U.S. patent application number 13/279312 was filed with the patent office on 2012-06-07 for neuromodulation cryotherapeutic devices and associated systems and methods.
This patent application is currently assigned to Medtronic Adrian Luxembourg S.a.r.l.. Invention is credited to Benjamin J. Clark, Tim Huynh, Micheal Moriarty, Eric Ryba, Roman Turovskiy.
Application Number | 20120143294 13/279312 |
Document ID | / |
Family ID | 46065020 |
Filed Date | 2012-06-07 |
United States Patent
Application |
20120143294 |
Kind Code |
A1 |
Clark; Benjamin J. ; et
al. |
June 7, 2012 |
NEUROMODULATION CRYOTHERAPEUTIC DEVICES AND ASSOCIATED SYSTEMS AND
METHODS
Abstract
Neuromodulation cryotherapeutic devices and associated systems
and methods are disclosed herein. A cryotherapeutic device
configured in accordance with a particular embodiment of the
present technology can include an elongated shaft having distal
portion and a supply lumen along at least a portion of the shaft.
The shaft can be configured to locate the distal portion
intravascularly at a treatment site proximate a renal artery or
renal ostium. The supply lumen can be configured to receive a
liquid refrigerant. The cryotherapeutic device can further include
a cooling assembly at the distal portion of the shaft. The cooling
assembly can include an applicator in fluid communication with the
supply lumen and configured to deliver cryotherapeutic cooling to
nerves proximate the target site when the cooling assembly is in a
deployed state.
Inventors: |
Clark; Benjamin J.; (Redwood
City, CA) ; Huynh; Tim; (Mountain View, CA) ;
Moriarty; Micheal; (Galway, IE) ; Ryba; Eric;
(Durango, CO) ; Turovskiy; Roman; (San Francisco,
CA) |
Assignee: |
Medtronic Adrian Luxembourg
S.a.r.l.
Luxembourg
LU
|
Family ID: |
46065020 |
Appl. No.: |
13/279312 |
Filed: |
October 23, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61406968 |
Oct 26, 2010 |
|
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|
61528091 |
Aug 26, 2011 |
|
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61528684 |
Aug 29, 2011 |
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61546510 |
Oct 12, 2011 |
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Current U.S.
Class: |
607/105 |
Current CPC
Class: |
A61B 2018/00577
20130101; A61B 2018/00232 20130101; A61B 2017/22067 20130101; A61B
2018/0212 20130101; A61B 2018/00166 20130101; A61B 2018/0025
20130101; A61B 2018/00434 20130101; A61B 2018/00023 20130101; A61B
2018/00404 20130101; A61B 18/02 20130101; A61B 2018/0262 20130101;
A61B 2017/22054 20130101; A61B 2018/00511 20130101; A61B 2018/0022
20130101; A61B 2018/00261 20130101 |
Class at
Publication: |
607/105 |
International
Class: |
A61F 7/12 20060101
A61F007/12 |
Claims
1. A cryotherapeutic device, comprising: a shaft having a distal
portion, wherein the shaft is configured to locate the distal
portion intravascularly at a treatment site at least proximate a
renal artery or renal ostium; a cooling assembly at the distal
portion of the shaft, the cooling assembly including an expansion
chamber having a rupture pressure and a threshold pressure below
the rupture pressure; pressure monitoring lumen along at least a
portion the shaft, the pressure monitoring lumen having a first
opening at the distal portion of the shaft and a second opening at
the proximal portion of the shaft, wherein the first opening is in
fluid communication with the expansion chamber; and a pressure
sensor configured to be located externally of the patient and
operatively coupled to the pressure monitoring lumen, wherein the
pressure monitoring lumen and pressure sensor are configured to
provide a signal indicating a change of pressure within the
expansion chamber.
2. The cryotherapeutic device of claim 1 wherein: the pressure
monitoring lumen has a length at least equal to a length of the
shaft; and the pressure monitoring lumen is configured to provide a
response time of at most 0.5 second from the expansion chamber to
the pressure sensor.
3. The cryotherapeutic device of claim 1, further comprising: a
supply lumen along at least a portion of the shaft, the supply
lumen being in fluid communication with the expansion chamber; an
exhaust lumen along at least a portion of the shaft, the exhaust
lumen being in fluid communication with the expansion chamber; a
valve coupled to the supply lumen and to the pressure sensor; and
wherein-- the expansion chamber comprises a balloon, the valve is
configured to at least partially reduce refrigerant flow through
the supply lumen when the pressure sensor measures a pressure
within the expandable member above the threshold pressure, the
pressure monitoring lumen has an inner diameter configured to
accurately gauge pressure within the expandable member and an outer
diameter configured to have a negligible effect on outflow of
refrigerant through the exhaust lumen, and the pressure monitoring
lumen is configured to provide a response time of less than 1
second from the expansion chamber to the pressure sensor.
4. The cryotherapeutic device of claim 1, further comprising: a
supply lumen along at least a portion of the shaft, the supply
lumen being configured to receive at least a substantially liquid
refrigerant; an exhaust lumen along at least a portion of the
shaft, the exhaust lumen being in fluid communication with the
expansion chamber; and wherein-- the exhaust lumen has an inner
cross-sectional dimension, the supply lumen and the pressure
monitoring lumen together have an outer cross-sectional dimension
at the distal portion of the shaft, and the inner and outer
cross-sectional dimensions have a ratio between 4:1 and 10:1.
5. The cryotherapeutic device of claim 1 wherein: the shaft has a
first length; and the pressure monitoring lumen has an inner
diameter of approximately 0.010, an outer diameter of approximately
0.015 inch (0.381 mm), and a second length at least equal to the
first length of the shaft.
6. The cryotherapeutic device of claim 5 wherein the shaft is
configured to fit within a 6 Fr guide sheath, the first length of
the shaft being at least 120 cm.
7. The cryotherapeutic device of claim 1, further comprising a
controller coupled to the shaft and to the pressure sensor, wherein
the controller is configured to at least reduce refrigerant flow to
the expansion chamber when the pressure sensor measures the
threshold pressure or higher.
8. The cryotherapeutic device of claim 1, further comprising an
adapter having a channel between the pressure sensor and the
pressure monitoring lumen, wherein the channel has a volume of no
more than 0.1 cc.
9. The cryotherapeutic device of claim 1 wherein the expansion
chamber comprises a compliant material having a rupture pressure of
at least 300 psi.
10. The cryotherapeutic device of claim 1 wherein the expansion
chamber comprises a compliant material having a rupture pressure of
at most 200 psi.
11. The cryotherapeutic device of claim 1 wherein: the shaft is
configured to fit within a 6 Fr guide sheath; and the cooling
assembly includes an expandable member having a delivery state and
an expanded state, at least a portion of the expandable member
defining the expansion chamber, wherein the expandable member has
an outer diameter from approximately 3 mm to approximately 10 mm in
the expanded state.
12. A cryotherapeutic device comprising: a shaft having a proximal
portion and a distal portion; a cooling assembly at the distal
portion of the shaft, wherein the cooling assembly includes an
expansion chamber in fluid communication with the distal portion of
the shaft; and a pressure sensor at the proximal portion of the
shaft and in fluid communication with the expansion chamber such
that a time delay between a change in pressure in the expansion
chamber and a measured pressure at the pressure sensor is within a
response time that prevents rupture of the expansion chamber.
13. The cryotherapeutic device of claim 12 wherein the response
time is less than 0.01 second.
14. The cryotherapeutic device of claim 12, further comprising a
pressure monitoring lumen having a proximal end portion coupled to
the pressure sensor and a distal end portion in fluid communication
with the expansion chamber.
15. The cryotherapeutic device of claim 14 wherein the pressure
monitoring lumen has an inner diameter of no greater than 0.030
inch (0.762 mm) and an outer diameter of no greater than 0.060 inch
(1.52 mm).
16. The cryotherapeutic device of claim 14 wherein the pressure
monitoring lumen has a length of at least 48 inches (122 cm).
17. The cryotherapeutic device of claim 14, further comprising an
adaptor coupled between the pressure sensor and the pressure
monitoring lumen, wherein the adaptor has an internal volume of
less than 0.1 cc.
18. The cryotherapeutic device of claim 12 wherein: the response
time is less than 0.1 second; and the cryotherapeutic device
further comprises a pressure monitoring lumen having a proximal end
portion coupled to the pressure sensor and a distal end portion in
fluid communication with the expansion chamber, the pressure
monitoring lumen having a length of at least 120 cm.
19. The cryotherapeutic device of claim 12 wherein: the shaft is
configured to fit with in 6 Fr guide sheath; and the cooling
assembly includes an expandable member having a delivery state and
an expanded state, at least a portion of the expandable member
defining the expansion chamber, wherein the expandable member has a
maximum outer diameter of 10 mm in the expanded state and a length
of at most 10 mm.
20. A method for treating a patient, the method comprising:
positioning a cooling assembly at a distal portion of a shaft at
least proximate a peripheral blood vessel, wherein the cooling
assembly includes an expansion chamber having a threshold pressure;
expanding a refrigerant in the expansion chamber; applying
therapeutic cooling with the cooling assembly to nerves proximate
the peripheral blood vessel; measuring a pressure within the
expansion chamber with an external pressure sensor, wherein the
external pressure sensor is coupled to a pressure monitoring lumen
in fluid communication with the expansion chamber; and indicating
when the measured pressure within the expansion chamber is at least
the threshold pressure.
21. The method of claim 20 wherein measuring a pressure within the
expansion chamber with an external pressure sensor comprises
measuring a pressure within the expansion chamber such that a time
delay between a change in pressure within the expansion chamber and
the measure pressure at the external pressure sensor is less than 1
second.
22. The method of claim 20 wherein indicating when the measured
pressure within the expansion chamber is at least at the threshold
pressure comprises indicating when the measured pressure is close
to a rupture pressure of the expansion chamber.
23. The method of claim 20, further comprising coupling the
external pressure sensor to the pressure monitoring lumen with an
adaptor having an internal volume of no more than 0.1 cc.
24. The method of claim 20 wherein: positioning the cooling
assembly at the distal portion of the shaft at least proximate the
peripheral blood vessel comprises positioning the cooling assembly
at the distal end of the shaft at least proximate a renal artery;
measuring a pressure within the expansion chamber with the external
pressure sensor comprises measuring a pressure within the expansion
chamber via a pressure monitoring lumen having a length of at least
120 cm; and indicating when the measured pressure within the
expansion chamber is at least the threshold pressure comprises
indicating the measured pressure within a response time that
prevents rupture of the expansion chamber.
25. A method for treating a patient, the method comprising:
intravascularly positioning an expansion chamber proximate
post-ganglionic neural fibers that innervate a kidney of the
patient; cryomodulating at least a portion of the neural fibers
proximate the expansion chamber; and measuring a pressure within
the expansion chamber with an external pressure sensor, wherein the
external pressure sensor is in fluid communication with the
expansion chamber.
26. The method of claim 24 wherein measuring a pressure within the
expansion chamber with an external pressure sensor comprises
coupling the external pressure sensor to a pressure monitoring
lumen extending from a distal portion of a shaft to a proximal
portion of the shaft, the expansion chamber being at the distal
portion of the shaft.
27. The method of claim 26 wherein measuring a pressure includes
measuring a pressure with the external pressure sensor via the
pressure monitoring lumen within 0.1 second of a change in pressure
at the expansion chamber.
28. The method of claim 27 wherein measuring a pressure includes
using a pressure monitoring lumen having a length of at least 120
mm and an inner diameter of no more than 0.762 mm.
Description
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application claims the benefit of the following pending
applications:
[0002] (a) U.S. Provisional Application No. 61/406,968, filed Oct.
