SYSTEMS, DEVICES, AND METHODS FOR MODULATING RENAL NERVE TISSUE
Methods for treating a patient using therapeutic renal neuromodulation and associated devices, system, and methods are disclosed herein. One aspect of the present technology is directed to neuromodulating nerve tissue in selected anatomical regions. In one embodiment, the method can include intravascularly advancing an elongate shaft of a catheter to renal vasculature of a human patient and locating a first neuromodulation element of the catheter within a distalmost portion of a main renal artery. The method includes locating a second neuromodulation element of the catheter within a branch vessel of the renal artery distal to a bifurcation at a distal end of the main renal artery. Neuromodulation of the nerve tissue surrounding the selected anatomical treatment locations can inhibit sympathetic neural activity in nerves proximate a portion of a renal artery and/or a renal branch artery proximate a renal parenchyma.
This application claims the benefit of the following pending applications:
U.S. Provisional Patent Application No. 61/994,744, filed May 16, 2014;
U.S. Provisional Patent Application No. 62/042,832, filed Aug. 28, 2014;
U.S. Provisional Patent Application No. 62/049,058, filed Sep. 11, 2014;
U.S. Provisional Patent Application No. 62/064,929, filed Oct. 16, 2014;
U.S. Provisional Patent Application No. 62/103,460, filed Jan. 14, 2015;
U.S. Provisional Patent Application No. 61/994,595, filed May 16, 2014; and
U.S. Provisional Patent Application No. 62/136,136, filed Mar. 20, 2015.
All of the foregoing applications are incorporated herein by reference in their entireties. Further, components and features of embodiments disclosed in the applications incorporated by reference may be combined with various components and features disclosed and claimed in the present application.
TECHNICAL FIELDThe present technology is related to neuromodulation, such as renal neuromodulation and systems, devices, and methods for performing renal neuromodulation on human patients.
BACKGROUNDThe sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Fibers of the SNS extend through 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 in 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 pathophysiologies of hypertension, states of volume overload (e.g., heart failure), and progressive renal disease.
Sympathetic nerves of the kidneys terminate in the renal blood vessels, the juxtaglomerular apparatus, and the renal tubules, among other structures. Stimulation of the renal sympathetic nerves can cause, for example, increased renin release, increased sodium reabsorption, and reduced renal blood flow. These and other neural-regulated components of renal function are considerably stimulated in disease states characterized by heightened sympathetic tone. For example, reduced 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. Pharmacologic strategies to mitigate adverse consequences of renal sympathetic stimulation often include the use of centrally-acting sympatholytic drugs, beta blockers, angiotensin-converting enzyme inhibitors, and/or diuretics. These and other pharmacologic strategies, however, tend to have significant limitations including limited efficacy, compliance issues, and undesirable side effects.
Many aspects of the present technology 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 technology. 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 related to neuromodulation, such as renal neuromodulation, and systems, devices, and methods for performing renal neuromodulation on human patients. The inventors have discovered, among other things, that targeting certain locations within a patient's renal vasculature may increase the efficacy of renal neuromodulation for achieving one or more desired clinical outcomes, such as lowering of a patient's blood pressure. Renal neuromodulation treatments can include, for example, targeting one or more anatomical regions of the patient's renal vasculature, and can include a combination of treating one or more proximal and/or central portions of the main artery, one or more distal portions of the main artery, one or more branch vessels, and/or at one or more bifurcations of the renal vasculature. A renal neuromodulation method in accordance with a particular embodiment of the present technology includes preferentially targeting nerve tissue for treatment within an anatomical region extending circumferentially around a distalmost portion (e.g., a distalmost third, quarter, or other suitable fraction) of a main vessel of a patient's renal vasculature. In addition or alternatively, the method can include preferentially targeting nerve tissue for treatment within an anatomical region extending circumferentially around one or more branch vessels of a patient's renal vasculature. In further embodiments, the method can include targeting nerve tissue within an anatomical region extending circumferentially around one or more branch vessels and around one or more portions (e.g., a proximal portion, a central portion, a distalmost portion) of the main vessel of a patient's renal vasculature. Targeting nerve tissue for treatment within these anatomical regions may allow a neuromodulation procedure to reliably achieve relatively comprehensive renal neuromodulation, i.e., adequately treating all or nearly all of these nerve fibers innervating a kidney.
In human patients, the main vessel 102 (main renal artery) generally has a diameter of 6.27+/−1.27 mm. The primary branch vessels 110a/110b generally have diameters of 2.86+/−0.84 mm. As noted above, subordinate branch vessels 114 may include segmental arteries (with diameters of 1.94+/−0.68 mm), interlobular arteries (diameters of 0.90+/−0.22 mm), and/or arcuate arteries (diameters of 0.30+/−0.19 mm).
The kidney 106 includes a pelvis 118 and a cortex 120 extending around the pelvis 118. Blood flows into the kidney 106 through arteries of the renal vasculature 100 via the pelvis 118 and flow out of the kidney 106 through veins (not shown) of the renal vasculature 100 also via the pelvis 118. The kidney 106 further includes a capsule 122 encasing the cortex 120. The capsule 122 may preclude passage of nerve tissue. Thus, all or substantially all renal neural communication follows the renal artery and flows into and out of the kidney 106 through the renal pelvis 118. Several examples of nerve fibers 124 are shown in
The nerve fibers 124 bifurcate at or near the primary and subordinate bifurcations 108, 116 and follow the subordinate branch vessels 114 fairly closely within the cortex 120. The nerve fibers 124 eventually terminate at various levels of the renal arterial tree up to and including the afferent arterioles where they can control vasodilation and vasoconstriction. In some cases, all of the nerve fibers 124 also follow the main vessel 102 fairly closely within a well-defined plexus and extend along the entire length 112 of the main vessel 102 or nearly the entire length 112 of the main vessel 102 at a relatively uniform distance from a wall of the main vessel 102. In these cases, a neuromodulation treatment at any portion of the first anatomical region 125a is expected to be efficacious.
By way of theory (and without wishing to be bound by theory), in certain other cases only some of the nerve fibers 124 (e.g., the nerve fiber 124a) are of a first type that extends along the entire length 112 of the main vessel 102 or nearly the entire length 112 of the main vessel 102 at a relatively uniform distance from a wall of the main vessel 102. As mentioned above, a renal neuromodulation treatment performed at any position along the length 112 of the main vessel 102 may be relatively effective for treating this first type of nerve fiber 124. Other nerve fibers 124 (e.g., the nerve fiber 124b), however, may be of a second type extending along a proximal part of the length 112 of the main vessel 102 and then diverging from the main vessel 102 toward a non-renal destination. Further, other nerve fibers 124 (e.g., the nerve fiber 124c) may be of a third type that approaches the wall of the main vessel 102 abruptly at a relatively distal position along the length 112 of the main vessel 102. Still further, other nerve fibers 124 (e.g., the nerve fiber 124d) may be of a fourth type that approaches the wall of the main vessel 102 gradually along the length 112 of the main vessel 102 from proximal to distal. Other types of nerve fibers 124 are also possible.
Renal neuromodulation treatments performed at certain positions along the length 112 of the main vessel 102 may have advantages relative to renal neuromodulation procedures performed at other positions along the length 112 of the main vessel 102. For example, a renal neuromodulation treatment performed from within the main vessel 102 at a relatively distal position along the length 112 of the main vessel 102 and/or from within one or more of the branch vessels 110a, 110b, 114 may avoid treating the second type of nerve fibers 124 (e.g., the nerve fiber 124b) unnecessarily. This can be useful, for example, because nerve fibers 124 of the second type do not terminate within the kidney 106. As another example, a renal neuromodulation treatment performed from within the main vessel 102 at a relatively distal position along the length 112 of the main vessel 102 and/or from within one or more of the branch vessels 110a, 110b, 114 may be well-suited for treating the third type of nerve fibers 124 (e.g., the nerve fiber 124c), such as by delivering energy distal to where the nerve fibers 124 join the path of the main vessel 102.
