Patent Application
20150066118
The present technology relates generally to intravascular neuromodulation and associated methods. In particular, several embodiments are directed to devices positionable along spiral tracks for intravascular renal neuromodulation and associated methods.
The sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Fibers of the SNS innervate tissue in almost every organ system of the human body and can affect characteristics such as pupil diameter, gut motility, and urinary output. Such regulation can have adaptive utility in maintaining homeostasis or preparing the body for rapid response to environmental factors. Chronic activation of the SNS, however, is a common maladaptive response that can drive the progression of many disease states. Excessive activation of the renal SNS in particular has been identified experimentally and in humans as a likely contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure), and progressive renal disease. For example, radiotracer dilution has demonstrated increased renal norepinephrine (“NE”) spillover rates in patients with essential hypertension.
Cardio-renal sympathetic nerve hyperactivity can be particularly pronounced in patients with heart failure. For example, an exaggerated NE overflow from the heart and kidneys of plasma is often found in these patients. Heightened SNS activation commonly characterizes both chronic and end stage renal disease. In patients with end stage renal disease, NE plasma levels above the median have been demonstrated to be predictive of cardiovascular diseases and several causes of death. This is also true for patients suffering from diabetic or contrast nephropathy. Evidence suggests that sensory afferent signals originating from diseased kidneys are major contributors to initiating and sustaining elevated central sympathetic outflow.
Sympathetic nerves innervating the kidneys terminate in the blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of the renal sympathetic nerves can cause increased renin release, increased sodium (Na+) reabsorption, and a reduction of renal blood flow. These neural regulation components of renal function are considerably stimulated in disease states characterized by heightened sympathetic tone and likely contribute to increased blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation is likely a cornerstone of the loss of renal function in cardio-renal syndrome (i.e., renal dysfunction as a progressive complication of chronic heart failure). Pharmacologic strategies to thwart the consequences of renal efferent sympathetic stimulation include centrally acting sympatholytic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to block the action of angiotensin II and aldosterone activation consequent to renin release), and diuretics (intended to counter the renal sympathetic mediated sodium and water retention). These pharmacologic strategies, however, have significant limitations including limited efficacy, compliance issues, 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 (e.g., via radio frequency ablation) have been shown to reduce blood pressure in patients with treatment-resistant hypertension.
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, emphasis is placed on illustrating clearly the principles of the present disclosure. Furthermore, components can be shown as transparent in certain views for clarity of illustration only and not to indicate that the illustrated component is necessarily transparent. For ease of reference, throughout this disclosure identical reference numbers may be used to identify identical or at least generally similar or analogous components or features.
The present technology is directed to apparatuses, and methods for achieving electrically- and/or thermally-induced renal neuromodulation (i.e., rendering neural fibers that innervate the kidney inert or inactive or otherwise completely or partially reduced in function) by percutaneous transluminal intravascular access. In particular, embodiments of the present technology relate to therapeutic assemblies having track elements and treatment devices (e.g., treatment catheters) slidably engaged with the track elements. The therapeutic assemblies include at least one neuromodulation element (e.g., at least one electrode) that can be located, for example, at a distal portion of the treatment device. After deployment in a target blood vessel of a human patient, a distal portion of the track element is transformable between a delivery or low-profile state (e.g., a generally straightened shape) to a deployed state (e.g., a radially expanded, generally spiral/helical shape) such that the track element defines a spiral-shaped track in apposition with an inner wall of the target blood vessel (e.g., renal artery).
The treatment device can include a treatment catheter or another elongate member that slidably engages the track element such that movement of the of the treatment device relative to the track element translates the neuromodulation element(s) along the track element to position the neuromodulation element(s) at various treatment positions within the target blood vessel. In one embodiment, for example, the track element can be a wire (e.g., nitinol wire) that is accommodated within a lumen of the treatment device (e.g., treatment catheter, microcatheter, tubular sheath, etc.) and has an expandable, pre-formed, helical shape at a distal portion thereof. Accordingly, movement of the treatment device proximally or distally along the deployed and stationary track element can displace the neuromodulation element both angularly or circumferentially and longitudinally relative to a longitudinal axis of the target blood vessel.