26, 2010;
[0003] (b) U.S. Provisional Application No. 61/528,091, filed Aug.
26, 2011;
[0004] (c) U.S. Provisional Application No. 61/528,684, filed Aug.
29, 2011; and
[0005] (d) U.S. Provisional Application No. 61/546,510, filed Oct.
12, 2011.
[0006] All of the foregoing applications are incorporated herein by
reference in their entireties. Further, components and features of
embodiments disclosed in the applications incorporated by reference
may be combined with various components and features disclosed and
claimed in the present application
RELATED APPLICATIONS INCORPORATED BY REFERENCE
[0007] U.S. Provisional Application No. 61/545,052, filed Oct. 7,
2011, U.S. patent application Ser. No. 13/204,504, filed Aug. 5,
2011, PCT International Application No. PCT/US2011/46845, filed
Aug. 5, 2011, and U.S. Provisional Application No. 61/371,110,
filed Aug. 5, 2010, are related to the present application, and the
foregoing applications are incorporated herein by reference in
their entireties. As such, components and features of embodiments
disclosed in the applications incorporated by reference may be
combined with various components and features disclosed and claimed
in the present application.
TECHNICAL FIELD
[0008] The present technology relates generally to cryotherapeutic
devices. In particular, several embodiments are directed to
cryotherapeutic devices for intravascular neuromodulation and
associated systems and methods.
BACKGROUND
[0009] The sympathetic nervous system (SNS) is a primarily
involuntary bodily control system typically associated with stress
responses. Fibers of the SNS innervate tissue in almost every organ
system of the human body and can affect characteristics such as
pupil diameter, gut motility, and urinary output. Such regulation
can have adaptive utility in maintaining homeostasis or in
preparing the body for rapid response to environmental factors.
Chronic activation of the SNS, however, is a common maladaptive
response that can drive the progression of many disease states.
Excessive activation of the renal SNS in particular has been
identified experimentally and in humans as a likely contributor to
the complex pathophysiology of hypertension, states of volume
overload (such as heart failure), and progressive renal disease.
For example, radiotracer dilution has demonstrated increased renal
norepinephrine (NE) spillover rates in patients with essential
hypertension.
[0010] Cardio-renal sympathetic nerve hyperactivity can be
particularly pronounced in patients with heart failure. For
example, an exaggerated NE overflow from the heart and kidneys to
plasma is often found in these patients. Heightened SNS activation
commonly characterizes both chronic and end stage renal disease. In
patients with end stage renal disease, NE plasma levels above the
median have been demonstrated to be predictive for cardiovascular
diseases and several causes of death. This is also true for
patients suffering from diabetic or contrast nephropathy. Evidence
suggests that sensory afferent signals originating from diseased
kidneys are major contributors to initiating and sustaining
elevated central sympathetic outflow.
[0011] Sympathetic nerves to the kidneys terminate in the blood
vessels, the juxtaglomerular apparatus, and the renal tubules.
Stimulation of the renal sympathetic nerves can cause increased
renin release, increased sodium (Na.sup.+) reabsorption, and a
reduction of renal blood flow. These neural regulation components
of renal function are considerably stimulated in disease states
characterized by heightened sympathetic tone and likely contribute
to increased blood pressure in hypertensive patients. The reduction
of renal blood flow and glomerular filtration rate as a result of
renal sympathetic efferent stimulation is likely a cornerstone of
the loss of renal function in cardio-renal syndrome (i.e., renal
dysfunction as a progressive complication of chronic heart
failure). Pharmacologic strategies to thwart the consequences of
renal efferent sympathetic stimulation include centrally acting
sympatholytic drugs, beta blockers (intended to reduce renin
release), angiotensin converting enzyme inhibitors and receptor
blockers (intended to block the action of angiotensin II and
aldosterone activation consequent to renin release), and diuretics
(intended to counter the renal sympathetic mediated sodium and
water retention). These pharmacologic strategies, however, have
significant limitations including limited efficacy, compliance
issues, side effects, and others. Accordingly, there is a strong
public-health need for alternative treatment strategies.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Many aspects of the present disclosure can be better
understood with reference to the following drawings. The components
in the drawings are not necessarily to scale. Instead, emphasis is
placed on illustrating clearly the principles of the present
disclosure. Furthermore, components can be shown as transparent in
certain views for clarity of illustration only and not to indicate
that the illustrated component is necessarily transparent.
[0013] FIG. 1 illustrates a cryotherapeutic system in accordance
with an embodiment of the present technology.
[0014] FIG. 2A is an enlarged cross-sectional view illustrating an
embodiment of a distal portion of a shaft and a cooling assembly in
a delivery state (e.g., low-profile or collapsed configuration) in
accordance with an embodiment of the present technology.
[0015] FIG. 2B is an enlarged cross-sectional view of the cooling
assembly of FIG. 2A in a deployed stated (e.g., expanded
configuration).
[0016] FIGS. 2C and 2D are enlarged side and end cross-sectional
views of a cooling assembly configured in accordance with another
embodiment of the present technology.
[0017] FIG. 2E is an enlarged cross-sectional view of proximal and
distal portions of a cryotherapeutic device configured in
accordance with yet another embodiment of the present
technology.
[0018] FIG. 3A illustrates cryogenically modulating renal nerves
with a cryotherapeutic system in accordance with an embodiment of
the technology.
[0019] FIG. 3B is a block diagram illustrating a method of
cryogenically modulating renal nerves in accordance with any
embodiment of the present technology.
[0020] FIGS. 4A and 4B are enlarged cross-sectional views of
cryotherapeutic devices having stepped distal end portions
configured in accordance with embodiments of the present
technology.
[0021] FIG. 5A is a partially schematic view of a cryotherapeutic
system configured in accordance with another embodiment of the
present technology.
[0022] FIG. 5B is an enlarged cross-sectional view of a distal
portion of a shaft and a cooling assembly in a deployed state in
accordance with an embodiment of the present technology.
[0023] FIG. 6A is a plan view illustrating a pre-cooling assembly
configured in accordance with an embodiment of the present
technology.
[0024] FIG. 6B is a cross-sectional view illustrating the
pre-cooling assembly of FIG. 6A.
[0025] FIG. 7 is a cross-sectional view illustrating a pre-cooling
assembly having a valve configured in accordance with an embodiment
of the present technology.
[0026] FIG. 8A is a cross-sectional view illustrating a pre-cooling
assembly having a flow separator configured in accordance with an
embodiment of the present technology.
[0027] FIG. 8B is a cross-sectional view illustrating the
pre-cooling assembly of FIG. 8A.
[0028] FIG. 9A is a cross-sectional view illustrating a pre-cooling
assembly having a flow separator configured in accordance with
another embodiment of the present technology.
[0029] FIG. 9B is a cross-sectional view illustrating the
pre-cooling assembly of FIG. 9A.
[0030] FIG. 10 is a partially schematic view illustrating a tubular
member of a pre-cooling assembly coiled around an exhaust portal
within a handle configured in accordance with an embodiment of the
present technology.
[0031] FIG. 11 is a partially schematic view illustrating a tubular
member of a pre-cooling assembly coiled near an exhaust portal
within a handle configured in accordance with an embodiment of the
present technology.
[0032] FIG. 12 is a cross-sectional view illustrating a cooling
assembly having supply tubes with angled distal portions configured
in accordance with an embodiment of the present technology.
[0033] FIG. 13 is a cross-sectional view illustrating a cooling
assembly having a supply tube with a helical portion wrapped around
an exhaust passage configured in accordance with an embodiment of
the present technology.
[0034] FIG. 14 is a cross-sectional view illustrating a cooling
assembly having a supply tube with a helical portion wrapped around
an exhaust passage configured in accordance with another embodiment
of the present technology.
[0035] FIG. 15A is a cross-sectional view illustrating a cooling
assembly having an inner balloon with inner-balloon orifices
configured in accordance with an embodiment of the present
technology.
[0036] FIG. 15B is a cross-sectional view illustrating the cooling
assembly of FIG. 15A.
[0037] FIG. 16A is a cross-sectional view illustrating a cooling
assembly having an inner balloon with inner-balloon orifices and an
outer balloon with a raised helical portion configured in
accordance with an embodiment of the present technology.
[0038] FIG. 16B is a cross-sectional view illustrating the cooling
assembly of FIG. 16A.
[0039] FIG. 17A is a cross-sectional view illustrating a cooling
assembly having elongated, thermally-insulative members configured
in accordance with an embodiment of the present technology.
[0040] FIG. 17B is a cross-sectional view illustrating the cooling
assembly of FIG. 17A.
[0041] FIG. 18A is a cross-sectional view illustrating a cooling
assembly having elongated, thermally-insulative members configured
in accordance with another embodiment of the present
technology.
[0042] FIG. 18B is a cross-sectional view illustrating the cooling
assembly of FIG. 18A.
[0043] FIG. 19A is a profile view illustrating a cooling assembly
having a helical thermally-insulative member configured in
accordance with an embodiment of the present technology.
[0044] FIGS. 19B and 19C are cross-sectional views illustrating the
cooling assembly of FIG. 19A.
[0045] FIG. 20A is a profile view illustrating a cooling assembly
having a thermally-insulative member resembling an intertwined
double helix configured in accordance with an embodiment of the
present technology.
[0046] FIGS. 20B and 20C are cross-sectional views illustrating the
cooling assembly of FIG. 20A.
[0047] FIG. 21A is a cross-sectional view illustrating a cooling
assembly having elongated, thermally-insulative members movable
within a balloon configured in accordance with another embodiment
of the present technology.
[0048] FIG. 21B is a cross-sectional view illustrating the cooling
assembly of FIG. 21A.
[0049] FIG. 21C is a cross-sectional view illustrating the cooling
assembly of FIG. 21A in a delivery state within a delivery
sheath.
[0050] FIG. 22A is a cross-sectional view illustrating a cooling
assembly having elongated, thermally-insulative members movable
within a balloon configured in accordance with an embodiment of the
present technology.
[0051] FIG. 22B is a cross-sectional view illustrating the cooling
assembly of FIG. 22A.
[0052] FIG. 23A is a profile view illustrating a cooling assembly
having multiple partially-circumferential balloons configured in
accordance with an embodiment of the present technology.
[0053] FIG. 23B is an isometric view illustrating the cooling
assembly of FIG. 23A.
[0054] FIG. 24A is a profile view illustrating a cooling assembly
having multiple partially-circumferential balloons configured in
accordance with another embodiment of the present technology.
[0055] FIG. 24B is an isometric view illustrating the cooling
assembly of FIG. 24A.
[0056] FIG. 25 is a profile view illustrating a cooling assembly
having a helical recess configured in accordance with an embodiment
of the present technology.
[0057] FIG. 26 is a profile view illustrating a cooling assembly
having spaced apart recesses configured in accordance with an
embodiment of the present technology.
[0058] FIG. 27A is a profile view illustrating a cooling assembly
having spaced apart recesses configured in accordance with another
embodiment of the present technology.
[0059] FIG. 27B is a cross-sectional view illustrating the cooling
assembly of FIG. 27A.
[0060] FIG. 27C is an isometric view illustrating the cooling
assembly of FIG. 27A.
[0061] FIG. 28 is a profile view illustrating a cooling assembly
having spaced apart protrusions configured in accordance with an
embodiment of the present technology.
[0062] FIG. 29 is a profile view illustrating a cooling assembly
having a helical balloon wrapped around an exhaust passage
configured in accordance with an embodiment of the present
technology.
[0063] FIG. 30 is a profile view illustrating a cooling assembly
having a helical balloon wrapped around a supply lumen configured
in accordance with an embodiment of the present technology.
