U.S. patent application number 14/636459 was filed with the patent office on 2015-08-27 for apparatus, systems, and methods for achieving intravascular, thermally-induced renal neuromodulation.
The applicant listed for this patent is Medtronic Ardian Luxembourg S.a.r.l.. Invention is credited to Benjamin J. Clark, Erik Thai, Andrew Wu, Denise Zarins.
Application Number | 20150238253 14/636459 |
Document ID | / |
Family ID | 42289584 |
Filed Date | 2015-08-27 |
United States Patent
Application |
20150238253 |
Kind Code |
A1 |
Wu; Andrew ; et al. |
August 27, 2015 |
APPARATUS, SYSTEMS, AND METHODS FOR ACHIEVING INTRAVASCULAR,
THERMALLY-INDUCED RENAL NEUROMODULATION
Abstract
Apparatus, systems, and methods for achieving thermally-induced
renal neuromodulation by intravascular access are disclosed herein.
One aspect of the present application, for example, is directed to
apparatuses, systems, and methods that incorporate a treatment
device comprising an elongated shaft. The elongated shaft is sized
and configured to deliver a thermal element to a renal artery via
an intravascular path. Thermally-induced renal neuromodulation may
be achieved via direct and/or via indirect application of thermal
energy to heat or cool neural fibers that contribute to renal
function, or of vascular structures that feed or perfuse the neural
fibers.
Inventors: |
Wu; Andrew; (Los Altos
Hills, CA) ; Clark; Benjamin J.; (Redwood City,
CA) ; Zarins; Denise; (Saratoga, CA) ; Thai;
Erik; (San Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Medtronic Ardian Luxembourg S.a.r.l. |
Luxembourg |
|
LU |
|
|
Family ID: |
42289584 |
Appl. No.: |
14/636459 |
Filed: |
March 3, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14284474 |
May 22, 2014 |
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14636459 |
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12910631 |
Oct 22, 2010 |
8777942 |
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14284474 |
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12545648 |
Aug 21, 2009 |
8652129 |
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12910631 |
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12495691 |
Jun 30, 2009 |
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12545648 |
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61142128 |
Dec 31, 2008 |
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61142128 |
Dec 31, 2008 |
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Current U.S.
Class: |
606/41 |
Current CPC
Class: |
A61B 2018/00577
20130101; A61B 2018/00172 20130101; A61B 18/1206 20130101; A61B
2018/00875 20130101; A61B 2018/00648 20130101; A61B 90/39 20160201;
A61B 18/1492 20130101; A61B 18/24 20130101; A61B 18/18 20130101;
A61B 2018/00791 20130101; A61M 25/0141 20130101; A61B 2018/00434
20130101; A61B 2017/003 20130101; A61B 18/02 20130101; A61B
2018/00404 20130101; A61N 2007/003 20130101; A61B 2018/00511
20130101 |
International
Class: |
A61B 18/14 20060101
A61B018/14; A61M 25/01 20060101 A61M025/01; A61B 18/12 20060101
A61B018/12 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 14, 2009 |
EP |
09167937.3 |
Aug 14, 2009 |
EP |
09168202.1 |
Aug 14, 2009 |
EP |
09168204.7 |
Claims
1-48. (canceled)
49. A method for treating hypertension in a patient in need
thereof, the method comprising: introducing an intravascular
treatment device over a guidewire and into a renal artery of the
patient, the intravascular treatment device comprising an elongated
shaft extending along an axis, and a distal flexure zone carrying
at least one electrode; manipulating the intravascular treatment
device so that the distal flexure zone provides contact between a
side of the at least one electrode and an interior wall of the
renal artery; and applying energy to form multiple focal lesions on
the interior wall of the renal artery, wherein the lesions are
circumferentially spaced along a longitudinal axis of the renal
artery, wherein the at least one electrode has a total surface area
(TSA) and an active surface area (ASA), and wherein the
intravascular treatment device achieves a ratio of ASA to TSA of
between 10% and 50%.
50. The method of claim 49, wherein applying energy at least
partially modulates neural fibers that contribute to renal
function.
51. The method of claim 49, wherein applying energy denervates a
kidney of the patient.
52. The method of claim 49, wherein applying energy comprises
delivering a monopolar electric field via the at least one
electrode.
53. The method of claim 49, wherein applying energy comprises
supplying a continuous delivery of radiofrequency (RF) energy to
the electrode.
54. The method of claim 49, wherein applying energy comprises
exposing the renal artery to a temperature above about 60.degree.
C. and less than about 90.degree. C.
55. The method of claim 49, wherein applying energy comprises
exposing the renal artery to a temperature above about 60.degree.
C. and less than about 80.degree. C.
56. The method of claim 49, wherein the at least one electrode is
generally cylindrical.
57. The method of claim 49, wherein the one or more thermal heating
effects comprise thermal ablation of tissue on the interior wall of
the renal artery.
58. The method of claim 49, wherein introducing an intravascular
treatment device into a renal artery of the patient comprises
routing the intravascular treatment device through a 6 French guide
catheter.
59. The method of claim 49, wherein the intravascular treatment
device further comprises a temperature sensor located proximate to
the at least one electrode.
60. The method of claim 49, wherein the at least one electrode
comprises multiple electrodes.
61. The method of claim 49, further comprising delivering a thermal
fluid into the renal artery.
62. The method of claim 61, wherein the thermal fluid comprises
saline.
63. The method of claim 49, wherein each of the lesions covers
approximately 20 percent to 50 percent of a circumferential area
surrounding the renal artery.
64. The method of claim 49, wherein each of the lesions covers
approximately 20 percent to 30 percent of a circumferential area
surrounding the renal artery.
65. The method of claim 49, further comprising monitoring feedback
and altering treatment delivered to the renal artery in response to
the feedback.
66. The method of claim 49, wherein the intravascular treatment
device comprises a catheter apparatus.
Description
REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of the following
pending applications: [0002] (a) U.S. Provisional Patent
Application No. 61/142,128, filed on Dec. 31, 2008; [0003] (b) U.S.
patent application Ser. No. 12/495,691, filed on Jun. 30, 2009;
[0004] (c) European Patent Application No. ______, filed Aug. 14,
2009; [0005] (d) European Patent Application No. ______, filed Aug.
19, 2009; and [0006] (e) European Patent Application No. ______,
filed Aug. 19, 2009.
[0007] All of these applications are incorporated herein by
reference in their entireties.
TECHNICAL FIELD
[0008] The technologies disclosed in the present application
generally relate to apparatus, systems, and methods for
intravascular neuromodulation. More particularly, the technologies
disclosed herein relate to apparatus, systems, and methods for
achieving intravascular renal neuromodulation via thermal
heating.
BACKGROUND
[0009] Hypertension, heart failure and chronic kidney disease
represent a significant and growing global health issue. Current
therapies for these conditions include non-pharmacological,
pharmacological and device-based approaches. Despite this variety
of treatment options the rates of control of blood pressure and the
therapeutic efforts to prevent progression of heart failure and
chronic kidney disease and their sequelae remain unsatisfactory.
Although the reasons for this situation are manifold and include
issues of non-compliance with prescribed therapy, heterogeneity in
responses both in terms of efficacy and adverse event profile, and
others, it is evident that alternative options are required to
supplement the current therapeutic treatment regimes for these
conditions.
[0010] Reduction of sympathetic renal nerve activity (e.g., via
denervation), can reverse these processes. Ardian, Inc. has
discovered that an energy field, including and comprising an
electric field, can initiate renal neuromodulation via denervation
caused by irreversible electroporation, electrofusion, apoptosis,
necrosis, ablation, thermal alteration, alteration of gene
expression or another suitable modality.
SUMMARY
[0011] The following summary is provided for the benefit of the
reader only, and is not intended to limit the disclosure in any
way. The present application provides apparatus, systems and
methods for achieving thermally-induced renal neuromodulation by
intravascular access.
[0012] One aspect of the present application provides apparatuses,
systems, and methods that incorporate a treatment device comprising
an elongated shaft. The elongated shaft is sized and configured to
deliver a thermal heating element to a renal artery via an
intravascular path that includes a femoral artery, an iliac artery,
and the aorta. Different sections of the elongated shaft serve
different mechanical functions when in use. The sections are
differentiated in terms of their size, configuration, and
mechanical properties for (i) percutaneous introduction into a
femoral artery through a small-diameter access site; (ii)
atraumatic passage through the tortuous intravascular path through
an iliac artery, into the aorta, and into a respective left/right
renal artery, including (iii) accommodating significant flexure at
the junction of the left/right renal arteries and aorta to gain
entry into the respective left or right renal artery; (iv)
accommodating controlled translation, deflection, and/or rotation
within the respective renal artery to attain proximity to and a
desired alignment with an interior wall of the respective renal
artery; and (v) allowing the placement of a thermal heating element
into contact with tissue on the interior wall in an orientation
that optimizes the active surface area of the thermal heating
element.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1A is an anatomic interior view of a thoracic cavity of
a human, with the intestines removed, showing the kidneys and
surrounding structures.
[0014] FIG. 1B in an anatomic view of the urinary system of a
human, of which the kidneys shown in FIG. 1A form a part.
[0015] FIGS. 2A, 2B, and 2C are a series of enlarged anatomic views
showing various interior regions of a human kidney.
[0016] FIG. 3A is a conceptual illustration of the sympathetic
nervous system (SNS) and how the brain communicates with the body
via the SNS.
[0017] FIG. 3B is an enlarged anatomic view of nerves innervating a
left kidney to form the renal plexus surrounding the left renal
artery.
[0018] FIGS. 3C and 3D provide anatomic and conceptual views of a
human body, respectively, depicting neural efferent and afferent
communication between the brain and kidneys
[0019] FIGS. 4A and 4B are, respectively, anatomic views of the
arterial and venous vasculatures of a human.
[0020] FIG. 5 is a perspective view of a system for achieving
intravascular, thermally-induced renal neuromodulation, comprising
a treatment device and a generator.
[0021] FIGS. 6A and 6B are anatomic views of the intravascular
delivery, deflection and placement of the treatment device shown in
FIG. 5 through the femoral artery and into a renal artery.
[0022] FIGS. 7A to 7D are a series of views of the elongated shaft
of the treatment device shown in FIG. 5, showing the different
mechanical and functional regions that the elongated shaft
incorporates.
[0023] FIG. 7E shows an anatomic view of the placement of the
treatment device shown in FIG. 5 within the dimensions of the renal
artery.
[0024] FIG. 8A to 8C show the placement of a thermal heating
element, which is carried at the distal end of the elongated shaft
of the treatment device shown in FIG. 5, into contact with tissue
along a renal artery.
[0025] FIGS. 9A and 9B show placement of the thermal heating
element shown in FIGS. 8A to 8C into contact with tissue along a
renal artery and delivery of thermal treatment to the renal
plexus.
[0026] FIGS. 10A and 10B show a representative embodiment of the
force transmitting section of the elongated shaft of the treatment
device shown in FIG. 5.
[0027] FIGS. 11A to 11C show a representative embodiment of the
proximal flexure zone of the elongated shaft of the treatment
device shown in FIG. 5.
[0028] FIGS. 12A to 12D show a representative embodiment of the
intermediate flexure zone of the elongated shaft of the treatment
device shown in FIG. 5.
[0029] FIGS. 13A to 13C show alternative embodiments of the
intermediate flexure zone of the elongated shaft of the treatment
device shown in FIG. 5.
[0030] FIGS. 14A to 14C show alternative embodiments of the
intermediate flexure zone of the elongated shaft of the treatment
device shown in FIG. 5.
[0031] FIGS. 15A to 15C show a representative embodiment of the
distal flexure zone of the elongated shaft of the treatment device
shown in FIG. 5.
[0032] FIGS. 15D to 15F show multiple planar views of the bending
capability of the distal flexure zone corresponding to the
elongated shaft of the treatment device shown in FIG. 5.
[0033] FIGS. 15G and 15H show alternative embodiments of the distal
flexure zone corresponding to the elongated shaft of the treatment
device shown in FIG. 5.
[0034] FIGS. 151 and 15J show an alternative catheter embodiment of
the treatment device shown in FIG. 5 comprising an intermediate
section comprising an arch wire.
[0035] FIGS. 16A and 16B show a representative embodiment of a
rotational control mechanism coupled to the handle of the treatment
device shown in FIG. 5.
[0036] FIGS. 16C and 16D show a handle of the treatment device
shown in FIG. 5 with a rotational control mechanism having a
rotational limiting element and an actuator lever.
[0037] FIGS. 17A and 17B show an alternative representative
embodiment of an elongated shaft for a treatment device like that
shown in FIG. 5, showing examples of the different mechanical and
functional regions that the elongated shaft can incorporate.
[0038] FIGS. 18A and 18B show another alternative representative
embodiment of an elongated shaft for a treatment device like that
shown in FIG. 5, showing examples of the different mechanical and
functional regions that the elongated shaft can incorporate.
[0039] FIGS. 19A to 19H show the intravascular delivery, placement,
deflection, rotation, retraction, repositioning and use of a
treatment device, like that shown in FIG. 5, to achieve
thermally-induced renal neuromodulation from within a renal
artery.
[0040] FIGS. 191 to 19K show the circumferential treatment effect
resulting from intravascular use of a treatment device, like that
shown in FIG. 5.
[0041] FIG. 19L shows an alternative intravascular treatment
approach using the treatment device shown in FIG. 5.
[0042] FIG. 20 shows an energy delivery algorithm corresponding to
the energy generator of the system shown in FIG. 5.
[0043] FIG. 21 shows several components of the system and treatment
device shown in FIG. 5 packaged within a single kit.
[0044] FIGS. 22A to 22C show fluoroscopic images of the treatment
device shown in FIG. 5 in multiple treatment positions within a
renal artery.
DETAILED DESCRIPTION
[0045] Although the disclosure hereof is detailed and exact to
enable those skilled in the art to practice the disclosed
technologies, the physical embodiments herein disclosed merely
exemplify the various aspects of the invention, which may be
embodied in other specific structure. While the preferred
embodiment has been described, the details may be changed without
departing from the invention, which is defined by the claims.
I. PERTINENT ANATOMY AND PHYSIOLOGY
[0046] A. The Kidneys
[0047] FIG. 1A is an anatomic view of the posterior abdominal wall,
showing the left and right kidneys, neighboring organs, and major
blood vessels. In FIG. 1A, most of the digestive system located
within the peritoneum has been omitted for clarity.
[0048] In humans, the kidneys are located in the posterior part of
the abdominal cavity. There are two, one on each side of the spine.
The right kidney sits just below the diaphragm and posterior to the
liver. The left kidney sits below the diaphragm and posterior to
the spleen. The asymmetry within the abdominal cavity caused by the
liver results in the right kidney being slightly lower than the
left one, while the left kidney is located slightly more
medial.
[0049] Above each kidney is an adrenal gland (also called the
suprarenal gland). The adrenal glands make hormones, such as (1)
cortisol, which is a natural steroid hormone; (2) aldosterone,
which is a hormone that helps to regulate the body's water balance;
and (3) adrenalin and noradrenaline.
[0050] The kidneys are complicated organs that have numerous
biological roles.
[0051] 1. The Blood Filtration Functions
[0052] As FIG. 1B shows, the kidneys are part of the body system
called the urinary system, which comprises the kidneys, ureters,
bladder, and urethra. Generally speaking, the urinary system
filters waste products out of the blood and makes urine.
[0053] A primary role of the kidneys is to maintain the homeostatic
balance of bodily fluids by filtering and secreting metabolites
(such as urea) and minerals from the blood and excreting them,
along with water, as urine.
[0054] The kidneys perform this vital function by filtering the
blood. The kidneys have a very rich blood supply. The kidneys
receive unfiltered blood directly from the heart through the
abdominal aorta, which branches to the left and right renal
arteries to serve the left and right kidneys, respectively.
Filtered blood then returns by the left and right renal veins to
the inferior vena cava and then the heart. Renal blood flow
accounts for approximately one quarter of cardiac output.
[0055] In each kidney, the renal artery transports blood with waste
products into the respective kidney. As the blood passes through
the kidneys, waste products and unneeded water and electrolytes are
collected and turned into urine. Filtered blood is returned to the
heart by the renal vein. From the kidneys, the urine drains into
the bladder down tubes called the ureters (one for each kidney).
Another tube called the urethra carries the urine from the bladder
out of the body.
[0056] As FIGS. 2A, 2B, and 2C show, inside the kidney, the blood
is filtered through very small networks of tubes called nephrons
(best shown in FIG. 2B). Each kidney has about 1 million nephrons.
As FIG. 2B shows, each nephron is made up of glomeruli, which are
covered by sacs (called Bowman's capsules) and connected to renal
tubules. Inside the nephrons, waste products in the blood move
across from the bloodstream (the capillaries) into the tubules. As
the blood passes through the blood vessels of the nephron, unwanted
waste is taken away. Any chemicals needed by the body are kept or
returned to the bloodstream by the nephrons.
[0057] About seventy-five percent of the constituents of crude
urine and about sixty-six percent of the fluid are reabsorbed in
the first portion of the renal tubules, called the proximal renal
tubules (see FIG. 2B). Readsorption is completed in the loop of
Henle and in the last portion of the renal tubules, called the
distal convoluted tubules, producing urine. The urine is carried by
collecting tubule of the nephron to the ureter. In this way, the
kidneys help to regulate the levels of chemicals in the blood such
as sodium and potassium, and keep the body healthy.
[0058] 2. The Physiologic Regulation Functions
[0059] Because the kidneys are poised to sense plasma
concentrations of ions such as sodium, potassium, hydrogen, oxygen,
and compounds such as amino acids, creatinine, bicarbonate, and
glucose in the blood, they are important regulators of blood
pressure, glucose metabolism, and erythropoiesis (the process by
which red blood cells are produced).
[0060] The kidney is one of the major organs involved in whole-body
homeostasis. Besides filtering the blood, the kidneys perform
acid-base balance, regulation of electrolyte concentrations,
control of blood volume, and regulation of blood pressure. The
kidneys accomplish theses homeostatic functions independently and
through coordination with other organs, particularly those of the
endocrine system.