As yet another example, a renal neuromodulation treatment performed from within the main vessel 102 at a relatively distal position along the length 112 of the main vessel 102 and/or from within one or more of the branch vessels 110a, 110b, 114 may be well-suited for providing a therapeutically effective amount of energy to the fourth type of nerve fibers 124 (e.g., the nerve fiber 124d), such as by delivering energy distal to a point along the length 112 of the main vessel 102 at which the nerve fibers 124 begin to travel along the length 112 of the main vessel 102 in close enough proximity to a wall of the main vessel 102 to be within a therapeutically effective range of a neuromodulation element. For example, in portions of the renal vasculature, a greater number of nerve fibers 124 are accessible (e.g., within range) to the neuromodulating treatment.
In a further example, the therapeutic energy (e.g., radiofrequency (RF) energy) can be delivered at different levels (e.g., intensities, power levels) at varying positions along the length 112 of the main vessel 102 and/or the branches. For example, in regions of the renal vasculature where the nerve fibers 124 are further from the inner wall of the vessel, the power may be increased. By increasing the power output from the electrode, the RF energy can increase the three-dimensional area of the resulting lesion. As such, the resultant larger lesion would reach greater tissue depths from the inner wall of the vessel. Likewise, where the nerve fibers 124 are found closer to the inner wall of the vessel, the power may be selectively decreased such that damage to non-target tissue is minimized while still achieving successful denervation. In some embodiments, the system (e.g., console 1402, discussed further with respect to
In further embodiments, the system and/or electrode(s) can be configured to vary the duration of power delivery either collectively or individually (e.g., in embodiments having multi-electrode neuromodulation elements). In various arrangements, the duration of power delivery can vary depending on the position of one or more electrodes along the vasculature. For example, the system can be configured such that an electrode positioned along the proximal portion of the main vessel 102 imparts power for a longer duration than an electrode positioned along the distalmost portion of the main vessel 102 and/or the branch vessels 110a, 110b, 114. In a particular embodiment, for example, the electrodes spaced apart along a multi-electrode neuromodulation element can be controlled to selectively deliver power at individually selected power levels and for individually selected durations such that power delivery is optimized for targeting nerve tissue at varying depths along the renal vasculature.
In yet further embodiments, the electrodes in a multi-electrode neuromodulation element can be configured to be optionally and selectively deactivated (e.g., in some instances in which a branch vessel 110a, 110b, 114 is short, narrow, or otherwise undesirable for treatment). In various arrangements, the deselection of electrodes can vary depending upon the relative position of the individual electrodes along the branch vasculature. For example, the multi-electrode neuromodulation element can be inserted in a branch vessel such that the proximal-most electrode is distal to the primary bifurcation (e.g., approximately 1 mm-5 mm distal to the primary bifurcation, approximately 2 mm-6 mm distal to the primary bifurcation, approximately 5 mm distal to the primary bifurcation, etc.). In this example, and in instances in which the branch vessel is short, narrow, or otherwise undesirable for treatment (e.g., tortuous, stenosed, etc.), one or more distalmost electrodes can be optionally and selectively deactivated. In another example, the multi-electrode neuromodulation element can be inserted into a branch vessel such that a proximal portion of the multi-electrode element can be close to or span across the first bifurcation. In such embodiments, one or more of the proximal electrodes can be optionally and selectively deactivated such that the electrodes at or near the bifurcation do not receive energy (e.g., RF energy) while the distalmost electrodes deliver energy to the vessel wall for performing ablations. In a further example, electrode(s) positioned between the distalmost and proximal-most electrodes (e.g., intermediate electrode(s)) can be deselected, for example, if sufficient or stable wall contact is prevented or undesirable because of patient-specific anatomical features (e.g., tortuous vessel, stenosed vessel, etc.).
In further examples, renal neuromodulation treatments can be performed at certain positions along the length 112 of the main vessel 102, the branch vessels 110a, 110b, 114, or both in a patient-specific dependent manner. For example, a clinician can assess via angiogram, fluoroscope, etc., a patient's particular anatomy and disease state (e.g., stenosis, arthrosclerosis, vessel diameter, degree of vessel torsion, vessel length, branch length distal to the bifurcation, etc.) and determine one or more desirable locations for renal neuromodulation treatment.
The main vessel 102 may be stented or unstented during renal neuromodulation in accordance with at least some embodiments of the present technology. In one example, the main vessel 102 is stented in an earlier attempt to achieve a desired clinical outcome. Renal neuromodulation in accordance with an embodiment of the present technology may be used when stenting the main vessel 102 is not effective or is insufficiently effective for achieving the clinical outcome. For example, renal neuromodulation in accordance with an embodiment of the present technology may be used to supplement the therapeutic effect, if any, of stenting the main vessel 102 on lowering a patient's blood pressure. Alternatively or in addition, stenting the main vessel 102 and renal neuromodulation in accordance with an embodiment of the present technology may have different purposes. Typically, when present, a renal stent (not shown) is located at a proximal portion of the main vessel 102. From this position, the stent is unlikely to interfere with the methods illustrated in
Specific details of systems, devices, and methods in accordance with several embodiments of the present technology are disclosed herein with reference to
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With reference to
In
In some embodiments, it may be desirable to avoid delivering energy in a pattern that causes a circumferentially continuous lesion to form within any plane perpendicular to the longitudinal axis 111 of the main vessel 102 or a longitudinal axis of any of the branch vessels 110a, 110b, 114. Such a lesion is thought to potentially increase the risk of stenosis. For this and/or other reasons relating to vessel wall preservation, it may be desirable to deliver energy to the anatomical regions 125 in a helical/spiral pattern. Beyond the wall of a vessel from which the energy is delivered, different portions of a lesion formed in this manner may expand toward one another while still remaining circumferentially discontinuous within any plane perpendicular to the longitudinal axis of the vessel. If the nerve fibers 124 extend parallel to the longitudinal axis of the vessel and the sum of different portions of the lesion along the longitudinal axis of the vessel extends around the entire circumference of the vessel, then such a lesion is expected to reach all or substantially all of the nerve fibers 124. In some cases, however, the nerve fibers 124 may not extend parallel to the longitudinal axis of the vessel. Instead, the individual nerve fibers 124 may be arborized, interwoven, or otherwise irregular in their respective paths through the anatomical regions 125. Accordingly, when a helical/spiral lesion extends over a relatively large portion of the length of the vessel, some of the nerve fibers 124 may follow paths that avoid contact with any part of the lesion. Accordingly, the neuromodulation elements 204, 304 can be configured to form more longitudinally compact lesions than those formed by at least some conventional neuromodulation elements.
With reference to
Once the first neuromodulation element 506 is located within the distal portion of the main vessel 102 and in the expanded treatment state, the method 400 includes using the first neuromodulation element 506 to modulate nerve tissue within a portion of the first anatomical region 125a extending circumferentially around the distal portion of the main vessel 102 (block 408). The distal portion of the main vessel 102 can be, for example, a distalmost third of the main vessel 102, a distalmost quarter of the main vessel 102, a distalmost centimeter of the main vessel 102, or another suitable relatively distal portion of the main vessel 102. Modulating nerve tissue within the portion of the first anatomical region 125a extending circumferentially around the distal portion of the main vessel 102 can include, for example, preferentially modulating this nerve tissue relative to nerve tissue within portions of the first anatomical region 125a extending circumferentially around a proximal portion (e.g., a proximal-most third) and a middle portion (e.g., a middle third) of the main vessel 102. While some energy may be delivered to proximal or middle portions of the first anatomical region 125a, at least in the illustrated embodiment, the bulk of the energy released from the first neuromodulation element 506 is delivered to the distal portion of the first anatomical region 125a.
In at least some cases, the first neuromodulation element 506 is more longitudinally compact than conventional counterparts. For example, the first neuromodulation element 506 can be configured to form one or more lesions that extend through a wall of the main vessel 102 into the first anatomical region 125a along a helical/spiral path with relatively little distance (e.g., less than 4 millimeters on average) between neighboring turns. Once formed, the one or more lesions can be circumferentially continuous within the first anatomical region 125a along a plane perpendicular to a portion of the longitudinal axis 111 of the main vessel 102. The lesion(s) may extend through the distal portion of the main vessel 102 while still being circumferentially discontinuous at the wall of the main vessel 102 along all planes perpendicular to this portion of the longitudinal axis 111. This is expected to reduce or eliminate the possibility of the one or more lesions missing arborized nerve fibers 124 without causing undue risk of stenosis within the main vessel 102.