The neuromodulation element(s) are in electrical communication with an energy source or energy generator external to the patient such that energy is delivered via the neuromodulation element(s) to portions of a renal artery after being advanced thereto along a percutaneous transluminal path (e.g., a femoral artery puncture, an iliac artery and the aorta, a radial artery, or another suitable intravascular path). Suitable energy modalities include, for example, electrical energy, radio frequency (RF) energy, pulsed electrical energy, or thermal energy. The treatment device carrying the neuromodulation element(s) can be sized, shaped and have suitable flexibility such that the neuromodulation element(s) are in constant apposition with the interior wall of the renal artery when the track element is in the deployed (e.g., spiral/helical) state. The pre-formed spiral/helical shape of the deployed portion of the track element carrying the treatment device allows blood to flow through the assembly during therapy, which is expected to help prevent occlusion of the renal artery during activation of the neuromodulation element(s).
Previous energy-delivery catheter systems for inducing neuromodulation that include arrays of electrodes can be expensive to manufacture. For example, multiple electrodes require separate wiring of each electrode as well as complex algorithms and design of the energy generator. Additionally, repositioning and specific lesion placement on the interior wall of the renal artery are challenging and time consuming when using conventional energy-delivery catheter systems. In contrast, a self-expanding spiral frame over which an elongate member (e.g., sheath, treatment catheter, microcatheter, etc.) can travel provides a simple design that is easy to deploy and use compared to the conventional catheter devices. Moreover, the neuromodulation element can, in some embodiments, include a single electrode that can be moved proximally or distally along the track element while the track element remains in situ. The movement can be achieved via a pull or push mechanism that slides the neuromodulation element along the spiral-shaped track to easily select and access new ablation or treatment locations. Additionally, because movement of the neuromodulation element along the track element is achievable to access a plurality of treatment locations (both circumferentially and longitudinally displaced from each other), a single neuromodulation element can be deployed on the treatment device. This design aspect avoids the separate wiring that multiple electrodes would require, which is expected to reduce manufacturing time and material costs associated with additional separate electrodes and wiring, as well as reduce the complexity of the control algorithm typically necessary to operate more than one independent electrode or energy delivery elements.
Specific details of several embodiments of the technology are described below with reference to
As used herein, the terms “distal” and “proximal” define a position or direction with respect to the treating clinician or clinician's control device (e.g., a handle assembly). “Distal” or “distally” are a position distant from or in a direction away from the clinician or clinician's control device. “Proximal” and “proximally” are a position near or in a direction toward the clinician or clinician's control device.
As explained in greater detail below, the therapeutic assembly 100 is configured to be intravascularly delivered to a target blood vessel (e.g., a renal blood vessel) of a human patient in a low-profile configuration. Upon delivery to the target treatment site, the therapeutic assembly 100 is further configured to be transformed into an expanded state (e.g., the distal portion of track element 110 is deployed into a generally spiral/helical configuration as shown schematically in
Alternatively, the deployed state may be non-spiral provided that the deployed state places the track element and specifically one or more energy delivery elements 122 in vessel wall apposition for delivering the energy to the treatment site. The treatment device 120 can then be slidably moved along the track element 110 to position the neuromodulation or energy delivery element 122 at desired location(s) for modulating target nerves proximate to the inner wall of the blood vessel, thereby providing therapeutically-effective electrically- and/or thermally-induced renal neuromodulation.
The therapeutic assembly 100 may be transformed between the delivery and deployed states using a variety of suitable mechanisms or techniques (e.g., self-expansion). In one specific example, the distal portion of track element 110 can be a pre-formed, self-expanding wire that will transform into the deployed state or arrangement when unrestricted (e.g., by retracting a guide catheter, straightening sheath, etc.).