[0061] The kidneys produce and secrete three important hormones:
(1) erythropoietin (EPO), which tells the bone marrow to make red
blood cells; (2) renin, which regulates blood pressure; and (3)
calcitriol (a form of Vitamin D), which helps the intestine to
absorb calcium from the diet, and so helps to keep the bones
healthy.
[0062] Renin is produced by a densely packed areas of specialized
cells, called macula densa, in the region of juxtaglomerular cells,
which line the wall of the distal convoluted tubule (DCT) (see FIG.
2C). The cells of the macula densa are sensitive to the ionic
content and water volume of the fluid in the DCT, producing
molecular signals that promote renin secretion by other cells of
the juxtaglomerular cell region. As will be described in greater
detail later, the release of renin is an essential component of the
renin-angiotensin-aldosterone system (RAAS), which regulates blood
pressure and volume. [0063] (i) The Renin-Angiotensin System
[0064] The renin-angiotensin system (RAS) or the
renin-angiotensin-aldosterone system (RAAS) is a hormone system
that regulates blood pressure and water (fluid) balance.
[0065] When blood pressure is low, the kidneys secrete renin, as
explained above. Renin stimulates the production of angiotensin.
Angiotensin and its derivatives cause blood vessels to constrict,
resulting in increased blood pressure. Angiotensin also stimulates
the secretion of the hormone aldosterone from the adrenal cortex.
Aldosterone causes the tubules of the kidneys to retain sodium and
water. This increases the volume of fluid in the body, which also
increases blood pressure.
[0066] If the renin-angiotensin-aldosterone system is too active,
blood pressure will be too high. There are many drugs which
interrupt different steps in this system to lower blood pressure.
These drugs are one of the main ways to control high blood pressure
(hypertension), heart failure, kidney failure, and harmful effects
of diabetes.
[0067] B. The Sympathetic Nervous System
[0068] The Sympathetic Nervous System (SNS) is a branch of the
autonomic nervous system along with the enteric nervous system and
parasympathetic nervous system. It is always active at a basal
level (called sympathetic tone) and becomes more active during
times of stress. Like other parts of the nervous system, the
sympathetic nervous system operates through a series of
interconnected neurons. Sympathetic neurons are frequently
considered part of the peripheral nervous system (PNS), although
many lie within the central nervous system (CNS). Sympathetic
neurons of the spinal cord (which is part of the CNS) communicate
with peripheral sympathetic neurons via a series of sympathetic
ganglia. Within the ganglia, spinal cord sympathetic neurons join
peripheral sympathetic neurons through synapses. Spinal cord
sympathetic neurons are therefore called presynaptic (or
preganglionic) neurons, while peripheral sympathetic neurons are
called postsynaptic (or postganglionic) neurons.
[0069] At synapses within the sympathetic ganglia, preganglionic
sympathetic neurons release acetylcholine, a chemical messenger
that binds and activates nicotinic acetylcholine receptors on
postganglionic neurons. In response to this stimulus,
postganglionic neurons principally release noradrenaline
(norepinephrine). Prolonged activation can elicit the release of
adrenaline from the adrenal medulla.
[0070] Once released, norepinephrine and epinephrine bind
adrenergic receptors on peripheral tissues. Binding to adrenergic
receptors causes a neuronal and hormonal response. The physiologic
manifestations include pupil dilation, increased heart rate,
occasional vomiting, and increased blood pressure. Increased
sweating is also seen due to binding of cholinergic receptors of
the sweat glands.
[0071] The sympathetic nervous system is responsible for up- and
down-regulating many homeostatic mechanisms in living organisms.
Fibers from the SNS innervate tissues in almost every organ system,
providing at least some regulatory function to things as diverse as
pupil diameter, gut motility, and urinary output. This response is
also known as sympatho-adrenal response of the body, as the
preganglionic sympathetic fibers that end in the adrenal medulla
(but also all other sympathetic fibers) secrete acetylcholine,
which activates the secretion of adrenaline (epinephrine) and to a
lesser extent noradrenaline (norepinephrine). Therefore, this
response that acts primarily on the cardiovascular system is
mediated directly via impulses transmitted through the sympathetic
nervous system and indirectly via catecholamines secreted from the
adrenal medulla.
[0072] Science typically looks at the SNS as an automatic
regulation system, that is, one that operates without the
intervention of conscious thought. Some evolutionary theorists
suggest that the sympathetic nervous system operated in early
organisms to maintain survival as the sympathetic nervous system is
responsible for priming the body for action. One example of this
priming is in the moments before waking, in which sympathetic
outflow spontaneously increases in preparation for action.
[0073] 1. The Sympathetic Chain
[0074] As shown in FIG. 3A, the SNS provides a network of nerves
that allows the brain to communicate with the body. Sympathetic
nerves originate inside the vertebral column, toward the middle of
the spinal cord in the intermediolateral cell column (or lateral
horn), beginning at the first thoracic segment of the spinal cord
and are thought to extend to the second or third lumbar segments.
Because its cells begin in the thoracic and lumbar regions of the
spinal cord, the SNS is said to have a thoracolumbar outflow. Axons
of these nerves leave the spinal cord through the anterior
rootlet/root. They pass near the spinal (sensory) ganglion, where
they enter the anterior rami of the spinal nerves. However, unlike
somatic innervation, they quickly separate out through white rami
connectors which connect to the either the paravertebral (which lie
near the vertebral column) or prevertebral (which lie near the
aortic bifurcation) ganglia extending alongside the spinal
column.
[0075] In order to reach the target organs and glands, the axons
must travel long distances in the body, and, to accomplish this,
many axons relay their message to a second cell through synaptic
transmission. The ends of the axons link across a space, the
synapse, to the dendrites of the second cell. The first cell (the
presynaptic cell) sends a neurotransmitter across the synaptic
cleft where it activates the second cell (the postsynaptic cell).
The message is then carried to the final destination.
[0076] In the SNS and other components of the peripheral nervous
system, these synapses are made at sites called ganglia. The cell
that sends its fiber is called a preganglionic cell, while the cell
whose fiber leaves the ganglion is called a postganglionic cell. As
mentioned previously, the preganglionic cells of the SNS are
located between the first thoracic segment and third lumbar
segments of the spinal cord. Postganglionic cells have their cell
bodies in the ganglia and send their axons to target organs or
glands.
[0077] The ganglia include not just the sympathetic trunks but also
the cervical ganglia (superior, middle and inferior), which sends
sympathetic nerve fibers to the head and thorax organs, and the
celiac and mesenteric ganglia (which send sympathetic fibers to the
gut).
[0078] 2. Innervation of the Kidneys
[0079] As FIG. 3B shows, the kidney is innervated by the renal
plexus (RP), which is intimately associated with the renal artery.
The renal plexus (RP) is an autonomic plexus that surrounds the
renal artery and is embedded within the adventitia of the renal
artery. The renal plexus extends along the renal artery until it
arrives at the substance of the kidney. Fibers contributing to the
renal plexus arise from the celiac ganglion, the superior
mesenteric ganglion, the aorticorenal ganglion and the aortic
plexus. The renal plexus (RP), also referred to as the renal nerve,
is predominantly comprised of sympathetic components. There is no
(or at least very minimum) parasympathetic innervation of the
kidney.
[0080] Preganglionic neuronal cell bodies are located in the
intermediolateral cell column of the spinal cord. Preganglionic
axons pass through the paravertebral ganglia (they do not synapse)
to become the lesser splanchnic nerve, the least splanchnic nerve,
first lumbar splanchnic nerve, second lumbar splanchnic nerve, and
travel to the celiac ganglion, the superior mesenteric ganglion,
and the aorticorenal ganglion. Postganglionic neuronal cell bodies
exit the celiac ganglion, the superior mesenteric ganglion, and the
aorticorenal ganglion to the renal plexus (RP) and are distributed
to the renal vasculature.
[0081] 3. Renal Sympathetic Neural Activity
[0082] Messages travel through the SNS in a bidirectional flow.
Efferent messages can trigger changes in different parts of the
body simultaneously. For example, the sympathetic nervous system
can accelerate heart rate; widen bronchial passages; decrease
motility (movement) of the large intestine; constrict blood
vessels; increase peristalsis in the esophagus; cause pupil
dilation, piloerection (goose bumps) and perspiration (sweating);
and raise blood pressure. Afferent messages carry signals from
various organs and sensory receptors in the body to other organs
and, particularly, the brain.
[0083] Hypertension, heart failure and chronic kidney disease are a
few of many disease states that result from chronic activation of
the SNS, especially the renal sympathetic nervous system. Chronic
activation of the SNS is a maladaptive response that drives the
progression of these disease states. As described above,
pharmaceutical management of the renin-angiotensin-aldosterone
system has been the longstanding for reducing over-activity of the
SNS.
[0084] As mentioned above, the renal sympathetic nervous system has
been identified as a major contributor to the complex
pathophysiology of hypertension, states of volume overload (such as
heart failure), and progressive renal disease, both experimentally
and in humans. Studies employing radiotracer dilution methodology
to measure overflow of norepinephrine from the kidneys to plasma
revealed increased renal norepinephrine (NE) spillover rates in
patients with essential hypertension, particularly so in young
hypertensive subjects, which in concert with increased NE spillover
from the heart, is consistent with the hemodynamic profile
typically seen in early hypertension and characterized by an
increased heart rate, cardiac output and renovascular resistance.
It is now known that essential hypertension is commonly neurogenic,
often accompanied by pronounced sympathetic nervous system
overactivity.
[0085] Activation of cardiorenal sympathetic nerve activity is even
more pronounced in heart failure, as demonstrated by an exaggerated
increase of NE overflow from the heart and the kidneys to plasma in
this patient group. In line with this notion is the recent
demonstration of a strong negative predictive value of renal
sympathetic activation on all-cause mortality and heart
transplantation in patients with congestive heart failure, which is
independent of overall sympathetic activity, glomerular filtration
rate and left ventricular ejection fraction. These findings support
the notion that treatment regimens that are designed to reduce
renal sympathetic stimulation have the potential to improve
survival in patients with heart failure.
[0086] Both chronic and end stage renal disease are characterized
by heightened sympathetic nervous activation. In patients with end
stage renal disease plasma levels of norepinephrine above the
median have been demonstrated to be predictive for both all cause
death and death from cardiovascular disease. This is also true for
patients suffering from diabetic or contrast nephropathy. There is
compelling evidence that suggests that sensory afferent signals
originating from the diseased kidneys are major contributors to
initiate and sustain elevated central sympathetic outflow in this
patient group, which facilitates the occurrence of the well known
adverse consequences of chronic sympathetic overactivity such as
hypertension, left ventricular hypertrophy, ventricular arrhythmias
and sudden cardiac death.
[0087] Several forms of "renal injury" can induce activation of
sensory afferent signals. For example, renal ischemia, reduction in
stroke volume or renal blood flow, or an abundance of adenosine
enzyme may trigger activation of afferent neural communication. As
shown in FIGS. 3C and 3D, this afferent communication might be from
the kidney to the brain or might be from one kidney to the other
kidney. These afferent signals are centrally integrated and result
in increased sympathetic outflow. This sympathetic drive is
directed towards the kidneys, thereby activating the RAAS and
inducing increased renin secretion, sodium retention, volume
retention and vasoconstriction. Central sympathetic overactivity
also impacts other organs and bodily structures innervated by
sympathetic nerves such as the heart and the peripheral
vasculature, resulting in the described adverse effects of
sympathetic activation, several aspects of which also contribute to
the rise in blood pressure.
[0088] (i) Renal Sympathetic Efferent Activity
[0089] Sympathetic nerves to the kidneys terminate in the blood
vessels, the juxtaglomerular apparatus and the renal tubules.
Stimulation of the renal sympathetic nerves causes increased renin
release, increased sodium (Na+) reabsorption and a reduction of
renal blood flow. These components of the neural regulation of
renal function are considerably stimulated in disease states
characterized by heightened sympathetic tone and clearly contribute
to the rise in blood pressure in hypertensive patients. The
reduction of renal blood flow and glomerular filtration rate as a
result of renal sympathetic efferent stimulation is likely a
cornerstone of the loss of renal function in cardio-renal syndrome,
which is renal dysfunction as a progressive complication of chronic
heart failure, with a clinical course that typically fluctuates
with the patient's clinical status and treatment. Pharmacologic
strategies to thwart the consequences of renal efferent sympathetic
stimulation include centrally acting sympatholytic drugs, beta
blockers (intended to reduce renin release), angiotensin converting
enzyme inhibitors and receptor blockers (intended to block the
action of angiotensin II and aldosterone activation consequent to
renin release) and diuretics (intended to counter the renal
sympathetic mediated sodium and water retention). However, the
current pharmacologic strategies have significant limitations
including limited efficacy, compliance issues, side effects, and
others.
[0090] (ii) Renal Sensory Afferent Nerve Activity
[0091] The kidneys communicate with integral structures in the
central nervous system via renal sensory afferent nerves.
Intra-renal pathology, such as ischemia, hypoxia or other injury,
results in an increase in renal afferent activity. Renal sensory
afferent nerve activity directly influences sympathetic outflow to
the kidneys and other highly innervated organs involved in
cardiovascular control such as the heart and peripheral blood
vessels, by modulating posterior hypothalamic activity.
[0092] The physiology therefore suggests that (i) denervation of
efferent sympathetic nerves will reduce inappropriate renin
release, salt retention, and reduction of renal blood flow, and
that (ii) denervation of afferent sensory nerves will reduce the
systemic contribution to hypertension through its direct effect on
the posterior hypothalamus as well as the contralateral kidney. In
addition to the central hypotensive effects of afferent renal
denervation, a desirable reduction of central sympathetic outflow
to various other sympathetically innervated organs such as the
heart and the vasculature is anticipated.
[0093] C. Additional Clinical Benefits of Renal Denervation
[0094] As provided above, renal denervation is likely to be
valuable in the treatment of several clinical conditions
characterized by increased overall and particularly renal
sympathetic activity such as hypertension, metabolic syndrome,
diabetes, left ventricular hypertrophy, chronic and end stage renal
disease, inappropriate fluid retention in heart failure,
cardio-renal syndrome and sudden death. Since the reduction of
afferent neural signals contributes to the systemic reduction of
sympathetic tone/drive, renal denervation might also be useful in
treating other conditions associated with systemic sympathetic
hyperactivity. Accordingly, renal denervation can also benefit
other organs and bodily structures innervated by sympathetic
nerves, including those identified in FIG. 3A. For example, a
reduction in central sympathetic drive may reduce the insulin
resistance that afflicts people with metabolic syndrome and Type II
diabetics. Additionally, patients with osteoporosis are also
sympathetically activated and might also benefit from the
downregulation of sympathetic drive that accompanies renal
denervation.
[0095] D. Achieving Intravascular Access to the Renal Artery
[0096] As FIG. 4A shows, blood moved by contractions of the heart
is conveyed from the left ventricle of the heart by the aorta. The
aorta descends through the thorax and branches into the left and
right renal arteries (as FIG. 1A also shows). Below the renal
arteries, the aorta bifurcates at the left and right iliac
arteries. The left and right iliac arteries descend, respectively,
through the left and right legs and join the left and right femoral
arteries.
[0097] As FIG. 4B shows, the blood collects in veins and retums to
the heart, through the femoral veins into the iliac veins and into
the inferior vena cava. The inferior vena cava branches into the
left and right renal veins (as FIG. 1A also shows). Above the renal
veins, the inferior vena cava ascends to convey blood into the
right atrium of the heart. From the right atrium, the blood is
pumped through the right ventricle into the lungs, where it is
oxygenated. From the lungs, the oxygenation blood is conveyed into
the left atrium. From the left atrium, the oxygenated blood is
conveyed by the left ventricle back to the aorta.
[0098] As will be described in greater detail later, the femoral
artery can be exposed and cannulated at the base of the femoral
triangle, just inferior to the midpoint of the inguinal ligament. A
catheter can be inserted through this access site, percutaneously
into the femoral artery and passed into the iliac artery and aorta,
into either the left or right renal artery. This comprises an
intravascular path that offers minimally invasive access to a
respective renal artery and/or other renal blood vessels.
[0099] The wrist, upper arm, and shoulder region provide other
locations for introduction of catheters into the arterial system.
Catheterization of either the radial, brachial, or axillary artery
may be utilized in select cases. Catheters introduced via these
access points may be passed through the subclavian artery on the
left side (or via the subclavian and brachiocephalic arteries on
the right side), through the aortic arch, down the descending aorta
and into the renal arteries using standard angiographic
technique.
II. APPARATUS, SYSTEMS AND METHODS FOR ACHIEVING INTRAVASCULAR,
THERMALLY INDUCED RENAL NEUROMODULATION
[0100] A. Overview
[0101] FIG. 5 shows a system 10 for thermally inducing
neuromodulation of a left and/or right renal plexus (RP) through
intravascular access.
[0102] As just described, the left and/or right renal plexus (RP)
surrounds the respective left and/or right renal artery. The renal
plexus (RP) extends in intimate association with the respective
renal artery into the substance of the kidney. The system thermally
induces neuromodulation of a renal plexus (RP) by intravascular
access into the respective left or right renal artery.
[0103] The system 10 includes an intravascular treatment device 12.
The treatment device 12 provides access to the renal plexus (RP)
through an intravascular path 14 that leads to a respective renal
artery, as FIG. 6A shows.
[0104] As FIG. 5 shows, the treatment device 12 includes an
elongated shaft 16 having a proximal end region 18 and a distal end
region 20.
[0105] The proximal end region 18 of the elongated shaft 16
includes a handle 22. The handle 22 is sized and configured to be
securely held and manipulated by a caregiver (not shown) outside an
intravascular path 14 (this is shown in FIG. 6A). By manipulating
the handle 22 from outside the intravascular path 14, the caregiver
can advance the elongated shaft 16 through the tortuous
intravascular path 14. Image guidance, e.g., CT, radiographic, or
another suitable guidance modality, or combinations thereof, can be
used to aid the caregiver's manipulation.
[0106] As shown in FIG. 6B, the distal end region 20 of the
elongated shaft 16 can flex in a substantial fashion to gain
entrance into a respective left/right renal artery by manipulation
of the elongated shaft 16. As shown in FIGS. 19A and 19B, the
distal end region 20 of the elongated shaft 16 can gain entrance to
the renal artery via passage within a guide catheter 94. The distal
end region 20 of the elongated shaft 16 carries at least one
thermal element 24 (e.g., thermal heating element). The thermal
heating element 24 is also specially sized and configured for
manipulation and use within a renal artery.
