U.S. patent application number 14/713604 was filed with the patent office on 2015-11-19 for systems, devices, and methods for modulating renal nerve tissue.
The applicant listed for this patent is Medtronic Ardian Luxembourg S.a.r.l.. Invention is credited to Robert Melder, Martin Rothman, Stefan Tunev.
Application Number | 20150327924 14/713604 |
Document ID | / |
Family ID | 53277086 |
Filed Date | 2015-11-19 |
United States Patent
Application |
20150327924 |
Kind Code |
A1 |
Melder; Robert ; et
al. |
November 19, 2015 |
SYSTEMS, DEVICES, AND METHODS FOR MODULATING RENAL NERVE TISSUE
Abstract
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.
Inventors: |
Melder; Robert; (Santa Rosa,
CA) ; Rothman; Martin; (Santa Rosa, CA) ;
Tunev; Stefan; (Santa Rosa, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Medtronic Ardian Luxembourg S.a.r.l. |
Luxembourg |
|
LU |
|
|
Family ID: |
53277086 |
Appl. No.: |
14/713604 |
Filed: |
May 15, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61994744 |
May 16, 2014 |
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62042832 |
Aug 28, 2014 |
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62049058 |
Sep 11, 2014 |
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62064929 |
Oct 16, 2014 |
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62103460 |
Jan 14, 2015 |
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61994595 |
May 16, 2014 |
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62136136 |
Mar 20, 2015 |
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Current U.S.
Class: |
606/41 |
Current CPC
Class: |
A61B 2018/1475 20130101;
A61N 7/022 20130101; A61B 18/24 20130101; A61B 2018/00261 20130101;
A61B 18/1492 20130101; A61B 2018/00434 20130101; A61B 2018/1861
20130101; A61B 2018/1435 20130101; A61B 2018/00404 20130101; A61B
18/082 20130101; A61B 2018/00285 20130101; A61B 2018/00214
20130101; A61B 2018/00511 20130101; A61B 2018/00577 20130101 |
International
Class: |
A61B 18/14 20060101
A61B018/14 |
Claims
1. 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.
2. The method of claim 1 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.
3. The method of claim 1 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.
4. The method of claim 1 wherein the second neuromodulation element
is operably connected to the shaft.
5. The method of claim 1 wherein the second neuromodulation element
is operably connected to the first neuromodulation element.
6. The method of claim 1 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.
7. The method of claim 1 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.
8. The method of claim 1 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.
9. The method of claim 1 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.
10. The method of claim 1 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.
11. The method of claim 1 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.
12. The method of claim 1 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.
13. The method of claim 1 wherein the branch vessel is modulated
before the main renal artery is modulated.
14. The method of claim 1 wherein the main renal artery is
modulated before the branch vessel is modulated.
15. The method of claim 1 wherein the main renal artery and the
branch vessel are modulated simultaneously.
16. 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.
17. The method of claim 16 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.
18. The method of claim 16 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.
19. The method of claim 16 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.
20. The method of claim 19, 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.
21. The method of claim 19 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.
22. The method of claim 16 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.
23. 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.
24. The method of claim 23 wherein ablating the renal nerves
results in a therapeutically beneficial reduction in clinical
symptoms of hypertension in the patient.
25. The method of claim 23 wherein ablating the renal nerves
comprises systemically reducing sympathetic tone in the
patient.
26. The method of claim 23 wherein ablating the renal nerves
reduces norepinephrine spillover in the patient.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of the following pending
applications:
[0002] U.S. Provisional Patent Application No. 61/994,744, filed
May 16, 2014;
[0003] U.S. Provisional Patent Application No. 62/042,832, filed
Aug. 28, 2014;
[0004] U.S. Provisional Patent Application No. 62/049,058, filed
Sep. 11, 2014;
[0005] U.S. Provisional Patent Application No. 62/064,929, filed
Oct. 16, 2014;
[0006] U.S. Provisional Patent Application No. 62/103,460, filed
Jan. 14, 2015;
[0007] U.S. Provisional Patent Application No. 61/994,595, filed
May 16, 2014; and
[0008] U.S. Provisional Patent Application No. 62/136,136, filed
Mar. 20, 2015.
[0009] 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 FIELD
[0010] The present technology is related to neuromodulation, such
as renal neuromodulation and systems, devices, and methods for
performing renal neuromodulation on human patients.
BACKGROUND
[0011] The 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.
[0012] 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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] 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.
[0014] FIG. 1 is a partially cross-sectional profile view
illustrating a neuromodulation element (shown schematically) of a
catheter delivering energy to nerve tissue within an anatomical
region extending circumferentially around a distalmost portion of a
main vessel of renal vasculature of a human patient in accordance
with an embodiment of the present technology.
[0015] FIGS. 1A-1D are cross-sectional histological images taken
from human cadavers and showing the proximity of the nerve fibers
124 along portions of the renal vasculature shown in FIG. 1.
[0016] FIG. 2 is a partially cross-sectional profile view
illustrating a neuromodulation element (shown schematically) of a
catheter delivering energy to nerve tissue within an anatomical
region extending circumferentially around a portion of a branch
vessel of the renal vasculature in accordance with an embodiment of
the present technology.
[0017] FIG. 3 is a flow chart illustrating a renal neuromodulation
method in accordance with an embodiment of the present
technology.
[0018] FIG. 4 is a partially cross-sectional profile view
illustrating a first sheath and a first catheter within the renal
vasculature in accordance with an embodiment of the present
technology. As shown in FIG. 4, the first catheter can include a
first shaft and a first neuromodulation element. The first
neuromodulation element can include a first balloon. In FIG. 4, the
first neuromodulation element is in an expanded treatment state
within the distalmost portion of the main vessel.
[0019] FIG. 5 is a partially cross-sectional profile view
illustrating a second sheath and a second catheter within the renal
vasculature in accordance with an embodiment of the present
technology. As shown in FIG. 5, the second catheter can include a
second shaft and a second neuromodulation element. The second
neuromodulation element can include a second balloon. In FIG. 5,
the second neuromodulation element is in a low-profile delivery
state within a branch vessel of the renal vasculature.
[0020] FIG. 6 is an enlarged, partially cross-sectional profile
view illustrating the second sheath and the second catheter of FIG.
5 within the renal vasculature. In FIG. 6, the second
neuromodulation element is in an expanded treatment state within
the branch vessel.
[0021] FIG. 7 is a flow chart illustrating a renal neuromodulation
method in accordance with an embodiment of the present
technology.
[0022] FIG. 8 is a partially cross-sectional profile view
illustrating a sheath within the renal vasculature in accordance
with an embodiment of the present technology. A catheter (not shown
in FIG. 8) is disposed within the sheath. The catheter can include
a first neuromodulation element and a second neuromodulation
element in respective low-profile delivery states within the main
vessel.
[0023] FIG. 9 is a partially cross-sectional profile view
illustrating the sheath and the catheter of FIG. 8 within the renal
vasculature in accordance with an embodiment of the present
technology. As shown in FIG. 9, the first neuromodulation element
is deployed from the sheath and in an expanded treatment state
within the distalmost portion of the main vessel and the second
neuromodulation element is deployed from the sheath and in its
low-profile delivery state within the distalmost portion of the
main vessel.
[0024] FIG. 10 is a partially cross-sectional profile view
illustrating the sheath and the catheter of FIG. 8 within the renal
vasculature in accordance with an embodiment of the present
technology. As shown in FIG. 10, the second neuromodulation element
is deployed from the sheath and in its low-profile delivery state
within the main vessel. The first neuromodulation element (not
shown in FIG. 10) is also in its low-profile delivery state within
the main vessel.