[0064] FIG. 31 is a profile view illustrating a cooling assembly
having a helical balloon wrapped around a supply lumen configured
in accordance with another embodiment of the present
technology.
[0065] FIG. 32A is a profile view illustrating a cooling assembly
having a shaping member with a shape memory configured in
accordance with an embodiment of the present technology.
[0066] FIG. 32B is a cross-sectional view illustrating the cooling
assembly of FIG. 32A.
[0067] FIG. 33A is a profile view illustrating a cooling assembly
having a balloon curved along its length configured in accordance
with an embodiment of the present technology.
[0068] FIGS. 33B and 33C are cross-sectional views illustrating the
cooling assembly of FIG. 33A.
[0069] FIG. 33D is a cross-sectional view illustrating the cooling
assembly of FIG. 33A in a delivery state within a delivery
sheath.
[0070] FIG. 34 is a cross-sectional view illustrating a cooling
assembly having a balloon curved along its length configured in
accordance with another embodiment of the present technology.
[0071] FIG. 35A is a profile view illustrating a cooling assembly
having a balloon having a constrained longitudinal portion
configured in accordance with an embodiment of the present
technology.
[0072] FIG. 35B is a cross-sectional view illustrating the cooling
assembly of FIG. 35A.
[0073] FIG. 36 is a cross-sectional view illustrating a cooling
assembly having a balloon having a constrained longitudinal portion
configured in accordance with another embodiment of the present
technology.
[0074] FIG. 37 is a profile view illustrating a cooling assembly
having a looped balloon configured in accordance with an embodiment
of the present technology.
[0075] FIG. 38A is a profile view illustrating a cooling assembly
having multiple elongated balloons configured in accordance with an
embodiment of the present technology.
[0076] FIG. 38B is a cross-sectional view illustrating the cooling
assembly of FIG. 38A.
[0077] FIG. 39A is a profile view illustrating a cooling assembly
having multiple elongated balloons configured in accordance with
another embodiment of the present technology.
[0078] FIGS. 39B and 39C are cross-sectional views illustrating the
cooling assembly of FIG. 39A.
[0079] FIG. 40 is a cross-sectional view illustrating a cooling
assembly having multiple elongated balloons configured in
accordance with another embodiment of the present technology.
[0080] FIG. 41 is a profile view illustrating a cooling assembly
having multiple helical balloons configured in accordance with an
embodiment of the present technology.
[0081] FIG. 42 is a profile view illustrating a cooling assembly
having multiple helical balloons configured in accordance with
another embodiment of the present technology.
[0082] FIG. 43A is a profile view illustrating a cooling assembly
having multiple elongated balloons attached to a shaping member
configured in accordance with an embodiment of the present
technology.
[0083] FIG. 43B is a cross-sectional view illustrating the cooling
assembly of FIG. 43A.
[0084] FIG. 43C is a profile view illustrating the cooling assembly
of FIG. 43A with the shaping member retracted.
[0085] FIG. 44A is a profile view illustrating a cooling assembly
having multiple elongated balloons attached to a shaping member
configured in accordance with another embodiment of the present
technology.
[0086] FIG. 44B is a cross-sectional view illustrating the cooling
assembly of FIG. 44A.
[0087] FIG. 44C is a profile view illustrating the cooling assembly
of FIG. 44A with the shaping member retracted.
[0088] FIG. 45A is a profile view illustrating a cooling assembly
having multiple elongated balloons of different composition
configured in accordance with an embodiment of the present
technology.
[0089] FIG. 45B is a cross-sectional view illustrating the cooling
assembly of FIG. 45A expanded to a first cross-sectional
dimension.
[0090] FIG. 45B-1 is an enlarged cross-sectional view illustrating
a partition shown in FIG. 45B.
[0091] FIG. 45C is a cross-sectional view illustrating the cooling
assembly of FIG. 45A expanded to a second cross-sectional
dimension, larger than the first cross-sectional dimension.
[0092] FIG. 46 is a cross-sectional view illustrating a cooling
assembly having multiple elongated balloons of different
composition configured in accordance with another embodiment of the
present technology.
[0093] FIG. 46-1 is an enlarged cross-sectional view illustrating a
partition shown in FIG. 46.
[0094] FIG. 47 is a profile view illustrating a cooling assembly
having a helical primary balloon wrapped around a secondary balloon
configured in accordance with an embodiment of the present
technology.
[0095] FIG. 48A is a profile view illustrating a cooling assembly
having a helical primary balloon within a secondary balloon
configured in accordance with an embodiment of the present
technology.
[0096] FIG. 48B is a cross-sectional view illustrating the cooling
assembly of FIG. 48A.
[0097] FIG. 49 is a profile view illustrating a cooling assembly
having a helical primary balloon wrapped around a secondary balloon
configured in accordance with another embodiment of the present
technology.
[0098] FIG. 50 is a profile view illustrating a cooling assembly
having a helical primary balloon wrapped around a secondary balloon
configured in accordance with another embodiment of the present
technology.
[0099] FIG. 51 is a profile view illustrating a cooling assembly
having a helical primary balloon wrapped around a secondary balloon
configured in accordance with another embodiment of the present
technology.
[0100] FIG. 52A is a profile view illustrating a distal portion of
a cryotherapeutic device including a cooling assembly and an
occlusion member configured in accordance with an embodiment of the
present technology.
[0101] FIG. 52B is a cross-sectional view illustrating the distal
portion of FIG. 52A.
[0102] FIG. 53 is a cross-sectional view illustrating a distal
portion of a cryotherapeutic device including a cooling assembly
and an occlusion member configured in accordance with another
embodiment of the present technology.
[0103] FIG. 54 is a cross-sectional view illustrating a cooling
assembly that can be well-suited for circulation of refrigerant
without phase change configured in accordance with an embodiment of
the present technology.
[0104] FIG. 55 is a cross-sectional view illustrating a cooling
assembly that can be well-suited for circulation of refrigerant
without phase change configured in accordance with another
embodiment of the present technology.
[0105] FIG. 56 is a conceptual illustration of the sympathetic
nervous system (SNS) and how the brain communicates with the body
via the SNS.
[0106] FIG. 57 is an enlarged anatomic view of nerves innervating a
left kidney to form the renal plexus surrounding the left renal
artery.
[0107] FIGS. 58A and 58B are anatomic and conceptual views,
respectively, of a human body depicting neural efferent and
afferent communication between the brain and kidneys.
[0108] FIGS. 59A and 59B are anatomic views of the arterial
vasculature and venous vasculature, respectively, of a human.
DETAILED DESCRIPTION
[0109] Specific details of several embodiments of the technology
are described below with reference to FIGS. 1-59B. Although many of
the embodiments are described below with respect to devices,
systems, and methods for intravascular modulation of renal nerves
using cryotherapeutic approaches, other applications and other
embodiments in addition to those described herein are within the
scope of the technology. Additionally, several other embodiments of
the technology can have different configurations, components, or
procedures than those described herein. A person of ordinary skill
in the art, therefore, will accordingly understand that the
technology can have other embodiments with additional elements, or
the technology can have other embodiments without several of the
features shown and described below with reference to FIGS.
1-59B.
[0110] With regard to the terms "distal" and "proximal" within this
description, unless otherwise specified, the terms can reference a
relative position of the portions of a cryotherapeutic device
and/or an associated delivery device with reference to an operator
and/or a location in the vasculature. For example, proximal can
refer to a position closer to the operator of the device or an
incision into the vasculature, and distal can refer to a position
that is more distant from the operator of the device or further
from the incision along the vasculature.
Renal Neuromodulation
[0111] Renal neuromodulation is the partial or complete
incapacitation or other effective disruption of nerves innervating
the kidneys. In particular, renal neuromodulation comprises
inhibiting, reducing, and/or blocking neural communication along
neural fibers (i.e., efferent and/or afferent nerve fibers)
innervating the kidneys. Such incapacitation can be long-term
(e.g., permanent or for periods of months, years, or decades) or
short-term (e.g., for periods of minutes, hours, days, or weeks).
Renal neuromodulation is expected to efficaciously treat several
clinical conditions characterized by increased overall sympathetic
activity, and in particular conditions associated with central
sympathetic overstimulation such as hypertension, heart failure,
acute myocardial infarction, metabolic syndrome, insulin
resistance, diabetes, left ventricular hypertrophy, chronic and end
stage renal disease, inappropriate fluid retention in heart
failure, cardio-renal syndrome, and sudden death. The reduction of
afferent neural signals contributes to the systemic reduction of
sympathetic tone/drive, and renal neuromodulation is expected to be
useful in treating several conditions associated with systemic
sympathetic overactivity or hyperactivity. Renal neuromodulation
can potentially benefit a variety of organs and bodily structures
innervated by sympathetic nerves. For example, a reduction in
central sympathetic drive may reduce insulin resistance that
afflicts patients with metabolic syndrome and Type II diabetics.
Additionally, osteoporosis can be sympathetically activated and
might benefit from the downregulation of sympathetic drive that
accompanies renal neuromodulation. A more detailed description of
pertinent patient anatomy and physiology is provided below.
[0112] Various techniques can be used to partially or completely
incapacitate neural pathways, such as those innervating the
kidneys. Cryotherapy, for example, includes cooling tissue at a
target site in a manner that modulates neural function. The
mechanisms of cryotherapeutic tissue damage include, for example,
direct cell injury (e.g., necrosis), vascular injury (e.g.,
starving the cell from nutrients by damaging supplying blood
vessels), and sublethal hypothermia with subsequent apoptosis.
Exposure to cryotherapeutic cooling can cause acute cell death
(e.g., immediately after exposure) and/or delayed cell death (e.g.,
during tissue thawing and subsequent hyperperfusion). Several
embodiments of the present technology include cooling a structure
at or near an inner surface of a renal artery wall such that
proximate (e.g., adjacent) tissue is effectively cooled to a depth
where sympathetic renal nerves reside. For example, the cooling
structure is cooled to the extent that it causes therapeutically
effective, cryogenic renal-nerve modulation. Sufficiently cooling
at least a portion of a sympathetic renal nerve is expected to slow
or potentially block conduction of neural signals to produce a
prolonged or permanent reduction in renal sympathetic activity.
[0113] Cryotherapy has certain characteristics that can be
beneficial for intravascular renal neuromodulation. For example,
rapidly cooling tissue provides an analgesic effect such that
cryotherapies may be less painful than ablating tissue at high
temperatures. Cryotherapies may thus require less analgesic
medication to maintain patient comfort during a procedure compared
to heat ablation procedures. Additionally, reducing pain mitigates
patient movement and thereby increases operator success and reduces
procedural complications. Cryotherapy also typically does not cause
significant collagen tightening, and thus cryotherapy is not
typically associated with vessel stenosis.
[0114] Cryotherapies generally operate at temperatures that cause
cryotherapeutic applicators to adhere to moist tissue. This can be
beneficial because it promotes stable, consistent, and continued
contact during treatment. The typical conditions of treatment can
make this an attractive feature because, for example, a patient can
move during treatment, a catheter associated with an applicator can
move, and/or respiration can cause the kidneys to rise and fall and
thereby move the renal arteries. In addition, blood flow is
pulsatile and causes the renal arteries to pulse. Adhesion
associated with cryotherapeutic cooling also can be advantageous
when treating short renal arteries in which stable intravascular
positioning can be more difficult to achieve.
Selected Embodiments of Renal Cryogenic Systems
[0115] FIG. 1 illustrates a cryotherapeutic system 100 configured
in accordance with several embodiments of the present technology.