After using the first neuromodulation element 506, the method 400 includes measuring a first degree of neuromodulation achieved by using the first neuromodulation element 506 (block 410). Techniques for measuring the first degree of neuromodulation include measuring biomarkers, as further described in International Patent Application No. PCT/US2013/030041 (published as International Publication No. WO2013/134733 and titled “Biomarker Sampling in the Context of Neuromodulation Devices and Associated Systems and Methods”) or inoperatively monitoring nerve activity, as further described in International Patent Application No. PCT/IB2012/003055 and titled “Endovascular Nerve Monitoring Devices and Associated Systems and Methods”, both of which are incorporated herein by reference in their entireties. If the first degree of neuromodulation is sufficient (e.g., if the kidney 106 is at least substantially denervated), the method 400 can end. If the first degree of neuromodulation is not sufficient (e.g., if the kidney 106 is not at least substantially denervated), the method 400 includes withdrawing the first shaft 504 (block 412) and advancing the second shaft 604 intravascularly toward the renal vasculature 100 (block 414), such as along a guide wire or a guide lumen (not shown) also used to advance the first shaft 504 toward the renal vasculature 100.
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At this point, as shown in
After using the second neuromodulation element 606, the method 400 includes measuring a second degree of neuromodulation achieved via the second neuromodulation element 606 (block 422). If the second degree of neuromodulation is sufficient, the method 400 can end. If the second degree of neuromodulation is not sufficient, however, and if there are untreated branch vessels 110a, 110b, 114, the method 400 includes locating the second neuromodulation element 606 within one of the untreated branch vessels 110a, 110b, 114 while the second neuromodulation element 606 is in the low-profile delivery state (block 424) and redeploying the second neuromodulation element 606 (block 426). Next, the method 400 includes using the second neuromodulation element 606 to modulate nerve tissue within a portion of the second and/or third anatomical regions 125b, 125c extending circumferentially around the branch vessel 110a, 110b, 114 in which the second neuromodulation element 606 is redeployed (block 428). The method 400 further includes measuring a degree of neuromodulation achieved by using the second neuromodulation element 606 (block 430). This process can continue until the measured degree of neuromodulation is sufficient or there are no more untreated branch vessel 110a, 110b, 114. In
In the embodiment illustrated in
In other embodiments, a single catheter can be used to treat the first anatomical region 125a and the second and/or third anatomical regions 125b, 125c.
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In several embodiments, the first neuromodulation element 1004 can be deployed in a branch vessel 110a, 110b, 114 and neuromodulation using the first neuromodulation element 1004 can result in a spiral/helical lesion pattern within the branch vessel. In particular embodiments, the spiral/helical lesion pattern can include a plurality of lesions formed along the branch vessel such that the proximal-most lesion is at least about 1 mm distal to the primary bifurcation. Accordingly, in some arrangements, one or more electrode(s) of the elongate support structure 1008 (e.g., the plurality of longitudinally spaced-apart electrodes 1010;
In some embodiments, more than one branch vessel 110a, 110b, 114 can be treated. In a particular example, all accessible branch vessels can be treated. Following neuromodulation of the one or more branch vessels 110a, 110b, 114, the first neuromodulation element can be retracted proximally to a segment (e.g., the distalmost portion, the central portion, the proximal portion) of the main vessel 102 for administering additional treatment(s). In various arrangements, the first neuromodulation element can be repositioned proximally from the branch vessel 110a, 110b, 114 to the main vessel 102 while fully deployed, partially compressed, or fully compressed into a low-profile delivery state before administering treatment to the main vessel 102.
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Any one of the catheters described above with references to
The console 1402 is configured to control, monitor, supply energy to, and/or otherwise support operation of the catheter 1408. Alternatively, the catheter 1408 can be self-contained or otherwise configured for operation without connection to the console 1402. When present, the console 1402 can be configured to generate a selected form and/or magnitude of energy for delivery to tissue at a treatment location via the neuromodulation element 1412. The console 1402 can have different configurations depending on the treatment modality of the catheter 1408. For example, when the catheter 1408 is configured for electrode-based, heat-element-based, or transducer-based treatment, the console 1402 can include an energy generator (not shown) configured to generate radio frequency (RF) energy (e.g., monopolar and/or bipolar RF energy), pulsed electrical energy, microwave energy, optical energy, ultrasound energy (e.g., high-intensity focused ultrasound energy), direct heat, radiation (e.g., infrared, visible, and/or gamma radiation), and/or one or more other suitable types of energy.
The system 1400 can include a mechanical control device 1413 (e.g., a lever) configured to mechanically control operation of one or more components of the catheter 1408. The system 1400 can further include an electrical control device 1414 configured to electrically control operation of one or more components of the catheter 1408 directly and/or via the console 1402. The electrical control device 1414 can be disposed along the cable 1406 as shown in
In some embodiments of a renal neuromodulation procedure (as an example, a procedure using a spiral/helical neuromodulation element), one or more ablations may be performed in any (e.g., all) renal vessels (e.g., renal arterial vessels) greater than 3 mm and less than 8 mm in diameter (e.g., accessory, branch and/or main renal arteries). In certain embodiments, initial placement of a renal neuromodulation element may be just proximal to the renal parenchyma (e.g., as identified on fluoroscopic imaging). In some embodiments, an operator may perform as many ablations within a segment as anatomy permits, starting distally and working proximally, without forming overlapping treatment zones. In certain embodiments, an operator may avoid forming ablations in a carina. In methods in which a multielectrode neuromodulation element (e.g., a multielectrode spiral/helical neuromodulation element, such as one including four or five electrodes) is used, if the vessel segment cannot accommodate all electrodes, then the operator may, for example, either 1) position a smaller number of electrodes and deselect proximal electrodes, or 2) advance all electrodes within the renal artery vessel segment and deselect the distal electrodes.
Renal NeuromodulationRenal neuromodulation is the partial or complete incapacitation or other effective disruption of nerves of the kidneys (e.g., nerves terminating in the kidneys or in structures closely associated with the kidneys). In particular, renal neuromodulation can include inhibiting, reducing, and/or blocking neural communication along nerve fibers (e.g., efferent and/or afferent nerve fibers) of 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 contribute to the systemic reduction of sympathetic tone or drive and/or to benefit at least some specific organs and/or other bodily structures innervated by sympathetic nerves. Accordingly, renal neuromodulation is expected to be useful in treating clinical conditions associated with systemic sympathetic overactivity or hyperactivity, particularly conditions associated with central sympathetic overstimulation. For example, renal neuromodulation is expected to efficaciously treat 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, polycystic kidney disease, polycystic ovary syndrome, osteoporosis, erectile dysfunction, and sudden death, among other conditions. Such clinical conditions may be the result of physiological parameters associated with systemic sympathetic overactivity or hyperactivity such as elevated blood pressure, elevated blood sugar levels, ovarian cysts, etc.
Renal neuromodulation can be electrically-induced, thermally-induced, or induced in another suitable manner or combination of manners at one or more suitable treatment locations during a neuromodulation procedure. The treatment location can be within or otherwise proximate to renal vasculature (e.g., a renal artery, a ureter, a renal pelvis, a major renal calyx, a minor renal calyx, or another suitable structure), and the treated tissue can include tissue at least proximate to a wall of the renal lumen. For example, with regard to a renal artery, a neuromodulation procedure can include modulating nerves in the renal plexus, which lay intimately within or adjacent to the adventitia of the renal artery. Various suitable modifications can be made to the catheters described above to accommodate different treatment modalities. For example, the electrodes 1010 (
Renal neuromodulation can include an electrode-based or treatment modality alone or in combination with another treatment modality. Electrode-based or transducer-based treatment can include delivering electricity and/or another form of energy to tissue at or near a treatment location to stimulate and/or heat the tissue in a manner that modulates nerve function. For example, sufficiently stimulating and/or heating at least a portion of a sympathetic renal nerve can slow or potentially block conduction of neural signals to produce a prolonged or permanent reduction in renal sympathetic activity (e.g., reducing sympathetic neural activity). A variety of suitable types of energy can be used to stimulate and/or heat tissue at or near a treatment location. For example, neuromodulation in accordance with embodiments of the present technology can include delivering RF energy, pulsed electrical energy, microwave energy, optical energy, focused ultrasound energy (e.g., high-intensity focused ultrasound energy), and/or another suitable type of energy. An electrode or transducer used to deliver this energy can be used alone or with other electrodes or transducers in a multi-electrode or multi-transducer array.