[0025] FIG. 11 is a partially cross-sectional profile view
illustrating the sheath and the catheter of FIG. 8 within the renal
vasculature in accordance with an embodiment of the present
technology. As shown in FIG. 11, the second neuromodulation element
is deployed from the sheath and in its low-profile delivery state
within a branch vessel. The first neuromodulation element (not
shown in FIG. 11) is in its low-profile delivery state within the
main vessel.
[0026] FIG. 12 is an enlarged, partially cross-sectional profile
view illustrating the sheath and the catheter of FIG. 8 within the
renal vasculature in accordance with an embodiment of the present
technology. As shown in FIG. 12, the second neuromodulation element
is in an expanded treatment state within the branch vessel. The
first neuromodulation element (not shown in FIG. 12) is its
low-profile delivery state within the main vessel.
[0027] FIG. 13 is a perspective view illustrating a neuromodulation
system configured in accordance with an embodiment of the present
technology.
[0028] FIG. 14 is a plot of mean norepinephrine concentration
before and after renal neuromodulation procedures performed at
different treatment sites within the renal vasculatures of animal
subjects.
[0029] FIG. 15A is another plot of mean norepinephrine
concentration before and after renal neuromodulation procedures
performed in the distal portions of the main renal artery, the
renal arterial branches, and the combination of the distal portions
of the main renal artery and the renal arterial branches of animal
subjects.
[0030] FIG. 15B is a plot of terminal axon density in the renal
cortex corresponding to the treatment sites within the renal
vasculature of the animal subjects shown in FIG. 15A.
[0031] FIG. 16A is a diagram illustrating results from a study to
determine the effects of renal denervation on cortical axon density
and mean norepinephrine concentration on animal subjects.
[0032] FIG. 16B is a series of graphs illustrating the response
correlation between normalized cortical axon area vs.
norepinephrine concentration and norepinephrine concentration vs.
extent of nerve ablation along the artery of the animal subjects of
FIG. 16A.
DETAILED DESCRIPTION
[0033] 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.
[0034] FIGS. 1 and 2 are partially cross-sectional profile views
illustrating neuromodulation methods in accordance with embodiments
of the present technology. FIGS. 1 and 2 also illustrate renal
vasculature 100 of a human patient and associated anatomy. The
renal vasculature 100 includes a main vessel 102 (e.g., a main
artery) directly connected to an aorta 104 and extending distally
toward a kidney 106. The renal vasculature 100 further includes a
primary bifurcation 108 at a distal end of the main vessel 102, a
first primary branch vessel 110a extending distally from the main
vessel 102 beginning at the primary bifurcation 108, and a second
primary branch vessel 110b extending distally from the main vessel
102 also beginning at the primary bifurcation 108. The main vessel
102 has a longitudinal axis 111 and a corresponding length 112
extending distally from the aorta 104 to the primary bifurcation
108. Distal to the first and second primary branch vessels 110a,
110b, the renal vasculature 100 includes a network 113 of
subordinate branch vessels 114 and subordinate bifurcations 116.
For clarity of illustration only one subordinate branch vessel 114
and one subordinate bifurcation 116 are identified in FIGS. 1 and
2. From the subordinate branch vessels 114, the network 113
branches into capillaries (not shown) that supply blood to the
kidney 106. The first and second primary branch vessels 110a, 110b
can be, for example, segmental arteries. The subordinate branch
vessels 114 can be, for example, segmental arteries, interlobular
arteries, and/or arcuate arteries. Collectively, the first primary
branch vessel 110a, the second primary branch vessel 110b, and the
subordinate branch vessels 114 are referred to herein as the branch
vessels 110a, 110b, 114.
[0035] 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).
[0036] 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 FIGS.
1 and 2. For clarity of illustration, the nerve fibers 124 are
shown in FIGS. 1 and 2 in two dimensions and extending through a
first anatomical region 125a adjacent to the main vessel 102, a
second anatomical region 125b adjacent to the first primary branch
vessel 110a, and a third anatomical region 125c adjacent to one of
the subordinate branch vessels 114. Also for clarity of
illustration, the nerve fibers 124 are shown as single fibers;
however, it is understood that nerves are typically arranged in
nerve bundles each having more than one nerve fiber along the
first, second and third anatomical regions 125a-c. It should be
understood that the first, second, and third anatomical regions
125a-125c extend circumferentially in three dimensions around the
main vessel 102, the first primary branch vessel 110a, and the
subordinate branch vessel 114, respectively. It should also be
understood that the anatomy associated with the renal vasculature
100 includes other anatomical regions extending circumferentially
in three dimensions around the second primary branch vessel 110b
and additional subordinate branch vessels 114, respectively, and
that the nerve fibers 124 can be distributed at various locations
in three dimensions within the first, second, and third anatomical
regions 125a-125c and within these other anatomical regions.
Collectively, the first, second, and third anatomical regions
125a-125c and these other anatomical regions are identified herein
as the anatomical regions 125. As shown in FIGS. 1 and 2, the
anatomical regions 125 can include tissue outside the capsule 122
as well as tissue inside the capsule 122.
[0037] 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.
[0038] 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.
[0039] 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.
[0040] 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. FIGS. 1A-1D are
cross-sectional histological images showing the proximity of the
nerve fibers 124 along portions of the renal vasculature shown in
FIG. 1. FIG. 1A shows the proximity of nerve fibers 124 to an inner
wall of the proximal portion of the main renal artery and FIG. 1B
shows the proximity of nerve fibers 124 to the inner wall of the
central/middle portion of the main renal artery. FIG. 1C shows the
proximity of nerve fibers 124 to an inner wall of branch vessels at
the bifurcation of the main renal artery and FIG. 1D shows the
proximity of nerve fibers 124 to an inner wall of a branch vessel
distal to the bifurcation. Referring to FIGS. 1A-1D together, the
nerve fibers 124 are shown to be closer in proximity (e.g., more
accessible to treatment originating from the inner lumen of the
renal arterial vasculature) at the bifurcation and branch vessels
as compared to the proximal and central/middle portions of the main
renal artery. Accordingly, systems, devices, and methods for
performing renal neuromodulation in accordance with embodiments of
the present technology are expected to be well-suited for
effectively treating the first, third, and fourth types of nerve
fibers 124, while avoiding unnecessary treatment of the second type
of nerve fibers 124.
[0041] 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 FIG. 13 below) and/or electrodes
spaced apart along a multi-electrode neuromodulation element, can
be configured such that the electrodes individually supply
different and/or varying amounts of energy (e.g., RF energy) based
on the electrode's location 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 higher power
than an electrode positioned along the distalmost portion of the
main vessel 102 and/or the branch vessels 110a, 110b, 114.
[0042] 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.
[0043] 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.).
[0044] 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.
[0045] 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 FIGS. 1 and 2. Thus, these methods and at
least some other methods in accordance embodiments of the present
technology may be more compatible with a stented main vessel 102
than at least some conventional counterparts.
[0046] Specific details of systems, devices, and methods in
accordance with several embodiments of the present technology are
disclosed herein with reference to FIGS. 1-15B. Although the
systems, devices, and methods may be disclosed herein primarily or
entirely with respect to intra-arterial renal neuromodulation,
other applications in addition to those disclosed herein are within
the scope of the present technology. For example, systems, devices,
and methods in accordance with at least some embodiments of the
present technology may be useful for neuromodulation within one or
more non-arterial or non-vessel body lumens, for extravascular
neuromodulation, for non-renal neuromodulation, and/or for use in
therapies other than neuromodulation. Furthermore, it should be
understood, in general, that other systems, devices, and methods in
addition to those disclosed herein are within the scope of the
present technology. For example, systems, devices, and methods in
accordance with embodiments of the present technology can have
different and/or additional configurations, components, and
procedures than those disclosed herein. Moreover, a person of
ordinary skill in the art will understand that systems, devices,
and methods in accordance with embodiments of the present
technology can be without one or more of the configurations,
components, and/or procedures disclosed herein without necessarily
deviating from the present technology.