The proximal end of the treatment device 120 is carried by or affixed to the distal portion 20 of the elongated shaft 14. A distal end of the track element 110 may include an atraumatic tip 112. In some embodiments, the distal end of the catheter 12 may include an atraumatic tip for preventing intravascular trauma during delivery of the therapeutic assembly 100 to the treatment site. The distal end of the catheter 12 may also be configured to engage another element of the system 10 or catheter 12. For example, the distal end of the catheter 12 may define a passageway for receiving a guidewire for delivery of the treatment device using OTW or rapid exchange (“RX”) techniques. Further details regarding such arrangements are described below with reference to
The neuromodulation element(s) 122 can be electrically coupled to the energy source 30 via a cable 32, and the energy source 30 (e.g., a RF energy generator) can be configured to produce a selected modality and magnitude of energy for delivery to the treatment site via the neuromodulation element 122 carried by the treatment device 120. As described in greater detail below, one or more supply wires (not shown) can extend along the elongated shaft 14 or through a lumen in the shaft 14 to the therapeutic assembly 100 and supply the treatment energy to the neuromodulation element 122.
A control mechanism 40, such as foot pedal or handheld remote control device, may be connected to the energy source 30 to allow the clinician to initiate, terminate and, optionally, adjust various operational characteristics of the energy source 30, including, but not limited to, power delivery. The remote control device can be positioned in a sterile field and operably coupled to the therapeutic assembly 100, and specifically to the neuromodulation element 122, and can be configured to allow the clinician to activate and deactivate the energy delivery to the neuromodulation element 122. In other embodiments, the remote control device may be built into the handle assembly 18.
The energy source or energy generator 30 can be configured to deliver the treatment energy via an automated control algorithm 34 and/or under the control of a clinician. For example, the energy source 30 can include computing devices (e.g., personal computers, server computers, tablets, etc.) having processing circuitry (e.g., a microprocessor) that is configured to execute stored instructions relating to the control algorithm 34. In addition, the processing circuitry may be configured to execute one or more evaluation/feedback algorithms 35, which can be communicated to the clinician. For example, the energy source 30 can include a monitor or display 36 and/or associated features that are configured to provide visual, audio, or other indications of power levels, sensor data, and/or other feedback. The energy source 30 can also be configured to communicate the feedback and other information to another device, such as a monitor in a catheterization laboratory.
The system 10 can also include one or more additional sensors (not shown) located proximate to or within the neuromodulation element 122. For example, the system 10 can include temperature sensors (e.g., additional thermocouples, thermistors, 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 convey energy to the therapeutic assembly 100.
Referring to
Referring to
In some methods of using the neuromodulation system 10, the intravascular catheter 12 may be delivered and deployed over a guidewire 50 (shown in
As best seen in
The spiral-shaped configuration of the distal portion of track element 110 is further illustrated in
In one embodiment, the track element 110 may be formed from suitable shape memory material, such as nitinol (nickel-titanium alloy) wire. In other embodiments, however, the track element 110 can be composed of different materials and/or have a different arrangement. For example, the track element 110 may be formed from other suitable materials such as metal wire (e.g., stainless steel), shape memory polymers, electro-active polymers, etc., that are pre-formed or pre-shaped into the desired deployed state (
Referring again to
In an alternative embodiment, the catheter 12 may include an operative wire (not shown) to facilitate pushing or pulling the treatment device 120 relative to the track element 110. The operative wire can extend proximally from the treatment device 120 (e.g. as an alternative to the shaft 14) to be accessible, for example, to a clinician outside the patient when the therapeutic assembly 100 is being delivered and deployed. In other embodiments, however, the treatment device 120 may have a different arrangement and/or different features.
In one embodiment, the neuromodulation element 122 can be an electrode configured to deliver energy (e.g., electrical energy, RF energy, pulsed electrical energy, non-pulsed electrical energy, thermal energy, etc.) across the wall of the renal artery RA. In a specific embodiment, the neuromodulation element 122 can deliver a thermal RF field to targeted renal nerves adjacent the wall of the renal artery RA. Referring to
The neuromodulation element 122 is electrically connected to an external energy source (such as energy source 30,
In some embodiments, the therapeutic assembly 100 can include radiopaque markers 140 or other indicia for facilitating navigation of the assembly 100 through the vasculature as well as positioning of the neuromodulation element 122 at one or more desired treatment locations within the renal artery RA using x-ray imaging techniques known in the art.