[0107] As FIG. 6B shows (and as will be described in greater detail
later), once entrance to a renal artery is gained, further
manipulation of the distal end region 20 and the thermal heating
element 24 within the respective renal artery establishes proximity
to and alignment between the thermal heating element 24 and tissue
along an interior wall of the respective renal artery. In some
embodiments, manipulation of the distal end region 20 will also
facilitate contact between the thermal heating element 24 and wall
of the renal artery.
[0108] As will also be described in greater detail later, different
sections of the elongated shaft 16 serve different mechanical
functions when in use. The sections are thereby desirably
differentiated in terms of their size, configuration, and
mechanical properties for (i) percutaneous introduction into a
femoral artery through a small-diameter access site; (ii)
atraumatic passage through the tortuous intravascular path 14
through an iliac artery, into the aorta, and into a respective
left/right renal artery, including (iii) significant flexure near
the junction of the left/right renal arteries and aorta to gain
entry into the respective left or right renal artery; (iv)
controlled translation, deflection, and/or rotation within the
respective renal artery to attain proximity to and a desired
alignment with an interior wall of the respective renal artery; and
(v) the placement of a thermal heating element 24 into contact with
tissue on the interior wall.
[0109] Referring back to FIG. 5, the system 10 also includes a
thermal generator 26 (e.g., a thermal energy generator). Under the
control of the caregiver or automated control algorithm 102 (as
will be described in greater detail later), the generator 26
generates a selected form and magnitude of thermal energy. A cable
28 operatively attached to the handle 22 electrically connects the
thermal heating element 24 to the generator 26. At least one supply
wire (not shown) passing along the elongated shaft 16 or through a
lumen in the elongated shaft 16 from the handle 22 to the thermal
heating element 24 conveys the treatment energy to the thermal
heating element 24. A foot pedal 100 is electrically connected to
the generator 26 to allow the operator to initiate, terminate and,
optionally, adjust various operational characteristics of the
generator, including, power delivery. For systems that provide for
the delivery of a monopolar electric field via the thermal heating
element 24, a neutral or dispersive electrode 38 can be
electrically connected to the generator 26. Additionally, a sensor
(not shown), such as a temperature (e.g., thermocouple, thermistor,
etc.) or impedance sensor, can be located proximate to or within
the thermal heating element and connected to one or more of the
supply wires. With two supply wires, one wire could convey the
energy to the thermal heating element and one wire could transmit
the signal from the sensor. Alternatively, both wires could
transmit energy to the thermal heating element.
[0110] Once proximity to, alignment with, and contact between the
thermal heating element 24 and tissue are established within the
respective renal artery (as FIG. 6B shows), the purposeful
application of energy from the generator 26 to tissue by the
thermal heating element 24 induces one or more desired thermal
heating effects on localized regions of the renal artery and
adjacent regions of the renal plexus (RP), which lay intimately
within or adjacent to the adventitia of the renal artery. The
purposeful application of the thermal heating effects can achieve
neuromodulation along all or a portion of the RP.
[0111] The thermal heating effects can include both thermal
ablation and non-ablative thermal alteration or damage (e.g., via
sustained heating and/or resistive heating). Desired thermal
heating effects may include raising the temperature of target
neural fibers above a desired threshold to achieve non-ablative
thermal alteration, or above a higher temperature to achieve
ablative thermal alteration. For example, the target temperature
can be above body temperature (e.g., approximately 37.degree. C.)
but less than about 45.degree. C. for non-ablative thermal
alteration, or the target temperature can be about 45.degree. C. or
higher for the ablative thermal alteration.
[0112] Further details of special size, configuration, and
mechanical properties of the elongated shaft 16 and the thermal
heating element 24, as well as other aspects of the system 10 will
now be described. In still other embodiments, the system 10 may
have a different configuration and/or include different features.
For example, multi-thermal heating element devices, such as
multi-electrode baskets or other balloon expandable devices may be
implemented to intravascularly deliver neuromodulatory treatment
with or without contact the vessel wall.
[0113] B. Size and Configuration of the Elongated Shaft for
Achieving Intravascular Access to a Renal Artery
[0114] As explained above, intravascular access to an interior of a
renal artery can be achieved through the femoral artery. As FIG. 6B
shows, the elongated shaft 16 is specially sized and configured to
accommodate passage through this intravascular path 14, which leads
from a percutaneous access site in the femoral artery to a targeted
treatment site within a renal artery. In this way, the caregiver is
able to orient the thermal heating element 24 within the renal
artery for its intended purpose.
[0115] For practical purposes, the maximum outer dimension (e.g.,
diameter) of any section of the elongated shaft 16, including the
thermal heating element 24 it carries, is dictated by the inner
diameter of the guide catheter through which the elongated shaft 16
is passed. Assuming, for example, that an 8 French guide catheter
(which has an inner diameter of approximately 0.091 inches) would
likely be, from a clinical perspective, the largest guide catheter
used to access the renal artery, and allowing for a reasonable
clearance tolerance between the thermal heating element 24 and the
guide catheter, the maximum outer dimension can be realistically
expressed as being less than or equal to approximately 0.085
inches. However, use of a smaller 5 French guide catheter 94 may
require the use of smaller outer diameters along the elongated
shaft 16. For example, a thermal heating element 24 that is to be
routed within a 5 French guide catheter would have an outer
dimension of no greater than 0.053 inches. In another example, a
thermal heating element 24 that is to be routed within a 6 French
guide catheter would have an outer dimension of no great than 0.070
inches.
[0116] 1. Proximal Force Transmitting Section
[0117] As FIG. 7A shows, the proximal end region 18 of the
elongated shaft 16 includes, coupled to the handle 22, a force
transmitting section 30. The force transmitting section 30 is sized
and configured to possess selected mechanical properties that
accommodate physical passage through and the transmission of forces
within the intravascular path 14, as it leads from the accessed
femoral artery (left or right), through the respective iliac branch
artery and into the aorta, and in proximity to the targeted renal
artery (left or right). The mechanical properties of the force
transmitting section 30 include at least a preferred effective
length (expressed in inches or centimeters).
[0118] As FIG. 7A shows, the force transmitting section 30 includes
a preferred effective length L1. The preferred effective length L1
is a function of the anatomic distance within the intravascular
path 14 between the access site and a location just proximate to
the junction of the aorta and renal arteries. The preferred
effective length L1 can be derived from textbooks of human anatomy,
augmented by a caregiver's knowledge of the targeted site generally
or as derived from prior analysis of the particular morphology of
the targeted site. The preferred effective length L1 is also
dependent on the length of the guide catheter that is used, if any.
In a representative embodiment, for a normal human, the preferred
effective length L1 comprises about 30 cm to about 110 cm. If no
guide catheter is used, then the preferred effective length L1
comprises about 30 cm to about 35 cm. If a 55 cm length guide
catheter is used, then the preferred effective length L1 comprises
about 65 cm to about 70 cm. If a 90 cm length guide catheter is
used, then the preferred effective length L1 comprises about 95 cm
to about 105 cm.
[0119] The force transmitting section 30 also includes a preferred
axial stiffness and a preferred torsional stiffness. The preferred
axial stiffness expresses the capability of the force transmitting
section 30 to be advanced or withdrawn along the length of the
intravascular path 14 without buckling or substantial deformation.
Since some axial deformation is necessary for the force
transmitting section 30 to navigate the tortuous intravascular path
14 without providing too much resistance, the preferred axial
stiffness of the force transmitting section should also provide
this capability. The preferred torsional stiffness expresses the
capability of the force transmitting section 30 to rotate the
elongated shaft 16 about its longitudinal axis along its length
without kinking or permanent deformation. As will be described in
greater detail later, the ability to advance and retract, as well
as rotate, the distal end region 20 of the elongated shaft 16
within the respective renal artery is desirable.
[0120] The desired magnitude of axial stiffness and rotational
stiffness for the force transmitting section 30 can be obtained by
selection of constituent material or materials to provide a desired
elastic modulus (expressed in terms, e.g., of a Young's Modulus
(E)) indicative of axial and torsional stiffnesses, as well as
selecting the construct and configuration of the force transmitted
section in terms of, e.g., its interior diameter, outer diameter,
wall thickness, and structural features, including cross-sectional
dimensions and geometry. Representative examples are described in
greater detail below.
[0121] 2. Proximal Flexure Zone
[0122] As FIGS. 7A and 7B show, the distal end region 20 of the
elongated shaft 16 is coupled to the force transmitting section 30.
The length L1 of the force transmitting section 30 generally serves
to bring the distal end region 20 into the vicinity of the junction
of the respective renal artery and aorta (as FIG. 6B shows). The
axial stiffness and torsional stiffness of the force transmitting
region transfer axial and rotation forces from the handle 22 to the
distal end region 20, as will be described in greater detail
later.
[0123] As shown in FIG. 7B, the distal end region 20 includes a
first or proximal flexure zone 32 proximate to the force
transmitting section 30. The proximal flexure zone 32 is sized and
configured to have mechanical properties that accommodate
significant flexure or bending at a prescribed preferred access
angle .alpha.1 and provide for the transmission of torque during
rotation, without fracture, collapse, substantial distortion, or
significant twisting of the elongated shaft 16. The proximal
flexure zone 32 should accommodate flexure sufficient for the
distal end region 20 to advance via a guide catheter into the renal
artery without substantially straightening out the guide
catheter.
[0124] Angle .alpha.1 is defined by the angular deviation that the
treatment device 12 must navigate to transition from the aorta
(along which the force transmitting section 30 is aligned) and the
targeted renal artery (along which the distal end region 20 is
aligned) (this is also shown in FIG. 6B). This is the angle that
the proximal flexure zone 32 must approximate to align the distal
end region 20 of the elongated shaft 16 with the targeted renal
artery, while the force transmitting section 30 of the elongated
shaft 16 remains aligned with the native axis of the aorta (as FIG.
6B shows). The more tortuous a vessel, the greater bend the
proximal flexure zone 32 will need to make for the distal end
region of the treatment device to access the renal artery and the
smaller the angle .alpha.1.
[0125] The proximal flexure zone 32 is sized and configured to
possess mechanical properties that accommodate significant, abrupt
flexure or bending at the access angle .alpha.1 near the junction
of the aorta and the renal artery. Due to its size, configuration,
and mechanical properties, the proximal flexure zone 32 must
resolve these flexure or bending forces without fracture, collapse,
distortion, or significant twisting. The resolution of these
flexure or bending forces by the proximal flexure zone 32 makes it
possible for the distal end region 20 of the elongated shaft 16 to
gain entry along the intravascular path 14 into a targeted left or
right renal artery.
[0126] The proximal flexure zone 32 is sized and configured in
length L2 to be less than length L1 (see FIG. 7A). That is because
the distance between the femoral access site and the junction of
the aorta and renal artery (typically approximating about 40 cm to
about 55 cm) is generally greater than the length of a renal artery
between the aorta and the most distal treatment site along the
length of the renal artery, which is typically about 4 cm to about
6 cm. The preferred effective length L2 can be derived from
textbooks of human anatomy, augmented with a caregiver's knowledge
of the site generally or as derived from prior analysis of the
particular morphology of the targeted site.
[0127] Desirably, the length L2 is selected to make it possible to
rest a portion of the proximal flexure zone 32 partially in the
aorta at or near the length L1, as well as rest the remaining
portion of the proximal flexure zone 32 partially within the renal
artery (as FIG. 6B shows). In this way, the proximal flexure zone
32 defines a transitional bend that is supported and stable within
the vasculature.
[0128] As will be described in greater detail later, and as shown
in FIG. 6B, the length L2 of the proximal flexure zone 32 desirably
does not extend the full length of the targeted length of the renal
artery. That is because the distal end region 20 of the elongated
shaft 16 desirably includes one or more additional flexure zones,
distal to the proximal flexure zone 32 (toward the substance of the
kidney), to accommodate other different functions important to the
therapeutic objectives of the treatment device 12. As will be
described later, the ability to transmit torque through the
proximal flexure zone 32 makes it possible to rotate the thermal
heating device to properly position the thermal heating element
within the renal artery for treatment.
[0129] In terms of axial and torsional stiffness, the mechanical
properties of proximal flexure zone 32 can and desirably do differ
from the mechanical properties of the force transmitting section
30. This is because the proximal flexure zone 32 and the force
transmitting region serve different functions while in use.
Alternatively, the mechanical properties of proximal flexure zone
32 and force transmitting section 30 can be similar.
[0130] The force transmitting section 30 serves in use to transmit
axial load and torque over a relatively long length (L1) within the
vascular pathway. In contrast, the proximal flexure zone 32 needs
to transmit axial load and torque over a lesser length L2 proximate
to or within a respective renal artery. Importantly, the proximal
flexure zone 32 must abruptly conform to an access angle .alpha.1
near the junction of the aorta and the respective renal artery,
without fracture, collapse, substantial distortion, or significant
twisting. This is a function that the force transmitting zone need
not perform. Accordingly, the proximal flexure zone 32 is sized and
configured to be less stiff and to possess greater flexibility than
the force transmitting section 30.
[0131] The desired magnitude of axial stiffness, rotational
stiffness, and flexibility for the proximal flexure zone 32 can be
obtained by selection of constituent material or materials to
provide a desired elastic modulus (expressed, e.g., in terms of a
Young's Modulus (E)) indicative of flexibility, as well as
selecting the construct and configuration of the force transmitting
section, e.g., in terms of its interior diameter, outer diameter,
wall thickness, and structural features, including cross-sectional
dimensions and geometry. Representative examples will be described
in greater detail later.
[0132] Although it is desirable that the force transmitting section
30 and the proximal flexure zone 32 have stiffness and flexibility
properties that are unique to their respective functions, it is
possible that the force transmitting section 30 and the proximal
flexure zone 32 comprise the same materials, size and geometric
configuration such that the force transmitting section 30 and the
proximal flexure zone 32 constitute the same section.
[0133] 3. Intermediate Flexure Zone
[0134] As shown in FIGS. 7A, 7B, and 7C, the distal end region 20
of the elongated shaft 16 may also include, distal to the proximal
flexure zone 32, a second or intermediate flexure zone 34. The
thermal heating element 24 may be supported by the intermediate
flexure zone 34.
[0135] The intermediate flexure zone 34 is sized, configured, and
has the mechanical properties that accommodate additional flexure
or bending, independent of the proximal flexure zone 32, at a
preferred contact angle .alpha.2, without fracture, collapse,
substantial distortion, or significant twisting. The intermediate
flexure zone 34 should also accommodate flexure sufficient for the
distal end region 20 to advance via a guide catheter into the renal
artery without straightening out the guide catheter.
[0136] The preferred contact angle .alpha.2 is defined by the angle
through which the thermal heating element 24 can be radially
deflected within the renal artery to establish contact between the
thermal heating element 24 and an inner wall of the respective
renal artery (as FIG. 6B shows). The size of the contact angle
.alpha.2 and the intermediate flexure zone length L3 are based on
the native inside diameter of the respective renal artery where the
thermal heating element 24 rests, which may vary between about 2 mm
and about 10 mm. It is most common for the diameter of the renal
artery to vary between about 3 mm and about 7 mm.
[0137] The intermediate flexure zone 34 extends from the proximal
flexure zone 32 for a length L3 into the targeted renal artery (see
FIG. 6B). Desirably, the length L3 is selected, taking into account
the length L2 of the proximal flexure zone 32 that extends into the
renal artery, as well as the anatomy of the respective renal
artery, to actively place the thermal heating element 24 (carried
at the end of the distal end region 20) at or near the targeted
treatment site (as FIG. 6B shows). The length L3 can be derived,
taking the length L2 into account, from textbooks of human anatomy,
together with a caregiver's knowledge of the site generally or as
derived from prior analysis of the particular morphology of the
targeted site. In a representative embodiment, L2 is about 9 cm and
L3 is about 5 mm to about 15 mm. In certain embodiments,
particularly for treatments in relatively long blood vessels, L3
can be as long as about 20 mm. In another representative
embodiment, and as described later in greater detail, L3 is about
12.5 mm.
[0138] As FIG. 7A shows, the intermediate flexure zone 34 is
desirably sized and configured in length L3 to be less than length
L2. This is because, in terms of length, the distance required for
actively deflecting the thermal heating element 24 into contact
with a wall of the renal artery is significantly less than the
distance required for bending the elongated shaft 16 to gain access
from the aorta into the renal artery. Thus, the length of the renal
artery is occupied in large part by the intermediate flexure zone
34 and not as much by the proximal flexure zone 32.
[0139] As FIG. 7C shows, having proximal and intermediate flexure
zones 32 and 34, the distal end region 20 of the elongated shaft 16
can, in use, be placed into a complex, multi-bend structure 36. The
complex, multi-bend structure 36 comprises one deflection region at
the access angle .alpha.1 over a length L2 (the proximal flexure
zone 32) and a second deflection region at the contact angle
.alpha.2 over a length L3 (the intermediate flexure zone 34). In
the complex, multi-bend, both L2 and L3 and angle .alpha.1 and
angle .alpha.2 can differ. This is because the angle .alpha.1 and
length L2 are specially sized and configured to gain access from an
aorta into a respective renal artery through a femoral artery
access point, and the angle .alpha.2 and length L3 are specially
sized and configured to align a thermal heating element 24 with an
interior wall inside the renal artery.
[0140] In the illustrated embodiment (see, e.g., FIG. 7C), the
intermediate flexure zone 34 is sized and configured to allow a
caregiver to remotely deflect the intermediate flexure zone 34
within the renal artery, to radially position the thermal heating
element 24 into contact with an inner wall of the renal artery.
[0141] In the illustrated embodiment, a control mechanism is
coupled to the intermediate flexure zone 34. The control mechanism
includes a control wire 40 attached to the distal end of the
intermediate flexure zone 34 (a representative embodiment is shown
in FIGS. 12B and 12C and will be described in greater detail
later). The control wire 40 is passed proximally through the
elongated shaft 16 and coupled to an actuator 42 on the handle 22.