Selected Examples of Neuromodulation Methods and Associated
Technology
[0047] As shown in FIG. 1, a catheter 200 including an elongate
shaft 202 and a neuromodulation element 204 (shown schematically)
operably connected to the shaft 202 can be located such that the
neuromodulation element 204 is distally positioned along the length
112 of the main vessel 102. In the illustrated embodiment, for
example, the neuromodulation element 204 is located at least
predominantly within a distal portion of the main vessel 102.
Portions of the length 112 of the main vessel 102 corresponding to
a distalmost third 112a, a middle third 112b, and a proximal-most
third 112c of the main vessel 102 are respectively indicated in
FIGS. 1 and 2.
[0048] As shown in FIG. 2, a catheter 300 including an elongate
shaft 302 and a neuromodulation element 304 (shown schematically)
operably connected to the shaft 302 can be located such that the
neuromodulation element 304 is within the first primary branch
vessel 110a. In the illustrated embodiment, the neuromodulation
element 304 partially extends into one of the subordinate branch
vessels 114. In other embodiments, however, the neuromodulation
element 304 can be entirely within the first primary branch vessel
110a or partially extended into more than one of the subordinate
branch vessels 114 and/or into the main vessel 102.
[0049] With reference to FIGS. 1 and 2 together, the
neuromodulation elements 204, 304 can be more longitudinally
compact than at least some conventional counterparts and can be
positioned at respective treatment sites within the renal
vasculature 100 relatively well-suited for comprehensively treating
the nerve fibers 124. From its position shown in FIG. 1, the
neuromodulation element 204 can be used to deliver energy
(represented by arrows 206) to the nerve fibers 124 within a
portion of the first anatomical region 125a extending around the
distal portion of the main vessel 102. From its position shown in
FIG. 2, the neuromodulation element 304 can be used to deliver
energy (represented by arrows 306) to the nerve fibers 124 within a
portion of the second anatomical region 125b extending around the
first primary branch vessel 110a and within a portion of the third
anatomical region 125c extending around one of the subordinate
branch vessels 114. Typically, all or substantially all nerve
fibers 124 targeted for treatment (e.g. nerve fibers 124 of the
first, third, and fourth types discussed above, among others) are
reliably found in close proximity to the renal vasculature 100
within the anatomical region 125 immediately distal and proximal to
the primary bifurcation 108.
[0050] In FIG. 1, energy from the neuromodulation element 204 is
shown extending in one planar direction toward the first anatomical
region 125a. Similarly, in FIG. 2, energy from the neuromodulation
element 304 is shown extending in one planar direction toward the
second anatomical region 125b. These are simplified representations
merely for clarity of illustration. Instead of extending in one
planar direction, energy from the neuromodulation element 204
generally extends in many planar directions radially distributed
about the longitudinal axis 111 of the main vessel 102. Similarly,
energy from the neuromodulation element 304 generally extends in
many planar directions radially distributed about a longitudinal
axis (not shown) of the first primary branch vessel 110a.
[0051] 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.
[0052] FIG. 3 is a flow chart illustrating a renal neuromodulation
method 400 in accordance with an embodiment of the present
technology. FIG. 4 is a partially cross-sectional profile view
illustrating a first sheath 500 and a first catheter 502 within the
renal vasculature 100 at one point during the method 400. As shown
in FIG. 4, the first catheter 502 can include an elongate first
shaft 504 and a first neuromodulation element 506 operably
connected to the first shaft 504. FIG. 5 is a partially
cross-sectional profile view illustrating a second sheath 600 and a
second catheter 602 within the renal vasculature 100 at another
point during the method 400. As shown in FIG. 5, the second
catheter 602 can include an elongate second shaft 604 and a second
neuromodulation element 606 operably connected to the second shaft
604. FIG. 6 is an enlarged, partially cross-sectional profile view
illustrating the second sheath 600 and the second catheter 602
within the renal vasculature 100 at yet another point during the
method 400.
[0053] With reference to FIGS. 3-6 together, the method 400
includes advancing the first shaft 504 intravascularly toward the
renal vasculature 100, such as via a femoral, trans-radial or
another suitable approach (block 402). While the first shaft 504 is
advanced toward the renal vasculature 100, the first
neuromodulation element 506 can be in a low-profile delivery state
(not shown). For example, the first neuromodulation element 506 can
include a first balloon 508, and the first balloon 508 can be
deflated or otherwise unexpanded when the first neuromodulation
element 506 is in the low-profile delivery state. After advancing
the first shaft 504, the method 400 includes locating the first
neuromodulation element 506 within the distal portion of the main
vessel 102 (block 404). At this point, as shown in FIG. 4, the
method 400 includes deploying the first neuromodulation element 506
into an expanded treatment state (block 406), such as by inflating
or otherwise expanding the first balloon 508. The first
neuromodulation element 506 can include first energy-delivery
elements 510 (e.g., electrodes or transducers) spaced apart from
one another and arranged in a helical/spiral pattern on an outside
surface of the first balloon 508. As the first neuromodulation
element 506 is deployed into the expanded treatment state, the
first energy-delivery elements 510 move into contact with an inner
surface of a wall of the main vessel 102.
[0054] 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 125 a 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.
[0055] 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.
[0056] 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.
[0057] As shown in FIG. 5, while the second shaft 604 is advanced
toward the renal vasculature 100, the second neuromodulation
element 606 can be in a low-profile delivery state. For example,
the second neuromodulation element 606 can include a second balloon
608, and the second balloon 608 can be deflated or otherwise
unexpanded when the second neuromodulation element 606 is in the
low-profile delivery state. After advancing the second shaft 604,
the method 400 includes locating the second neuromodulation element
606 within one of the branch vessels 110a, 110b, 114 distal to the
primary bifurcation 108 (block 416). As discussed above, the second
neuromodulation element 606 can also extend partially into one or
more other vessels within the renal vasculature 100. In at least
some cases, it can be useful to avoid positioning the second
neuromodulation element 606 in direct contact with the primary
bifurcation 108 so as to reduce the likelihood that the primary
bifurcation 108 will be damaged during energy delivery. In some
embodiments, such damage may contribute to stenosis.
[0058] At this point, as shown in FIG. 6, the method 400 can
include deploying the second neuromodulation element 606 into an
expanded treatment state (block 418), such as by inflating or
otherwise expanding the second balloon 608. The second balloon 608
can carry one or more second energy-delivery elements (not shown)
(e.g., electrodes or transducers) arranged in a helical pattern. As
the second neuromodulation element 606 is deployed into the
expanded treatment state, the second energy-delivery elements move
into contact with an inner surface of a wall of the branch vessel
110a, 110b, 114 in which the second neuromodulation element 606 is
deployed. 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 deployed
(block 420).
[0059] 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 FIG. 6,
treatment of two additional branch vessels 110a, 110b, 114 is shown
in dashed lines. In some cases, each treated branch vessel 110a,
110b, 114 is independently connected to the main vessel 102. In
other cases, multiple branch vessels 110a, 110b, 114 can be treated
along a single pathway extending from the main vessel 102 to the
kidney 106.
