. 9 at 604, where a 10 mA stimulation signal is imparted on the blood vessel 100 wall via electrodes 56 on a proximal therapeutic device 50.
  • ECAP is detected by electrodes 56 on a distal therapeutic device 50 at step 506.
  • ECAP ECAP is being detected at step 508. If no ECAP is detected therapy and stimulation are ended at step 510 and an indication of therapy end may be presented in the user interface 28 on the display 26. If ECAP is still detected at the end of time tl, the method proceeds to steps 510 where the stimulation magnitude is increased to 20 mA as shown graphically in FIG. 9 at 606. In addition to the stimulation magnitude increase, the therapy power is also increased. At step 512 the stimulation is applied at the increased magnitude and the therapy is applied at the increased power. At step 514 a determination is made whether ECAP is still being detected at time t2, following application of therapy at the increased power.
  • step 514 the method proceeds to step 510 where the therapy and stimulation application are ended. If yes, however, the method moves to step 516 where the stimulation magnitude is again increased, now to for example, 30 mA, as shown graphically at 608 in FIG. 9 at and the therapy power is also increased. Therapy is applied at the level associated with the 30 mA stimulation.
  • the therapy power level is calibrated to achieve and ablation zone 404 and total ablation area 406, such that the nerves at a distance from the blood vessel that they can only be stimulated with a 30 mA stimulation signal receive therapy and are denervated.
  • a determination is made at step 520 whether the therapy has timed out. If not, the method returns to step 518 and therapy and stimulation application continues, if the therapy has timed out, the method returns to step 510 where therapy and stimulation application ends, and an indication of therapy end may be presented in the user interface 28 on the display 26.
  • step 518 where therapy is applied at a power level associated with the stimulation saturation point (e.g., 30 mA)
  • the method may proceed to step 244, and steps 244-260 as described above in connection with method 200 can be employed to confirm a successful therapy application, or to identify the need for further application of therapy in the blood vessel branch 102.
  • the therapeutic device 50 has been primarily described in connection with a shape memory construction where exit from a guide catheter 58 frees the shape memory alloy to achieve a desired spiral and/or helical shape of the distal end and place the electrodes 56 against the blood vessel walls.
  • the present disclosure is not so limited and the therapeutic device 50 may be formed such that the electrodes are placed on a balloon or other mechanism to achieve the desired contact with the blood vessel walls without departing from the scope of the disclosure.
  • the memory 32 may include any non-transitory computer-readable storage media for storing data and/or software including instructions that are executable by the processor 30 and which control the operation of the workstation 20 and, in some embodiments, may also control the operation of the therapeutic device 50.
  • memory 32 may include one or more storage devices such as solid-state storage devices, e.g., flash memory chips.
  • the memory 32 may include one or more mass storage devices connected to the processor 30 through a mass storage controller (not shown) and a communications bus (not shown).
  • computer-readable media refers to solid-state storage. It should be appreciated by those skilled in the art that computer-readable storage media can be any available media that can be accessed by the processor 30. That is, computer readable storage media may include non-transitory, volatile, and non-volatile, removable, and nonremovable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data.
  • computer-readable storage media may include RAM, ROM, EPROM, EEPROM, flash memory or other solid-state memory technology, CD-ROM, DVD, Blu-Ray or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which may be used to store the desired information, and which may be accessed by the workstation 20.
  • Example 2 The system of example 1, wherein the first catheter is configured for placement with the blood vessel and the second catheter is configured for placement within a branch of the blood vessel.
  • Example 3 The system of one of the preceding examples, wherein the memory stores instructions that, when executed, cause the processor to cause the stimulation source to output a series of increasing magnitude stimulation signals, wherein the stimulation source is configured to transmit the series of increasing magnitude stimulation signals to the first plurality of electrodes to be applied to a wall of the blood vessel.