Operation of the actuator 42 (e.g., by the caregiver pulling
proximally on or pushing forward the actuator 42) pulls the control
wire 40 back to apply a compressive and bending force to the
intermediate flexure zone 34 (as FIGS. 7C and 12C show) resulting
in bending. The compressive force in combination with the optional
directionally biased stiffness (described further below) of the
intermediate flexure zone 34 deflects the intermediate flexure zone
34 and, thereby, radially moves the thermal heating element 24
toward an interior wall of the renal artery (as FIG. 6B shows).
[0142] Desirably, as will be described in greater detail later, the
distal end region 20 of the elongated shaft 16 can be sized and
configured to vary the stiffness of the intermediate flexure zone
34 about its circumference. The variable circumferential stiffness
imparts preferential and directional bending to the intermediate
flexure zone 34 (i.e., directionally biased stiffness). In response
to operation of the actuator 42, the intermediate flexure zone 34
may be configured to bend in a single preferential direction.
Representative embodiments exemplifying this feature will be
described in greater detail later.
[0143] The compressive and bending force and resulting directional
bending from the deflection of the intermediate flexure zone 34 has
the consequence of altering the axial stiffness of the intermediate
flexure zone. The actuation of the control wire 40 serves to
increase the axial stiffness of the intermediate flexure zone.
[0144] In terms of axial and torsional stiffnesses, the mechanical
properties of intermediate flexure zone 34 can and desirably do
differ from the mechanical properties of the proximal flexure zone
32. This is because the proximal flexure zone 32 and the
intermediate flexure zone 34 serve different functions while in
use.
[0145] The proximal flexure zone 32 transmits axial load and torque
over a longer length (L2) than the intermediate flexure zone 34
(L3). Importantly, the intermediate flexure zone 34 is also sized
and configured to be deflected remotely within the renal artery by
the caregiver. In this arrangement, less resistance to deflection
is desirable. This is a function that the proximal flexure zone 32
need not perform. Accordingly, the intermediate flexure zone 34 is
desirably sized and configured to be less stiff (when the control
wire 40 is not actuated) and, importantly, to possess greater
flexibility than the proximal flexure zone 32 in at least one plane
of motion.
[0146] Still, because the intermediate flexure zone 34, being
distal to the proximal flexure zone 32, precedes the proximal
flexure zone 32 through the access angle access angle .alpha.1, the
intermediate flexure zone 34 also includes mechanical properties
that accommodate its flexure or bending at the preferred access
angle .alpha.1, without fracture, collapse, substantial distortion,
or significant twisting of the elongated shaft 16.
[0147] The desired magnitude of axial stiffness, rotational
stiffness, and flexibility for the intermediate flexure zone 34 can
be obtained by selection of constituent material or materials to
provide a desired elastic modulus (expressed, e.g., in terms of a
Young's Modulus (E)) indicative of flexibility, as well as by
selecting the construct and configuration of the intermediate
flexure zone 34, e.g., in terms of its interior diameter, outer
diameter, wall thickness, and structural features, including
cross-sectional dimensions and geometry. Representative examples
will be described in greater detail later. Axial stiffness,
torsional stiffness, and flexibility are properties that can be
measured and characterized in conventional ways.
[0148] As before described, both the proximal and intermediate
flexure zones 32 and 34 desirably include the mechanical properties
of axial stiffness sufficient to transmit to the thermal heating
element 24 an axial locating force. By pulling back on the handle
22, axial forces are transmitted by the force transmitting section
30 and the proximal and intermediate flexure zones 32 and 34 to
retract the thermal heating element 24 in a proximal direction
(away from the kidney) within the renal artery. Likewise, by
pushing forward on the handle 22, axial forces are transmitted by
the force transmitting section 30 and the proximal and intermediate
flexure zones 32 and 34 to advance the thermal heating element 24
in a distal direction (toward the kidney) within the renal artery.
Thus, proximal retraction of the distal end region 20 and thermal
heating element 24 within the renal artery can be accomplished by
the caregiver by manipulating the handle 22 or shaft from outside
the intravascular path 14.
[0149] As before described, both the proximal and intermediate
flexure zones 32 and 34 also desirably include torsional strength
properties that will allow the transmission of sufficient
rotational torque to rotate the distal end region 20 of the
treatment device 12 such that the thermal heating element 24 is
alongside the circumference of the blood vessel wall when the
intermediate flexure zone 34 is deflected. By pulling or pushing on
the actuator to deflect the thermal heating element 24 such that it
achieves vessel wall contact, and then rotating the force
transmitting section 30 and, with it, the first and intermediate
flexure zones 32 and 34, the thermal heating element 24 can be
rotated in a circumferential path within the renal artery. As
described later, this rotating feature enables the clinical
operator to maintain vessel wall contact as the thermal heating
element 24 is being relocated to another treatment site. By
maintaining wall contact in between treatments, the clinical
operator is able to achieve wall contact in subsequent treatments
with higher certainty in orientations with poor visualization.
[0150] 4. Distal Flexure Zone
[0151] As FIGS. 7A, 7B, 7C, and 7D, the distal end region 20 of the
elongated shaft 16 can also include, distal to the intermediate
flexure zone 34, a third or distal flexure zone 44. In this
arrangement, the length L3 of the intermediate flexure zone 34 may
be shortened by a length L4, which comprises the length of the
distal flexure zone 44. In this arrangement, the thermal heating
element 24 is carried at the end of the distal flexure zone 44. In
effect the distal flexure zone 44 buttresses the thermal heating
element 24 at the distal end of distal end region 20.
[0152] As FIG. 7D shows, the distal flexure zone 44 is sized,
configured, and has the mechanical properties that accommodate
additional flexure or bending, independent of the proximal flexure
zone 32 and the intermediate flexure zone 34, at a preferred
treatment angle .alpha.3. The distal flexure zone 44 should also
accommodate flexure sufficient for the distal end region 20 to
advance via a guide catheter into the renal artery without
straightening out the guide catheter or causing injury to the blood
vessel. The treatment angle .alpha.3 provides for significant
flexure about the axis of the distal end region 20 (a
representative embodiment is shown in FIG. 15C). Not under the
direct control of the physician, flexure at the distal flexure zone
occurs in response to contact between the thermal heating element
24 and wall tissue occasioned by the radial deflection of the
thermal heating element 24 at the intermediate flexure zone 34 (see
FIG. 6B). Passive deflection of the distal flexure zone provides
the clinical operator with visual feedback via fluoroscopy or other
angiographic guidance of vessel wall contact. Additionally, the
distal flexure zone desirably orients the region of tissue contact
along a side of the thermal heating element 24, thereby increasing
the area of contact. The distal flexure zone 44 also biases the
thermal heating element 24 against tissue, thereby stabilizing the
thermal heating element 24.
[0153] The function of the distal flexure zone 44 provides
additional benefits to the therapy. As actuation of the control
wire 40 increases the axial stiffness of the intermediate flexure
zone 34, the distal flexure zone effectively reduces the contact
force between the thermal heating element 24 and the vessel wall.
By relieving or reducing this contact force, the distal flexure
zone minimizes the chance of mechanical injury to the vessel wall
and avoids excessive contact between the thermal heating element
and vessel wall (see discussion of active surface area).
[0154] As FIG. 7A shows, the distal flexure zone 44 is desirably
sized and configured in length L4 to be less than length L3. This
is because, in terms of length, the distance required for orienting
and stabilizing the thermal heating element 24 in contact with a
wall of the renal artery is significantly less than the distance
required for radially deflecting the thermal heating element 24
within the renal artery. In some embodiments, length L4 can be as
long as about 1 cm. In other embodiments, the length L4 is from
about 2 mm to about 5 mm. In a preferred embodiment, the length L4
is about 5 mm. In other embodiments, the length L4 is about 2
mm.
[0155] The mechanical properties of distal flexure zone 44 and the
intermediate flexure zone 34 in terms of axial stiffness, torsional
stiffness, and flexibility can be comparable. However, the distal
flexure zone 44 can be sized and configured to be less stiff and,
importantly, to possess greater flexibility than the intermediate
flexure zone 34.
[0156] In the embodiment just described (and as shown in FIG. 7D),
the distal end region 20 may comprise a proximal flexure zone 32, a
intermediate flexure zone 34, and a distal flexure zone 44. The
proximal, intermediate and distal flexure zones function
independent from each other, so that the distal end region 20 of
the elongated shaft 16 can, in use, be placed into a more compound,
complex, multi-bend structure 36. The compound, complex, multi-bend
structure 36 comprises a proximal deflection region at the access
angle .alpha.1 over a length L2 (the proximal flexure zone 32); an
intermediate deflection region at the contact angle .alpha.2 over a
length L3 (the intermediate flexure zone 34); and a distal
deflection region at the treatment angle .alpha.3 over a length L4
(the distal flexure zone 44). In the compound, complex, multi-bend
structure 36, all lengths L2, L3, and L3 and all angles .alpha.1,
.alpha.2, and .alpha.3 can differ. This is because the angle
.alpha.1 and length L2 are specially sized and configured to gain
access from an aorta into a respective renal artery through a
femoral artery access point; the angle .alpha.2 and length L3 are
specially sized and configured to align a thermal heating element
24 element with an interior wall inside the renal artery; and the
angle .alpha.3 and length L4 are specially sized and configured to
optimize surface contact between tissue and the thermal heating
element/heat transfer element.
[0157] C. Size and Configuration of the Thermal Heating Element for
Achieving Neuromodulation in a Renal Artery
[0158] As described in co-pending patent application Ser. No.
11/599,890 filed Nov. 14, 2006, which is incorporated herein by
reference in its entirety, it is desirable to create multiple focal
lesions that are circumferentially spaced along the longitudinal
axis of the renal artery. This treatment approach avoids the
creation of a full-circle lesion, thereby mitigating and reducing
the risk of vessel stenosis, while still providing the opportunity
to circumferentially treat the renal plexus, which is distributed
about the renal artery. It is desirable for each lesion to cover at
least 10% of the vessel circumference to increase the probability
of affecting the renal plexus. However, it is important that each
lesion not be too large (e.g., >60% of vessel circumference)
lest the risk of a stenotic effect increases (or other undesirable
healing responses such as thrombus formation or collateral damage).
It is also important that each lesion be sufficiently deep to
penetrate into and beyond the adventitia to thereby affect the
renal plexus.
[0159] As described (and as FIG. 8A shows), the thermal heating
element 24 is sized and configured, in use, to contact an internal
wall of the renal artery. In the illustrated embodiment (see FIG.
8A), the thermal heating element 24 takes the form of an electrode
46 sized and configured to apply an electrical field comprising
radiofrequency (RF) energy from the generator 26 to a vessel wall.
In the illustrated embodiment, the electrode 46 is operated in a
monopolar or unipolar mode. In this arrangement, a return path for
the applied RF electric field is established, e.g., by an external
dispersive electrode (not shown), also called an indifferent
electrode or neutral electrode. The monopolar application of RF
electric field energy serves to ohmically or resistively heat
tissue in the vicinity of the electrode 46. The application of the
RF electrical field thermally injures tissue. The treatment
objective is to thermally induce neuromodulation (e.g., necrosis,
thermal alteration or ablation) in the targeted neural fibers. The
thermal injury forms a lesion in the vessel wall, which is shown,
e.g., in FIG. 9B.
[0160] The active surface area of contact (ASA) between the thermal
heating element 24 or electrode 46 and the vessel wall has great
bearing on the efficiency and control of the transfer of a thermal
energy field across the vessel wall to thermally affect targeted
neural fibers in the renal plexus (RP). The active surface area of
the thermal heating element 24 and electrode 46 is defined as the
energy transmitting area of the element 24 or electrode 46 that can
be placed in intimate contact against tissue. Too much contact
between the thermal heating element and the vessel wall may create
unduly high temperatures at or around the interface between the
tissue and the thermal heating element, thereby creating excessive
heat generation at this interface. This excessive heat can create a
lesion that is circumferentially too large. This can also lead to
undesirable thermal damage at the vessel wall. In addition to
potentially causing stenotic injury, this undesirable thermal
damage can cause tissue desiccation (i.e., dehydration) which
reduces the thermal conductivity of the tissue, thereby potentially
creating a lesion that is too shallow to reach the neural fibers.
Too little contact between the thermal heating element and the
vessel wall may result in superficial heating of the vessel wall,
thereby creating a lesion that is too small (e.g., <10% of
vessel circumference) and/or too shallow.
[0161] While the active surface area (ASA) of the thermal heating
element 24 and electrode 46 is important to creating lesions of
desirable size and depth, the ratio between the active surface area
(ASA) and total surface area (TSA) of the thermal heating element
24 and electrode 46 is also important. The ASA to TSA ratio
influences lesion formation in two ways: (1) the degree of
resistive heating via the electric field, and (2) the effects of
blood flow or other convective cooling elements such as injected
saline. As discussed above, the RF electric field causes lesion
formation via resistive heating of tissue exposed to the electric
field. The higher the ASA to TSA ratio (i.e., the greater the
contact between the electrode and tissue), the greater the
resistive heating. As discussed in greater detail below, the flow
of blood over the exposed portion of the electrode (TSA-ASA)
provides conductive and convective cooling of the electrode,
thereby carrying excess thermal energy away from the interface
between the vessel wall and electrode. If the ratio of ASA to TSA
is too high (e.g., 50%), resistive heating of the tissue can be too
aggressive and not enough excess thermal energy is being carried
away, resulting in excessive heat generation and increased
potential for stenotic injury, thrombus formation and undesirable
lesion size. If the ratio of ASA to TSA is too low (e.g., 10%),
then there is too little resistive heating of tissue, thereby
resulting in superficial heating and smaller and shallower
lesions.
[0162] Various size constraints for the thermal heating element 24
may be imposed for clinical reasons by the maximum desired
dimensions of the guide catheter as well as by the size and anatomy
of the renal artery itself. Typically, the maximum outer diameter
(or cross-sectional dimension for non-circular cross-section) of
the electrode 46 comprises the largest diameter encountered along
the length of the elongated shaft 16 distal to the handle 22. Thus,
the outer diameters of the force transmitting section 30 and
proximal, intermediate and distal flexure zones 32, 34, and 44 are
equal to or (desirably) less than the maximum outer diameter of the
electrode 46.
[0163] In a representative embodiment shown in FIG. 8A, the
electrode 46 takes the form of a right circular cylinder,
possessing a length L5 that is greater than its diameter. The
electrode 46 further desirably includes a distal region that is
rounded to form an atraumatic end surface 48. In the representative
embodiment shown in FIG. 8B, the electrode 46 is spherical in
shape. The spherical shape, too, presents an atraumatic surface to
the tissue interface.
[0164] As shown in FIGS. 8A and 8B, the angle .alpha.3 and length
L4 of the distal flexure zone 44 are specially sized and
configured, given the TSA of the respective electrode, to optimize
an active surface area of contact between tissue and the respective
electrode 46 (ASA). The angle .alpha.3 and the length L4 of the
distal flexure zone 44 make it possible to desirably lay at least a
side quadrant 50 of the electrode 46 against tissue (see FIG. 8C).
The active surface area of the electrode 46 contacting tissue (ASA)
can therefore be expressed ASA.gtoreq.0.25 TSA and ASA.gtoreq.0.50
TSA.
[0165] The above ASA-TSA relationship applies to the power delivery
algorithm described in co-pending patent application Ser. No.
12/147,154, filed Jun. 26, 2008, which is incorporated herein by
reference in its entirety. An ASA to TSA ratio of over 50% may be
effective with a reduced power delivery profile. Alternatively, a
higher ASA to TSA ratio can be compensated for by increasing the
convective cooling of the electrode that is exposed to blood flow.
As discussed further below, this could be achieved by injecting
cooling fluids such as chilled saline over the electrode and into
the blood stream.
[0166] The stiffnesses of each of the intermediate and distal
flexure zones 34 and 44 are also selected to apply via the
electrode a stabilizing force that positions the electrode 46 in
substantially secure contact with the vessel wall tissue. This
stabilizing force also influences the amount of wall contact
achieved by the thermal heating element (i.e., the ASA to TSA
ratio). With greater stabilizing force, the thermal heating element
has more wall contact and with less stabilizing force, less wall
contact is achieved. Additional advantages of the stabilizing force
include, (1) softening the contact force between the distal end 20
and vessel wall to minimize risk of mechanical injury to vessel
wall, (2) consistent positioning of the electrode 46 flat against
the vessel wall, and (3) stabilizing the electrode 46 against the
vessel wall. The stabilizing force also allows the electrode to
return to a neutral position after the electrode is removed from
contact with the wall.
[0167] As previously discussed, for clinical reasons, the maximum
outer diameter (or cross-sectional dimension) of the electrode 46
is constrained by the maximum inner diameter of the guide catheter
through which the elongated shaft 16 is to be passed through the
intravascular path 14. Assuming that an 8 French guide catheter 94
(which has an inner diameter of approximately 0.091 inches) is,
from a clinical perspective, the largest desired catheter to be
used to access the renal artery, and allowing for a reasonable
clearance tolerances between the electrode 46 and the guide
catheter, the maximum diameter of the electrode 46 is constrained
to about 0.085 inches. In the event a 6 French guide catheter is
used instead of an 8 French guide catheter, then the maximum
diameter of the electrode 46 is constrained to about 0.070 inches.
In the event a 5 French guide catheter is used, then maximum
diameter of the electrode 46 is constrained to about 0.053 inches.
Based upon these constraints and the aforementioned power delivery
considerations, the electrode 46 desirably has an outer diameter of
from about 0.049 to about 0.051 inches.