[0060] In the embodiment illustrated in FIGS. 3-6, one catheter
(i.e., the first catheter 502) is used to treat the first
anatomical region 125a and another catheter (i.e., the second
catheter 602) is used to treat the second and/or third anatomical
regions 125b, 125c. Further, while the embodiment illustrated in
FIGS. 3-6 describe treating the first anatomical region 125a
followed by treating the second and/or third anatomical regions
125b, 125c, it should be understood that in other embodiments, the
second and/or third anatomical regions 125b, 125c can be treated in
a first instance (e.g., using the second catheter 602) or prior to
treatment of the first anatomical region 125a. Optionally, a degree
of neuromodulation can be assessed after treating the second and/or
third anatomical regions 125b, 125c. In such embodiments, if the
degree of neuromodulation is insufficient, the first anatomical
region 125a can be treated (e.g., using the first catheter 502)
following treatment of the second and/or third regions 125b, 125c.
For example, in a specific example, the second catheter 602 can be
used to treat the second and/or third anatomical region 125b, 125c
(e.g., in one or more branch segments of the renal vasculature). If
desirable, the first catheter 502 can be used subsequently to treat
the first anatomical region 125a in a distalmost portion (e.g., a
distal third of the main renal artery).
[0061] 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. FIGS. 7-12 illustrate such an
embodiment. FIG. 7, for example, is a flow chart illustrating a
renal neuromodulation method 800 in accordance with an embodiment
of the present technology. The method 800 generally corresponds to
the method 400 (FIG. 3) without the need to withdraw one shaft
(e.g., the first shaft 504) and advance another shaft (e.g., the
second shaft 604) if a first degree of neuromodulation is
insufficient.
[0062] FIG. 8 is a partially cross-sectional profile view
illustrating a sheath 900 within the renal vasculature 100 at one
point during the method 800. FIG. 9 is a partially cross-sectional
profile view illustrating the sheath 900 and a catheter 1000 within
the renal vasculature 100 at another point during the method 800.
As shown in FIG. 9, the catheter 1000 includes an elongate shaft
1002 and a first neuromodulation element 1004 operably connected to
the shaft 1002. FIGS. 10 and 11 are partially cross-sectional
profile views illustrating the sheath 900 and a catheter 1000
within the renal vasculature 100 at still other respective points
during the method 800. FIG. 12 is an enlarged, partially
cross-sectional profile view illustrating the sheath 900 and one
embodiment of the catheter 1000 within the renal vasculature 100 at
yet another point during the method 800.
[0063] As shown in FIG. 9, the catheter 1000 includes a first
neuromodulation element 1004 operably connected to the shaft 1002.
In one embodiment, the first neuromodulation element 1004 can
include an elongate support structure 1008 carrying a plurality of
longitudinally spaced-apart electrodes 1010 (e.g., between about 2
electrodes and about 8 electrodes, greater than 2 electrodes,
etc.). As shown in FIG. 9, the elongate support structure 1008 can
have a helical/spiral form when unconstrained. In some embodiments,
for example, the catheter 1000 can be delivered over a guidewire
(not shown) and the guidewire can be retracted to release a
preformed helical/spiral configuration of the support structure
1008. In other embodiments, the sheath 900 can be a straining
sheath or guide catheter and the treatment catheter 1000 can be
deployed into the helical/spiral form when pushed or otherwise
presented distally from the sheath 900. Once deployed, the
plurality of longitudinally spaced-apart electrodes 1010 can be
positioned in apposition with an inner wall of the vessel lumen for
treatment (e.g., neuromodulation of nervous tissue proximal the
inner wall). Examples of suitable multi-electrode devices are
described in U.S. patent application Ser. No. 13/281,360, filed
Oct. 25, 2011, and incorporated herein by reference in its
entirety. Other suitable devices and technologies, are described in
U.S. patent application Ser. No. 13/279,330, filed Oct. 23, 2011,
and additional thermal devices are described in U.S. patent
application Ser. No. 13/279,205, filed Oct. 21, 2011, each of which
are incorporated herein by reference in their entireties.
[0064] As shown in FIG. 9, the helical/spiral form of the elongate
support structure 1008 can be deployed in the distalmost portion of
the main vessel 102 and/or in one or more of the branch vessels
110a, 110b, 114. The helical/spiral shape can be longitudinally
compressed, longitudinally stretched/elongated and/or be capable of
accommodating a variety of anatomically restricted or expanded
vessel architectures. As such, neuromodulation using the catheter
100 can result in a compressed spiral lesion pattern (e.g., lesions
radially spaced about 2 mm apart), an elongated spiral lesion
pattern (e.g., lesions longitudinally spaced about 2 mm to about 5
mm apart) and/or some combination of both a compressed and
elongated spiral lesion pattern at one or more anatomical locations
along the inner wall of the renal vasculature.
[0065] 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; FIG. 9)
may be deselected such that only the selected electrode(s) deliver
energy (e.g., RF energy) to the branch vessel for forming the
lesion pattern. In one example, the elongate support structure 1008
can be inserted into a branch vessel 110a, 110b, 114 such that the
proximal-most electrode(s) 1010 are distal to the primary
bifurcation (e.g., about 1 to about 5 mm distal to the primary
bifurcation, about 2 mm to about 6 mm distal to the primary
bifurcation, about 5 mm distal to the primary bifurcation, etc.).
In the event that the branch vessel 110a, 110b, 114 is short,
narrow or the distal-most portion of the branch vessel is not
desirable for treatment, the distal-most electrode(s) 1010 can be
selectively deselected from delivering energy (e.g., RF energy) to
the branch vessel wall during treatment. In another example, the
elongate support structure 1008 can be inserted into a branch
vessel 110a, 110b, 114 such that a portion of the electrodes 1010
are positioned within the branch vessel and a proximal portion of
the elongate support structure 1008 can be positioned across the
primary bifurcation, In this example, electrode(s) 1010 at or near
the primary bifurcation (e.g., proximal-most electrode(s)) can be
deselected prior to treatment such that energy will not be
delivered via the deselected electrode(s).
[0066] 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.
[0067] Referring to FIG. 9, and in another embodiment, the catheter
1000 can optionally include a second neuromodulation element 1006
operably connected to the shaft 1002 and/or the first
neuromodulation element 1004. The second neuromodulation element
1006 can include an elongate conduit 1011 directly connected to a
distal end of the support structure 1008. For example, in the
embodiment shown in FIG. 12, the second neuromodulation element
1006 further includes a wire electrode 1300. The support structure
1008 and the wire electrode 1300 can have respective helical/spiral
forms when unconstrained. In another embodiment, the second
neuromodulation element 1006 includes an elongate support structure
similar to the support structure 1008 and includes electrodes
similar to the electrodes 1010. Other variations of the first and
second neuromodulation elements 1004, 1006 are also possible.
[0068] In FIG. 8, the first and second neuromodulation elements
1004, 1006 are in their respective low-profile delivery states
within the sheath 900. The shaft 1002 can be advanced to the renal
vasculature 100 with the first and second neuromodulation elements
1004, 1006 in these respective low-profile delivery states. For
example, the sheath 900 and the conduit 1011 can constrain the
support structure 1008 and the wire electrode 1300, respectively,
into generally linear forms. As shown in FIG. 9, when the first
neuromodulation element 1004 is at a desired position within the
renal vasculature 100, constraint on the support structure 1008 can
be reduced, such as by uncovering the support structure 1008 from
within the sheath 900. This causes the support structure 1008 to
assume its helical/spiral form, thereby moving the electrodes 1010
toward an inner surface of a wall of the main vessel 102.