Neuromodulation using focused ultrasound energy (e.g., high-intensity focused ultrasound energy) can be beneficial relative to neuromodulation using other treatment modalities. Focused ultrasound is an example of a transducer-based treatment modality that can be delivered from outside the body. Focused ultrasound treatment can be performed in close association with imaging (e.g., magnetic resonance, computed tomography, fluoroscopy, ultrasound (e.g., intravascular or intraluminal), optical coherence tomography, or another suitable imaging modality). For example, imaging can be used to identify an anatomical position of a treatment location (e.g., as a set of coordinates relative to a reference point). The coordinates can then entered into a focused ultrasound device configured to change the power, angle, phase, or other suitable parameters to generate an ultrasound focal zone at the location corresponding to the coordinates. The focal zone can be small enough to localize therapeutically-effective heating at the treatment location while partially or fully avoiding potentially harmful disruption of nearby structures. To generate the focal zone, the ultrasound device can be configured to pass ultrasound energy through a lens, and/or the ultrasound energy can be generated by a curved transducer or by multiple transducers in a phased array, which can be curved or straight.
Heating effects of electrode-based or transducer-based treatment can include ablation and/or non-ablative alteration or damage (e.g., via sustained heating and/or resistive heating). For example, a neuromodulation procedure can include raising the temperature of target nerve fibers to a target temperature above a first threshold to achieve non-ablative alteration, or above a second, higher threshold to achieve ablation. The target temperature can be higher than about body temperature (e.g., about 37° C.) but less than about 45° C. for non-ablative alteration, and the target temperature can be higher than about 43° C. for ablation. Heating tissue to a temperature between about body temperature and about 43° C. can induce non-ablative alteration with reversible consequences, for example, via moderate heating of target nerve fibers or of luminal structures that perfuse the target nerve fibers. In cases where luminal structures are affected, the target nerve fibers can be denied perfusion resulting in necrosis of the nerve tissue. Heating tissue to a target temperature higher than about 43° C. (e.g., higher than about 60° C.) can induce ablation, for example, via substantial heating of target nerve fibers or of luminal structures that perfuse the target fibers. In some patients, it can be desirable to heat tissue to temperatures that are sufficient to ablate the target nerve fibers or the luminal structures, but that are less than about 90° C. (e.g., less than about 85° C., less than about 80° C., or less than about 75° C.).
EXPERIMENTAL EXAMPLES Example 1This section describes an example of the outcome of renal neuromodulation on animal subjects. In this example, and referring to
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These findings suggest that the positioning of the treatment device within the renal vasculature at a branch vessel or a distal portion of the main renal artery, as measured by NE concentration in renal tissue, results in increased efficacy of modulation of targeted renal nerves. These findings also suggest that the position in the distal segment of the main renal artery (e.g., distalmost third of the main renal vessel, distalmost quarter of the main renal vessel, approximately 1 cm proximal of the branch point to approximately 6 cm proximal of the branch point, between approximately 1 cm and approximately 10 cm proximal of the main renal vessel bifurcation, etc.) can provide a target for RF nerve ablation due to the proximity of the renal nerves. For example, in some embodiments, a compressed spiral/helical lesion pattern in a segment of the renal artery wherein the renal nerves are consistently in closer proximity to the inner wall of the renal vessel can effectively treat more nerves than a set of helical lesions spaced further apart along the full length of the main renal artery where distribution of the renal nerves vary in number, orientation and proximity to the to the inner wall of the renal vessel.
Example 2Example 2 also describes the outcome of renal neuromodulation on animal subjects in an additional experiment. In this example, and referring to
For pigs undergoing distal main renal artery treatment, six lesions were formed at the distal segment of the renal artery and within a distance of 6 mm proximal to the branch point within the renal artery using the Symplicity Flex™ catheter (
In pigs undergoing a combination treatment approach that includes both treatment of the branches and the distal portion of the main renal artery, a Symplicity Spyral™ catheter was inserted into the first renal artery branch for treatment, followed by the second renal artery branch for treatment, and finally retracted and deployed for treatment in the distal portion of the main renal artery.
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These findings suggest that the positioning of the treatment device within the renal vasculature at a branch vessel for treatment followed by treatment of the main renal artery, as measured by NE concentration in renal tissue and histologically by measuring terminal axon density in the renal cortex, is expected to result in increased efficacy of modulation of targeted renal nerves. These findings also suggest that a combination approach of treating the branches (e.g., at least two branches) in addition to one or more segments of the main renal artery (e.g., the proximal portion, the central portion, the distalmost third of the main renal vessel, distalmost quarter of the main renal vessel, approximately 1 cm proximal of the branch point to approximately 6 cm proximal of the branch point, between approximately 1 cm and approximately 10 cm proximal of the main renal vessel bifurcation, etc.), can provide a targeted therapeutic approach for RF nerve ablation. Without being bound by theory, the targeted therapeutic approach for RF nerve ablation is expected to have higher efficacy in the combined treatment approach in certain instances due to the proximity of the renal nerves to the renal vessel wall in the distal segment of the main renal artery (e.g., distalmost third of the main renal vessel, distalmost quarter of the main renal vessel, approximately 1 cm proximal of the branch point to approximately 6 cm proximal of the branch point, between approximately 1 cm and approximately 10 cm proximal of the main renal vessel bifurcation, etc.) and in the branches. Additionally, by combining the treatment locations (e.g., branches and main renal artery) into a treatment session, more renal nerves may be ablated.
Example 3Example 3 describes the outcome of catheter-based renal neuromodulation on animal subjects in an additional experiment. In this example (and referring to
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Example 4 describes a method for treating human patients with renal denervation and anticipated outcomes of such treatment. In this example, human patients will be treated with renal denervation and a method of treatment includes modulating nerve tissue surrounding one or more primary branch trunks (e.g., one or more primary branch vessels distal to the primary bifurcation). In this example, modulating nerve tissue includes forming up to about four lesions (e.g., about 2 lesions to about 4 lesions) in the primary branch in the region spanning from about 5 mm distal to the primary bifurcation to about 5 mm proximal to the ureter or the kidney. Modulation of nerve tissue at branch treatment sites and/or different combinations of treatment sites within the renal vasculature can be performed using a multi-electrode Symplicity Spyral™ catheter, from Medtronic, Inc. Other multi-electrode, spiral/helical-shaped catheters for forming multiple lesions along the length of the vessel are contemplated for these methods. Systemic catecholamines and/or their subsequent degradation products could be measured in either plasma, serum or urine to serve as surrogate markers to measure procedural efficacy such as described in U.S. Provisional Patent Application No. 62/042,821, filed Aug. 28, 2014, and incorporated herein by reference in its entirety.
A method for efficaciously neuromodulating renal nerve tissue in a human patient can include assessing the diameter of the branch vessel to be treated. Renal artery branch vessels having a diameter greater than 3 mm (e.g., about 3 mm to about 8 mm in diameter) can be treated by advancing a multi-electrode Symplicity Spyral™ catheter (e.g., under fluoroscopic guidance) to the first renal artery branch vessel such that the proximal-most electrode is positioned approximately 5 mm distal to the bifurcation. In one procedure, if the distalmost electrode is not positioned within 5 mm of the ureter or the kidney, energy (e.g., RF energy) can be delivered by all electrodes along the catheter to form a spiral/helical-shaped lesion pattern. If the catheter does not achieve stable wall contact with the branch vessel wall, or if the first renal artery branch vessel is short and/or narrow and/or the distal-most portion of the branch vessel is not desirable for treatment, the distalmost electrode(s) can optionally and selectively be deselected for delivery of energy prior to ablation treatment.
In procedures where a branch tapers down to a diameter smaller than 3 mm and/or is not long enough to accommodate multiple electrodes (e.g., 4 electrodes), the catheter can be advanced to insert a fewer number of electrodes into the renal artery branch vessel such that the proximal portion (e.g., carrying the proximal-most electrodes) of the catheter can be positioned across the first bifurcation. Electrodes that are located at or near the primary bifurcation can be deselected by the operator (e.g., via the electrical control device, user interface, etc.) prior to ablation treatment. Energy (e.g., RF energy, etc.) will not be delivered to deselected electrodes when the energy generator is activated.