[0168] While it may be possible to provide a catheter apparatus or
device having multiple electrodes at or proximate to the distal end
of the apparatus, it is desirable for the catheter apparatus
described herein to have only a single electrode at or proximate to
the distal end. There are several reasons why a single electrode
apparatus may have clinical and/or functional benefits over a
multiple electrode apparatus. For example, as indicated below, an
electrode with a relatively large surface area may create larger,
more effective lesions via increased energy delivery and higher
power since blood flow carries away excess heat and effectively
cools the electrode. As discussed above, the maximum
diameter/crossing profile of the electrode is constrained by the
inner diameter of the guide catheter through which the electrode is
delivered. It would be difficult for a multiple electrode apparatus
to have electrodes that are as large as a single electrode at the
distal end of the apparatus since the crossing profile of the
multiple electrodes would have to take into account the diameter of
the apparatus shaft. Attempts to design an apparatus having
multiple electrodes that individually approach the surface area of
a single electrode at the distal end are expected to increase
complexity and cost. Additionally, multiple electrode arrangements
can also increase stiffness of the apparatus, which may not only
compromise the deliverability of the apparatus, but also increase
risk of injury to the blood vessels. For example, a catheter
apparatus that is too stiff would not be able to make the
significant bend that is necessary to access a renal artery from
the abdominal aorta.
[0169] Not only may delivery to and through a tortuous blood
vessel, such as a renal artery, be difficult with a multiple
electrode apparatus, but placement and use within a tortuous blood
vessel may also be challenging. Since vascular anatomy may vary
significantly because of tortuosity and the unpredictable location
of vessel branches and vessel disease (e.g., atherosclerosis)
successful delivery and placement of an apparatus can be very
complicated with multiple electrodes. Additionally, it would be
very difficult to ensure proper wall contact for all electrodes due
to the variable anatomy of the vessel where treatment is to be
administered. Although sensors and software could be developed and
implemented to address some of these issues, it would increase the
cost of the system and increase complexity for the user. Hence, a
single electrode apparatus such as that described herein may be
more effective than a multiple electrode apparatus, particularly in
tortuous blood vessels where there is a high degree of anatomic
variability.
[0170] D. Applying Energy to Tissue Via the Thermal Heating
Element
[0171] Referring back to FIG. 5, in the illustrated embodiment, the
generator 26 may supply to the electrode 46 a pulsed or continuous
RF electric field. Although a continuous delivery of RF energy is
desirable, the application of thermal energy in pulses may allow
the application of relatively higher energy levels (e.g., higher
power), longer or shorter total duration times, and/or better
controlled intravascular renal neuromodulation therapy. Pulsed
energy may also allow for the use of a smaller electrode.
[0172] The thermal therapy may be monitored and controlled, for
example, via data collected with thermocouples, impedance sensors,
pressure sensors, optical sensors or other sensors 52 (see FIG.
9A), which may be incorporated into or on electrode 46 or in/on
adjacent areas on the distal end region 20. Additionally or
alternatively, various microsensors can be used to acquire data
corresponding to the thermal heating element, the vessel wall
and/or the blood flowing across the thermal heating element. For
example, arrays of micro thermocouples and/or impedance sensors can
be implemented to acquire data along the thermal heating element or
other parts of the treatment device. Sensor data can be acquired or
monitored prior to, simultaneous with, or after the delivery of
energy or in between pulses of energy, when applicable. The
monitored data may be used in a feedback loop to better control
therapy, e.g., to determine whether to continue or stop treatment,
and it may facilitate controlled delivery of an increased or
reduced power or a longer or shorter duration therapy.
[0173] Non-target tissue may be protected by blood flow (F) within
the respective renal artery as a conductive and/or convective heat
sink that carries away excess thermal energy. For example (as FIGS.
9A and 9B show), since blood flow (F) is not blocked by the
elongated shaft 16 and the electrode 46 it carries, the native
circulation of blood in the respective renal artery serves to
remove excess thermal energy from the non-target tissue and the
thermal heating element. The removal of excess thermal energy by
blood flow also allows for treatments of higher power, where more
energy can be delivered to the target tissue as thermal energy is
carried away from the electrode and non-target tissue. In this way,
intravascularly-delivered thermal energy heats target neural fibers
located proximate to the vessel wall to modulate the target neural
fibers, while blood flow (F) within the respective renal artery
protects non-target tissue of the vessel wall from excessive or
undesirable thermal injury. When energy is delivered in pulses, the
time interval between delivery of thermal energy pulses may
facilitate additional convective or other cooling of the non-target
tissue of the vessel wall compared to applying an equivalent
magnitude or duration of continuous thermal energy.
[0174] In addition, or as an alternative, to utilizing blood flow
(F) as a heat sink, a thermal fluid may be injected, infused, or
otherwise delivered into the vessel to remove excess thermal energy
and protect the non-target tissues. The thermal fluid may, for
example, comprise a saline or other biocompatible fluid. The
thermal fluid may, for example, be injected through the treatment
device 12 via an infusion lumen and/or port (not shown) or through
a guide catheter at a location upstream from an energy delivery
element, or at other locations relative to the tissue for which
protection is sought. The use of a thermal fluid may allow for the
delivery of increased/higher power, smaller electrode size and/or
reduced treatment time.
[0175] Although many of the embodiments described herein pertain to
electrical systems configured for the delivery of RF energy, it is
contemplated that the desired treatment can be can be accomplished
by other means, e.g., by coherent or incoherent light; heated or
cooled fluid; microwave; ultrasound (including high intensity
focused ultrasound); diode laser; a tissue heating fluid; or
cryogenic fluid.
III. REPRESENTATIVE EMBODIMENTS
A. First Representative Embodiment
Proximal, Intermediate, and Distal Flexure Zones with Distally
Carried Thermal Heating Element 24
[0176] FIGS. 10A to 15H show a representative embodiment of an
elongated shaft 16 that includes a proximal force transmitting
section 30, as well as proximal, intermediate and distal flexure
zones 32, 34, and 44, having the physical and mechanical features
described above. In this embodiment, the thermal heating element 24
is carried distally of the distal flexure zone 44 (see, e.g., FIG.
11A).
[0177] 1. Force Transmitting Section
[0178] In the illustrated embodiment, as shown in FIGS. 10A and
10B, the proximal force transmitting section 30 comprises a first
elongated and desirably tubular structure, which can take the form
of, e.g., a first tubular structure 54. The first tubular structure
54 is desirably a hypo tube that is made of a metal material, e.g.
of stainless steel, or a shape memory alloy, e.g., nickel titanium
(a.k.a., nitinol or NiTi), to possess the requisite axial stiffness
and torsional stiffness, as already described, for the force
transmitting section 30. As already described, the force
transmitting section 30 comprises the most stiff section along the
elongated shaft 16, to facilitate axially movement of the elongated
shaft 16, as well as rotational manipulation of the elongated shaft
16 within the intravascular path 14. Alternatively, the first
tubular structure 54 may comprise a hollow coil, hollow cable,
solid cable (wI embedded wires), braided shaft, etc.
[0179] The stiffness is a function of material selection as well as
structural features such as interior diameter, outside diameter,
wall thickness, geometry and other features that are made by
micro-engineering, machining, cutting and/or skiving the hypo tube
material to provide the desired axial and torsional stiffness
characteristics. For example, the elongated shaft can be a hypo
tube that is laser cut to various shapes and cross-sectional
geometries to achieve the desired functional properties.
[0180] When the first tubular structure 54 is made from an
electrically conductive metal material, the first tubular structure
54 includes a sheath 56 or covering made from an electrically
insulating polymer material or materials, which is placed over the
outer diameter of the underlying tubular structure. The polymer
material can also be selected to possess a desired durometer
(expressing a degree of stiffness or lack thereof) to contribute to
the desired overall stiffness of the first tubular structure 54.
Candidate materials for the polymer material include polyethylene
terephthalate (PET); Pebax.RTM. material; nylon; polyurethane,
Grilamid.RTM. material or combinations thereof. The polymer
material can be laminated, dip-coated, spray-coated, or otherwise
deposited/attached to the outer diameter of the tube.
[0181] 2. Proximal Flexure Zone
[0182] As FIGS. 11A, 11B, and 11C show, the proximal flexure zone
32 comprises a second elongated and desirably tubular structure,
which can take the form of, e.g., a second tubular structure 58.
The second tubular structure 58 can be made from the same or
different material as the first tubular structure 54. The axial
stiffness and torsional stiffness of the second tubular structure
58 possesses the requisite axial stiffness and torsional stiffness,
as already described, for the proximal flexure zone 32. As already
described, the proximal flexure zone 32 may be less stiff and more
flexible than the force transmitting section 30, to navigate the
severe bend at and prior to the junction of the aorta and
respective renal artery. The second tubular structure is desirably
a hypo tube, but can alternatively comprise a hollow coil, hollow
cable, braided shaft, etc.
[0183] It may be desirable for the first and second tubular
structures 54 and 58 to share the same material. In this event, the
form and physical features of the second tubular structure 58 may
be altered, compared to the first tubular structure 54, to achieve
the desired stiffness and flexibility differences. For example, the
interior diameter, outside diameter, wall thickness, and other
engineered features of the second tubular structure 58 can be
tailored to provide the desired axial and torsional stiffness and
flexibility characteristics. For example, the second tubular
structure 58 can be laser cut along its length to provide a
bendable, spring-like structure. Depending on the ease of
manufacturability the first and second tubular structures may be
produced from the same piece of material or from two separate
pieces. In the event the first tubular structure and second tubular
structure are not of the same material, the outside diameter of the
second tubular structure 58 can be less than the outer diameter of
first tubular structure 54 (or have a smaller wall thickness) to
create the desired differentiation in stiffness between the first
and second tubular structures 54 and 58.
[0184] When the second tubular structure 58 is made from an
electrically conductive metal material, the second tubular
structure 58, like the first tubular structure 54, includes a
sheath 60 (see FIGS. 11B and 11C) or covering made from an
electrically insulating polymer material or materials, as already
described. The sheath 60 or covering can also be selected to
possess a desired durometer to contribute to the desired
differentiation in stiffness and flexibility between the first and
second tubular structures 58.
[0185] The second tubular structure 58 can comprise a different
material than the first tubular structure 54 to impart the desired
differentiation in stiffness and flexibility between the first and
second tubular structures 58. For example, the second tubular
structure 58 can comprise a cobalt-chromium-nickel alloy, instead
of stainless steel. Alternatively, the second tubular structure 58
can comprise a less rigid polymer, braid-reinforced shaft, nitinol
or hollow cable-like structure. In addition to material selection,
the desired differentiation in stiffness and overall flexibility
can be achieved by selection of the interior diameter, outside
diameter, wall thickness, and other engineered features of the
second tubular structure 58, as already described. Further, a
sheath 60 or covering made from an electrically insulating polymer
material, as above described, can also be placed over the outer
diameter of the second tubular structure 58 to impart the desired
differentiation between the first and second tubular structures 54
and 58.
[0186] 3. Intermediate Flexure Zone
[0187] As FIGS. 12A, 12B, 12C, and 12D show, the intermediate
flexure zone 34 comprises a third elongated and desirably tubular
structure, which can take the form of, e.g., a third tubular
structure 62. The third tubular structure 62 can be made from the
same or different material as the first and/or second tubular
structures 54 and 58. The axial stiffness and torsional stiffness
of the third tubular structure 62 possesses the requisite axial
stiffness and torsional stiffness, as already described, for the
intermediate flexure zone 34. As already described, the
intermediate flexure zone 34 may be less stiff and more flexible
than the proximal flexure zone 32, to facilitate controlled
deflection of the intermediate flexure zone 34 within the
respective renal artery.
[0188] If the second and third tubular structures 58 and 62 share
the same material, the form and physical features of the third
tubular structure 62 are altered, compared to the second tubular
structure 58, to achieve the desired stiffness and flexibility
differences. For example, the interior diameter, outside diameter,
wall thickness, and other engineered features of the third tubular
structure 62 can be tailored to provide the desired axial and
torsional stiffness and flexibility characteristics. For example,
the third tubular structure 62 can be laser cut along its length to
provide a more bendable, more spring-like structure than the second
tubular structure 58.
[0189] When the third tubular structure 62 is made from an
electrically conductive metal material, the third tubular structure
62 also includes a sheath 64 (see FIGS. 12B, 12C, and 12D) or
covering made from an electrically insulating polymer material or
materials, as already descried. The sheath 64 or covering can also
be selected to possess a desired durometer to contribute to the
desired differentiation in stiffness and flexibility between the
second and third tubular structure 62s.
[0190] The third tubular structure 62 can comprise a different
material than the second tubular structure to impart the desired
differentiation in stiffness and flexibility between the second and
third tubular structures 62. For example, the third tubular
structure 62 can include a Nitinol material, to impart the desired
differentiation in stiffness between the second and third tubular
structures 58 and 62. In addition to material selection, the
desired differentiation in stiffness and overall flexibility can be
achieved by selection of the interior diameter, outside diameter,
wall thickness, and other engineered features of the third tubular
structure 62, as already described.
[0191] For example, in diameter, the outside diameter of the third
tubular structure 62 is desirably less than the outer diameter of
second tubular structure 58. Reduction of outside diameter or wall
thickness influences the desired differentiation in stiffness
between the second and third tubular structures 58 and 62.
[0192] As discussed in greater detail above, preferential
deflection of the intermediate flexure zone is desirable. This can
be achieved by making the third tubular structure 62 less stiff in
the desired direction of deflection and/or more stiff opposite the
direction of deflection. For example, as shown in FIGS. 12B and
12C, the third tubular structure 62 (unlike the second tubular
structure 58) can include a laser-cut pattern that includes a spine
66 with connecting ribs 68. The pattern biases the deflection of
the third tubular structure 62, in response to pulling on the
control wire 40 coupled to the distal end of the third tubular
structure 62, toward a desired direction. The control wire 40 is
attached to a distal end of the intermediate flexure zone with
solder 130. The benefits of preferential deflection within a renal
artery have already been described.
[0193] As also shown in FIG. 12D, a flat ribbon material 70 (e.g.,
Nitinol, stainless steel, or spring stainless steel) can be
attached to the third tubular structure 62. When the pulling force
is removed from the control wire 40, the flat ribbon, which serves
to reinforce the deflectable third tubular structure 62, will
straighten out the deflectable third tubular structure 62.
[0194] Further, a sheath 72 (see FIGS. 12B, 12C, and 12D) or
covering made from an electrically insulating polymer material, as
above described, and having a desired durometer can also be placed
over the outer diameter of the second tubular structure 58 to
impart the desired differentiation between the first and second
tubular structures 54 and 58.
[0195] Preferential deflection from reduced stiffness in the
direction of deflection, as described above, can be achieved in a
number of additional ways. For example, as FIGS. 13B and 13C show,
the third tubular structure 62 can comprise a tubular polymer or
metal/polymer composite having segments with different stiffnesses
D1 and D2, in which D1>D2 (that is, the segment with D1 is
mechanically stiffer than the segment with D2. The third tubular
structure 62 can also take the form of an oval, or rectangular, or
flattened metal coil or polymer having segments with different
stiffnesses D1 and D2, in which D1>D2 (as shown in FIG. 13C). In
either arrangement, the segment having the lower stiffness D2 is
oriented on the third tubular structure 62 on the same side as the
actuator wire is attached.
[0196] Alternatively, as FIGS. 14B and 14C show, the third tubular
structure 62 can comprise an eccentric polymer or metal/polymer
composite, which can be braided or coiled. The third tubular
structure 62 can also take the form of an eccentric oval, or
rectangular, or flattened metal coil or polymer (as FIG. 14C
shows). In either arrangement, the thinner wall segment 76 (less
stiff) is oriented on the third tubular structure 62 on the same
side as the actuator wire attached.
[0197] 4. Distal Flexure Zone
[0198] As shown in FIGS. 15A to 15H, the distal flexure zone 44
comprises a spring-like flexible tubular structure 74. The flexible
structure 74 can comprise a metal, a polymer, or a metal/polymer
composite. The material and physical features of the flexible
structure 74 are selected so that the axial stiffness and torsional
stiffness of the flexible structure 74 is not greater than the
axial stiffness and torsional stiffness of the third tubular
structure 62. The overall flexibility of the flexible structure 74
is at least equal to and desirably greater than the flexibility of
third tubular structure 62 when the third tubular structure has not
been deflected by the control wire 40.
[0199] As shown in FIG. 15B, the thermal heating element 24 is
carried at the distal end of the flexible structure 74 for
placement in contact with tissue along a vessel wall of a
respective renal artery.
[0200] The material selected for the flexible structure 74 can be
radiopaque or non-radiopaque. Desirably, the flexible member
includes a radiopaque material, e.g., stainless steel, platinum,
platinum iridium, or gold, to enable visualization and image
guidance. Alternatively, a non-radiopaque material can be used that
is doped with a radiopaque substance, such as barium sulfate.
[0201] The configuration of the flexible structure 74 can vary. For
example, in the embodiment depicted in FIGS. 15B and 15C, the
flexible structure 74 comprises a thread 104 encased in or covered
with a polymer coating or wrapping 110. The thread 104 is routed
through a proximal anchor 108, which is attached to the distal end
of the intermediate flexure zone 34, and a distal anchor 106, which
is fixed within or integrated into the heating element 24/electrode
46 using solder. Although various types of materials can be used to
construct the aforementioned structures, in order to have a
flexible structure 74 that securely connects to the intermediate
flexure zone 34 and the thermal heating element 24, it is desirable
for thread 104 to be comprised of Kevlar or similar polymer thread
and for the proximal anchor 108 and distal anchor 106 to be
comprised of stainless steel. While the coating 110 can be
comprised of any electrically insulative material, and particularly
those listed later with respect to sheath 80, is desirable for the
structures of the flexible structure 74 to be
encased/coated/covered by a low-durometer polymer such as
carbothane laminate 110. As shown in FIG. 15C, one or more supply
wires 112 may run alongside or within the flexible structure 74. As
previously mentioned these wires may provide the thermal heating
element 24 with electrical current/energy from the generator 26 and
also convey data signals acquired by sensor 52. Also as previously
mentioned and depicted in FIG. 15C, the control wire 40 from the
handle actuator 42 can be formed into the proximal anchor 108 and
attached to the elongated shaft using solder 130.
[0202] One advantage of the above-described configuration of the
flexible structure 74 is that the flexible structure 74 creates a
region of electrical isolation between the thermal heating element
and the rest of the elongated shaft. Both the Kevlar thread 104 and
laminate 110 are electrically insulative, thereby providing the
supply wire(s) 112 as the sole means for electrical
connectivity.