The cryotherapeutic system 100 can include a console 102 and a
cryotherapeutic device 120. In the embodiment shown in FIG. 1, the
console 102 includes a supply container 104, a refrigerant 106 in
the supply container 104, and a supply control valve 108 in fluid
communication with the supply container 104. The supply container
104 can be a single-use cartridge or a larger container that
contains a sufficient volume of refrigerant 106 to perform multiple
procedures. The larger supply containers, for example, can be
refillable cylinders. The supply container 104 is configured to
retain the refrigerant 106 at a desired pressure. For example, in
one embodiment, liquid N.sub.2O is contained in the supply
container 104 at a pressure of 750 psi or greater so it is in at
least a substantially liquid state at ambient temperatures. In
other embodiments, the refrigerant 106 can include carbon dioxide,
a hydrofluorocarbon ("HFC"; e.g., Freon.RTM., R-410A, etc.), and/or
other suitable compressed or condensed refrigerants that can be
retained in the supply container 104 at a sufficiently high
pressure to maintain the refrigerant 106 in at least a
substantially liquid state at ambient temperatures (e.g.,
approximately 210 psi for R-410A).
[0116] The supply control valve 108 is coupled to a supply line 110
configured to transport the refrigerant 106 to the cryotherapeutic
device 120. The supply control valve 108 can be operated manually
or automatically. The console 102 can optionally include a pump
111, such as a vacuum pump or a DC power pump, and/or a
backpressure control valve 113 coupled to an exhaust line 115
configured to receive exhausted refrigerant 117 from the
cryotherapeutic device 120. The pump 111 can reduce the
backpressure of evaporated refrigerant and, in conjunction with the
supply flow rate, increase refrigeration power. In other
embodiments, the expanded refrigerant 117 can exhaust to ambient
pressure.
[0117] The console 102 can further include an optional controller
118 that operates the supply control valve 108 and the backpressure
control valve 113. The controller 118, for example, can be a
processor or dedicated circuitry that implements a computerized
algorithm for executing a procedure automatically. The console 102
may also include an optional user interface that receives user
input and/or provides information to the user and/or circuitry for
monitoring optional sensors (e.g., pressure or temperature) if
present in the cryotherapeutic device 120. In one embodiment, the
controller 118 operates the backpressure control valve 113 to
control the amount of vacuum applied to the exhausted refrigerant
117 returning from the cryotherapeutic device 120. This modulates
the backpressure of the evaporated refrigerant to control the
temperature in the cryotherapeutic device 120. In another
embodiment, the supply control valve 108 and/or the backpressure
control valve 113 can be used to increase the backpressure of
exhausted refrigerant 117. Increasing the backpressure of exhausted
refrigerant 117 could increase the boiling point of the
refrigerant. For example, in the case of N.sub.2O, a slight
increase in backpressure from 1 atm to about 2 atm would raise the
boiling point from about 88.degree. C. to about -75.degree. C.; an
increase in backpressure to 3 atm would raise the boiling point to
about -65.degree. C.
[0118] In certain embodiments, the cryotherapeutic system 100 may
also precool the refrigerant 106 to provide greater refrigeration
power in the refrigerant 106 by the time it reaches the cooling
system. The system 100, for example, can include a precooler 119
(shown in dashed lines) in the console 102. In other embodiments,
the system 100 can include a precooler along the supply line 110,
at a handle at a proximal region of the system 100, or elsewhere
coupled to the cryotherapeutic device 120.
[0119] The cryotherapeutic device 120 includes a shaft 122 that has
a proximal portion 124, a handle 125 at a proximal region of the
proximal portion 124, and a distal portion 126 extending distally
relative to the proximal portion 124. The cryotherapeutic device
120 can further include a cooling assembly 130 at the distal
portion 126 of the shaft 122. The shaft 122 is configured to locate
the distal portion 126 intravascularly at a treatment site
proximate (e.g., in or near) a renal artery or renal ostium, and
the cooling assembly 130 is configured to provide
therapeutically-effective cryogenic renal-nerve modulation.
[0120] FIG. 2A is an enlarged cross-sectional view illustrating an
embodiment of the distal portion 126 of the shaft 122 and the
cooling assembly 130 in a delivery state (e.g., low-profile or
collapsed configuration), and FIG. 2B is an enlarged
cross-sectional view of the cooling assembly 130 in a deployed
stated (e.g., expanded configuration). In the embodiment shown in
FIG. 2A, the distal portion 126 of the shaft 122 can include a
first zone 127a and a second zone 127b (separated by broken lines)
recessed inwardly relative to the first zone 127a. The first zone
127a can be demarcated from the second zone 127b by a step 128,
such as a rabbet (e.g., an annular or other circumferential groove
configured to be fitted with another member). The first zone 127a
can accordingly have a first outer dimension or first
cross-sectional dimension (e.g., area or diameter), and the second
zone 127b can have a second outer dimension or second
cross-sectional dimension less than the first dimension. The shaft
122 can be sized to fit within a sheath 150 of 8 Fr or smaller
(e.g., a 6 Fr guide sheath) to accommodate small renal
arteries.
[0121] The cryotherapeutic device 120 can also include a supply
tube or lumen 132 and an exhaust tube or lumen 134 along at least a
portion of the shaft 122. The supply lumen 132 can be a small tube
configured to retain the refrigerant in a liquid state at a high
pressure. The inner diameter of the supply lumen 132 is selected
such that at least a portion of the refrigerant reaching the
cooling assembly 130 is in a liquid state at a distal end 135 of
the supply lumen 132. The exhaust lumen 134 can be an outer tube,
and the supply lumen 132 can extend within the exhaust lumen 134
along at least the distal portion 126 of the shaft. As described in
further detail below, several embodiments of the cryotherapeutic
device 120 can further include one or more sensors 138, such as a
temperature sensor or pressure sensor, coupled to the controller
118 (FIG. 1) by a lead 139. In several embodiments, the
cryotherapeutic system 100 can be configured to verify the proper
calibration of the sensors 138 before a cryotherapeutic treatment.
For example, the cryotherapeutic system 100 can automatically
compare a measured temperature from a temperature sensor with room
temperature as the cryotherapeutic system 100 initiates a power up
cycle to check that the temperature sensor is functioning
properly.
[0122] The embodiment of the cooling assembly 130 shown in FIGS. 2A
and 2B can have an applicator 140 including a balloon 142 or other
type of expandable member that defines an expansion chamber
configured to fully occlude a renal artery or renal ostium. The
balloon 142 can be relatively short (e.g., 10 mm or less) to
accommodate the length and tortuosity of a renal artery (e.g.,
between 4-6 cm) and can have a diameter in an expanded
configuration large enough to contact a significant portion of the
inner circumference of the renal artery (e.g., between 3-10 mm in
diameter). In other embodiments described below, balloons can be
configured to only partially occlude a renal artery or renal
ostium. The balloon 142 can comprise a compliant material, a
non-compliant material, and/or a combination of compliant and
non-compliant materials. In various embodiments, for example, the
balloon 142 can be made from polyurethane and/or other compliant or
semi-compliant materials that can expand and conform to vessel
walls to fully occlude vessels of varying sizes (e.g., vessels
having an inner diameter from approximately 3 mm to approximately
10 mm, or in specific applications approximately 4 mm to
approximately 8 mm). In other embodiments, the balloon 142 can be
made from nylon and/or other non-compliant materials and sized to
accommodate vessels within a certain size range. For example, a
non-compliant nylon balloon can be sized to accommodate vessels
having an inner diameter between approximately 3 mm and 6 mm, and a
larger non-compliant nylon balloon can be sized to accommodate
vessels having an inner diameter between approximately 7 mm and 10
mm.
[0123] In the embodiment illustrated in FIGS. 2A and 2B, the distal
portion of the balloon 142 is not connected to a support member
(e.g., the supply lumen 132 and/or other support), and can
therefore be dip molded and/or otherwise formed to have a
continuous distal portion. The continuous distal portion of the
balloon 142 provides a gentle surface with which to contact vessel
walls so as to avoid tearing, puncturing, and/or otherwise damaging
vessel walls. Additionally, the cooling assembly 130 shown in FIG.
2B can have a shorter overall length than a distally connected
balloon, which may facilitate positioning the cooling assembly 130
in relatively short vessels (e.g., a renal artery having a length
of 6 cm or less).
[0124] The cooling assembly 130 can further include an orifice 144
in fluid communication with the expansion chamber. In one
embodiment, the orifice 144 can be defined by a distal end of a
capillary tube 146 inserted into the distal end 135 of the supply
lumen 132. Alternatively, the opening at the distal end 135 of the
supply lumen 132 can define an orifice. The capillary tube 146
and/or the orifice 144 can have a diameter less than that of the
supply lumen 132 to impede the flow of refrigerant proximate the
expansion chamber, thereby increasing the pressure drop of the
refrigerant 106 entering the expansion chamber and concentrating
the refrigeration power at the cooling assembly 130. In other
embodiments, the supply lumen 132 may have a substantially constant
inner diameter (e.g., 0.008 inch (0.203 mm), 0.009 inch (0.023 mm),
0.010 inch (0.254 mm), etc.) such that the orifice 144 has a
diameter at least equal to that of the supply lumen 132. The
cryotherapeutic device 120 can then further include additional
hardware (e.g., valves, flow and pressure gauges, etc.) and/or
software in the handle 125 (FIG. 1) and/or in the console 102 (FIG.
1) to control the refrigerant 106 through the supply lumen 132 and
focus the refrigeration power toward the distal end portion 126 of
the shaft 122.
[0125] The orifice 144 can be sized relative to the area and/or
length of the exhaust lumen 134 at the distal portion 126 of the
shaft 122 to provide a sufficient flow rate of refrigerant, produce
a sufficient pressure drop in the expansion chamber, and allow for
sufficient venting of the exhausted refrigerant 117 through the
exhaust lumen 134. In one embodiment, the orifice 144 can have a
diameter of approximately 0.003 inch (0.076 mm) or more, such as
about 0.004 inch (0.101 mm) to about 0.009 inch (0.229 mm). In
various embodiments, the inner diameter and/or cross-sectional area
of the exhaust lumen 132 and the diameter and/or cross-sectional
area of the orifice 144 can have a ratio between approximately 4:1
and 10:1. For example, the exhaust lumen 132 can have an inner
diameter between approximately 0.030 inch (0.762 mm) and
approximately 0.050 inch (1.27 mm), and the orifice 144 can have a
diameter of approximately 0.003 inch (0.0762 mm) to approximately
0.008 inch (0.203 mm; e.g., 0.004 inch (0.101 mm)). In other
embodiments, the exhaust lumen 134 and the orifice 144 can have
other suitable dimensions. In further embodiments, the shaft 122
may include additional lumens or devices extending there through
(e.g., pressure sensing lumens, additional fluid passageways, etc.)
and the ratio of the cross-sectional dimension of the exhaust lumen
132 to the total cross-sectional dimension occupied by the supply
lumen and/or other members within the shaft 122 can be
approximately 4:1 and 10:1.
[0126] The flow rate of the refrigerant 106 can also be manipulated
by changing the lengths of the supply lumen 132 and the capillary
tube 146 relative to one another. For example, in certain
embodiments, the capillary tube 146 can be at most 1/3 the length
of the supply lumen 132. In various embodiments, the capillary tube
146 can have a length between 2 inches (5.08 cm) and 30 inches
(76.2 cm) and the supply lumen 132 can be sized accordingly. In
other embodiments, the capillary tube 146 can be shorter or longer
relative to the supply lumen 132 and/or the capillary tube 146 can
be omitted.
[0127] The cooling assembly 130 is passed intravascularly to a
target site T in a vessel V while in the delivery configuration
shown in FIG. 2A. Referring to FIG. 2B, the cooling assembly 130
and the sheath 150 are then moved relative to each other such that
the cooling assembly 130 extends distally beyond the sheath 150.