  • Example 4 The system of example 3, wherein the memory stores instructions that, when executed, cause the processor to determine a corresponding ECAP value for each magnitude of stimulation signal applied to the wall of the blood vessel.
  • Example 5 The system of examples 3 or 4, wherein the memory stores instructions that, when executed, cause the processor to determine an ECAP saturation point.
  • Example 6 The system of example 5, wherein the memory stores instructions that, when executed, cause the processor to correlate the ECAP saturation point with a therapy power level.
  • Example 7 The system of example 3, wherein the memory stores instructions that, when executed, cause the processor to cause the stimulation source to cease generation of stimulation signals when no ECAP is detected after two or more different magnitudes of stimulation signal are applied to the wall of the blood vessel, and output for display in a user interface an indicator that no nerves are detected at a location of the first catheter, or that movement of the first catheter is required.
  • Example 8 The system of any one of the preceding examples, further comprising a therapy source in communication with the first catheter.
  • Example 9 The system of example 8, wherein the memory stores instructions that, when executed, cause the processor to, during application of a therapy via the first electrodes, determine a change in ECAP in excess of a threshold and stops the therapy source from outputting therapy to the first plurality of electrodes.
  • Example 10 The system of any one of examples 8 or 9, wherein the therapy and stimulation signals are simultaneously applied to the wall of the blood vessel via the first plurality of electrodes.
  • Example 11 The system of any one of examples 8 to 10, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, an ultrasound therapy, a cryogenic therapy, or a chemical therapy.
  • Example 12 A method of performing a therapeutic procedure, including applying a stimulation signal to a blood vessel wall via at least one of a first plurality of electrodes on a distal portion of a first catheter located within the blood vessel, receiving a signal emitted from nerves adjacent the blood vessel via at least one of a second plurality of electrodes on a distal portion of a second catheter located within a branch of the blood vessel, and determining an evoked compound action potential (ECAP) value based on the received signal.
  • ECAP evoked compound action potential
  • Example 13 The method of example 12, further including causing a stimulation source to output a series of increasing magnitude stimulation signals, wherein the stimulation source is configured to transmit the series of increasing magnitude stimulation signals to the first plurality of electrodes and applied to a wall of the blood vessel.
  • Example 14 The method of example 13, further including determining corresponding ECAP values for each magnitude of stimulation signal applied to the wall of the blood vessel.
  • Example 15 The method of one of examples 12 or 13, further including determining an ECAP saturation point.
  • Example 16 The method of example 15, further including correlating the ECAP saturation point with a therapy power level.
  • Example 17 The method of example 13, further including ceasing generation of stimulation signals when no ECAP is detected after two or more different magnitudes of stimulation signal are applied to the wall of the blood vessel, and displaying in a user interface an indicator that no nerves are detected at the location of the first catheter, or that movement of the first catheter is required.
  • Example 18 The method of any one of examples 12 to 17, further including generating a therapy at a therapy source, transmitting the therapy to at least one of the first or second catheters; and applying the therapy to the wall of the blood vessel.
  • Example 19 The method of example 18, further including detecting, during application of therapy, a change in ECAP in excess of a threshold, and stopping the therapy source from outputting therapy.
  • Example 20 The method of any one of examples 18 or 19, wherein the therapy and stimulation signals are simultaneously applied to the wall of the blood vessel via the first plurality of electrodes.
  • Example 21 A system including a catheter configured to be navigated within a blood vessel of a patient, the catheter comprising a first plurality of electrodes and a second plurality of electrodes, wherein the first plurality of electrodes are configured to deliver stimulation and therapy to nerves adjacent the blood vessel, and wherein the second plurality of electrodes are configured to detect a signal emitted by nerves to which stimulation is applied via at least one electrode of the first plurality of electrodes, a stimulation source in electrical communication with the at least one electrode of the first plurality of electrodes and configured to output a stimulation signal to the at least one electrode of the first plurality of electrodes and a computing device including a memory and a processor, wherein the memory stores instructions that when executed, cause the processor to receive the signal detected by the second plurality of electrodes and determine an evoked compound action potential (ECAP) value based at least in part on the signal.