[0203] As shown in FIGS. 15D through 15F, the flexible structure 74
allows considerable passive deflection of the distal flexure zone
44 when the thermal heating element 24 is put into contact with the
vessel wall. As already described, this flexibility has several
potential benefits. The size and configuration of the flexible
structure 74 enables the thermal heating element to deflect in many
directions because the distal flexure zone may bend by angle
.theta. in any plane through the axis of the distal end region. For
treatments within a peripheral blood vessel such as the renal
artery, it is desirable that angle .theta..ltoreq.90 degrees.
[0204] In alternative embodiments for the distal flexure zone 44,
the flexible structure 74 can take the form of a tubular metal
coil, cable, braid or polymer, as FIG. 15H shows. Alternatively,
the flexible structure 74 can take the form of an oval, or
rectangular, or flattened metal coil or polymer, as FIG. 15G shows.
In alternate embodiments, the flexible structure 74 may comprise
other mechanical structures or systems that allow the thermal
heating element 24 to pivot in at least one plane of movement. For
example, the flexible structure 74 may comprise a hinge or
ball/socket combination.
[0205] The flexible structure 74 as a part of the distal flexure
zone can be coupled to the intermediate flexure zone as describe
above. Alternatively, in embodiments that do not provide an
intermediate flexure zone, the distal flexure zone can be coupled
to the proximal flexure zone. Still alternatively, the distal
flexure zone can be coupled to an intermediate section comprising
an arch wire as described in co-pending patent application Ser. No.
12/159,306, filed Jun. 26, 2008, which is incorporated herein in
its entirety. For example, FIGS. 15I and 15J provide a catheter
comprising a shaft 16 and a distal end region 20, wherein the
distal end region 20 comprises an intermediate section 34, a distal
flexure zone 44 and a thermal heating element 24. More
specifically, the catheter may comprise an intermediate section
comprising an arch wire 114, a distal flexure zone comprising a
flexible structure, and a thermal heating element comprising an
electrode 46, wherein the flexible structure is coupled to the arch
wire and electrode.
[0206] If the flexible member comprises, in whole or in part, an
electrically conductive material, the distal flexure zone 44
desirably includes an outer sheath 80 (see FIGS. 15G and 15H) or
covering over the flexible structure 74 made from an electrically
insulating polymer material. The polymer material also possesses a
desired durometer for flexibility of the flexible member (e.g., 25D
to 55D).
[0207] Candidate materials for the polymer material include
polyethylene terephthalate (PET); Pebax; polyurethane; urethane,
carbothane, tecothane, low density polyethylene (LDPE); silicone;
or combinations thereof. The polymer material can be laminated,
dip-coated, spray-coated, or otherwise deposited/applied over the
flexible structure 74. Alternatively, a thin film of the polymer
material (e.g., PTFE) can be wrapped about the flexible structure
74. Alternatively, the flexible structure 74 can be inherently
insulated, and not require a separate sheath 56 or covering. For
example, the flexible member can comprise a polymer-coated coiled
wire.
[0208] 5. Rotation Controller
[0209] As will be discussed later in greater detail, it is
desirable to rotate the device within the renal artery after the
thermal heating element is in contact the vessel wall. However, it
may be cumbersome and awkward for a clinical practitioner to rotate
the entire handle at the proximal end of the device, particularly
given the dimensions of the renal anatomy. In one representative
embodiment, as shown in FIGS. 16A and 16B, the proximal end of the
shaft 16 is coupled to the handle 22 by a rotating fitting 82.
[0210] The rotating fitting 82 is mounted by a tab 84 (see FIG.
16B) carried in a circumferential channel 86 formed on the distal
end of the handle 22. The rotating fitting 82 can thus be rotated
at the distal end of the handle 22 independent of rotation of the
handle 22.
[0211] The proximal end of the force transmitting section 30 is
attached to a stationary coupling 88 on the rotating fitting 82.
Rotation of the rotating fitting 82 (as FIG. 16A shows) thereby
rotates the force transmitting section 30, and, with it, the entire
elongated shaft 16, without rotation of the handle 22. As FIG. 16A
shows, a caregiver is thereby able to hold the proximal portion of
the handle 22 rotationally stationary in one hand and, with the
same or different hand, apply a torsional force to the rotating
fitting 82 to rotate the elongated shaft 16. This allows the
actuator to remain easily accessed for controlled deflection.
[0212] Since there are cables and wires running from the handle
through the shaft of the device (e.g., actuation wire/cable,
electrical transmission wire(s), thermocouple wire(s), etc.), it is
desirable to limit rotation of the shaft relative to these wires in
order to avoid unnecessary entanglement and twisting of these
wires. The handle embodiment depicted in FIG. 16C provides a
rotational limiting element to address this need. In this
embodiment, the rotating fitting 82 includes an axial groove 116
and the distal portion of the handle 22 comprises a fitting
interface 118 having a helical channel 120. A ball 122 comprising
stainless steel or another metal or a polymer is placed within the
fitting interface 118 so that it, upon rotation of the fitting, may
simultaneously travel within the helical channel 120 of the fitting
interface 118 and along the axial groove 116 of the fitting. When
the ball 122 reaches the end of the channel and/or groove, the ball
will no longer move and, consequently, the fitting will not be able
to rotate any further in that direction. The rotational fitting 82
and handle fitting interface 118 can be configured to allow for the
optimal number of revolutions for the shaft, given structural or
dimensional constraints (e.g., wires). For example, the components
of the handle could be configured to allow for two revolutions of
the shaft independent of the handle.
[0213] As has been described and will be described in greater
detail later, by intravascular access, the caregiver can manipulate
the handle 22 to locate the distal end region 20 of the elongated
shaft 16 within the respective renal artery. The caregiver can then
operate the actuator 42 on the handle 22 (see FIG. 16A) to deflect
the thermal heating element 24 about the intermediate flexure zone
34. The caregiver can then operate the rotating fitting 82 on the
handle 22 (see FIGS. 16A and 16D) to apply a rotational force along
the elongated shaft 16. The rotation of the elongated shaft 16 when
the intermediate flexure zone 34 is deflected within the respective
renal artery rotates the thermal heating element 24 within the
respective renal artery, making it easier to achieve contact with
the vessel wall and determine whether there is wall contact,
particularly in planes where there is poor angiographic
visualization.
[0214] In an additional aspect of the disclosed technology, the
handle 22 may be configured to minimize operator/caregiver handling
of the device while it is within the patient. As shown in FIG. 16D,
the handle also comprises a lower surface 132 that substantially
conforms to the surface beneath (e.g., operating table). This lower
surface 132, which is shown to be substantially flat in FIG. 16D,
can alternatively be curved, shaped or angled depending on the
configuration and/or geometry of the beneath surface. The
conforming lower surface 132 enables the clinical operator to keep
the handle 22 stable when the treatment device 12 is within the
patient. In order to rotate the device when it is inside the
patient, the operator can simply dial the rotating fitting 82
without any need to lift the handle. When the operator desires to
retract the device for subsequent treatments, the operator can
simply slide the handle along the beneath surface to the next
position. Again, this mitigates the risk of injury due to operator
error or over handling of the treatment device. Additionally or
alternatively, the lower surface can engage the surface undemeath
using clips, texture, adhesive, etc.
[0215] Additional enhancements to the rotation mechanism disclosed
herein include providing tactile and/or visual feedback on the
rotational fitting so that the operator can exercise greater
control and care in rotating the device. The rotating fitting 82
can also be selectively locked to the interface, thereby preventing
further rotation, if the operator wishes to hold the treatment
device in a particular angular position. Another potential
enhancement includes providing distance markers along the
shaft/handle to enable the operator to gage distance when
retracting the treatment device.
B. Second Representative Embodiment
Distal Flexure Zone Comprises a Flexible Active Electrode
[0216] FIGS. 17A and 17B show a representative embodiment of an
elongated shaft 16 that includes a proximal force transmitting
section 30, proximal flexure zone 32, intermediate flexure zone 34,
and a distal flexure zone 44. In this embodiment, the materials,
size, and configuration of the proximal force transmitting section
30, proximal flexure zone 32, and intermediate flexure zone 34 are
comparable to the respective counterparts described in the first
representative embodiment.
[0217] In this embodiment, however, the distal flexure zone 44 is
sized and configured to itself serve as an active, flexible
electrode 90. In diameter, the active, flexible electrode 90 is
sized and configured to be equal to or greater than the
intermediate flexure zone 34. The total surface area TSA of the
active, flexible electrode 90 is thereby increased, so that the
possible active surface area of the electrode 46 is increased as
well.
[0218] Also, in this arrangement, the entire length of the active
flexible electrode 90 shares the flexibility properties of the
distal flexure zone 44, as previously described. Materials are
selected that, in addition to imparting the desired flexibility,
are electrically conductive as well. The active electrode 90 is
thereby flexible enough along its entire length to conform closely
against the vessel wall, thereby further increasing the possible
active surface area of the electrode. The active flexible electrode
90 may also more readily deflect away from the vessel wall when
engaging the vessel wall head-on, to thereby minimize the forces
exerted against the vessel wall as the electrode 90 is placed into
side-on relationship with the vessel wall. The active, flexible
electrode 90 can thereby be considered more atraumatic.
[0219] In the illustrated embodiment, the active, flexible
electrode 90 further desirably includes a distal region that is
tapered to form a blunt, atraumatic end surface 48. The end surface
48 can be formed from metal materials by laser, resistive welding,
or machining techniques. The end surface 48 can also be formed from
polymer materials by bonding, lamination, or insert molding
techniques.
C. Third Representative Embodiment
Distal Flexure Zone Includes Substantially Spherical Active
Electrode
[0220] FIGS. 18A and 18B show a representative embodiment of an
elongated shaft 16 that includes a proximal force transmitting
section 30, proximal flexure zone 32, and a intermediate flexure
zone 34, and a distal flexure zone 44. In this embodiment, the
materials, size, and configuration of the proximal force
transmitting section 30, proximal flexure zone 32, and intermediate
flexure zone 34 are comparable to the respective counterparts in
the first and second embodiments.
[0221] In this embodiment, however, the distal flexure zone 44 is
sized and configured to carry a substantially spherical or
cylindrical active electrode 92 at a location more proximally
spaced from its distal end. In this embodiment, the distal flexure
zone 44 shares the flexibility characteristics of the distal
flexure zone 44, as previously described. In diameter, however, the
distal flexure zone 44 is sized and configured to be approximately
equal to the intermediate flexure zone 34. In diameter, the
spherical active electrode 92 is sized to be larger than the
diameter of the distal flexure zone 44. Therefore, flexure of the
distal flexure zone 44 can place the spherical electrode 92 into
contact with a greater tissue area, thereby increasing the active
surface area (ASA) of the electrode.
[0222] In the illustrated embodiment, the distal flexure zone 44
desirably includes a distal region that is tapered to form a blunt,
atraumatic end surface 48. The end surface 48 can be formed from
metal materials by laser, resistive welding, or machining
techniques. The end surface 48 can also be formed from polymer
materials by bonding, lamination, or insert molding techniques.
[0223] The spherical electrode 92 can be attached to the distal
flexure zone 44 e.g., by spot welding, laser welding, or soldering
techniques. The placement of the spherical electrode 92 along the
length of the distal flexure zone 44 can vary. It can be placed,
e.g., in the approximate mid-region of the distal flexure zone 44,
or closer to the distal end than the proximal end, or vice
versa.
IV. USE OF THE SYSTEM
[0224] A. Intravascular Delivery, Deflection and Placement of the
Treatment Device
[0225] Any one of the embodiments of the treatment devices 12
described herein can be delivered over a guide wire using
conventional over-the-wire techniques. When delivered in this
manner (not shown), the elongated shaft 16 includes a passage or
lumen accommodating passage of a guide wire.
[0226] Alternatively, any one of the treatment devices 12 described
herein can be deployed using a conventional guide catheter or
pre-curved renal guide catheter 94.
[0227] When using a guide catheter 94 (see FIG. 6A), the femoral
artery is exposed and cannulated at the base of the femoral
triangle, using conventional techniques. In one exemplary approach,
a guide wire (not shown) is inserted through the access site and
passed using image guidance through the femoral artery, into the
iliac artery and aorta, and into either the left or right renal
artery. A guide catheter can be passed over the guide wire into the
accessed renal artery. The guide wire is then removed.
Alternatively, a renal guide catheter (shown in FIG. 19A), which is
specifically shaped and configured to access a renal artery, can be
used to avoid using a guide wire. Still alternatively, the
treatment device can be routed from the femoral artery to the renal
artery using angiographic guidance and without the need of a guide
catheter.
[0228] When a guide catheter is used, at least three delivery
approaches can be implemented. In one exemplary approach, one or
more of the aforementioned delivery techniques can be used to
position a guide catheter within the renal artery just distal to
the entrance of the renal artery. The treatment device is then
routed via the guide catheter into the renal artery. Once the
treatment device is properly positioned within the renal artery,
the guide catheter is retracted from the renal artery into the
abdominal aorta. In this approach, the guide catheter should be
sized and configured to accommodate passage of the treatment
device. For example, a 6 French guide catheter can be used.
[0229] In a second exemplary approach, a first guide catheter is
placed at the entrance of the renal artery (with or without a guide
wire). A second guide catheter is passed via the first guide
catheter (with or without the assistance of a guide wire) into the
renal artery. The treatment device is then routed via the second
guide catheter into the renal artery. Once the treatment device is
properly positioned within the renal artery the second guide
catheter is retracted, leaving the first guide catheter at the
entrance to the renal artery. In this approach the first and second
guide catheters should be sized and configured to accommodate
passage of the second guide catheter within the first guide
catheter (i.e., the inner diameter of the first guide catheter
should be greater than the outer diameter of the second guide
catheter). For example, the first guide catheter could be 8 French
in size and the second guide catheter could be 5 French in
size.
[0230] In a third exemplary approach, and as shown in FIG. 19A, a
renal guide catheter 94 is positioned within the abdominal aorta,
just proximal to the entrance of the renal artery. As now shown in
FIG. 19B, the treatment device 12 as described herein is passed
through the guide catheter 94 and into the accessed renal artery.
The elongated shaft makes atraumatic passage through the guide
catheter 94, in response to forces applied to the force
transmitting section 30 through the handle 22. The proximal flexure
zone 32 accommodates significant flexure at the junction of the
left/right renal arteries and aorta to gain entry into the
respective left or right renal artery through the guide catheter 94
(as FIG. 19B shows).
[0231] As FIG. 19C shows, the intermediate flexure zone 34 on the
distal end portion of the elongated shaft 16 can now be axially
translated into the respective renal artery, remotely deflected
and/or rotated in a controlled fashion within the respective renal
artery to attain proximity to and a desired alignment with an
interior wall of the respective renal artery. As FIG. 19C further
shows, the distal flexure zone 44 bends to place the thermal energy
heating element into contact with tissue on the interior wall.
[0232] As FIG. 19D shows, the complex, multi-bend structure formed
by the proximal, intermediate and distal zones 32, 24, and 44 of
the distal end region 20 of the elongated shaft 16 creates a
consistent and reliable active surface area of contact between the
thermal heating element 24 and tissue within the respective renal
artery (refer back to FIG. 8C). Thermal energy can now be applied
through the thermal heating element 24 to induce one or more
thermal heating effects on localized regions of tissue along the
respective renal artery.
[0233] B. Facilitating Contact with the Vessel Wall
[0234] As previously described, the actuation of the control wire
40 to deflect the intermediate flexure zone 32 helps position the
thermal heating element 24 in contact with the vessel wall. This is
particularly useful when the distal end region 20 of the treatment
device 12 is delivered into the renal artery, as shown in FIG. 19B.
Due to the curve and placement of the renal guide catheter 94 and
orientation of the treatment device 12, the distal end region 20 of
the treatment device is oriented up against the superior region of
the vessel wall when first delivered into the renal artery, as
shown in FIG. 19B. Once the distal end region is positioned at the
most distal portion of the main renal artery, the operator may
deflect the intermediate flexure zone 34 via the actuator 42 to
position the thermal heating element 24 into contact with the
vessel wall at a more inferior location, as shown in FIG. 19C. This
deflection of the intermediate flexure zone 34 establishes wall
contact and provides, via the distal flexure zone 44, a stabilizing
force between the thermal heating element 24 and vessel wall to
position the thermal heating element in contact with the vessel
wall. The operator can then initiate treatment at this generally
inferior (bottom) location or rotate the treatment device as shown
in FIG. 19E for an alternate treatment location.
[0235] The active deflection of intermediate flexure zone 34 is
facilitated by not only operation of actuator 42, but also contact
between a proximal region of the intermediate flexure zone 44 and a
superior region of the renal artery. As shown in FIG. 19C, this
contact region 124 generally occurs at the apex of the bend of the
intermediate flexure zone 34. This contact region 124 is in radial
opposition to the contact between the thermal heating element 24
and vessel wall following deflection of the intermediate flexure
zone 34. The stabilizing force provided by the intermediate flexure
zone 44 to the thermal heating element 24 is also facilitated by
the opposing force at contact region 124. Even when the operator
rotates the treatment device to circumferentially reposition the
thermal heating element, as shown in FIG. 19E, this opposition
contact will be maintained, but at a different circumferential
position. FIG. 19F shows the circumferential rotation of the
thermal heating element 24 from a first treatment location
corresponding to lesion 98(a) to a second treatment location
corresponding to lesion 98(b) and the circumferential translation
of the intermediate flexure zone 32 to a new contact region 124. It
should be noted, however, that while having such opposition contact
at contact region 124 facilitates wall contact and the stabilizing
force, it is not generally required to achieve contact between the
thermal heating element 24 and the vessel wall.
[0236] It certain embodiments, it may also be beneficial to equip
the catheter apparatus with a second thermal heating element (not
shown) at or in the vicinity of the intermediate flexure zone.
Placement of the second thermal heating element on or proximate to
the intermediate flexure zone may enable the creation of a
thermally affected tissue region at or around contact region 124
(i.e., the portion of the vessel wall that is in contact with the
intermediate flexure zone). Activation of the first thermal element
and the second thermal element would allow the operator to create
two treatment zones that are circumferentially and longitudinally
offset during a single placement of the catheter apparatus.