For example, the sheath 150 can be pulled proximally and/or the
cooling assembly 130 can be pushed distally. In operation, the
refrigerant 106 passes through the supply lumen 132, through the
orifice 144, and into the expansion chamber defined by the balloon
142. As the refrigerant 106 passes through the orifice 144, it
expands into a gaseous phase, thereby inflating the balloon and
causing a significant temperature drop in the expansion chamber.
The portion of the applicator 140 contacting the tissue at the
target T can be a heat-transfer region 149 or heat-transfer zone
that, together with the refrigerant 106 in the expansion chamber,
causes therapeutically-effective, cryogenic renal-nerve modulation.
Exhausted refrigerant 117 passes in a proximal direction through
the exhaust lumen 134. In various embodiments, the length of shaft
122 can be minimized to decrease the losses (e.g., friction losses)
of the refrigerant flowing through the supply lumen 132 and through
the exhaust lumen 134, thereby enhancing the refrigeration
potential and the efficiency of the cooling assembly 130. The
additional friction losses that may be caused by longer exhaust
lumens, for example, may inhibit venting of the exhausted
refrigerant 117, and thereby increase the pressure and temperature
within the balloon 142. Accordingly, the shaft 122 can be
configured to have a total overall length of less than 90 cm (e.g.,
80 cm to 85 cm, 70 cm to 80 cm, etc.). In other embodiments, the
shaft 122 can be longer and/or include additional features to
enhance the refrigeration power at the cooling assembly 130.
[0128] The embodiment of the cooling assembly 130 illustrated in
FIGS. 2A and 2B fully occludes the vessel V and produces a
full-circumferential treatment at the target site T (i.e., a
continuous cooled region extending completely around the inner
circumference of the vessel V in a plane that is perpendicular or
otherwise transverse relative to a longitudinal direction of the
vessel V at the target T). Fully occluding the vessel V limits
blood flow from heating the heat-transfer region 149 such that the
cooling power of the refrigerant can be more efficiently applied to
the target T. Although occlusion of the renal blood vessel for an
excessive period of time can potentially cause ischemia of a
kidney, it has been found that renal blood flow can be fully
occluded for a period of time sufficient to complete cryotherapy at
the target T (e.g., 2-5 minutes). The controller 118 (FIG. 1) can
be programmed to limit the duration of refrigerant flow (e.g., 2-5
minutes) by using an electronic or mechanical timer to control a
valve. Alternatively, a timer can be incorporated into the handle
125 (FIG. 1) or other portion of the cryotherapeutic device 120. If
present, the sensor 138 may provide feedback to the controller 118
to regulate or control the system 100. In some embodiments, it may
be desirable for the control algorithm to be fully automated, but
in other embodiments the delivered therapy may utilize user input.
In further embodiments, the duration of refrigerant flow can be
limited by the volume of the refrigerant in the supply container
104. As described in greater detail below, in other embodiments,
the cooling assembly 130 can be configured to partially occlude
blood flow.
[0129] In various embodiments, the sensor 138 can be a thermocouple
positioned on an outer surface of the balloon 142 and configured to
provide a real-time temperature reading of the external temperature
of the balloon 142. As such, the cryotherapeutic system 100 can be
regulated via the controller 118 (e.g., using a software control
loop) such that it ramps the cooling power output up and down based
on the difference between the real-time external balloon
temperature and a predetermined treatment temperature (e.g.,
-40.degree. C., -60.degree. C., etc.). For example, the cooling
power output can be regulated by switching valves (e.g., the supply
control valve 108 and/or the backpressure control valve 113) on and
off at various stages of a cryotherapeutic treatment in response to
measured temperatures. In other embodiments, the cooling power
output can be modulated using proportional control wherein the
delivery pressure of the refrigerant 106 and/or the flow rate of
the vacuum pump 111 can be varied in response to the measured
external balloon temperature. Accordingly, the external
thermocouple allows the cryotherapeutic system 100 to compensate
for variables that affect cooling at the target site T, such as
variations in artery diameter, blood flow through the artery,
and/or blood flow through other vessels in the vicinity of the
renal artery.
[0130] FIGS. 2C-2E are enlarged cross-sectional views illustrating
the distal portion 126 of the cryotherapeutic device 120 configured
in accordance with other embodiments of the present technology.
Referring to FIG. 2C, a distal portion 152 of the balloon 142 can
be connected to a distal connector 162 via thermal bonding,
adhesives, and/or other suitable attachment mechanisms. The distal
connector 162 can have a curved, bullet-like tip as shown in FIG.
2C or can be otherwise configured to provide an atraumatic tip for
navigation through the vasculature.
[0131] The cryotherapeutic device 120 further includes a guide wire
lumen 133a through which a guide wire 133b can be received to guide
the distal portion 126 of the shaft 122 through the vasculature. In
the embodiment illustrated in FIG. 2C, the guide wire lumen 133a
extends completely through the shaft 122 from the proximal opening
of the shaft 122 at an adaptor 201 (e.g., at the handle 125 shown
in FIG. 1) to beyond the distal opening of the shaft 122 in an
over-the-wire (OTW) configuration, whereas in the embodiment
illustrated in FIG. 2E, the guide wire lumen 133a extends through
only a portion of the shaft 122 in a rapid exchange (RX)
configuration. Although the proximal end of the guide wire lumen
133a is shown in FIG. 2E extending through the sidewall of the
shaft 122 at the distal portion 126, in other embodiments, the
proximal end of the guide wire lumen 133a can be accessible
anywhere between the proximal and distal ends of the shaft 122. The
guide wire lumen 133a shown in FIGS. 2C-2E, or variations thereof,
may be included in various embodiments described herein to
facilitate navigation through the vasculature. Suitable OTW and RX
guide wire configurations are disclosed in U.S. Pat. No. 545,134,
filed Oct. 27, 1994, U.S. Pat. No. 5,782,760, filed May 23, 1995,
U.S. Patent Publication No. 2003/0040769, filed Aug. 23, 2001, and
U.S. Patent Publication No. 2008/0171979, filed Oct. 17, 2006, each
of which is incorporated herein by reference in its entirety.
[0132] FIG. 3A illustrates cryogenically modulating renal nerves
with an embodiment of the system 100. The cryotherapeutic device
120 provides access to the renal plexus through an intravascular
path P that leads to a respective renal artery RA. As illustrated,
a section of the proximal portion 124 of the shaft 122 is exposed
externally of the patient. By manipulating the proximal portion 124
of the shaft 122 from outside the intravascular path P, the
caregiver may advance the shaft 122 through the tortuous
intravascular path P (e.g., via the femoral artery or a radial
artery) and remotely manipulate the distal portion 126 (e.g., with
an actuator in the handle 125). For example, the shaft 122 may
further include one or more pull-wires or other guidance devices to
direct the distal portion 126 through the vasculature. Image
guidance, e.g., CT, radiographic, IVUS, OCT or another suitable
guidance modality, or combinations thereof, may be used to aid the
caregiver's manipulation. After the cooling applicator 140 is
adequately positioned in the renal artery RA or at the renal
ostium, it can be expanded or otherwise deployed using the console
102 (FIG. 1), the handle 125 (FIG. 1), and/or another means until
the applicator 140 contacts the inner wall of the renal artery RA.
The purposeful application of cooling power from the applicator 140
is then applied to tissue to induce one or more desired
neuromodulating effects on localized regions of the renal artery
and adjacent regions of the renal plexus, which lay intimately
within, adjacent to, or in close proximity to the adventitia of the
renal artery. The purposeful application of the neuromodulating
effects may achieve neuromodulation along all or a portion of the
renal plexus.
[0133] The neuromodulating effects are generally a function of, at
least in part, the temperature of the applicator 140, contact
between the applicator 140 and vessel wall, dwell time of the
applicator 140 while cooling, number of cooling cycles (e.g., one
or more cooling cycles separated by a warming period), and blood
flow through the vessel. Desired cooling effects may include
cooling the applicator such that the temperatures of target neural
fibers are below a desired threshold to achieve cryo alteration or
ablation. For example, the refrigerant gas in the applicator 140
can be cooled to a temperature of about -88.degree. C. to about
-60.degree. C., or in other embodiments the gas in the applicator
140 can have a temperature of about -80.degree. C. to about
-40.degree. C.
[0134] In various embodiments, neuromodulating effects can occur
within 100 seconds (e.g., 90 seconds, 75 seconds, 60 seconds, 30
seconds, etc.) of applying the cooled applicator 140 to the renal
artery RA or renal ostium in one or more cooling cycles. In one
embodiment, the process can include two cooling cycles separated by
a warming period, but in other embodiments the process can have
more than two cooling cycles separated by warming periods. The
cooling cycles can have the same duration or different durations,
such as approximately 10 seconds to approximately 90 seconds each.
The duration(s) of the warming periods can be sufficient to
partially or completely thaw frozen matter at the cooling
interface. In several embodiments, the duration(s) of the warming
periods can be from about 5 seconds to about 90 seconds. Individual
warming periods between cooling cycles may last for the same amount
of time or for different amounts of time. The durations of the
cooling and warming cycles can be predetermined and programmed into
an algorithm, or the system can include an automatic control
algorithm using a feedback loop based on the pressure and/or
temperature within and/or on the external surface of the balloon.
For example, the control algorithm can terminate a warming cycle
and initiate a cooling cycle by assessing when the frozen matter
has sufficiently thawed based on the pressure and/or temperature
measurements. Depending upon the number and length of cooling
cycles, the total procedure time from the deployment of the cooling
assembly 130 (e.g., as shown in FIG. 2B) to retraction of the
cooling assembly to the delivery state (e.g., as shown in FIG. 2A)
can be less than five minutes (e.g., less than 3 minutes). When
both renal arteries RA are treated, the total procedure time from
the time of deployment of the cooling assembly 130 in the first
renal artery RA, to repositioning, deployment, and retraction of
the cooling assembly 130 in the second renal artery RA can be less
than 12 minutes (e.g., 10 minutes, 6 minutes, etc.). In certain
embodiments, the procedure time can be decreased by locating the
applicator 140 around a full circumference of the renal artery RA
(e.g., along the same plane or along parallel planes spaced
laterally apart) and performing neuromodulation in a single
application. In other embodiments, the applicator 140 can be
applied to less than a full circumference of the renal artery RA
and/or in more than one application.
[0135] FIG. 3B is a block diagram illustrating a method 300 of
cryogenically modulating renal nerves using the system 100
described above with reference to FIGS. 1-3A or another suitable
system in accordance with an embodiment of the present technology
described below. Referring to FIGS. 1-3B together, the method 300
can include intravascularly locating the cooling assembly 130 in
the delivery state (e.g., as shown in FIG. 2A) in a renal artery or
renal ostium (block 305). The cryotherapeutic device 120 and/or
portions thereof (e.g., the cooling assembly 130) can be inserted
into a guide catheter (e.g., the sheath 150 shown in FIGS. 2A-2C)
to facilitate intravascular delivery of the cooling assembly 130.
In certain embodiments, for example, the cryotherapeutic device 120
can be configured to fit within an 8 Fr guide catheter or smaller
(e.g., 7 Fr, 6 Fr, etc.) to access small peripheral vessels. As
described above, an OTW or RX guide wire can also be used to
manipulate and enhance control of the shaft 122 and the cooling
assembly 130.