Following treatment at the first renal artery branch, the catheter can be withdrawn into the main renal vessel and then advanced under fluoroscopy into a second renal artery branch and the treatment procedure can be repeated. Some methods can include treating two branch vessels with different anatomical geometries (e.g., varying diameters, varying lengths, etc.), wherein an operator can select and deselect active electrode(s) along the multi-electrode Symplicity Spyral™ catheter depending on the positioning of the catheter within the different branches. Other methods can include treating greater than two or all of the primary branch vessels branching from the main renal vessel (e.g., distal to a primary bifurcation). As described above, these methods may also include combining neuromodulation of renal nerve tissue surrounding one or more primary branch vessels with neuromodulation of renal nerve tissue at one or more additional treatment locations (e.g., one or more locations along the main renal vessel).
It is anticipated that the positioning of the treatment device within the renal vasculature at a branch vessel and forming lesions in a spiral/helical-shaped or near spiral/helical-shaped pattern distal to the bifurcation (e.g., from about 5 mm distal to the primary bifurcation, from about 2-6 mm distal to the primary bifurcation, etc.) will result in increased efficacy of modulation of targeted nerves, as measured by levels of catecholamines and degradation products thereof in plasma, serum or urine pre- and post-procedure (described in above-referenced U.S. Provisional Patent Application No. 62/042,821).
ADDITIONAL EXAMPLES
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- 1. A method, comprising:
- intravascularly advancing an elongate shaft of a catheter to renal vasculature of a human patient, the renal vasculature including—
- a main vessel directly connected to an aorta of the patient and extending distally toward a kidney, and
- a bifurcation at a distal end of the main vessel;
- locating a neuromodulation element of the catheter within a distalmost portion of the main vessel; and
- modulating nerve tissue within an anatomical region extending circumferentially around the distalmost portion of the main vessel via the neuromodulation element.
- 2. The method of example 1 wherein:
- the main vessel has a longitudinal axis extending from the aorta to the bifurcation;
- modulating nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel includes using the neuromodulation element to form one or more lesions extending through a wall of the main vessel into the anatomical region extending circumferentially around the distalmost portion of the main vessel; and
- the one or more lesions collectively are—
- circumferentially continuous within the anatomical region along a plane perpendicular to a portion of the longitudinal axis extending through the distalmost portion of the main vessel, and
- circumferentially discontinuous at the wall of the main vessel along all planes perpendicular to the portion of the longitudinal axis extending through the distalmost portion of the main vessel.
- 3. The method of example 1 or example 2 wherein the main vessel is stented, and wherein locating a neuromodulation element of the catheter within a distalmost portion of the main vessel includes locating the neuromodulation element distal to a stent.
- 4. The method of example 1 or example 2 wherein modulating nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel includes using the neuromodulation element to preferentially modulate nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel relative to nerve tissue within an anatomical region extending circumferentially around a proximal-most portion of the main vessel and relative to nerve tissue within an anatomical region extending circumferentially around a middle portion of the main vessel between the proximal-most and distalmost portions of the main vessel.
- 5. The method of any one of example 1-4 wherein:
- the catheter, the shaft, and the neuromodulation element are a first catheter, a first shaft, and a first neuromodulation element, respectively; and
- the method further comprises—
- withdrawing the first catheter from the patient,
- intravascularly advancing an elongate second shaft of a second catheter to the renal vasculature,
- locating a second neuromodulation element of the second catheter within a branch vessel of the renal vasculature distal to the bifurcation, and
- modulating nerve tissue within an anatomical region extending circumferentially around the branch vessel via the second neuromodulation element.
- 6. The method of example 5, further comprising measuring a degree of neuromodulation achieved using the first neuromodulation element to modulate nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel, and wherein locating the second neuromodulation element and modulating nerve tissue within the anatomical region extending circumferentially around the branch vessel includes locating the second neuromodulation element and using the second neuromodulation element to modulate nerve tissue within the anatomical region extending circumferentially around the branch vessel in response to an insufficiency of the degree of neuromodulation.
- 7. The method of any one of example 1-4 wherein:
- advancing the shaft includes advancing the shaft while the neuromodulation element is in a low-profile delivery state; and
- the method further comprises transforming the neuromodulation element between the low-profile delivery state and an expanded treatment state after locating the neuromodulation element within the distalmost portion of the main vessel and before modulating nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel.
- 8. The method of example 7 wherein:
- the neuromodulation element includes a balloon; and
- transforming the neuromodulation element includes inflating the balloon.
- 9. The method of example 7 wherein:
- the neuromodulation element includes an elongate support structure carrying a plurality of electrodes, the support structure having a helical form when unconstrained;
- advancing the shaft includes advancing the shaft while the support structure is constrained; and
- transforming the neuromodulation element includes reducing constraint on the support structure such that the support structure moves toward having the helical form.
- 10. The method of example 7 wherein:
- the neuromodulation element includes an elongate electrode having a helical form when unconstrained;
- advancing the shaft includes advancing the shaft while the electrode is constrained; and
- transforming the neuromodulation element includes reducing constraint on the electrode such that the electrode moves toward having the helical form.
- 11. The method of any one of example 1-4 wherein:
- the neuromodulation element is a first neuromodulation element; and the method further comprises—
- locating a second neuromodulation element of the catheter within a branch vessel of the renal vasculature distal to the bifurcation, and
- modulating nerve tissue within an anatomical region extending circumferentially around the branch vessel after locating the second neuromodulation element.
- 12. The method of example 11 wherein:
- advancing the shaft includes advancing the shaft while the second neuromodulation element is in a low-profile delivery state; and
- the method further comprises transforming the second neuromodulation element between the low-profile delivery state and an expanded treatment state after locating the second neuromodulation element and modulating nerve tissue within the anatomical region extending circumferentially around the branch vessel.
- 13. The method of example 11 wherein:
- the second neuromodulation element includes a balloon; and
- transforming the second neuromodulation element includes inflating the balloon.
- 14. The method of example 11 wherein:
- the second neuromodulation element includes an elongate support structure carrying a plurality of electrodes, the support structure having a helical form when unconstrained;
- advancing the shaft includes advancing the shaft while the support structure is constrained; and
- transforming the second neuromodulation element includes reducing constraint on the support structure such that the support structure moves toward having the helical form.
- 15. The method of example 11 wherein:
- the second neuromodulation element includes an elongate electrode having a helical form when unconstrained;
- advancing the shaft includes advancing the shaft while the electrode is constrained; and
- deploying the second neuromodulation element includes reducing constraint on the electrode such that the electrode moves toward having the helical form.
- 16. The method of any one of example 11-15, further comprising measuring a degree of neuromodulation achieved using the first neuromodulation element to modulate nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel, wherein locating the second neuromodulation element and modulating nerve tissue within the anatomical region extending circumferentially around the branch vessel includes locating the second neuromodulation element and modulating nerve tissue within the anatomical region extending circumferentially around the branch vessel in response to an insufficiency of the degree of neuromodulation.
- 17. A method, comprising:
- intravascularly advancing an elongate shaft of a catheter to renal vasculature of a human patient, the renal vasculature including—
- a main vessel directly connected to an aorta of the patient and extending distally toward a kidney,
- a bifurcation at a distal end of the main vessel, and
- a branch vessel distal to the bifurcation;
- modulating nerve tissue within an anatomical region extending circumferentially around the main vessel;
- measuring a degree of neuromodulation achieved by modulating nerve tissue within the anatomical region extending circumferentially around the main vessel; and
- in response to an insufficiency of the degree of neuromodulation, modulating nerve tissue within an anatomical region extending circumferentially around the branch vessel.
- 18. The method of example 17 wherein the main vessel is stented.
- 19. The method of example 17 or example 18 wherein:
- the degree of neuromodulation is a first degree of neuromodulation;
- the branch vessel is a first branch vessel;
- the renal vasculature includes a second branch vessel, the first and second branch vessels being independently connected to the main vessel; and
- the method further comprises—
- measuring a second degree of neuromodulation after modulating nerve tissue within the anatomical region extending circumferentially around the first branch vessel; and
- in response to an insufficiency of the second degree of neuromodulation, modulating nerve tissue within an anatomical region extending circumferentially around the second branch vessel.