[0237] As described above, the size and configuration of the
intermediate flexure zone 34 play a valuable role in the
positioning of the device for treatment and in facilitating contact
between the thermal heating element and the vessel wall. The
dimensioning of the intermediate flexure zone also plays a valuable
role in this regard, particularly with respect to the constraints
imposed by the renal anatomy.
[0238] Referring back to FIG. 7E, the length of the main branch of
a renal artery (i.e., from the junction of the aorta and renal
artery to just before the artery branches into multiple blood
vessels going to the kidney) is RA.sub.L and the diameter of the
main branch of a renal artery is RA.sub.DIA. It is desirable for
the length L3 of the intermediate flexure zone 34 to be long enough
for the distal end region 20 of the treatment device 12 to reach a
distal treatment location within the renal artery and, to be able
to, upon deflection, translate the thermal heating element 24 to
the radially opposite wall of the renal artery. However, if L3 were
too long, then too much of the intermediate flexure zone's proximal
region would reside within the aorta (even for distal treatments),
thereby preventing contact at contact region 124 since the apex of
the bend of the intermediate flexure zone would likely be in the
aorta. Also, an L3 that is too long would deflect with a large
radius of curvature (i.e., .alpha.2) and make it difficult for the
operator to reliably achieve wall contact at both distal and
proximal locations.
[0239] Additionally, as a practical matter, L3 is limited by the
most distal treatment location (i.e., length of the renal artery)
on one end and the location within the aorta of the renal guide
catheter 94 on the other end. It would be undesirable for L3 to be
so long that a portion of the intermediate flexure zone resides
within the renal guide catheter during distal treatments since the
deflection of the intermediate flexure zone within the guide could
impair the ability of the operator to rotate and torque the
catheter without whipping.
[0240] In an average human renal artery, RA.sub.L is about 20 mm to
about 30 mm from the junction of the aorta and renal artery and the
diameter of the main branch of a renal artery RA.sub.DIA is
typically about 3 mm to about 7 mm or 8 mm. Given these and the
above considerations, it is desirable that L3 range from about 5 mm
to about 15 mm. In certain embodiments, particularly for treatments
in relatively long blood vessels, L3 can be as long as about 20 mm.
In another representative embodiment, L3 can be about 12.5 mm.
[0241] C. Creation of Thermally Affected Tissue Regions
[0242] As previously described (and as FIG. 19B shows), the thermal
heating element 24 can be positioned by bending along the proximal
flexure zone 32 at a first desired axial location within the
respective renal artery. As FIG. 19C shows, the thermal heating
element 24 can be radially positioned by deflection of intermediate
flexure zone 34 toward the vessel wall. As FIG. 19C also shows, the
thermal heating element 24 can be placed into a condition of
optimal surface area contact with the vessel wall by further
deflection of the distal flexure zone 44.
[0243] Once the thermal heating element 24 is positioned in the
desired location by a combination of deflection of the intermediate
flexure zone 34, deflection of the distal flexure zone 44 and
rotation of the catheter, the first focal treatment can be
administered. By applying energy through the thermal heating
element 24, a first thermally affected tissue region 98(a) can be
formed, as FIG. 19D shows. In the illustrated embodiment, the
thermally affected region 98(a) takes the form of a lesion on the
vessel wall of the respective renal artery.
[0244] After forming the first thermally affected tissue region
98(a), the catheter needs to be repositioned for another thermal
treatment. As described above in greater detail, it is desirable to
create multiple focal lesions that are circumferentially spaced
along the longitudinal axis of the renal artery. To achieve this
result, the catheter is retracted and, optionally, rotated to
position the thermal heating element proximally along the
longitudinal axis of the blood vessel. Rotation of the elongated
shaft 16 from outside the access site (see FIG. 19E) serves to
circumferentially reposition the thermal heating element 24 about
the renal artery. Once the thermal heating element 24 is positioned
at a second axial and circumferential location within the renal
artery spaced from the first-described axial position, as shown in
FIG. 19E (e.g., 98(b)), another focal treatment can be
administered. By repeating the manipulative steps just described
(as shown in FIGS. 19F through 19K), the caregiver can create
several thermally affected tissue regions 98(a), 98(b), 98(c) and
98(d) on the vessel wall that are axially and circumferentially
spaced apart, with the first thermally affected tissue region 98(a)
being the most distal and the subsequent thermally affected tissue
regions being more proximal. FIG. 191 provides a cross-sectional
view of the lesions formed in several layers of the treated renal
artery. This figure shows that several circumferentially and
axially spaced-apart treatments (e.g., 98(a)-98(d)) can provide
substantial circumferential coverage and, accordingly, cause a
neuromodulatory affect to the renal plexus. Clinical investigation
indicates that each lesion will cover approximately 20-30 percent
of the circumferential area surrounding the renal artery. In other
embodiments, the circumferential coverage of each lesion can be as
much as 50 percent.
[0245] In an alternative treatment approach, the treatment device
can be administered to create a complex pattern/array of thermally
affected tissue regions along the vessel wall of the renal artery.
As FIG. 19L shows, this alternative treatment approach provides for
multiple circumferential treatments at each axial site (e.g., 98,
99 and 101) along the renal artery. Increasing the density of
thermally affected tissue regions along the vessel wall of the
renal artery using this approach might increase the probability of
thermally-blocking the neural fibers within the renal plexus.
[0246] The rotation of the thermal heating element 24 within the
renal artery as shown in FIG. 19G helps improve the reliability and
consistency of the treatment. Since angiographic guidance such as
fluoroscopy only provides visualization in two dimensions, it is
generally only possible in the anterior/posterior view to obtain
visual confirmation of wall contact at the superior (vertex) and
inferior (bottom) of the renal artery. For anterior and posterior
treatments, it is desirable to first obtain confirmation of contact
at a superior or inferior location and then rotate the catheter
such that the thermal heating element travels circumferentially
along the vessel wall until the desired treatment location is
reached. Physiologic data such as impedance can be concurrently
monitored to ensure that wall contact is maintained or optimized
during catheter rotation. Alternatively, the C-arm of the
fluoroscope can be rotated to achieve a better angle for
determining wall contact.
[0247] FIGS. 22A to 22C provide fluoroscopic images of the
treatment device within a renal artery during an animal study. FIG.
22A shows positioning of the treatment device and thermal heating
element 24 at a distal treatment location. The intermediate flexure
zone 34 has been deflected to position the thermal heating element
24 in contact with the vessel wall and to cause flexure in the
distal flexure zone 44. FIG. 22A also shows contact region 124
where the apex of the bend of the intermediate flexure zone 34 is
in contact with the vessel wall in radial opposition to contact
between the thermal heating element and vessel wall. FIG. 22B shows
the placement of the treatment device at a more proximal treatment
location following circumferential rotation and axial retraction.
FIG. 22C shows the placement of the treatment device at a proximal
treatment location just distal to the junction of the aorta and
renal artery.
[0248] Since both the thermal heating element 24 and solder 130 at
the distal end of the intermediate flexure zone 34 can be
radiopaque, as shown in FIGS. 22A to 22C, the operator using
angiographic visualization can use the image corresponding to the
first treatment location to relatively position the treatment
device for the second treatment. For example, in renal arteries of
average length, it is desirable for the clinical operator to treat
at about every 5 mm along the length of the main artery. In
embodiments where the length of the distal flexure zone 44 is 5 mm,
the operator can simply retract the device such that the current
position of the thermal heating element 24 is longitudinally
aligned with the position of the solder 130 in the previous
treatment.
[0249] In another embodiment, solder 130 can be replaced by a
different type of radiopaque marker. For example, a band of
platinum can be attached to the distal end of the intermediate
flexure zone to serve as a radiopaque marker.
[0250] Since angiographic visualization of the vasculature
generally requires contrast agent to be infused into the renal
artery, it may be desirable to incorporate within or alongside the
treatment device a lumen and/or port for infusing contrast agent
into the blood stream. Alternatively, the contrast agent can be
delivered into the blood alongside the treatment device within the
annular space between the treatment device and the guide catheter
through which the device is delivered.
[0251] Exposure to thermal energy (heat) in excess of a body
temperature of about 37.degree. C., but below a temperature of
about 45.degree. C., may induce thermal alteration via moderate
heating of the target neural fibers or of vascular structures that
perfuse the target fibers. In cases where vascular structures are
affected, the target neural fibers are denied perfusion resulting
in necrosis of the neural tissue. For example, this may induce
non-ablative thermal alteration in the fibers or structures.
Exposure to heat above a temperature of about 45.degree. C., or
above about 60.degree. C., may induce thermal alteration via
substantial heating of the fibers or structures. For example, such
higher temperatures may thermally ablate the target neural fibers
or the vascular structures. In some patients, it may be desirable
to achieve temperatures that thermally ablate the target neural
fibers or the vascular structures, but that are less than about
90.degree. C., or less than about 85.degree. C., or less than about
80.degree. C., and/or less than about 75.degree. C. Regardless of
the type of heat exposure utilized to induce the thermal
neuromodulation, a reduction in renal sympathetic nerve activity
("RSNA") is expected.
[0252] D. Control of Applied Energy
[0253] Desirably, the generator 26 includes programmed instructions
comprising an algorithm 102 (see FIG. 5) for controlling the
delivery of energy to the thermal heating device. The algorithm
102, as shown in FIG. 20, can be implemented as a conventional
computer program for execution by a processor coupled to the
generator 26. Algorithm 102 is substantially similar to the power
delivery algorithm described in co-pending patent application Ser.
No. 12/147,154, filed Jun. 26, 2008, which is incorporated herein
by reference in its entirety. The algorithm 102 can also be
implemented manually by a caregiver using step-by-step
instructions.
[0254] When a caregiver initiates treatment (e.g., via the foot
pedal), the algorithm 102 commands the generator 26 to gradually
adjust its power output to a first power level P.sub.1 (e.g., 5
watts) over a first time period t.sub.1 (e.g., 15 seconds). The
power increase during the first time period is generally linear. As
a result, the generator 26 increases its power output at a
generally constant rate of P.sub.1/t.sub.1. Alternatively, the
power increase can be non-linear (e.g., exponential or parabolic)
with a variable rate of increase. Once P.sub.1 and t.sub.1 are
achieved, the algorithm can hold at P.sub.1 until a new time
t.sub.2 for a predetermined period of time t.sub.2-t.sub.1 (e.g., 3
seconds). At t.sub.2 power is increased by a predetermined
increment (e.g., 1 watt) to P.sub.2 over a predetermined period of
time, t.sub.3-t.sub.2 (e.g., 1 second). This gradual power ramp can
continue until a maximum power P.sub.MAX is achieved or some other
condition is satisfied. In one embodiment, P.sub.MAX is 8 watts. In
another embodiment P.sub.MAX is 10 watts.
[0255] The algorithm 102 includes monitoring certain operating
parameters (e.g., temperature, time, impedance, power, etc.). The
operating parameters can be monitored continuously or periodically.
The algorithm 102 checks the monitored parameters against
predetermined parameter profiles to determine whether the
parameters individually or in combination fall within the ranges
set by the predetermined parameter profiles. If the monitored
parameters fall within the ranges set by the predetermined
parameter profiles, then treatment can continues at the commanded
power output. If monitored parameters fall outside the ranges set
by the predetermined parameter profiles, the algorithm 102 adjusts
the commanded power output accordingly. For example, if a target
temperature (e.g., 65 degrees C) is achieved, then power delivery
is kept constant until the total treatment time (e.g., 120 seconds)
has expired. If a first power threshold (e.g., 70 degrees C) is
achieved or exceeded, then power is reduced in predetermined
increments (e.g., 0.5 watts, 1.0 watts, etc.) until a target
temperature is achieved. If a second power threshold (e.g., 85
degrees C) is achieved or exceeded, thereby indicating an
undesirable condition, then power delivery can be terminated. The
system can be equipped with various audible and visual alarms to
alert the operator of certain conditions.
V. PREPACKAGED KIT FOR DISTRIBUTION, TRANSPORT AND SALE OF THE
DISCLOSED APPARATUSES AND SYSTEMS
[0256] As shown in FIG. 21, one or more components of the system 10
shown in FIG. 5 can be packaged together for convenient delivery to
and use by the customer/clinical operator. Components suitable for
packaging include, the treatment device 12, the cable 28 for
connecting the treatment device 12 to the generator 26, the neutral
or dispersive electrode 38, and one or more guide catheters 94
(e.g., a renal guide catheter). Cable 28 can also be integrated
into the treatment device 12 such that both components are packaged
together. Each component may have its own sterile packaging (for
components requiring sterilization) or the components may have
dedicated sterilized compartments within the kit packaging. This
kit may also include step-by-step instructions for use 126 that
provides the operator technical product features and operating
instructions for using the system 10 and treatment device 12,
including all methods of insertion, delivery, placement and use of
the treatment device disclosed herein.
VI. Additional Clinical Uses of the Disclosed Apparatuses, Methods
and Systems
[0257] Although much of the disclosure in this Specification
relates to at least partially denervating a kidney of a patient to
block afferent and/or efferent neural communication from within a
renal blood vessel (e.g., renal artery), the apparatuses, methods
and systems described herein may also be used for other
intravascular treatments. For example, the aforementioned catheter
system, or select aspects of such system, can be placed in other
peripheral blood vessels to deliver energy and/or electric fields
to achieve a neuromodulatory affect by altering nerves proximate to
these other peripheral blood vessels. There are a number of
arterial vessels arising from the aorta which travel alongside a
rich collection of nerves to target organs. Utilizing the arteries
to access and modulate these nerves may have clear therapeutic
potential in a number of disease states. Some examples include the
nerves encircling the celiac trunk, superior mesenteric artery, and
inferior mesenteric artery.
[0258] Sympathetic nerves proximate to or encircling the arterial
blood vessel known as the celiac trunk may pass through the celiac
ganglion and follow branches of the celiac trunk to innervate the
stomach, small intestine, abdominal blood vessels, liver, bile
ducts, gallbladder, pancreas, adrenal glands, and kidneys.
Modulating these nerves either in whole (or in part via selective
modulation) may enable treatment of conditions including (but not
limited to) diabetes, pancreatitis, obesity, hypertension, obesity
related hypertension, hepatitis, hepatorenal syndrome, gastric
ulcers, gastric motility disorders, irritable bowel syndrome, and
autoimmune disorders such as Chron's disease.
[0259] Sympathetic nerves proximate to or encircling the arterial
blood vessel known as the inferior mesenteric artery may pass
through the inferior mesenteric ganglion and follow branches of the
inferior mesenteric artery to innervate the colon, rectum, bladder,
sex organs, and external genitalia. Modulating these nerves either
in whole (or in part via selective modulation) may enable treatment
of conditions including (but not limited to) GI motility disorders,
colitis, urinary retention, hyperactive bladder, incontinence,
infertility, polycystic ovarian syndrome, premature ejaculation,
erectile dysfunction, dyspareunia, and vaginismus.
[0260] While arterial access and treatments have received attention
in this Specification, the disclosed apparatuses, methods and
systems can also be used to deliver treatment from within a
peripheral vein or lymphatic vessel.
VII. ADDITIONAL DESCRIPTION
[0261] The term apparatus makes reference to any apparatus of the
disclosure. In particular, this term relates to devices for
achieving intravascular renal neuromodulation via thermal effects,
such as heating. This term covers references to apparatus
catheters, catheters, and treatment devices in general. In the
specific description, the term catheter is used, but it should be
understood that this is merely a particular example of the
apparatuses of the disclosure.
[0262] Generally, the apparatus comprises an elongated shaft. The
elongated shaft is sized and configured to deliver a thermal
element to a renal artery via an intravascular path that includes a
femoral artery, an iliac artery, and the abdominal aorta. As
described in more detail above, different sectors of the elongated
shaft serve different mechanical functions when in use. The
elongated shaft may be in the form of a flexible tube.
[0263] The term apparatus includes, but is not necessarily limited
to, a catheter. As will be appreciated by one skilled in the art, a
catheter is a solid or tubular structure that can be inserted into
a body cavity, lumen, duct or vessel. A process of inserting a
catheter is catheterisation. The catheter, for example, may be an
intravascular catheter suitable for insertion into and delivery
through an intravascular path.
[0264] The intravascular path may be via a femoral artery, an iliac
artery, and/or the aorta. The passage may be through an access
site, percutaneously into the femoral artery and passed into the
iliac artery and aorta, into either the left or right renal artery.
This comprises an intravascular path that offers minimally invasive
access to a respective renal artery and/or other renal blood
vessels. For example, passage through an intravascular path
comprises a first vascular region and a second vascular region
deviating from the first vascular region at an angular
junction.
[0265] An angular junction could, for example, be the junction of
the left/right renal arteries and the aorta. Such an angular
junction requires significant flexure of the apparatus in order to
gain entry into the respective left or right renal artery;
[0266] A force transmitting section is sized and configured to
possess selected mechanical properties that accommodate physical
passage through and the transmission of forces within the
intravascular path. For example, as it leads from an accessed
femoral artery (left or right), through the respective iliac branch
artery and into the aorta, and in proximity to the targeted renal
artery (left or right).
[0267] The axis of the elongated shaft, as used above, refers to
the longitudinal access of the elongated shaft.
[0268] The proximal region of the apparatus refers to the proximal
end region of the elongated shaft. This region may include, for
example, the handle and the force transmitting section of the
apparatus.
[0269] The distal region or distal section of the apparatus refers
to the distal end region of the apparatus; the end of the apparatus
that is furthest away from the handle. The distal end region
includes, for example, a first or proximal flexure zone, a second
or intermediate flexure zone, and/or a distal flexure zone.
[0270] The first flexure zone refers to the flexure zone that is
closest to the proximal end region of the apparatus. The first
flexure zone is equivalent to the proximal flexure zone (see
discussion of FIGS. 11A to 11C above). The first or proximal
flexure zone is proximal to the handle or the force transmitting
section, which is part of the proximal end region.
[0271] The first flexure zone or proximal flexure zone may also be
referred to as a proximal section. The proximal section may be
flexible to enable it to be placed into the angular junction. For
example, a proximal flexible section is adapted to bend within a
guide catheter to form a transitional bend.
[0272] A transitional bend that is supported and stable within the
vasculature is defined as a proximal flexure zone or proximal
section.