[0136] The method 300 can further include connecting the
cryotherapeutic device 120 to the console 102 (block 310), and
partially or fully inflating an expandable member of the cooling
assembly 130 (e.g., the balloon 142) to determine whether the
cooling assembly 130 is in the correct position at the target site
(blocks 315 and 320). The expandable member can be inflated via the
supply lumen 132 with refrigerant from the supply container 104 at
the console 102 and/or with other suitable fluids (e.g., air) from
a secondary fluid supply reservoir in fluid communication the
expandable member. If the cooling assembly 130 is not in the
desired location, at least some of the pressure in the expandable
member can be released (block 325). In certain embodiments, for
example, the expandable member can be fully deflated by
disconnecting the cryotherapeutic device 120 from the console 102
and using a syringe to manually deflate the expandable member via a
proximal end portion of the shaft 122. In other embodiments, the
cryotherapeutic device 120 can remain attached to the console 102,
and a syringe can be connected along the length of the shaft 122
(e.g., a stopcock syringe) to deflate the expandable member. In
further embodiments, the controller 118 at the console 102 can
include algorithms for partially or fully deflating the expandable
member. In still further embodiments, the cooling assembly 130 can
be positioned at the target site using radiopaque markers and/or
markings.
[0137] Once the cooling assembly 130 is properly located within the
first renal artery or ostium thereof, the console 102 can be
manipulated to initiate cooling at the cooling assembly 130 that
modulates the renal nerves to cause partial or full denervation of
the kidney (block 330). Cryogenic cooling can be applied for one or
more cycles (e.g., for 30 second increments, 60 second increments,
90 second increments, etc.) in one or more locations along the
circumference and/or length of the first renal artery or first
renal ostium. In one particular embodiment, for example, two 90
second cycles may be used. In various embodiments, the expandable
member can remain fully or partially inflated to maintain the
position of the cooling assembly 130 at the target site between
cooling cycles.
[0138] After renal-neuromodulation at the first renal artery, the
method 300 can further include deflating the expandable member and
retracting the cooling assembly 130 into the delivery state (block
335). The expandable member can be deflated manually by detaching
the cryotherapeutic device 120 from the console 102 and connecting
a syringe or other suitable evacuation device to the proximal end
of the shaft 122. In other embodiments, a syringe can be connected
along the length of the shaft 122 without detaching the
cryotherapeutic device 120 from the console 102, or the expandable
member can be deflated automatically (e.g., via the controller
118). In certain embodiments, the cooling assembly 130 can be
withdrawn back into the guide catheter after the expandable member
is deflated. Optionally, the cooling assembly 130 can be removed
from the guide catheter during repositioning and temporarily stored
in a sterile location (e.g., in a saline solution).
[0139] The cooling assembly 130 can then be located in a second
renal artery or second renal ostium (block 340), and the expandable
member can be expanded to confirm the position of the cooling
assembly 130 (block 345). In selected embodiments, a contrast
material can be delivered distally beyond the cooling assembly 130
and fluoroscopy and/or other suitable imaging techniques can be
used to locate the second renal artery. If necessary, the used
supply container 104 in the console 102 can be refilled or removed
and replaced with a new supply container (e.g., a disposable
refrigerant cartridge) to provide sufficient refrigerant for
renal-neuromodulation at the second renal artery or second renal
ostium. In embodiments where the console 102 was detached from the
cryotherapeutic device 120 during repositioning of the cooling
assembly 130, the console 102 can be reconnected to the
cryotherapeutic device 120 such that the method 300 continues by
applying cryogenic cooling to effectuate renal-neuromodulation at
the second renal artery or second renal ostium (block 350).
[0140] In other embodiments, various steps in the method 300 can be
modified, omitted, and/or additional steps may be added. For
example, the console 102 can be turned on and loaded with the
supply container 104 outside the sterile field in which the
cryotherapy occurs, and positioned in a sterile bag or housing such
that it can be brought into the sterile field. If the supply
container 104 must be reloaded or refilled during cryotherapy, the
console 102 can be removed from the sterile field, reloaded, and
placed back into the sterile field (e.g., in a sterile bag or
housing). In other embodiments, the empty supply container 104 can
be removed from the console 102 and deposited within a sterile bag
or housing surrounding the console 102, and a new supply container
can be attached to the console 102 within the sterile bag or
housing such that the console 102 does not leave the sterile field
during treatment. In further embodiments, the console 102 can
remain outside the sterile field and operated remotely.
[0141] FIG. 4A is an enlarged cross-sectional view of a distal
portion 426 of a cryotherapeutic device 420 configured in
accordance with another embodiment of the present technology. The
cryotherapeutic device 420 includes features generally similar to
the features of the cryotherapeutic device 120 described above with
reference to FIGS. 1-3B. For example, the cryotherapeutic device
420 includes the elongated shaft 122, the supply and exhaust lumens
132 and 134 extending along at least a portion of the shaft 122,
and the cooling assembly 130 at the distal portion 426 of the shaft
102. The cooling assembly 130 includes an expandable member, such
as the balloon 142 or other suitable expandable member, that
defines at least a portion of the expansion chamber and receives
the refrigerant 106 in an at least substantially gas phase via the
orifice 144.
[0142] In the illustrated embodiment, the distal end 135 of the
supply lumen 132 is coupled to a distal portion 452 of the balloon
142 to provide additional support and/or control for the cooling
assembly 130, and the orifice 144 is an opening positioned along
the length of the supply lumen 132 (e.g., rather than at the distal
end 135 of the supply lumen 132 or at the end of a capillary tube).
The supply lumen 132 and the distal portion 452 of the balloon 142
can be attached together using adhesives (e.g., thermal bonds),
fasteners, and/or other suitable attachment mechanisms known in the
art. In other embodiments, the supply lumen 132 can terminate at or
in the expansion chamber, and/or the cryotherapeutic device 420 can
further include a support member (not shown) that extends from the
shaft 122 to at least the distal portion 452 of the balloon
142.
[0143] As shown in FIG. 4A, the cryotherapeutic device 420 can
further include a connector 454 at the proximal portion of the
balloon 142 that can be attached over the distal portion 426 of the
shaft 122 and thereby couple the balloon 142 to the shaft 122. The
connector 454 can be defined by a proximal portion of the balloon
142 (e.g., the neck of the balloon 142) that is integral with the
expandable portion as shown in FIG. 4A, or the connector 454 can be
a separate and distinct component from the balloon 142, such as a
collar or other suitable retainer. The connector 454 can be
attached to the distal portion 426 of the shaft 122 using thermal
bonds, adhesives, interlocking surfaces (e.g., threads), friction
fit, snap fit, suction, and/or other suitable attachment
mechanisms, or the connector 454 can be formed integrally with the
distal portion 426.
[0144] In the illustrated embodiment, the connector 454 is
positioned proximate the step 128 over the second zone 127b of the
distal portion 426 of the shaft 122. As shown in FIG. 4A, the first
zone 127a of the distal portion 426 can have a first outer
cross-sectional dimension or diameter OD.sub.1 and the second zone
127b distal to the step 128 can have a second outer cross-sectional
dimension or diameter OD.sub.2 less than the first outer
cross-sectional dimension OD.sub.1. The reduction in the outer
dimension of the distal portion 426 at the step 128 forms an inward
recess relative to the first zone 127a in which at least a portion
of the connector 454 and the proximal region of the expandable
portion of the balloon 142 can sit, and thereby reduces the profile
of the distal portion 426 of the shaft 122. In certain embodiments,
the step 128 can be dimensioned such that an outer surface 455 of
the first zone 127a is at least substantially flush with an outer
surface 457 of the connector 454. Accordingly, the outer diameter
OD.sub.2 of the second zone 127b can be equivalent to the outer
diameter OD.sub.1 of the first zone 127a less twice the thickness
of the connector 454. In other embodiments, the outer diameter
OD.sub.2 of the second zone 127b can be greater than or less than
twice the thickness of the connector 454.
[0145] In selected embodiments, the connector 454 is non-expandable
such that it remains within the recess and/or substantially flush
with the outer surface 455 of the first zone 127a when the cooling
assembly 130 moves to the deployed state (e.g., as shown in FIG.
4A). In other embodiments, the connector 454 may be expandable and
increase in cross-sectional area as the cooling assembly 130 moves
to the deployed state.
[0146] In the embodiment shown in FIG. 4A, the cross-sectional area
of the exhaust lumen (e.g., defined by the inner surface(s) of the
shaft 122) also decreases at the transition between the first zone
127a and the second zone 127b such that the distal portion 426 of
the shaft 122 has a first inner cross-sectional dimension or
diameter ID.sub.1 at the first zone 127a and a lesser second inner
cross-sectional dimension or diameter ID.sub.2 at the second zone
127b. To avoid a build up of pressure in the expansion chamber that
may be caused by insufficient venting through the necked-down
exhaust lumen 134, the second zone 127b can be positioned only at
the distal-most end of the shaft 122 proximate the expansion
chamber where the density of the exhausted refrigerant 117 is the
highest. For example, the second zone 127b can have a length of
less than 4 cm (e.g., 2 cm, 1 cm, etc.). The exhausted refrigerant
117 also vents adequately through the smaller inner diameter
ID.sub.2 of the second zone 127b without undue restriction because
the length of the second zone 127b along the longitudinal axis of
the shaft 122 can be relatively short. For example, the length of
the second zone 127b can be minimized to sufficiently accommodate
the connector 454. Accordingly, the smaller exhaust lumen 134 at
the second zone 127b can transport primarily high density exhausted
refrigerant 117 and can expel the exhausted refrigerant 117 into
the larger exhaust lumen 134 at the first zone 127a as the
exhausted refrigerant 117 decreases in density, thereby
facilitating adequate venting through the smaller second inner
diameter ID.sub.2 of the second zone 127b.
[0147] In operation, the inwardly recessed second zone 127b can
reduce the profile of the distal portion 426 of the shaft 122
and/or provide a substantially smooth transition from the shaft 122
to the connector 454 without jeopardizing the venting
characteristics of the exhaust lumen 134. The low-profile distal
portion 426 of the shaft 122 can also facilitate the delivery of a
fluidic contrast material between the shaft 122 and the sheath 150
from the proximal portion 124 (FIG. 1) of the shaft 122 to the
distal portion 426 and around the cooling assembly 130 in the
delivery state (e.g., as shown in FIG. 2A) to image and locate
(e.g., using fluoroscopy) a target in the vasculature. As shown in
FIG. 4A, for example, the recessed second zone 127b provides one or
more passageways or channels C around the distal portion 426 of the
shaft 122 that are large enough to deliver contrast material
distally beyond the cooling assembly 130 without being blocked by a
protruding connector or balloon. In certain embodiments, a
sufficient channel C for the contrast material can be formed when
the difference between the first outer diameter OD.sub.1 and the
second outer diameter OD.sub.2 of the corresponding first and
second zones 127a and 127b is less than 0.01 inch (0.254 mm). In
other embodiments, the difference between the outer dimensions
OD.sub.1 and OD.sub.2 of the first and second zones 127a and 127b
may be greater or smaller. When used during renal-neuromodulation,
a first renal artery can be located by delivering contrast material
distally beyond the cooling assembly 130 in the delivery state via
the channel C. After renal-neuromodulation at the first renal
artery, the cooling assembly 130 can be retracted back from the
deployed state to the delivery state wherein additional contrast
material can be delivered distally beyond the cooling assembly 130
via the channel C to locate a second renal artery.
[0148] In other embodiments, the distal portion 426 of the shaft
122 does not include the stepped-down exhaust lumen 134 shown in
FIG. 4A and, instead, may have a substantially uniform
cross-sectional dimension. Such an exhaust lumen may relatively
easily accommodate a guide wire lumen (e.g., as shown in FIGS.
2C-2E) through which a guide wire can be extended to locate the
cooling assembly 130 at the target site T in the vessel V. In this
embodiment, contrast material for imaging target sites (e.g., two
renal arteries) can be delivered distally via the guide wire lumen
after the guide wire has been retracted.