[0069] As shown in FIG. 10, after delivering energy to the nerve
fibers 124 within a distal portion of the first anatomical region
125a, the support structure 1008 is refracted relative to the
sheath 900 and/or the sheath 900 advanced relative to the support
structure 1008 to force the support structure 1008 back into its
low-profile delivery state. The second neuromodulation element 1006
may remain protruding from a distal end of the sheath 900. As shown
in FIG. 11, the second neuromodulation element 1006 can then be
positioned within one of the branch vessels 110a, 110b, 114 while
the wire electrode 1300 is in its low-profile delivery state. When
the second neuromodulation element 1006 is properly positioned (as
shown in FIG. 12), the second neuromodulation element 1006 is
deployed into an expanded treatment state. For example, the wire
electrode 1300 can be pushed distally out of the conduit 1011
(e.g., by pushing a control wire (not shown)) distally. This is
expected to reduce constraint on the wire electrode 1300 such that
the wire electrode 1300 assumes its helical/spiral form and
contacts an inner surface of a wall of the branch vessel 110a,
110b, 114. In another example, the second neuromodulation element
1006 can have a single element tapering distally (e.g., a
cross-sectional dimension of the second neuromodulation element
1006 may decrease from proximal to distal) to accommodate the
inferior dimensions of the branch vessels 110a, 110b, 114. In these
and other cases, the first and second neuromodulation elements
1004, 1006 can be continuous. For example, a distal portion of a
single elongate support element can be deployed within one of the
branch vessels 110a, 110b, 114 while a proximal portion of the same
element is deployed within the distal portion of the main vessel
102. This can allow nerve fibers 124 on both sides of the primary
bifurcation 108 to be treated simultaneously or consecutively, if
desired.
[0070] Although FIGS. 7-12 illustrate neuromodulation of nerve
tissue in the anatomical region 125a surrounding the main vessel
102 prior to neuromodulation of the nerve tissue in the anatomical
regions 125b, 125c surrounding the branches 110a, 110b, 114, it
should be understood that, in some embodiments, the anatomical
regions 125b, 125c may be treated prior to the anatomical region
125a surrounding the main vessel 102.
[0071] With reference again to FIGS. 7-12 together, after reducing
constraint on the wire electrode 1300, the method 800 includes
using the second neuromodulation element 1006 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
1006 is deployed. In FIG. 12, treatment of the second primary
branch vessel 110b and two additional subordinate branch vessels
114 is shown in dashed lines. With respect to some embodiments, the
dashed lines represent sequential treatment of these additional
vessels. In another embodiment, the second neuromodulation element
includes multiple wire electrodes 1300 that are individually guided
into respective additional vessels. With respect to these
embodiments, the dashed lines represent simultaneous treatment of
the additional vessels.
[0072] Any one of the catheters described above with references to
FIGS. 1-12 can be incorporated into a suitable neuromodulation
system. FIG. 13, for example, is a partially schematic perspective
view illustrating a neuromodulation system 1400 configured in
accordance with one embodiment of the present technology. The
system 1400 includes a console 1402, a catheter 1408, and a cable
1406 extending therebetween. The catheter 1408 can be identical or
similar to any of the catheters described herein. The catheter
1408, for example, includes a handle 1404 and an elongate shaft
1410 having a proximal end portion 1410a and a distal end portion
1410b. The catheter 1408 further includes a neuromodulation element
1412 at the distal end portion 1410b of the shaft 1410. The shaft
1410 is configured to locate the neuromodulation element 1412 at a
treatment location within a body lumen, such as a suitable blood
vessel, duct, airway, or other naturally occurring lumen within the
human body at any suitable branching level. Once located, the
neuromodulation element 1412 is configured to provide or support a
neuromodulation treatment.
[0073] 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.
[0074] 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 FIG. 13, incorporated into the handle 1404, or have another
suitable position within the system 1400. During use of the system
1400, an operator can use the electrical control device 1414 to
provide instructions to the console 1402, such as to initiate or
terminate a neuromodulation treatment, operatively deselect
electrode(s) in multi-electrode neuromodulation elements, etc. In
addition to being configured to execute such instructions, the
console 1402 can be configured to execute an automated control
algorithm 1416. Furthermore, the console 1402 can be configured to
provide information to an operator before, during, and/or after a
neuromodulation procedure via a feedback algorithm 1418. Feedback
from the feedback algorithm 1418 can be audible, visual, haptic, or
have another suitable form. The feedback can be based on output
from a monitoring system (not shown). For example, such a
monitoring system can include a monitoring device (e.g., a sensor)
configured to measure a condition at a treatment location (e.g., a
temperature of tissue being treated), a systemic condition (e.g., a
patient vital sign), or another condition germane to the treatment,
health, and/or safety of a patient. The monitoring device can be
integrated into the catheter 1408 or separate from the catheter
1408.
[0075] 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 Neuromodulation
[0076] Renal 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.
[0077] 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 (FIG. 9) can be replaced with
transducers to facilitate transducer-based treatment
modalities.
[0078] 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.
[0079] 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.
[0080] 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.degree. C.) but less than about 45.degree. C. for non-ablative
alteration, and the target temperature can be higher than about
43.degree. C. for ablation. Heating tissue to a temperature between
about body temperature and about 43.degree. 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.degree. C.
(e.g., higher than about 60.degree. 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.degree. C. (e.g., less
than about 85.degree. C., less than about 80.degree. C., or less
than about 75.degree. C.).
EXPERIMENTAL EXAMPLES
Example 1
[0081] This section describes an example of the outcome of renal
neuromodulation on animal subjects. In this example, and referring
to FIG. 14, studies using the pig model have been performed
directed to modulation of nerve tissue at different treatment sites
within the renal vasculatures using a multi-electrode Symplicity
Spyral.TM. catheter or a single-electrode Symplicity Flex.TM.
catheter, from Medtronic, Inc., of 710 Medtronic Parkway,
Minneapolis, Minn. 55432-5604. Renal cortical norepinephrine (NE)
concentration was used as a surrogate marker to measure procedural
efficacy.
[0082] FIG. 14 is a plot of mean NE concentration before and after
renal neuromodulation procedures performed at the central segment
(e.g., "Central") of the main renal artery, the distal segment
(e.g., "Distal") of the main renal artery, and in two renal artery
branches (e.g., "Branch") of pig subjects. For pigs undergoing
treatment of a branch vessel site, a Symplicity Spyral.TM. catheter
was inserted entirely into the cranial renal artery branch and used
to treat the branch with four lesions at the furthest distance into
the branch vessel that could accommodate the device given
dimensional constraints. The catheter was then withdrawn into the
main renal vessel and then advanced under fluoroscopy into the
caudal renal artery branch and treatment procedure was repeated. In
all cases with three or more renal artery branches only the cranial
and caudal branch were treated. Accordingly, the multi-electrode
device was advanced so that the electrodes were inserted as far as
possible into the branches. 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.TM.
catheter (FIG. 14, "Distal Portion"). The longitudinal spacing
between the lesions was approximately 2 mm, with a lesion footprint
of approximately 2 mm each. In this experimental example, a first
lesion was formed about 5-6 mm from the bifurcation. The catheter
was then proximally retracted 1-2 mm (e.g., maximum of 2 mm) and
rotated 90 degrees followed by formation of a second lesion.
Further lesions were formed by sequential movement of the catheter
proximally 1-2 mm, rotation of 90 degrees followed by lesion
formation. As such, a longitudinal separation of lesions occurred
approximately 1-2 mm apart along the longitudinal length of the
distal segment of the main renal artery. For pigs undergoing main
artery treatment at a central segment of the main renal artery, a
Symplicity Flex.TM. catheter was used to form between 4 and 6
ablations in a spiral/helical pattern along the central segment of
the main renal artery. In these animals, the first lesion was
placed approximately 5 mm proximal to the bifurcation. Each
subsequent lesion was placed 5 mm proximally and rotated at 90
degrees forming a spiral/helical pattern.