- 20. The method of example 19 wherein:
- the renal vasculature includes a third branch vessel, the first, second, and third branch vessels being independently connected to the main vessel; and
- the method further comprises—
- measuring a third degree of neuromodulation after modulating nerve tissue within the anatomical region extending circumferentially around the second branch vessel; and
- in response to an insufficiency of the third degree of neuromodulation, modulating nerve tissue within an anatomical region extending circumferentially around the third branch vessel.
- 21. A method including any non-conflicting combination of the preceding example 1-20.
- 22. A method, comprising:
- intravascularly positioning a neuromodulation element of a catheter within renal vasculature of a human patient, the renal vasculature including—
- a main vessel directly connected to an aorta of the patient and extending distally toward a kidney,
- a bifurcation at a distal end of the main vessel, and
- a branch vessel distal to the bifurcation;
- modulating nerve tissue within an anatomical region extending circumferentially around the branch vessel; and
- modulating nerve tissue within an anatomical region extending circumferentially around the main vessel.
- 23. The method of example 22 wherein the branch vessel is a first branch vessel, and wherein the method further comprises modulating nerve tissue within an anatomical region extending circumferentially around a second branch vessel, the second branch vessel distal to the bifurcation.
- 24. The method of example 23 wherein the second branch vessel is modulated before the main vessel is modulated.
- 25. The method of any one of example 22-24 wherein modulating nerve tissue within an anatomical region extending circumferentially around the main vessel includes using the neuromodulation element to preferentially modulate nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel relative to nerve tissue within an anatomical region extending circumferentially around a proximal-most portion of the main vessel and relative to nerve tissue within an anatomical region extending circumferentially around a middle portion of the main vessel between the proximal-most and distalmost portions of the main vessel.
- 26. The method of any one of example 22-24 wherein modulating nerve tissue within an anatomical region extending circumferentially around the main vessel includes using the neuromodulation element to preferentially modulate nerve tissue within the anatomical region extending circumferentially around the distalmost third of the main vessel.
- 27. The method of any one of example 22-26 wherein modulating nerve tissue within an anatomical region extending circumferentially around the branch vessel includes using the neuromodulation element to form between two and four lesions extending through a wall of the main vessel into the anatomical region extending circumferentially around the branch vessel.
- 28. The method of any one of example 22-27 wherein modulating nerve tissue within an anatomical region extending circumferentially around the branch vessel includes modulating nerve tissue with a first power level, and wherein modulating nerve tissue within an anatomical region extending circumferentially around the main vessel includes modulating nerve tissue with a second power level greater than the first power level.
- 29. The method of any one of example 22-28 wherein:
- the neuromodulation element includes an elongate support structure carrying a plurality of electrodes, the support structure having a helical form when unconstrained;
- positioning the neuromodulation element includes positioning the neuromodulation element such that a proximal-most electrode is distal to the bifurcation when unconstrained; and
- wherein the method further includes deselecting one or more distal electrode(s) on the elongate support structure prior to modulating the nerve tissue.
- 30. The method of any one of example 22-28 wherein:
- the neuromodulation element includes an elongate support structure carrying a plurality of electrodes, the support structure having a helical form when unconstrained;
- positioning the neuromodulation element includes positioning the neuromodulation element such that the support structure is positioned across the bifurcation when unconstrained; and
- wherein the method further includes deselecting one or more proximal electrode(s) on the elongate support structure prior to modulating the nerve tissue.
- 31. The method of any one of example 22-30 wherein the method reduces sympathetic neural activity in the human patient.
- 32. The method of any one of example 22-30 wherein the method reduces norepinephrine spillover in the human patient.
- 33. A method for treating a human patient diagnosed with a measurable physiological parameter associated with systemic sympathetic overactivity or hyperactivity, comprising:
- neuromodulating renal nerve tissue within an anatomical region extending circumferentially around a branch renal vessel, wherein the branch renal vessel is located distal to a bifurcation in a main renal artery of the human patient;
- neuromodulating renal nerve tissue within an anatomical region extending circumferentially around the main renal artery of the human patient; and
- wherein the method reduces sympathetic neural activity in the human patient.
- 34. The method of example 33 wherein the measurable physiological parameter is elevated blood pressure.
- 35. The method of example 33 or example 34 wherein the human patient is hypertensive.
- 36. The method of any one of example 33-35 wherein the method reduces norepinephrine spillover in the human patient.
- 37. A device configured to perform any of the methods of the preceding example 1-36.
- 38. A device for performing renal neuromodulation, comprising:
- a catheter having an elongate shaft, the catheter comprising
- a first neuromodulation element operably connected to the shaft, and
- a second neuromodulation element,
- wherein the first neuromodulation element is configured to be located within a distalmost portion of a main renal artery connected to an aorta of the patient and extending distally toward a kidney, and
- wherein the second neuromodulation element is configured to be located within a branch vessel of the renal artery distal to a bifurcation at a distal end of the main renal artery.
- 39. The device of example 38, wherein the first neuromodulation element includes an elongate support structure having a plurality of longitudinally spaced-apart electrodes.
- 40. The device of example 39, wherein the elongate support structure has a helical or spiral form when unconstrained.
- 41. The device of example 39 or 40, wherein the catheter is configured to be delivered over a guidewire and wherein the support structure is configured to assume a preformed helical or spiral configuration when the guidewire is retracted.
- 42. The device of any of the preceding examples, wherein the device further comprises a sheath and wherein the catheter assumes a helical or spiral configuration when pushed or otherwise presented distally from the sheath.
- 43. The device of any of the preceding examples, wherein the second neuromodulation element is operably connected to the shaft and/or to the first neuromodulation element.
- 44. The device of any of the preceding examples, wherein the second neuromodulation element includes an elongate conduit connected to a distal end of the support structure.
- 45. The device of any of example 38 to 44, wherein the second neuromodulation element includes at least one wire electrode.
- 46. The device of example 45, wherein the at least one wire electrode has a low-profile delivery state and a helical or a spiral form when unconstrained.
- 47. The device of example 45 or 46, wherein the at least one wire electrode has a low-profile delivery state when constrained within the elongate conduit.
- 48. The device of any of example 45 to 47, wherein the second neuromodulation element includes multiple wire electrodes which can be individually guided into respective branch vessels.
- 49. The device of any of example 38 to 44, wherein the second neuromodulation element includes an elongate support and electrodes.
- 50. The device of any of example 38 to 44, wherein the second neuromodulation element has a single element tapering distally.
- 51. The device of example 50, wherein the first and second neuromodulation elements are continuous.
- 52. The device of example 51, wherein the device is configured so that a distal portion of a single elongate support element can be deployed within one of the branch vessels while a proximal portion of the single elongate support element is deployed within the distal portion of a main vessel.
- 53. The device of example 51, wherein the second neuromodulation element includes a balloon.
- 54. The device according to example 51, wherein the first neuromodulation element includes a balloon.
- 55. The device of any of example 38 to 54, wherein the device is configured such that the proximal-most lesion is at least about 5 mm distal to a bifurcation of the main renal vessel.
- 56. The device of any of example 38 to 55, wherein the device is configured such that the proximal-most electrodes is distal to the primary bifurcation, preferably about 2 to about 6 mm distal to the primary bifurcation.
- 57. The device of any of example 39 to 56, wherein the device is configured such that one or more electrodes of the elongate support structure may be deselected such that only the selected electrodes deliver energy.
- 58. A system for performing renal neuromodulation, comprising
- a device of any of the preceding claims, and
- a console configured to control, monitor, supply energy to, and/or otherwise support operation of the catheter.
- 59. A system for performing renal neuromodulation, comprising
- a catheter having an elongate shaft, the catheter comprising a first neuromodulation element operably connected to the shaft, wherein the first neuromodulation element includes an elongate support structure having a plurality of longitudinally spaced-apart electrodes, and
- a console configured to control, monitor, supply energy to, and/or otherwise support operation of the catheter.
- 60. The system of example 58 or 59, wherein the system is configured to individually supply different and/or varying amounts of energy to electrodes based on an electrode's location along the vasculature when deployed.