[0149] FIG. 4B is an enlarged cross-sectional view of a distal
portion 456 of a cryotherapeutic device 460 configured in
accordance with another embodiment of the present technology. The
cryotherapeutic device 460 includes features generally similar to
the features of the cryotherapeutic device 420 described above with
reference to FIG. 4A. For example, the distal portion 456 of the
shaft 122 has the step 128 that demarcates the first zone 127a from
the smaller second zone 127b. However, in the embodiment shown in
FIG. 4B, the second zone 127b is defined by a separate tube 459
that protrudes from the shaft 122. The tube 459 decreases the
cross-sectional area of the exhaust lumen 134 at the second zone
127b similar to the inwardly stepped portion of the shaft 122 shown
in FIG. 4A.
[0150] As shown in FIG. 4B, the cryotherapeutic device 460 can
further include a proximal connector 458 that attaches the balloon
142 to the distal portion 456 of the shaft 122. Unlike the
connector 456 of FIG. 4A that sits substantially within the recess
formed by the step 128, the proximal connector 458 shown in FIG. 4B
extends over the second zone 127b onto the outer surface 455 of the
first zone 127a. By extending the proximal connector 456 over the
first zone 127a, a larger surface area is made available for
attaching the balloon 142 to the distal portion 456 of the shaft
122. Accordingly, the length of the second zone 127b can be reduced
to facilitate adequate venting of the refrigerant 117 through the
necked-down exhaust lumen 134 (e.g., as shown in FIGS. 4A and
4B).
[0151] In certain embodiments, the proximal connector 458 is
non-expandable such that it maintains a substantially low profile
against the outer surface 455 of the first zone 127a in both the
deployed and delivery states. This can reduce or prevent the
proximal connector 458 from catching on the sheath 150 as it is
retracted from the deployed to the delivery configuration. In other
embodiments, at least a portion of the proximal connector 458 can
be expandable, but configured to maintain the low profile of the
distal portion 456 while the cooling assembly 130 is in the
delivery state. Accordingly, the cryotherapeutic device 460 with
the extended proximal connector 458 can provide a substantially low
profile for intravascularly delivering the cooling assembly 130 at
a target site within a small, peripheral vessel (e.g., a renal
artery) and/or can provide one or more channels C through which a
fluidic contrast material can be delivered distally beyond the
cooling assembly 130.
[0152] As further shown in FIG. 4B, the cryotherapeutic device 460
also includes a distal connector 462 that retains the distal
portion 452 of the balloon 142 and a support member 433 extending
through the balloon 142 that braces the balloon 142 in both the
delivery and deployed states. The distal connector 462 can also be
attached to (e.g., by thermal bonding) or formed integrally with an
atraumatic tip 464 that extends distally therefrom. The atraumatic
tip 464 can extend approximately 0.5 cm to 5 cm (e.g.,
approximately 1-2 cm) from the distal connector 462 and have an
outer diameter between approximately 0.010 inch (0.254 mm) to
approximately 0.050 inch (1.27 mm). In one embodiment, for example,
the atraumatic tip 464 can have a length of approximately 2 cm and
an outer diameter of at least 0.035 inch (0.889 mm; e.g., 0.038
inch (0.965 mm)). In other embodiments, the atraumatic tip 464 can
have other suitable lengths and/or outer diameters. The atraumatic
tip 464 can serve as a fixed guide to facilitate navigation through
the vasculature. In several embodiments, the angle and/or
rotational orientation of the atraumatic tip 464 can be adjusted by
a control wire 467 (e.g., a pull-wire) that extends through at
least a portion of the shaft 122. A user can manipulate the control
wire 467 to torsionally deflect or otherwise move the atraumatic
tip 464 to steer the distal portion 456 of the shaft 122 to the
target site T. In other embodiments, the atraumatic tip 464 can be
defined by a distal end portion of a guide wire (e.g., the guide
wire 133b shown in FIG. 2C) that extends through the shaft 122 and
beyond the distal connector 462.
[0153] The atraumatic tip 464 can be made from substantially smooth
and flexible materials or structures such that it can gently
contact and deflect off of vessel walls as the cryotherapeutic
device 460 navigates the vasculature, and therefore avoids
perforation and/or other trauma to the vessels through which it
navigates. For example, the atraumatic tip 464 can be made from a
flexible coil (e.g., a platinum coil) over a core or wire (e.g., a
stainless steel wire). In various embodiments, the wire can be
configured to gradually taper from a proximal portion 469a of the
atraumatic tip 464 to a distal portion 469b of the atraumatic tip
464. A tapered wire, for example, can be generally round at the
proximal portion 469a having an outer diameter between
approximately 0.005 inch (0.127 mm) and 0.015 inch (0.381 mm; e.g.,
0.009 inch (0.229 mm)) and can flatten toward the distal portion
469b to a thickness between approximately 0.001 inch (0.025 mm) and
approximately 0.005 inch (0.127 mm; e.g., 0.003 inch (0.076 mm)).
In selected embodiments, the wire is substantially flat by about
1/3 to 1/2 of the length of the atraumatic tip 464 from the
proximal terminus. In other embodiments, the atraumatic tip 464 can
have a tapered or non-tapered generally circular cross-section
throughout. In several embodiments, at least a portion of the
atraumatic tip 464 (e.g., a coil wrapped around the wire) can be
made from platinum and/or other radiopaque materials (e.g., a
platinum/iridium alloy) that can facilitate navigation of the
cryotherapeutic device 460 through the vasculature using imaging
techniques known in the art. In certain aspects of the technology,
the balloon 142 can also include radiopaque markers and/or
radiopaque markings (e.g., made with radiopaque ink) at both its
proximal and distal end portions to further facilitate navigation
and deployment. In other embodiments, the atraumatic tip 464 can be
made from other deflectable and gentle materials and structures,
such as a polymer material (e.g., Pebax.RTM. polymer, nylon, etc.),
a polymer material over a metallic wire (e.g., a stainless steel
wire), and/or other suitable materials.
[0154] In the embodiment illustrated in FIG. 4B, the atraumatic tip
464 is shaped and/or otherwise formed into a curve or angled
portion. When the atraumatic tip 464 is made from a shapeable
material (e.g., stainless steel, platinum, etc.), the atraumatic
tip 464 can be formed and/or reformed into the desired curvature.
In other embodiments, the atraumatic tip 464 can be pre-formed from
a non-shapeable material such that it has a non-adjustable, set
curve. The curve in the atraumatic tip 464 can further aid in
navigation of the vasculature. For example, the curve can aid in
keeping the cooling assembly 130 within a desired vessel (e.g., a
renal artery) and avoiding side branches thereof.
Pressure Monitoring in Cryotherapeutic Systems
[0155] FIG. 5A is a partially schematic view of a cryotherapeutic
system 500 configured in accordance with another embodiment of the
present technology, and FIG. 5B is an enlarged cross-sectional view
of a distal end portion of the system 500 of FIG. 5A. The
cryotherapeutic system 500 can include features generally similar
to the features of the cryotherapeutic system 100 described above
with reference to FIGS. 1-3B. Referring to FIG. 5A, for example,
the cryotherapeutic system 500 can include a cryotherapeutic device
520 and a console 502. The console 502 can include a refrigerant
supply container 504 and a supply control valve 508 that are
coupled to a supply line 510 configured to transport the
refrigerant 506 to the cryotherapeutic device 520. The console 502
can also optionally include a pump 511 and/or a backpressure
control valve 513 that are coupled to an exhaust line 515
configured to receive evaporated refrigerant 517 from the
cryotherapeutic device 520. A controller 518 can be operably
coupled to the supply control valve 508 and/or the backpressure
control valve 513 to regulate refrigerant flow through the
cryotherapeutic device 520. In the illustrated embodiment, the
cryotherapeutic device 520 includes a shaft 522, a handle 525 at a
proximal region of a proximal portion 524 of the shaft 522, and a
distal portion 526 having a cooling assembly 530 at a distal end
region of a distal portion 526 of the shaft 522.
[0156] As further shown in FIG. 5A, the console 502 can also
include a pressure transducer or sensor 570 (e.g., a PX209-100G5V
pressure transducer made by Omega Engineering of Stamford, Conn.)
coupled to a pressure line 571 to monitor pressure within a portion
of the cooling assembly 530 (e.g., an expansion chamber) during
cryotherapy. In various embodiments, the pressure sensor 570 can be
coupled to the controller 518 to serve as a feedback mechanism that
controls the supply control valve 508 and/or the backpressure
control valve 513, and thereby regulates refrigerant flow to and/or
from the cooling assembly 530 in response to a pressure sensed at
the cooling assembly 530. For example, the pressure sensor 570 can
be configured to indicate a pressure above a predetermined
threshold (e.g., within a range of a burst pressure of the
expansion chamber). In response, the controller 518 can decrease or
terminate refrigerant flow by at least partially closing the supply
control valve 508 and/or increasing refrigerant flow from the
cooling assembly 530 by decreasing the backpressure in the exhaust
line 515 (e.g., using the vacuum pump 511). In other embodiments,
the pressure sensor 570 can be coupled directly to the supply
control valve 508 and/or the backpressure control valve 513 to
automatically regulate the valves 508 and 513 on and/or off in
response to a sensed pressure. In several embodiments, the
cryotherapeutic system 500 can be configured to verify that the
pressure sensor 570 is calibrated properly before cryotherapy. For
example, the system 500 can automatically check the functionality
of the pressure sensor 570 as the system 500 powers on by comparing
a pressure reading from the pressure sensor 570 with the ambient
pressure.
[0157] Referring now to FIG. 5B, the distal region of the
cryotherapeutic device 520 can include features generally similar
to the features of the cryotherapeutic device 120 described above
with reference to FIGS. 2A-2E. For example, the cryotherapeutic
device 520 includes the supply lumen 132 coupled to the supply line
510 (FIG. 5A), the exhaust lumen 134 coupled to the exhaust line
515 (FIG. 5A), and the applicator 140 including the balloon 142 or
other type of expandable member that defines the expansion
chamber.
[0158] As shown in FIG. 5B, the cryotherapeutic device 520 can
further include a pressure monitoring lumen 572 coupled to the
pressure sensor 570 (FIG. 5A) via the pressure line 571 (FIG. 5A).
The pressure monitoring lumen 572 can extend through the shaft 522
and have a distal opening 574 in fluid communication with the
expansion chamber (e.g., defined by the balloon 142). The
dimensions (e.g., cross-sectional area, inner diameter, and/or
outer diameter) of the pressure monitoring lumen 572 can be large
enough to sense a pressure reading within the expansion chamber
with substantial accuracy, but small enough to reduce or prevent
interference with the outflow of refrigerant through the exhaust
lumen 134. For example, the supply lumen 132 and the pressure
monitoring lumen 572 together can have a first cross-sectional
dimension (e.g., a first cross-sectional area) and the exhaust
lumen 134 can have a second cross-sectional dimension (e.g., a
second cross-sectional area) such that the ratio of the second
cross-sectional dimension to the first cross-sectional dimension is
between 4:1 and 10:1. In certain embodiments, the pressure
monitoring lumen 572 can have an inner diameter of no more than
0.03 inch (0.762 mm; e.g., 0.015 inch (0.381 mm), 0.010 inch (0.762
mm), etc.) and an outer diameter of no more than 0.060 inch (1.52
mm; e.g., 0.02 inch (0.508 mm), 0.015 inch (0.381 mm), etc.), and
the exhaust lumen 134 can be sized accordingly. In the embodiment
illustrated in FIG. 5B, the pressure monitoring lumen 572
terminates in the shaft 522 before the outer diameter necks down at
the second zone 127b of the distal portion 520. This configuration
may be used in embodiments where the inner diameter of the shaft
522 necks down (e.g., as shown in FIGS. 4A and 4B) so as not to
restrict the venting of the expanded refrigerant 517 at the smaller
second zone 127b. In other embodiments, the opening 574 of the
pressure monitoring lumen 572 can be at or in the balloon 542.