[0083] As shown in FIG. 14, mean renal cortical NE levels dropped
approximately 84% between control and experimental groups for pigs
undergoing treatment at the distal segment of the main renal artery
or at a branch artery. Pigs undergoing treatment at the central
segment of the main renal artery exhibited an approximate 47%
decrease in mean NE levels following treatment. Accordingly, the
distal segment and branch treatment sites exhibited an increased
effectiveness of neuromodulation as compared to treatment at the
central segment as indicated by NE concentration in renal tissue
(FIG. 14).
[0084] 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 2
[0085] Example 2 also describes the outcome of renal
neuromodulation on animal subjects in an additional experiment. In
this example, and referring to FIGS. 15A and 15B, studies using the
pig model have been performed directed to modulation of nerve
tissue at different treatment sites and/or different combinations
of treatment sites within the renal vasculature using a
multi-electrode Symplicity Spyral.TM. catheter or a
single-electrode Symplicity Flex.TM. catheter along with a
Symplicity G3.TM. generator. The catheters and generator are from
Medtronic, Inc. Renal cortical NE concentration (FIG. 15A) and
terminal axon density in the renal cortex (FIG. 15B) were used as
markers to measure procedural efficacy.
[0086] FIG. 15A is a plot of mean NE concentration before and after
renal neuromodulation procedures performed at the distal segment
(e.g., distal third) of the main renal artery (e.g., "Distal
Main"), in two renal artery branches (e.g., "Branch"), at the renal
artery branches and the main renal artery (e.g., "Branch+Main"),
and at the renal artery branches and two cycles of treatment in the
main renal artery (e.g., "Branch+Main x2") of pig subjects (N=12
pigs). For pigs undergoing treatment of a branch vessel site, a
Symplicity Spyral.TM. catheter was inserted into the first renal
artery branch (e.g., the cranial branch) and used to treat the
branch with up to four lesions (e.g., 2 lesions, 3 lesions, 4
lesions) with distalmost electrodes being optionally and
selectively deactivated in some instances in which the branch
vessel was short, narrow, or otherwise undesirable for treatment.
The catheter was placed in the first branch location such that the
proximal-most electrode was distal to the bifurcation and, when
deployed, the lesions were approximately 2 mm apart. The catheter
was then withdrawn into the main renal vessel and then advanced
under fluoroscopy into the second renal artery branch (e.g., the
caudal branch) and the treatment procedure was repeated. In all
cases with three or more renal artery branches only the cranial and
caudal branch were treated. Accordingly, the multi-electrode device
was advanced such that the first electrode (e.g., proximal
electrode) was placed approximately 1-3 mm distal to the
bifurcation.
[0087] 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.TM. catheter (FIGS. 15A-15B,
"Distal Main"). The longitudinal spacing between the lesions was
approximately 2 mm, with a lesion footprint of approximately 2 mm
each. In this experimental example, a first lesion was formed about
5-6 mm proximal to the bifurcation. The catheter was then
proximally retracted 1-2 mm (e.g., maximum of 2 mm) and rotated 90
degrees followed by formation of a second lesion. Further lesions
were formed by sequential movement of the catheter proximally 1-2
mm, rotation of 90 degrees followed by lesion formation. As such, a
longitudinal separation of lesions occurred approximately 1-2 mm
apart along the longitudinal length of the distal segment of the
main renal artery.
[0088] 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.TM. 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.
[0089] As shown in FIG. 15A, mean renal cortical NE levels dropped
approximately greater than 80% between control and experimental
groups for pigs undergoing treatment at the distal segment of the
main renal artery (e.g., "Distal Main") or at the branch arteries
(e.g., "Branch"). Neuromodulation in these pigs also resulted in
approximately 70% reduction ("Distal Main") and greater than 80%
reduction ("Branch") in cortical axonal density (FIG. 15B). In this
example, untreated or undertreated segments (e.g., branches treated
with only 2 or 3 lesions) can give rise to outliers in the data set
(e.g., note two outliers approaching 200 pg/mg NE in the treated
branch column "Branch (1R)" of FIG. 15A). Pigs undergoing a
combination treatment approach that combined treatment of the
branches and the distal portion of the main renal artery using a
Symplicity Spyral.TM. catheter demonstrated a greater than 90%
reduction in mean renal NE concentration. The 90% reduction in NE
was corroborated with a 92% reduction terminal axon density as
shown in FIG. 15B. Pigs undergoing another combination treatment
approach that combined treatment of the branches and two treatment
cycles of the distal portion of the main renal artery using a
Symplicity Spyral.TM. catheter also exhibited a greater than 90%
reduction in mean renal NE concentration levels and a 90% reduction
in terminal axon density following treatment (FIGS. 15A and 15B,
respectively), but did not statistically improve the response more
than the combination treatment approach that included a single
cycle of treatment in the main renal artery. Accordingly, the
branch treatment sites combined with treatment of the distal
portion of the main renal artery exhibited an increased
effectiveness of neuromodulation as compared to treatment at the
distal segment or the branches alone as indicated by NE
concentration levels and terminal axon density in renal tissue
(FIGS. 15A and 15B).
[0090] 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 3
[0091] Example 3 describes the outcome of catheter-based renal
neuromodulation on animal subjects in an additional experiment. In
this example (and referring to FIGS. 16A and 16B), studies using
the pig model were performed using a multi-electrode Symplicity
Spyral.TM. catheter or a single-electrode Symplicity Flex.TM.
catheter along with a Symplicity G3.TM. generator. The catheters
and generator are from Medtronic, Inc. The catheters were used in a
number of animals (n=66) to create multiple RF ablations in the
renal vasculature. Cortical axon density in the renal cortex (FIG.
16A) and renal cortical NE concentration (FIG. 16B) were used as
markers to measure procedural efficacy.
[0092] As shown in FIG. 16A, cortical axon area (per mm.sup.2)
dropped approximately greater than 54% between a control group
(n=64) and treated groups of pigs (n=66) undergoing treatment. For
pigs undergoing treatment with the Symplicity Flex.TM. catheter
(n=54), an average of 4.1 lesions were formed in each animal. These
pigs demonstrated a 56.9% increase in non-functional axonal area
along the renal artery, and a 68% decrease in cortical axon area as
compared with the control group. For pigs undergoing treatment with
the Symplicity Spyral.TM. catheter (n=12), an average of 4.0
lesions were formed in each animal. The pigs undergoing treatment
with the Symplicity Spyral.TM. catheter demonstrated a 47.3%
increase in non-functional area along the renal artery, and a 54%
decrease in cortical axon area relative to the control group.
Without being bound by theory, it is believed that the loss of
cortical axons is a likely consequence of nerve atrophy distal to
the ablation sites.
[0093] FIG. 16B includes (a) a graph of normalized cortical axon
area vs. renal NE concentration, and (b) a graph of renal NE
concentration vs. extent (%) of nerve ablation. Referring to the
table of FIG. 16A and the two graphs of FIG. 16B together, cortical
axon area correlates directly with renal NE. In particular, pigs
undergoing treatment with the Symplicity Flex.TM. catheter
exhibited a 65% decrease in mean NE level compared with the pigs in
the control group. The pigs treated with the Symplicity Spyral.TM.
catheter exhibited a 68% decrease in mean NE level. This is further
shown by the first graph of FIG. 16B, which demonstrates that a
decrease in cortical axon area correlates with a decrease in NE
levels. Referring to the second graph of FIG. 16B, renal NE
decrease is non-linear with increased loss of nerve viability along
the artery (further extent (%) of nerve ablation). These findings
suggest that catheter-based renal neuromodulation exhibits a
relatively consistent impact on sympathetic nerve function and
viability.