- 61. The system of any of example 58 to 60, wherein the system is configured such that an electrode positioned along the proximal portion of a main vessel imparts higher power than an electrode positioned along a distalmost portion of the main vessel and/or a branch vessel.
- 62. The system of any of example 58 to 61, wherein the system is further configured such that the duration of power delivery can vary depending on the position of one or more electrodes along the vasculature.
- 63. The system of any of example 58 to 62, wherein the system is further configured such that that an electrode positioned along the proximal portion of a main vessel imparts power for a longer duration than an electrode positioned along a distalmost portion of the main vessel and/or a branch vessel.
- 64. A method for controlling therapeutic energy delivery to a multi-electrode neuromodulation element positioned in a renal vessel during a neuromodulation treatment, the method comprising
- individually supplying different and/or varying amounts of energy to the electrodes based on an electrode's location along the vasculature.
- 65. The method of example 64, further comprising
- imparting higher power to an electrode positioned along the proximal portion of a main vessel than to an electrode positioned along a distalmost portion of the main vessel and/or a branch vessel.
- 66. The method of example 64 or 65, further comprising
- varying the duration of power delivery depending on the position of one or more electrodes along the vasculature.
- 67. The method of any of example 64 to 66, further comprising imparting power to an electrode positioned along the proximal portion of a main vessel for a longer duration than to an electrode positioned along a distalmost portion of the main vessel and/or a branch vessel.
- 68. A method, comprising:
- intravascularly advancing an elongate shaft of a catheter to renal vasculature of a human patient;
- locating a first neuromodulation element of the catheter within a distalmost portion of a main renal artery directly connected to an aorta of the patient and extending distally toward a kidney of the patient;
- locating a second neuromodulation element of the catheter within a branch vessel of the renal artery distal to a bifurcation at a distal end of the main renal artery;
- modulating nerve tissue within an anatomical region extending about the distalmost portion of the main renal artery via the first neuromodulation element; and
- modulating nerve tissue within an anatomical region extending about the branch vessel via the second neuromodulation element.
- 69. The method of example 68 wherein intravascularly advancing an elongate shaft of a catheter to renal vasculature comprises delivering the catheter over a guidewire, and wherein the first neuromodulation element assumes a preformed spiral/helical configuration within the distalmost portion of the main renal artery when the guidewire is retracted.
- 70. The method of example 68 wherein intravascularly advancing an elongate shaft of a catheter to renal vasculature comprises delivering the catheter within a sheath, and wherein the first neuromodulation element assumes a preformed spiral/helical configuration within the distalmost portion of the main renal artery when removed from the sheath.
- 71. The method of example 68 wherein the second neuromodulation element is operably connected to the shaft.
- 72. The method of example 68 wherein the second neuromodulation element is operably connected to the first neuromodulation element.
- 73. The method of example 68 wherein the second neuromodulation element comprises at least one wire electrode, and wherein locating the second neuromodulation element of the catheter within the branch vessel comprises delivering the second neuromodulation element to the branch vessel in a low-profile state and transforming the second neuromodulation element to an unconstrained spiral/helical state within the branch vessel.
- 74. The method of example 68 wherein the second neuromodulation element comprises multiple wire electrodes, and wherein locating the second neuromodulation element of the catheter within the branch vessel comprises locating a first wire electrode within a first branch vessel and a second wire electrode within a second, different branch vessel.
- 75. The method of example 68 wherein the first and second neuromodulation elements are a single continuous elongate element, and wherein:
- locating a first neuromodulation element of the catheter within a distalmost portion of a main renal artery comprises locating a proximal portion of the single elongate element within the distalmost portion of the main renal artery; and
- locating a second neuromodulation element of the catheter within a branch vessel comprises locating a distal portion of the single elongate element within the branch vessel.
- 76. The method of example 68 wherein the first neuromodulation element further comprises a balloon, and wherein locating the first neuromodulation element of the catheter within the distalmost portion of the main renal artery comprises inflating the balloon before modulating nerve tissue via the first neuromodulation element.
- 77. The method of example 68 wherein the second neuromodulation element further comprises a balloon, and wherein locating the second neuromodulation element of the catheter within the branch vessel comprises inflating the balloon before modulating nerve tissue via the second neuromodulation element.
- 78. The method of any one of example 68 to 77 wherein modulating nerve tissue via the second neuromodulation element comprises forming a plurality of lesions, and wherein the proximalmost lesion is at least about 5 mm distal to the bifurcation of the main renal artery.
- 79. The method of any one of example 68 to 77 wherein modulating nerve tissue via the first neuromodulation element comprises forming a plurality of lesions, and wherein the proximalmost lesion is at least about 2 mm to 6 mm distal to the bifurcation of the main renal artery.
- 80. The method of any one of example 68 to 79 wherein the branch vessel is modulated before the main renal artery is modulated.
- 81. The method of any one of example 68 to 79 wherein the main renal artery is modulated before the branch vessel is modulated.
- 82. The method of any one of example 68 to 79 wherein the main renal artery and the branch vessel are modulated simultaneously.
- 83. A method, comprising:
- intravascularly advancing an elongate shaft of a catheter to renal vasculature of a human patient;
- locating a neuromodulation element of the catheter within a distalmost portion of a main vessel directly connected to an aorta of the patient and extending distally toward a kidney, wherein the neuromodulation element includes an elongate support structure having a plurality of longitudinally spaced-apart electrodes; and
- ablating nerve tissue within an anatomical region extending circumferentially around the distalmost portion of the main vessel via the electrodes of the neuromodulation element.
- 84. The method of example 83 wherein:
- the main vessel has a longitudinal axis extending from the aorta to a bifurcation at a distal end of the main renal artery;
- ablating nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel includes using the neuromodulation element to form one or more lesions extending through a wall of the main vessel into the anatomical region extending circumferentially around the distalmost portion of the main vessel; and
- the one or more lesions collectively are—
- circumferentially continuous within the anatomical region along a plane perpendicular to a portion of the longitudinal axis extending through the distalmost portion of the main vessel, and
- circumferentially discontinuous at the wall of the main vessel along all planes perpendicular to the portion of the longitudinal axis extending through the distalmost portion of the main vessel.
- 85. The method of example 83 or 84 wherein the main vessel is stented, and wherein locating a neuromodulation element of the catheter within a distalmost portion of the main vessel includes locating the neuromodulation element distal to a stent.
- 86. The method of example 83 wherein:
- the catheter, the shaft, and the neuromodulation element are a first catheter, a first shaft, and a first neuromodulation element, respectively; and
- the method further comprises—
- withdrawing the first catheter from the patient;
- intravascularly advancing an elongate second shaft of a second catheter to the renal vasculature;
- locating a second neuromodulation element of the second catheter within a branch vessel of the renal vasculature distal to the bifurcation;
- ablating nerve tissue within an anatomical region extending circumferentially around the branch vessel via the second neuromodulation element; and
- withdrawing the second catheter from the patient.
- 87. The method of example 86, further comprising measuring a degree of neuromodulation achieved using the first neuromodulation element to modulate nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel, and wherein locating the second neuromodulation element and ablating nerve tissue within the anatomical region extending circumferentially around the branch vessel includes locating the second neuromodulation element and using the second neuromodulation element to modulate nerve tissue within the anatomical region extending circumferentially around the branch vessel in response to an insufficiency of the degree of neuromodulation.
- 88. The method of example 86 wherein ablating nerve tissue within an anatomical region extending circumferentially around the branch vessel includes modulating nerve tissue with a first power level, and wherein modulating nerve tissue within an anatomical region extending circumferentially around the main vessel includes modulating nerve tissue with a second power level greater than the first power level.
- 89. The method of example 83 wherein:
- advancing the shaft includes advancing the shaft while the neuromodulation element is in a low-profile delivery state; and
- the method further comprises transforming the neuromodulation element between the low-profile delivery state and an expanded treatment state after locating the neuromodulation element within the distalmost portion of the main vessel and before ablating nerve tissue within the anatomical region extending circumferentially around the distalmost portion of the main vessel,
- wherein, in the extended treatment state, the neuromodulation element has a helical form.