[0273] The second flexure zone refers to the flexure zone distal
from the first flexure zone (or proximal flexure zone). In
embodiments having more than two flexure zones, the second flexure
zone is equivalent to the intermediate flexure zone described in
more detail above. The thermal element may be supported by the
second or intermediate flexure zone. In embodiments having only two
flexure zones, the second flexure zone is equivalent to the distal
flexure zone outlined above.
[0274] The second flexure zone or intermediate flexure zone may
also be referred to as an intermediate section. The intermediate
section may be deflectable to enable it to extend distally from an
angular junction. For example, an intermediate section may extend
distally from a transitional bend of a flexible proximal
section.
[0275] The third flexure zone refers to the flexure zone distal to
the second flexure zone (or intermediate flexure zone). The third
flexure zone is equivalent to the distal flexure zone described in
more detail above. The thermal element may be carried at the end of
or coupled to the distal flexure zone. The thermal element is
positioned at the distal end or buttresses the distal end of the
distal flexure zone.
[0276] The third flexure zone or distal flexure zone may also be
referred to as a flexible distal section. The flexible distal
section may extend distally from an intermediate section, as
described in more detail above.
[0277] The thermal element may be any suitable element for thermal
heating. The thermal element is sized and configured for
manipulation and use within a renal artery. The thermal element is
coupled to or carried by the distal flexure zone. Additionally, the
distal flexure zone is configured to orient a portion of the
thermal element alongside a region of tissue, thereby providing
consistent tissue contact at each treatment location. The distal
flexure zone also biases the thermal heating element against
tissue, thereby stabilizing the thermal element.
[0278] The apparatus may further comprise a second thermal element
coupled to the second or intermediate flexure zone, wherein the
second thermal element is configured to contact the first wall
region of the peripheral blood vessel.
[0279] The distal flexure zone separates the thermal element from
the elongated shaft. In certain embodiments of the disclosure, the
apparatus may have only one flexure zone, i.e. a distal flexure
zone. The distal flexure zone having the flexible structure creates
a region of electrical isolation between the thermal element and
the rest of the elongated shaft, whereby the thermal element is
operatively coupled to the rest of the apparatus via at least one
supply wire.
[0280] In one embodiment, the distal flexure zone is approximately
2 to 5 mm in length. In other embodiments, however, the distal
flexure zone can be as long as about 1 cm.
[0281] In some embodiments, the length of the intermediate flexure
zone can range from approximately 5 mm to 15 mm. In other
embodiments, particularly for treatments in relatively long blood
vessels, the length of the intermediate flexure zone can be as long
as about 20 mm. In another embodiment, the length of the
intermediate flexure zone can be about 12.5 mm.
[0282] A flexure control element may be coupled to the first or
second flexure zones, or proximal, or intermediate flexural zones.
The flexure control element is configured to apply a force to the
coupled zone such that the zone flexes in a radial direction from
the axis of the longitudinal axis of the zone. The flexure control
element may be carried by the handle.
[0283] A flexure controller is coupled to the flexure control
element and can be operated to cause the flexure control element to
apply a first force suitable to flex or move the respective zone
that is coupled to the flexure control element. The flexure
controller may be part of or coupled to the handle of the
apparatus, catheter apparatus or device.
[0284] The flexure control element and flexure controller may be
part of a control mechanism coupled to first, second, proximal, or
intermediate zones. The control mechanism may include a flexure
controller in the form of a control wire attached/coupled to the
distal end portion of the respective zone. The control wire may be
passed proximally through or alongside the elongated shaft of the
apparatus/device and coupled to a flexure controller in the form of
an actuator on or part of the handle.
[0285] Operation of the actuator by the caregiver pulling
proximally on or pushing forward the actuator pulls the control
wire back to apply a compressive and/or bending force to the
coupled flexure zone resulting in bending. The compressive force in
combination with the optional directionally biased stiffness of the
flexure zone deflects the flexure zone and, thereby, radially moves
the flexure zone with respect to its longitudinal axis.
[0286] Desirably, as described in more detail above, the distal end
region of the elongated shaft can be sized and configured to vary
the stiffness of the flexure zone(s) about its circumference. The
variable circumferential stiffness imparts preferential and
directional bending to the flexure zone (i.e., directionally biased
stiffness). In response to operation of the actuator, the flexure
zone may be configured to bend in a single preferential direction.
The compressive and/or bending force and resulting directional
bending from the deflection of the flexure zone has the consequence
of altering the axial stiffness of the flexure zone. The actuation
of the control wire serves to increase the axial stiffness of the
flexure zone. The directionally biased stiffness of the flexure
zone causes the flexure zone to move in a predetermined radial
direction in response to a first force applied by the flexure
control element.
[0287] The stiffness of each of the flexure zones, such as the
first and the second flexure zones, can apply via the thermal
element a stabilizing force that positions the thermal element in
substantially secure contact with the tissue surface during
actuation of the flexure control element. This stabilizing force
also influences the amount of tissue surface contact achieved by
the thermal heating element (i.e., the ASA to TSA ratio). In one
embodiment, for example, the stabilizing force may cause at least
twenty-five percent of the total surface area of the thermal
element to contact the tissue surface.
[0288] A second flexure element is part of or coupled to the distal
flexure zone, which may be the second or third flexure zone. The
second flexure element is also coupled to the thermal element. The
second flexure element has mechanical properties that accommodate
additional flexure or bending, independent of the proximal flexure
zone and the intermediate flexure zone, at a preferred treatment
angle .alpha.3. The second flexure element may be or have a
flexible structure.
[0289] A flexible structure accommodates passive flexure of the
thermal element in any plane through the axis of the elongated
shaft. The thermal element may flex up to ninety degrees, or less
than or equal to ninety degrees from the axis.
[0290] The flexible structure may be in the form of a thread, such
as a polymer thread. It is desirable for thread be comprised of
Kevlar or similar polymer thread. The thread may be encased in or
covered with a coating or wrapping, such as a polymer coating. The
thread may be covered with a polymer laminate, coating, or sheath
that can be comprised of any electrically insulative material, and
particularly those listed above with respect to the sheath (e.g.,
carbothane). The flexible structure may further comprise a metal
coil.
[0291] The thread may mechanically couple the flexible structure to
at least one of the thermal element and the elongated shaft. In one
embodiment, the thread is routed through a proximal anchor, which
is attached to the distal end of a flexure zone (e.g., intermediate
flexure zone), and a distal anchor, which is fixed within or
integrated into the thermal element using solder.
[0292] The flexible structure can include, for example, a
spring-like flexible tubular structure as described in more detail
above. Alternatively, the flexible structure may be in the form of
a tubular metal coil, cable, braid or polymer. The flexible
structure can take the form of an oval, rectangular, or flattened
metal coil or polymer. In alternate embodiments, the flexible
structure may comprise other mechanical structures or systems that
allow the thermal element to pivot in at least one plane of
movement. For example, the flexible structure may comprise a hinge
or ball/socket combination.
[0293] Not under the direct control of the physician, passive
flexure of the second flexure element at the distal flexure zone
occurs in response to contact between the thermal element and wall
tissue occasioned by the radial deflection of the thermal element
at the first, second or intermediate flexure zone.
[0294] The force transmitting section is sized and configured for
transmitting along a compound flexure or compound structure of the
elongated shaft.
[0295] A compound structure in the elongated shaft is formed by the
flexure of the proximal, intermediate, and distal flexure zones.
The compound structure positions a thermal element carried by the
distal flexure zone for placement in contact with tissue along the
intravascular path,
[0296] A connector on or carried by the handle is configured to
connect the thermal element to a thermal energy source. The
connector may be a cable plugged into or operatively attached to
the handle. The energy source may be a generator or any other
energy source. At least one supply wire may pass along the
elongated shaft or through a lumen in the elongated shaft from the
cable plugged into or operatively attached to the handle to convey
the energy to the thermal element.
[0297] The energy supplied to the thermal element may be at least
one of radiofrequency, microwave energy, ultrasound energy,
laser/light energy, thermal fluid, and cryogenic fluid. The thermal
element may be an electrode for applying radiofrequency energy.
[0298] Additionally, a sensor such as a temperature sensor (e.g.,
thermocouple, thermistor, etc.), optical sensor, microsensor or
impedance sensor can be located adjacent to, on or within the
thermal element. The sensor can monitor a parameter of the
apparatus and/or the tissue surface. The sensor may be connected to
one or more supply wires. With two supply wires, one wire could
convey the energy to the thermal heating element and one wire could
transmit the signal from the sensor. Alternatively, both wires
could transmit energy to the thermal heating element.
[0299] A feedback control system is configured to alter treatment
delivered to the tissue surface in response to the monitored
parameter. The feedback control system may form part of the
catheter or may be attached to the energy source, such as a
generator. The feedback control system may be a processor coupled
to the catheter or the energy source. The sensor data can be
acquired or monitored by the feedback control system prior to,
simultaneous with, or after the delivery of energy or in between
pulses of energy, when applicable. The monitored data may be used
in a feedback loop to better control therapy, e.g., to determine
whether to continue or stop treatment, and it may facilitate
controlled delivery of an increased or reduced power or a longer or
shorter duration therapy.
[0300] The feedback control system, such as the generator, can
include an algorithm for controlling the delivery/output of energy
to the thermal element. The algorithm can be implemented, for
example, as a conventional computer program for execution by a
processor coupled to the energy source.
[0301] The handle may comprise a rotating fitting coupled to the
elongated shaft and configured to rotate the elongated shaft about
the axis without rotating the handle. The rotating fitting can
comprise a rotational limiting element configured to prevent
rotation of the elongated shaft beyond a predetermined number of
revolutions.
[0302] The rotational limiting element may be in the form of an
axial groove and the distal portion of the handle can include a
fitting interface having a helical channel, A traveling element,
for example in the form of a ball comprising stainless steel,
another metal, or a polymer, can be placed within the fitting
interfaceso that it, upon rotation of the fitting, may
simultaneously travel within the helical channel of the fitting
interface and along the axial groove of the fitting. When the
ball=reaches the end of the channel and/or groove, the ball will no
longer move and, consequently, the fitting will not be able to
rotate any further in that direction, i.e. the travel of the
traveling element is limited by the structural confines of the
interface. The rotational fitting and handle fitting interface can
be configured to allow for the optimal number of revolutions for
the shaft, given structural or dimensional constraints (e.g.,
wires). For example, the components of the handle could be
configured to allow for two revolutions of the shaft independent of
the handle.
[0303] A controlled flexure zone may comprise a first or proximal
flexure zone or second or intermediate flexure zone. The controlled
flexure zone refers to the part of the elongated shaft that may be
controlled by a remotely controlled element. The controlled flexure
zone may be in the form of a tubular structure.
[0304] A remotely controlled element may be in the form of, but is
not limited to, a control wire attached to the distal end of the
controlled flexure zone. The control wire may be passed proximally
through the elongated shaft of the apparatus and coupled to an
actuator on or part of the handle. An operator may remotely operate
the actuator by pulling proximally on or pushing forward the
actuator and pulling the control wire back to apply a compressive
and/or bending force to the flexure zone resulting in bending. The
compressive force in combination with the optional directionally
biased stiffness of the controlled flexure zone deflects the
controlled flexure zone and, thereby, radially moves the controlled
flexure zone with respect to its longitudinal axis.
[0305] Desirably, as described in more detail above, the distal end
region of the elongated shaft can be sized and configured to vary
the stiffness of the flexure zone(s) about its circumference. The
variable circumferential stiffness imparts preferential and
directional bending to the controlled flexure zone (i.e.,
directionally biased stiffness). This enables the flexure of the
controlled flexure zone in a predetermined radial direction. In
response to operation of the actuator, the controlled flexure zone
may be configured to bend in a single preferential direction. The
compressive and bending force and resulting directional bending
from the deflection of the controlled flexure zone has the
consequence of altering the axial stiffness of the controlled
flexure zone. The actuation of the control wire serves to increase
the axial stiffness of the controlled flexure zone. The
directionally biased stiffness of the controlled flexure zone
causes the flexure zone to move in a predetermined radial direction
in response to a first force applied by the flexure control
element.
[0306] The stiffness of the controlled zone can apply via the
thermal element a stabilizing force that positions the thermal
element in substantially secure contact with the tissue surface,
during actuation of the flexure control element. This stabilizing
force also influences the amount of tissue surface contact achieved
by the thermal heating element (i.e., the ASA to TSA ratio). In one
embodiment, for example, the stabilizing force may cause at least
twenty-five percent of the total surface area of the thermal
element to contact the tissue surface.
[0307] The controlled flexure zone in the form of a tubular
structure may provide the directionally biased stiffness. The
tubular structure may be made of a metal material, e.g. of
stainless steel, or a shape memory alloy, e.g., nickel titanium
(a.k.a., nitinol or NiTi), to possess the requisite axial stiffness
and torsional stiffness. The tubular structure may comprise a
tubular polymer or metal/polymer composite having segments with
different stiffnesses. The tubular structure may be in the form of
an oval, or rectangular, or flattened metal coil or polymer having
segments with different stiffnesses.
[0308] The tubular structure, when made from metal, may be laser
cut. For example, the tubular structure may be laser cut along its
length to provide a bendable, spring-like structure. The tubular
structure can include a laser-cut pattern having a spine with a
plurality of connecting ribs. The pattern biases the deflection of
the tubular structure, in response to pulling on the control
flexure element coupled to the distal end of the tubular structure,
toward a desired direction. The directionally-biased stiffness of
the tubular structure may be determined by the location of the
spine in relation to the plurality of connecting ribs on the
tubular structure.
[0309] The tubular structure may further comprise a polymer
laminate, coating, or sheath.
[0310] An unrestrained flexure zone is distal to the controlled
flexure zone. The unrestrained flexure zone has or is coupled to a
thermal or tissue heating element. The unrestrained flexure zone
has mechanical properties that accommodate additional flexure or
bending, independent to or in response to the flexure of the
controlled flexure zone. The unrestrained flexure zone may have or
be coupled to a flexible structure as described in more detail
above.
[0311] The apparatus may further comprise a second thermal element
coupled to the controlled flexure zone, wherein the second thermal
element is configured to contact the first wall region of the
peripheral blood vessel.
[0312] A connector on or carried by the handle is configured to
connect the thermal element to a thermal energy source. The
connector may be a cable plugged into or operatively attached to
the handle. The energy source may be a generator or any other
energy source. At least one supply wire may pass along the
elongated shaft or through a lumen in the elongated shaft from the
cable plugged into or operatively attached to the handle convey the
energy to the thermal element.
[0313] The elongated shaft may be configured for rotation within
the peripheral blood vessel when the controlled flexure zone is in
flexure against the first wall region and when the thermal element
is in contact with the second wall region. Rotation of the
elongated shaft positions the controlled flexure zone against a
third wall region and positions the thermal element against a
fourth wall region, wherein the third wall region is
circumferentially offset from the first wall region and the fourth
wall region is circumferentially offset from the second wall
region, and wherein the third wall region is generally opposite the
fourth wall region.
[0314] As described in more detail above, the apparatus of the
disclosure may form part of a system. The system may further
comprise instructions that command the energy generator/source to
deliver energy to the thermal element according to a predetermined
energy delivery profile. The predetermined energy delivery profile
may comprise increasing energy delivery to a predetermined power
level for a first period of time, maintaining energy delivery at
the first power level for a second period of time; and increasing
energy delivery to a second power level if the temperature value is
less than a preset threshold following the second period of
time.
[0315] As described in more detail above, the apparatus of the
disclosure may be provided in the form of a kit, such as a medical
kit. The kit may further comprise a cable configured to
electrically connect the catheter apparatus to the thermal energy
source and a dispersive electrode configured to provide a retum
path for an energy field from the catheter. The kit may further
comprise one or more guide catheters (e.g., a renal guide
catheter). The cable can also be integrated into the apparatus such
that both components are packaged together. Each component may have
its own sterile packaging (for components requiring sterilization)
or the components may have dedicated sterilized compartments within
the kit packaging.
[0316] The kit may further comprise instructions for delivering the
catheter apparatus into a renal artery of the patient and at least
partially denervating the kidney corresponding to the renal artery
to treat the patient for a condition associated with at least one
of hypertension, heart failure, kidney disease, chronic renal
failure, sympathetic hyperactivity, diabetes, metabolic disorder,
arrhythmia, acute myocardial infarction and cardio-renal
syndrome
VIII. CONCLUSION
[0317] The above detailed descriptions of embodiments of the
invention are not intended to be exhaustive or to limit the
invention to the precise form disclosed above. Although specific
embodiments of, and examples for, the invention are described above
for illustrative purposes, various equivalent modifications are
possible within the scope of the invention, as those skilled in the
relevant art will recognize. For example, while steps are presented
in a given order, alternative embodiments may perform steps in a
different order. The various embodiments described herein can also
be combined to provide further embodiments.
[0318] From the foregoing, it will be appreciated that specific
embodiments of the invention have been described herein for
purposes of illustration, but well-known structures and functions
have not been shown or described in detail to avoid unnecessarily
obscuring the description of the embodiments of the invention.
Where the context permits, singular or plural terms may also
include the plural or singular term, respectively. For example,
much of the disclosure herein describes a thermal heating element
24 or electrode 46 in the singular. It should be understood that
this application does not exclude two or more thermal heating
elements or electrodes. In one embodiment representative of a
multi-electrode configuration, a second electrode could be placed
on the intermediate flexure zone 34 opposite the direction of
deflection of the intermediate flexure zone 34 such that the second
electrode could deliver treatment to the vessel wall at or near
contact region 124. This approach would allow two spaced apart
treatments per position of the treatment device, one distal
treatment via the first electrode 46 and one proximal treatment via
the second electrode.
[0319] Moreover, unless the word "or" is expressly limited to mean
only a single item exclusive from the other items in reference to a
list of two or more items, then the use of "or" in such a list is
to be interpreted as including (a) any single item in the list, (b)
all of the items in the list, or (c) any combination of the items
in the list. Additionally, the term "comprising" is used throughout
to mean including at least the recited feature(s) such that any
greater number of the same feature and/or additional types of other
features are not precluded. It will also be appreciated that
specific embodiments have been described herein for purposes of
illustration, but that various modifications may be made without
deviating from the invention. Accordingly, the invention is not
limited except as by the appended claims.
* * * * *