In operation and referring to
In some embodiments, the second treatment location can be longitudinally spaced away from the first treatment location along the renal artery RA in either a proximal or distal direction. Sliding the treatment device 120 between first and second treatment locations can also translate the second treatment location circumferentially about the interior wall of the blood vessel with respect to the first treatment location. For example, as the treatment device 120 slides along the spiral-shaped track provided by the distal portion of the track element 110 (
Several suitable delivery methods are disclosed herein and discussed further below; however, one of ordinary skill in the art will recognize a plurality of methods suitable to deliver the therapeutic assembly 100 to the treatment site and to deploy the distal portion of track element 110 from the delivery configuration to the deployed configuration. With respect to the embodiment illustrated in
In the method step illustrated in
In another method of delivery,
In an alternate method step, the guidewire 50 including the distalmost portion 52 may be withdrawn completely from the therapeutic assembly 100 while remaining within the shaft 14 (not shown) to permit the transformation of therapeutic assembly 100. In yet another method step, the guidewire 50 may be withdrawn completely from the shaft 14. In any of the foregoing examples, the clinician can withdraw the guidewire 50 sufficiently to observe transformation of the therapeutic assembly 100 to the deployed configuration and/or until an X-ray image shows that the distal tip of the guidewire 50 is at a desired location relative to the therapeutic assembly 100 (e.g., at least partially withdrawn from the therapeutic assembly 100, or completely withdrawn from the therapeutic assembly 100, etc.). In some methods, the extent of withdrawal of the guidewire 50 can be based, at least in part, on the clinician's judgment with respect to the selected guidewire and the extent of withdrawal necessary to achieve deployment of the therapeutic assembly 100.
After formation of lesions or treatment zones suitable for achieving neuromodulation, and in accordance with one method, the therapeutic assembly 100 may be transformed back to the low-profile delivery configuration by axially advancing the guidewire 50 relative to the therapeutic assembly 100 (e.g., within the lumen 126 of the treatment device 120). Following advancement of the guidewire 50, the track element 110 can be withdrawn from the renal artery RA, or in another embodiment, the guidewire 50 can be exchanged for the track element 110 in lumen 126 of the treatment device 120 (
Image guidance, e.g., computed tomography (CT), fluoroscopy, intravascular ultrasound (IVUS), optical coherence tomography (OCT), intracardiac echocardiography (ICE), or another suitable guidance modality, or combinations thereof, may be used to aid the clinician's positioning and manipulation of the therapeutic assembly 100. For example, a fluoroscopy system (e.g., including a flat-panel detector, x-ray, or c-arm) can be rotated to accurately visualize and identify the target treatment site. In other embodiments, the treatment site can be determined using IVUS, OCT, and/or other suitable image mapping modalities that can correlate the target treatment site with an identifiable anatomical structure (e.g., a spinal feature) and/or a radiopaque ruler (e.g., positioned under or on the patient) before delivering the catheter 12 and/or the therapeutic assembly 100. Further, in some embodiments, image guidance components (e.g., IVUS, OCT) may be integrated with the catheter 12, the track element 110, the treatment device 120 and/or run in parallel with the catheter 12 to provide image guidance during positioning and removal of the therapeutic assembly 100. For example, image guidance components (e.g., IVUS or OCT) can be coupled to at least one of the therapeutic assembly 100 to provide three-dimensional images of the vasculature proximate the target site to facilitate positioning or deploying the therapeutic assembly 100 within the target renal blood vessel.