- 90. A method for treating a human patient diagnosed with a measurable physiological parameter associated with systemic sympathetic overactivity or hyperactivity, the method comprising:
- ablating renal nerves within an anatomical region extending about a branch renal vessel of the patient, wherein the branch renal vessel is located distal to a bifurcation in a main renal artery of the patient; and
- ablating renal nerves within an anatomical region extending circumferentially around the main renal artery of the patient,
- wherein ablating the renal nerves results in a decrease in renal sympathetic neural activity in the patient.
- 91. The method of example 90 wherein ablating the renal nerves results in a therapeutically beneficial reduction in clinical symptoms of hypertension in the patient.
- 92. The method of example 90 or 91 wherein ablating the renal nerves comprises systemically reducing sympathetic tone in the patient.
- 93. The method of any of example 90 to 92 wherein ablating the renal nerves reduces norepinephrine spillover in the patient.
This disclosure is not intended to be exhaustive or to limit the present technology to the precise forms disclosed herein. Although specific embodiments are disclosed herein for illustrative purposes, various equivalent modifications are possible without deviating from the present technology, as those of ordinary skill in the relevant art will recognize. In some cases, well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the present technology. Although steps of methods may be presented herein in a particular order, in alternative embodiments the steps may have another suitable order. Similarly, certain aspects of the present technology disclosed in the context of particular embodiments can be combined or eliminated in other embodiments. Furthermore, while advantages associated with certain embodiments may have been disclosed in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages or other advantages disclosed herein to fall within the scope of the present technology. Accordingly, this disclosure and associated technology can encompass other embodiments not expressly shown and/or described herein.
The methods disclosed herein include and encompass, in addition to methods of practicing the present technology (e.g., methods of making and using the disclosed devices and systems), methods of instructing others to practice the present technology. For example, a method in accordance with a particular embodiment includes intravascularly advancing an elongate shaft of a catheter to renal vasculature of a human patient, locating a neuromodulation element of the catheter within a distalmost portion of a main vessel of the renal vasculature, and modulating nerve tissue within an anatomical region extending circumferentially around the distalmost portion of the main vessel via the neuromodulation element. A method in accordance with another embodiment includes instructing such a method.
The headings provided herein are for convenience only and should not be construed as limiting the subject matter disclosed. As used herein, the terms “distal” and “proximal” define a position or direction with respect to a clinician or a clinician's control device (e.g., a handle of a catheter). The terms “distal” and “distally” refer to a position distant from or in a direction away from a clinician or a clinician's control device. The terms “proximal” and “proximally” refer to a position near or in a direction toward a clinician or a clinician's control device. Within an un-catheterized renal artery, the terms “distal” and “distally” refer to a position distant from or in a direction away from the renal artery ostium. The terms “proximal” and “proximally” refer to a position near or in a direction toward the renal artery ostium. Throughout this disclosure, the singular terms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. Similarly, 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 terms “comprising” and the like are used throughout this disclosure to mean including at least the recited feature(s) such that any greater number of the same feature(s) and/or one or more additional types of features are not precluded. Directional terms, such as “upper,” “lower,” “front,” “back,” “vertical,” and “horizontal,” may be used herein to express and clarify the relationship between various elements. It should be understood that such terms do not denote absolute orientation.
Reference herein to “one embodiment,” “an embodiment,” or similar formulations means that a particular feature, structure, operation, or characteristic described in connection with the embodiment can be included in at least one embodiment of the present technology. Thus, the appearances of such phrases or formulations herein are not necessarily all referring to the same embodiment. Furthermore, various particular features, structures, operations, or characteristics may be combined in any suitable manner in one or more embodiments of the present technology.
Claims
1-26. (canceled)
27. A method, comprising:
- intravascularly advancing an elongate shaft of a catheter to renal blood vessel of a human patient;
- locating a first neuromodulation element of the catheter within a distalmost portion of a main renal artery directly connected to an aorta of the patient and extending distally toward a kidney of the patient;
- locating a second neuromodulation element of the catheter within a branch vessel of the renal artery distal to a bifurcation at a distal end of the main renal artery;
- modulating nerve tissue within an anatomical region extending about the distalmost portion of the main renal artery via the first neuromodulation element, wherein modulating nerve tissue via the first neuromodulation element comprises forming a plurality of lesions within the anatomical region extending around the main renal artery, and wherein the distalmost lesion is approximately 1-6 mm proximal of the bifurcation of the main renal artery; and
- modulating nerve tissue within an anatomical region extending about the branch vessel via the second neuromodulation element.
28. The method of claim 27 wherein intravascularly advancing an elongate shaft of a catheter to renal vasculature comprises delivering the catheter over a guidewire, and wherein the first neuromodulation element assumes a preformed spiral/helical configuration within the distalmost portion of the main renal artery when the guidewire is retracted.
29. The method of claim 27 wherein intravascularly advancing an elongate shaft of a catheter to renal vasculature comprises delivering the catheter within a sheath, and wherein the first neuromodulation element assumes a preformed spiral/helical configuration within the distalmost portion of the main renal artery when removed from the sheath.
30. The method of claim 27 wherein the second neuromodulation element is operably connected to the shaft.
31. The method of claim 27 wherein the second neuromodulation element is operably connected to the first neuromodulation element.
32. The method of claim 27 wherein the second neuromodulation element comprises at least one wire electrode, and wherein locating the second neuromodulation element of the catheter within the branch vessel comprises delivering the second neuromodulation element to the branch vessel in a low-profile state and transforming the second neuromodulation element to an unconstrained spiral/helical state within the branch vessel.
33. The method of claim 27 wherein the second neuromodulation element comprises multiple wire electrodes, and wherein locating the second neuromodulation element of the catheter within the branch vessel comprises locating a first wire electrode within a first branch vessel and a second wire electrode within a second, different branch vessel.
34. The method of claim 27 wherein the first and second neuromodulation elements are a single continuous elongate element, and wherein:
- locating a first neuromodulation element of the catheter within a distalmost portion of a main renal artery comprises locating a proximal portion of the single elongate element within the distalmost portion of the main renal artery; and
- locating a second neuromodulation element of the catheter within a branch vessel comprises locating a distal portion of the single elongate element within the branch vessel.
35. The method of claim 27 wherein the first neuromodulation element further comprises a balloon, and wherein locating the first neuromodulation element of the catheter within the distalmost portion of the main renal artery comprises inflating the balloon before modulating nerve tissue via the first neuromodulation element.
36. The method of claim 27 wherein the second neuromodulation element further comprises a balloon, and wherein locating the second neuromodulation element of the catheter within the branch vessel comprises inflating the balloon before modulating nerve tissue via the second neuromodulation element.
37. The method of claim 27 wherein modulating nerve tissue via the second neuromodulation element comprises forming a plurality of lesions, and wherein the proximalmost lesion is at least about 5 mm distal to the bifurcation of the main renal artery.
38. The method of claim 27 wherein modulating nerve tissue via the first neuromodulation element comprises forming a plurality of lesions, and wherein the proximalmost lesion is at least about 2 mm to 6 mm distal to the bifurcation of the main renal artery.
39. The method of claim 27 wherein the branch vessel is modulated before the main renal artery is modulated.
40. The method of claim 27 wherein the main renal artery is modulated before the branch vessel is modulated.
41. The method of claim 27 wherein the main renal artery and the branch vessel are modulated simultaneously.
42. The method of claim 27 wherein locating the second neuromodulation element within the branch vessel comprises locating at least one electrode in each branch of the main renal artery, and wherein modulating nerve tissue within an anatomical region extending about the branch vessel comprises modulating each branch of the main renal artery.
43. The method of claim 42 wherein each branch of the main renal artery is modulated simultaneously.
44. The method of claim 42 wherein each branch of the main renal artery is modulated sequentially.
45. The method of claim 27 wherein the branch vessel is a first branch vessel, and wherein the method further comprises:
- retracting the second neuromodulation element from the first branch vessel;
- locating the second neuromodulation element of the catheter within a second branch vessel of the renal artery distal to the bifurcation at the distal end of the main renal artery; and
- modulating nerve tissue within an anatomical region extending about the second branch vessel via the second neuromodulation element.
Type: Application
Filed: Feb 8, 2019
Publication Date: Aug 1, 2019
Inventors: Robert Melder (Santa Rosa, CA), Martin Rothman (Santa Rosa, CA), Stefan Tunev (Santa Rosa, CA)
Application Number: 16/271,742