Example 4
[0094] 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.TM. 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.
[0095] 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.TM. 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.
[0096] 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.
[0097] 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.TM. 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).
[0098] 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
[0099] 1. A method, comprising: [0100] intravascularly advancing an
elongate shaft of a catheter to renal vasculature of a human
patient, the renal vasculature including-- [0101] a main vessel
directly connected to an aorta of the patient and extending
distally toward a kidney, and [0102] a bifurcation at a distal end
of the main vessel; [0103] locating a neuromodulation element of
the catheter within a distalmost portion of the main vessel; and
[0104] modulating nerve tissue within an anatomical region
extending circumferentially around the distalmost portion of the
main vessel via the neuromodulation element.
[0105] 2. The method of example 1 wherein: [0106] the main vessel
has a longitudinal axis extending from the aorta to the
bifurcation; [0107] 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 [0108] the one or more
lesions collectively are-- [0109] 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 [0110] 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.
[0111] 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.
[0112] 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.
[0113] 5. The method of any one of examples 1-4 wherein: [0114] the
catheter, the shaft, and the neuromodulation element are a first
catheter, a first shaft, and a first neuromodulation element,
respectively; and [0115] the method further comprises-- [0116]
withdrawing the first catheter from the patient, [0117]
intravascularly advancing an elongate second shaft of a second
catheter to the renal vasculature, [0118] locating a second
neuromodulation element of the second catheter within a branch
vessel of the renal vasculature distal to the bifurcation, and
[0119] modulating nerve tissue within an anatomical region
extending circumferentially around the branch vessel via the second
neuromodulation element.
[0120] 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.
[0121] 7. The method of any one of examples 1-4 wherein: [0122]
advancing the shaft includes advancing the shaft while the
neuromodulation element is in a low-profile delivery state; and
[0123] 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.
[0124] 8. The method of example 7 wherein: [0125] the
neuromodulation element includes a balloon; and [0126] transforming
the neuromodulation element includes inflating the balloon.
[0127] 9. The method of example 7 wherein: [0128] the
neuromodulation element includes an elongate support structure
carrying a plurality of electrodes, the support structure having a
helical form when unconstrained; [0129] advancing the shaft
includes advancing the shaft while the support structure is
constrained; and [0130] transforming the neuromodulation element
includes reducing constraint on the support structure such that the
support structure moves toward having the helical form.
[0131] 10. The method of example 7 wherein: [0132] the
neuromodulation element includes an elongate electrode having a
helical form when unconstrained; [0133] advancing the shaft
includes advancing the shaft while the electrode is constrained;
and [0134] transforming the neuromodulation element includes
reducing constraint on the electrode such that the electrode moves
toward having the helical form.
[0135] 11. The method of any one of examples 1-4 wherein: [0136]
the neuromodulation element is a first neuromodulation element; and
[0137] the method further comprises-- [0138] locating a second
neuromodulation element of the catheter within a branch vessel of
the renal vasculature distal to the bifurcation, and [0139]
modulating nerve tissue within an anatomical region extending
circumferentially around the branch vessel after locating the
second neuromodulation element.
[0140] 12. The method of example 11 wherein: [0141] advancing the
shaft includes advancing the shaft while the second neuromodulation
element is in a low-profile delivery state; and [0142] 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.
[0143] 13. The method of example 11 wherein: [0144] the second
neuromodulation element includes a balloon; and [0145] transforming
the second neuromodulation element includes inflating the
balloon.
[0146] 14. The method of example 11 wherein: [0147] the second
neuromodulation element includes an elongate support structure
carrying a plurality of electrodes, the support structure having a
helical form when unconstrained; [0148] advancing the shaft
includes advancing the shaft while the support structure is
constrained; and [0149] transforming the second neuromodulation
element includes reducing constraint on the support structure such
that the support structure moves toward having the helical
form.
[0150] 15. The method of example 11 wherein: [0151] the second
neuromodulation element includes an elongate electrode having a
helical form when unconstrained; [0152] advancing the shaft
includes advancing the shaft while the electrode is constrained;
and [0153] deploying the second neuromodulation element includes
reducing constraint on the electrode such that the electrode moves
toward having the helical form.
[0154] 16. The method of any one of examples 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.
[0155] 17. A method, comprising: [0156] intravascularly advancing
an elongate shaft of a catheter to renal vasculature of a human
patient, the renal vasculature including-- [0157] a main vessel
directly connected to an aorta of the patient and extending
distally toward a kidney, [0158] a bifurcation at a distal end of
the main vessel, and [0159] a branch vessel distal to the
bifurcation; [0160] modulating nerve tissue within an anatomical
region extending circumferentially around the main vessel; [0161]
measuring a degree of neuromodulation achieved by modulating nerve
tissue within the anatomical region extending circumferentially
around the main vessel; and [0162] in response to an insufficiency
of the degree of neuromodulation, modulating nerve tissue within an
anatomical region extending circumferentially around the branch
vessel.
[0163] 18. The method of example 17 wherein the main vessel is
stented.
[0164] 19. The method of example 17 or example 18 wherein: [0165]
the degree of neuromodulation is a first degree of neuromodulation;
[0166] the branch vessel is a first branch vessel; [0167] the renal
vasculature includes a second branch vessel, the first and second
branch vessels being independently connected to the main vessel;
and [0168] the method further comprises-- [0169] measuring a second
degree of neuromodulation after modulating nerve tissue within the
anatomical region extending circumferentially around the first
branch vessel; and [0170] 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.
[0171] 20. The method of example 19 wherein: [0172] the renal
vasculature includes a third branch vessel, the first, second, and
third branch vessels being independently connected to the main
vessel; and [0173] the method further comprises-- [0174] measuring
a third degree of neuromodulation after modulating nerve tissue
within the anatomical region extending circumferentially around the
second branch vessel; and [0175] 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.
[0176] 21. A method including any non-conflicting combination of
the preceding examples 1-20.
[0177] 22. A method, comprising: [0178] intravascularly positioning
a neuromodulation element of a catheter within renal vasculature of
a human patient, the renal vasculature including-- [0179] a main
vessel directly connected to an aorta of the patient and extending
distally toward a kidney, [0180] a bifurcation at a distal end of
the main vessel, and [0181] a branch vessel distal to the
bifurcation; [0182] modulating nerve tissue within an anatomical
region extending circumferentially around the branch vessel; and
[0183] modulating nerve tissue within an anatomical region
extending circumferentially around the main vessel.
[0184] 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.
[0185] 24. The method of example 23 wherein the second branch
vessel is modulated before the main vessel is modulated.
[0186] 25. The method of any one of examples 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.
[0187] 26. The method of any one of examples 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.
[0188] 27. The method of any one of examples 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.
[0189] 28. The method of any one of examples 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.
[0190] 29. The method of any one of examples 22-28 wherein: [0191]
the neuromodulation element includes an elongate support structure
carrying a plurality of electrodes, the support structure having a
helical form when unconstrained; [0192] positioning the
neuromodulation element includes positioning the neuromodulation
element such that a proximal-most electrode is distal to the
bifurcation when unconstrained; and [0193] wherein the method
further includes deselecting one or more distal electrode(s) on the
elongate support structure prior to modulating the nerve
tissue.