In one embodiment, the catheter can include a guide catheter or straightening sheath configured to hold the track element in the delivery configuration. Accordingly, the step of transforming the catheter can include a step of at least partially withdrawing the guide catheter (or the straightening sheath) to expose the track element within an interior lumen of the renal artery. In certain embodiments, the therapeutic device components as illustrated in
The method 700 can further include modulating the renal nerve (block 706). In this step, energy can be delivered to the renal nerve via the neuromodulation element at a first treatment location along the renal artery. The treatment device can then be moved along the relatively stationary track element to position the neuromodulation element at a second treatment location along the renal artery, and energy can be delivered to the renal nerve via the neuromodulation element at the second treatment location. For example, the treatment device can slide along the relatively stationary track element having the generally helical shape to position the neuromodulation element at the one or more treatment locations along an inner wall of the renal artery. Moving the treatment device transposes the neuromodulation element circumferentially and longitudinally relative to a longitudinal axis of the renal artery. In one embodiment, the neuromodulation element can emit RF energy for modulating the renal nerve adjacent the inner wall of the renal artery at the targeted treatment locations. Delivering energy at the first and second treatment locations can form an interrupted lesion along the inner wall of the renal artery. In other embodiments, however, energy can be delivered during movement of the treatment device to form a continuous lesion along the inner wall. In certain other embodiments, modulation of the renal nerve can occur by delivering energy via the neuromodulation element at a single treatment location.
Features of the catheter device components described above and illustrated in
Various method steps described above for delivery and deployment of the therapeutic assembly components also can be interchanged to form additional embodiments of the present technology. For example, while the method steps described above are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.
Renal neuromodulation is the partial or complete incapacitation or other effective disruption of nerves innervating 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) innervating the kidneys. Such incapacitation can be long-term (e.g., permanent or for periods of months, years, or decades) or short-term (e.g., for periods of minutes, hours, days, or weeks). Renal neuromodulation is expected to efficaciously treat several clinical conditions characterized by increased overall sympathetic activity, and in particular conditions associated with central sympathetic over-stimulation such as hypertension, heart failure, acute myocardial infarction, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end stage renal disease, inappropriate fluid retention in heart failure, cardio-renal syndrome, osteoporosis, and sudden death. The reduction of afferent neural signals contributes to the systemic reduction of sympathetic tone/drive, and renal neuromodulation is expected to be useful in treating several conditions associated with systemic sympathetic over activity or hyperactivity. Renal neuromodulation can potentially benefit a variety of organs and bodily structures innervated by sympathetic nerves.
Various techniques can be used to partially or completely incapacitate neural pathways, such as those innervating the kidney. The purposeful application of energy (e.g., electrical energy, thermal energy) to tissue by energy delivery element(s) or components such as those described in conjunction with the intravascular treatment assemblies above, can induce one or more desired thermal heating effects on localized regions of the renal artery and adjacent regions of the renal plexus, which lay intimately within or adjacent to the adventitia of the renal artery. The purposeful application of the thermal heating effects can achieve neuromodulation along all or a portion of the renal plexus.
The thermal heating effects can include both thermal ablation and non-ablative thermal alteration or damage (e.g., via sustained heating and/or resistive heating). 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 can be above body temperature (e.g., approximately 37° C.) but less than about 45° C. for non-ablative thermal alteration, or the target temperature can be about 45° C. or higher for the ablative thermal alteration.
More specifically, exposure to thermal energy (heat) in excess of a body temperature of about 37° C., but below a temperature of about 45° C., may induce thermal alteration via moderate heating of the target neural fibers or of vascular structures that 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 may induce non-ablative thermal alteration in the fibers or structures. Exposure to heat above a temperature of about 45° C., or above about 60° C., may induce thermal alteration via substantial heating of the fibers or structures. For example, such higher temperatures may thermally ablate the target neural fibers or the vascular structures. In some patients, it may be desirable to achieve temperatures that thermally ablate the target neural fibers or the 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 utilized to induce the thermal neuromodulation, a reduction in renal sympathetic nerve activity (RSNA) is expected.
The above detailed descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.
From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the technology. Where the context permits, singular or plural terms may also include the plural or singular term, respectively.
Moreover, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 14012431 | Aug 2013 | US |
| Child | 14041270 | US |