  • ECAP evoked compound action potential
  • Example 22 The system of example 21, wherein the first plurality of electrodes is configured for placement with the blood vessel and the second plurality of electrodes is configured for placement within a branch of the blood vessel.
  • Example 23 The system of example 21 or 22, further comprising a therapy source in communication with a therapy delivery device coupled to the catheter.
  • Example 24 The system of example 23, wherein the therapy delivery device comprises the first plurality of electrodes.
  • Example 25 The system of example 23 to 24, wherein the therapy source is configured to generate one or more of a monopolar radio frequency therapy, a bipolar radio frequency therapy, a microwave therapy, an ultrasound therapy, a cryogenic therapy, or a chemical therapy.

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Abstract

L'invention concerne un procédé et un système de dénervation de nerfs d'un vaisseau sanguin comprenant un premier cathéter conçu pour une navigation à l'intérieur d'un vaisseau sanguin d'un patient, le cathéter présentant une première pluralité d'électrodes servant à appliquer une stimulation et une thérapie à des nerfs adjacents au vaisseau sanguin, un second cathéter conçu pour une navigation à l'intérieur du vaisseau sanguin d'un patient, le second cathéter présentant une seconde pluralité d'électrodes servant à détecter un signal émis par des nerfs auxquels une stimulation a été appliquée, une source de stimulation en communication électrique avec la première pluralité d'électrodes et conçue pour délivrer un signal de stimulation à la première pluralité d'électrodes du premier cathéter, ainsi qu'un dispositif informatique comprenant une mémoire et un processeur, la mémoire stockant des instructions qui, lors de leur exécution, amènent le processeur à recevoir le signal détecté par la seconde pluralité d'électrodes et à déterminer une valeur de potentiel d'action composé évoqué (ECAP).
PCT/EP2025/064003 2024-05-30 2025-05-21 Stimulation prédictive et thérapie par ablation pour une dénervation rénale Pending WO2025247725A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140213873A1 (en) * 2011-08-26 2014-07-31 Symap Holding Limited System and method for locating and identifying the functional nerves innervating the wall of arteries and catheters for same
US20140276707A1 (en) * 2013-03-15 2014-09-18 Boston Scientific Neuromodulation Corporation System and method of using evoked compound action potentials to minimize vessel trauma during nerve ablation
US20180325576A1 (en) * 2013-05-02 2018-11-15 Halcyon Medical, Inc. Devices and methods for detection and treatment of the aorticorenal ganglion
US20230293229A1 (en) * 2022-03-15 2023-09-21 Otsuka Medical Devices Co., Ltd. Using characteristics of native or evoked sensed neural activity to select denervation parameters
WO2024200141A1 (fr) * 2023-03-30 2024-10-03 Medtronic Ireland Manufacturing Unlimited Company Stimulation ultrasonore focalisée pour dénervation rénale

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140213873A1 (en) * 2011-08-26 2014-07-31 Symap Holding Limited System and method for locating and identifying the functional nerves innervating the wall of arteries and catheters for same
US20140276707A1 (en) * 2013-03-15 2014-09-18 Boston Scientific Neuromodulation Corporation System and method of using evoked compound action potentials to minimize vessel trauma during nerve ablation
US20180325576A1 (en) * 2013-05-02 2018-11-15 Halcyon Medical, Inc. Devices and methods for detection and treatment of the aorticorenal ganglion
US20230293229A1 (en) * 2022-03-15 2023-09-21 Otsuka Medical Devices Co., Ltd. Using characteristics of native or evoked sensed neural activity to select denervation parameters
WO2024200141A1 (fr) * 2023-03-30 2024-10-03 Medtronic Ireland Manufacturing Unlimited Company Stimulation ultrasonore focalisée pour dénervation rénale

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