[0194] 30. The method of any one of examples 22-28 wherein: [0195]
the neuromodulation element includes an elongate support structure
carrying a plurality of electrodes, the support structure having a
helical form when unconstrained; [0196] positioning the
neuromodulation element includes positioning the neuromodulation
element such that the support structure is positioned across the
bifurcation when unconstrained; and [0197] wherein the method
further includes deselecting one or more proximal electrode(s) on
the elongate support structure prior to modulating the nerve
tissue.
[0198] 31. The method of any one of examples 22-30 wherein the
method reduces sympathetic neural activity in the human
patient.
[0199] 32. The method of any one of examples 22-30 wherein the
method reduces norepinephrine spillover in the human patient.
[0200] 33. A method for treating a human patient diagnosed with a
measurable physiological parameter associated with systemic
sympathetic overactivity or hyperactivity, comprising: [0201]
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; [0202] neuromodulating
renal nerve tissue within an anatomical region extending
circumferentially around the main renal artery of the human
patient; and [0203] wherein the method reduces sympathetic neural
activity in the human patient.
[0204] 34. The method of example 33 wherein the measurable
physiological parameter is elevated blood pressure.
[0205] 35. The method of example 33 or example 34 wherein the human
patient is hypertensive.
[0206] 36. The method of any one of examples 33-35 wherein the
method reduces norepinephrine spillover in the human patient.
[0207] 37. A device configured to perform any of the methods of the
preceding examples 1-36.
[0208] 38. A device for performing renal neuromodulation,
comprising: [0209] a catheter having an elongate shaft, the
catheter comprising [0210] a first neuromodulation element operably
connected to the shaft, and [0211] a second neuromodulation
element, [0212] 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 [0213] 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.
[0214] 39. The device of example 38, wherein the first
neuromodulation element includes an elongate support structure
having a plurality of longitudinally spaced-apart electrodes.
[0215] 40. The device of example 39, wherein the elongate support
structure has a helical or spiral form when unconstrained.
[0216] 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 refracted.
[0217] 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.
[0218] 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.
[0219] 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.
[0220] 45. The device of any of examples 38 to 44, wherein the
second neuromodulation element includes at least one wire
electrode.
[0221] 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.
[0222] 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.
[0223] 48. The device of any of examples 45 to 47, wherein the
second neuromodulation element includes multiple wire electrodes
which can be individually guided into respective branch
vessels.
[0224] 49. The device of any of examples 38 to 44, wherein the
second neuromodulation element includes an elongate support and
electrodes.
[0225] 50. The device of any of examples 38 to 44, wherein the
second neuromodulation element has a single element tapering
distally.
[0226] 51. The device of example 50, wherein the first and second
neuromodulation elements are continuous.
[0227] 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.
[0228] 53. The device of example 51, wherein the second
neuromodulation element includes a balloon.
[0229] 54. The device according to example 51, wherein the first
neuromodulation element includes a balloon.
[0230] 55. The device of any of examples 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.
[0231] 56. The device of any of examples 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.
[0232] 57. The device of any of examples 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.
[0233] 58. A system for performing renal neuromodulation,
comprising [0234] a device of any of the preceding claims, and
[0235] a console configured to control, monitor, supply energy to,
and/or otherwise support operation of the catheter.
[0236] 59. A system for performing renal neuromodulation,
comprising [0237] 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 [0238] a console configured to
control, monitor, supply energy to, and/or otherwise support
operation of the catheter.
[0239] 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.
[0240] 61. The system of any of examples 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.
[0241] 62. The system of any of examples 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.
[0242] 63. The system of any of examples 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.
[0243] 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
[0244] individually supplying different and/or varying amounts of
energy to the electrodes based on an electrode's location along the
vasculature.
[0245] 65. The method of example 64, further comprising [0246]
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.
[0247] 66. The method of example 64 or 65, further comprising
[0248] varying the duration of power delivery depending on the
position of one or more electrodes along the vasculature.
[0249] 67. The method of any of examples 64 to 66, further
comprising [0250] 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.
[0251] 68. A method, comprising: [0252] intravascularly advancing
an elongate shaft of a catheter to renal vasculature of a human
patient; [0253] 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; [0254] 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; [0255] modulating nerve tissue within an
anatomical region extending about the distalmost portion of the
main renal artery via the first neuromodulation element; and [0256]
modulating nerve tissue within an anatomical region extending about
the branch vessel via the second neuromodulation element.
[0257] 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.
[0258] 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.
[0259] 71. The method of example 68 wherein the second
neuromodulation element is operably connected to the shaft.
[0260] 72. The method of example 68 wherein the second
neuromodulation element is operably connected to the first
neuromodulation element.
[0261] 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.
[0262] 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.
[0263] 75. The method of example 68 wherein the first and second
neuromodulation elements are a single continuous elongate element,
and wherein: [0264] 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
[0265] 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.
[0266] 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.
[0267] 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.
[0268] 78. The method of any one of examples 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.
[0269] 79. The method of any one of examples 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.
[0270] 80. The method of any one of examples 68 to 79 wherein the
branch vessel is modulated before the main renal artery is
modulated.
[0271] 81. The method of any one of examples 68 to 79 wherein the
main renal artery is modulated before the branch vessel is
modulated.
[0272] 82. The method of any one of examples 68 to 79 wherein the
main renal artery and the branch vessel are modulated
simultaneously.
[0273] 83. A method, comprising: [0274] intravascularly advancing
an elongate shaft of a catheter to renal vasculature of a human
patient; [0275] 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 [0276] ablating nerve tissue within an anatomical
region extending circumferentially around the distalmost portion of
the main vessel via the electrodes of the neuromodulation
element.
[0277] 84. The method of example 83 wherein: [0278] the main vessel
has a longitudinal axis extending from the aorta to a bifurcation
at a distal end of the main renal artery; [0279] 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 [0280] the one or more lesions collectively are--
[0281] 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
[0282] 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.
[0283] 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.
[0284] 86. The method of example 83 wherein: [0285] the catheter,
the shaft, and the neuromodulation element are a first catheter, a
first shaft, and a first neuromodulation element, respectively; and
[0286] the method further comprises-- [0287] withdrawing the first
catheter from the patient; [0288] intravascularly advancing an
elongate second shaft of a second catheter to the renal
vasculature; [0289] locating a second neuromodulation element of
the second catheter within a branch vessel of the renal vasculature
distal to the bifurcation; [0290] ablating nerve tissue within an
anatomical region extending circumferentially around the branch
vessel via the second neuromodulation element; and [0291]
withdrawing the second catheter from the patient.
[0292] 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.
[0293] 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.
[0294] 89. The method of example 83 wherein: [0295] advancing the
shaft includes advancing the shaft while the neuromodulation
element is in a low-profile delivery state; and [0296] 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, [0297] wherein, in the
extended treatment state, the neuromodulation element has a helical
form.
[0298] 90. A method for treating a human patient diagnosed with a
measurable physiological parameter associated with systemic
sympathetic overactivity or hyperactivity, the method comprising:
[0299] 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 [0300] ablating renal nerves within an
anatomical region extending circumferentially around the main renal
artery of the patient, [0301] wherein ablating the renal nerves
results in a decrease in renal sympathetic neural activity in the
patient.
[0302] 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.
[0303] 92. The method of example 90 or 91 wherein ablating the
renal nerves comprises systemically reducing sympathetic tone in
the patient.
[0304] 93. The method of any of examples 90 to 92 wherein ablating
the renal nerves reduces norepinephrine spillover in the
patient.
CONCLUSION
[0305] 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.
[0306] 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.
[0307] 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.
[0308] 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.
* * * * *