[0159] The pressure monitoring lumen 572 can also have a length
sufficient to intravascularly locate the opening 574 along with the
cooling assembly 530 at the target site T (e.g., a renal artery or
renal ostium via a femoral artery or a radial artery). For example,
the pressure monitoring lumen 572 can have a length equivalent to
the full length of the shaft 522 (e.g., at least 48 inches (122
cm)). In other embodiments, the pressure monitoring lumen 572 can
have other suitable different lengths and/or dimensions. For
example, the pressure monitoring lumen 572 can have a first length
and the pressure line 571 attached thereto can have a second length
(e.g., 48 inches (122 cm), 30 inches (76 cm), 12 inches (30 cm),
etc.) to extend the pressure monitoring lumen 572 to the pressure
sensor 570, thereby allowing the console 502 to be positioned in a
desired location (e.g., on a table) during cryotherapeutic
treatments.
[0160] During cryotherapeutic treatments, the pressure monitoring
lumen 572 and the pressure sensor 570 (FIG. 5A) may be configured
to provide a signal indicating a change in pressure within the
expansion chamber. For example, the pressure sensor 570 can be
configured to indicate a threshold pressure below the rupture
pressure of the balloon 142 to reduce the likelihood that the
balloon 142 bursts during cryotherapy. The balloon 142 may have a
burst pressure dependent at least in part on the material from
which the balloon 142 is made. Compliant materials (e.g.,
polyurethane), for example, typically have lower burst pressures
(e.g., 80 psi, 100 psi, 200 psi, etc.) than non-compliant materials
(e.g., nylon) that can have burst pressures of 300 psi or higher.
The pressure sensor 570 can be configured to monitor a threshold
pressure, which may be equal to a pressure value below the burst
pressure that provides an adequate response time to react to the
change in pressure before the balloon 142 ruptures. In other
embodiments, the pressure sensor 570 can be configured to indicate
when the balloon 142 operates outside its desired operating
pressure (e.g., 20-60 psi).
[0161] The time delay between the pressure at the opening 574 of
the pressure monitoring lumen 572 at the expansion chamber and the
pressure reading at the pressure sensor 570 may depend on the
volume of the pressure monitoring lumen 572. As such, the pressure
monitoring lumen 572 can have a volume that has a response time
sufficient to adequately respond to the change in pressure in the
expansion chamber (e.g., before rupture of the balloon 142). In
certain embodiments, for example, the pressure sensor 570 has a
response time of less than 1.5 seconds, such as a response time of
less than 1 second, 0.2 second, 0.1 second, or 15 milliseconds. To
enhance the accuracy of the pressure reading and decrease the
response time of the pressure sensor 570, the length of the
pressure monitoring lumen 572 can be shortened and significant
increases in volume in the pressure monitoring lumen 572 before
connecting to the pressure sensor 570 can be reduced. For example,
the pressure monitoring lumen 572 can be coupled to the pressure
line 571 at the proximal portion 524 (FIG. 5A) of the shaft 522
(e.g., at the handle 525), and the pressure line 571 can have a
cross-sectional area similar to that of the pressure monitoring
lumen 572. In other embodiments, the pressure monitoring lumen 572
can be coupled to the pressure sensor 570 at the handle 525 (e.g.,
omitting the pressure line 571) to shorten the total length of the
pressure tube to the pressure sensor 570, and electrical wires can
be coupled to the pressure sensor 570 to carry a signal to the
console 502.
[0162] Referring to FIGS. 5A and 5B together, in certain
embodiments, the pressure line 571 and/or the pressure monitoring
lumen 572 can be coupled to the pressure sensor 570 using a fitting
or adaptor 576 (e.g., a quick connect adapter). In the embodiment
illustrated in FIG. 5A, for example, the adaptor 576 includes an
internal reservoir or channel 578 that fluidly connects the
pressure line 571 with the pressure sensor 570. The channel 578 can
have a substantially small volume so as not to disrupt the pressure
differential from the pressure line 571 to the pressure sensor 570
and enhance the accuracy of the pressure measurement. For example,
in one embodiment, the channel 578 has an internal volume of no
more than 0.1 cc. In other embodiments, the channel 578 can have a
larger internal volume. In further embodiments, the adaptor 576 can
couple the pressure monitoring lumen 572 to the pressure line 571
at the handle 525 or other position proximate the proximal portion
524 of the shaft 522. The adaptor 576, therefore, allows the
pressure monitoring lumen 572 and/or the pressure line 571 to be
detached from the pressure transducer 570 after a cryotherapeutic
treatment such that the pressure monitoring lumen 572 can be
discarded and the pressure transducer 570 can be stored (e.g.,
along with the handle 525 and/or the console 502) for subsequent
cryotherapy treatments without disrupting the accuracy of the
pressure reading at the pressure sensor 570.
[0163] Referring back to FIG. 5B, in various other embodiments, the
cryotherapeutic device 520 can further include an additional gas
supply lumen 579 coupled to the supply container 504 (FIG. 5A) or
other gas supply reservoir to deliver additional gas to the
expansion chamber and thereby modulate the temperature of the
applicator 140. For example, the gas supply lumen 579 can deliver
the refrigerant 506 (e.g., nitrous oxide) and/or other pressurized
or non-pressurized gas (e.g., air) into the balloon 142 before or
during delivery of the refrigerant 506 via the orifice 144 to
increase the pressure within the balloon 142 (e.g., from
approximately 5 psi to approximately 60 psi). The additional gas in
the balloon 142 decreases the pressure drop of the refrigerant 506
in the expansion chamber, and thereby increases the temperature
within the balloon 142. As such, the gas supply lumen 579 can be
used to initiate, restrict, and/or suspend the inflow of additional
gas to the expansion chamber (e.g., using a valve) and regulate the
temperature of the balloon 142 without requiring complex components
in the console 502 (e.g., a pressure regulator, a sub-cooler, etc.)
to change the pressure drop within the balloon 142. Additionally,
when the gas supply lumen 579 is coupled to a separate gas
reservoir (e.g., an air supply), the gas supply lumen 579 can be
used to deliver a gas into the balloon 142 before delivering the
refrigerant 506 into the balloon 142 to monitor the position of the
applicator 140 at the target site T.
[0164] In further embodiments, a pressure regulator (not shown;
e.g., a pressure relief valve) can be added to the exhaust lumen
134 to trap the evaporated refrigerant 517 from exiting the balloon
142 and/or in the exhaust lumen 134 until the pressure within the
balloon 142 is at a predetermined value (e.g., as sensed using the
pressure monitoring lumen 572). In still further embodiments, the
cryotherapeutic device 520 can include both a pressure regulator
for the exhaust lumen 134 and the gas supply lumen 579 such that
the pressure within the balloon 142 can be modulated during
cryotherapeutic treatment.
Pre-Cooling in Cryotherapeutic Systems
[0165] In cryogenic renal nerve modulation, the volume of
refrigerant available for cooling can be limited. Accordingly, it
can be useful to increase the cooling capacity of a refrigerant.
Pre-cooling the refrigerant before expanding the refrigerant in a
cooling assembly is one example of a process that can increase the
cooling capacity of a refrigerant. Even when cooling occurs
primarily through phase change, using colder refrigerant before the
phase change can increase the amount of cooling. Moreover, if a
supply tube is in thermal communication with an exhaust tube,
decreasing the temperature of refrigerant in the supply tube can
cool refrigerant exhaust in the exhaust tube, which can reduce back
pressure in an associated cooling assembly and thereby further
increase cooling at the associated cooling assembly. Pre-cooling
can reduce the volume of refrigerant needed for cryogenic renal
nerve modulation, which can allow smaller and more flexible shafts
to be used within the vasculature. Pre-cooling also can mitigate
reductions in cooling capacity associated with other components of
a cryotherapeutic system, such as thermally-insulative members
within an applicator and in-line solenoid valves that release heat
during operation.
[0166] Pressurized refrigerant used in cryogenic renal nerve
modulation typically is supplied outside the vasculature at room
temperature (e.g., from a room-temperature dewar). As the
pressurized refrigerant travels along a supply tube within the
vasculature, it can increase in temperature via heat transfer with
warm blood and tissue. For example, as pressurized refrigerant
supplied at about room temperature (e.g., about 23.degree. C.)
passes through the vasculature at body temperature (e.g., about
37.degree. C.), the temperature of the pressurized refrigerant can
increase to about 25.degree. C. to 37.degree. C. before reaching a
cooling assembly. Cryotherapeutic devices configured in accordance
with several embodiments of the present technology can include a
pre-cooling assembly configured to cool pressurized refrigerant
before the pressurized refrigerant expands in an associated cooling
assembly. For example, pressurized refrigerant can be cooled to
have a temperature just before expansion in an associated cooling
assembly that is less than body temperature (e.g., less than about
20.degree. C. or less than about 10.degree. C.). Such pre-cooling
assemblies can be configured to be outside the vasculature and/or
to utilize the same refrigerant supply as an associated cooling
assembly. In several embodiments configured in accordance with the
present technology, pre-cooling can be useful to maintain
refrigerant in liquid form until it reaches a cooling assembly
where cryogenic cooling is desired. For example, evaporation
associated with warming of refrigerant passing through portions of
a cryotherapeutic device proximal to a cooling assembly can be
reduced. In this section, the terms "proximal" and "distal" can
reference a position relative to a pressurized refrigerant source.
For example, proximal can refer to a position closer to a
pressurized refrigerant source, and distal can refer to a position
farther from a pressurized refrigerant source.
[0167] FIGS. 6A-6B illustrate a portion of a cryotherapeutic device
600 including a pre-cooling assembly 602, an elongated shaft 604
defining an exhaust passage, and a hub 606 between the pre-cooling
assembly and the shaft. The pre-cooling assembly 602 includes a
flexible tubular member 608 extending between the hub 606 and an
adapter 610 configured to connect to a pressurized-refrigerant
source (not shown). The hub 606 can include a primary connector 612
attached to the shaft 604, an exhaust portal 614 venting to the
atmosphere, a first branch 616 attached to the tubular member 608,
and a second branch 618 attached to a control-wire conduit 620. In
several embodiments, the hub 606 can include one or more additional
branches, such as a branch including a tube fluidly connected to a
proximal syringe adapter (e.g., a proximal syringe adapter
including a diaphragm configured to be punctured with a needle of a
syringe). Such a structure can be useful, for example, to introduce
contrast agent in the vicinity of a cooling assembly within the
vasculature and/or to introduce filler material into a filler lumen
of a cooling assembly within the vasculature. Filler materials are
discussed in greater detail below.
[0168] With reference again to FIGS. 6A-6B, two control wires 621
(FIG. 6B) can extend from the control-wire conduit 620, through the
hub 606, and into the shaft 604. The hub 606 can define a generally
straight primary-exhaust flow path from the shaft 604 to the
atmosphere through the exhaust portal 614. The tubular member 608
includes a tubular proximal portion 622 at the adapter 610 and a
tubular distal portion 624 at the first branch 616. As most clearly
shown in FIG. 6B, the tubular proximal portion 622 can include a
first plug 626 and a second plug 628, and the adapter 610 can
include an opening 630 proximate the second plug 628. The adapter
610 can include a variety of suitable structures for connection to
a pressurized-refrigerant source, such as a threaded fitting, a
compression fitting, or a barbed fitting.
[0169] In the embodiment shown in FIG. 6B, the device 600 includes
a primary-supply tube 632 defining a primary-supply lumen, and the
pre-cooling assembly 602 includes a pre-cooling supply tube 634
defining a pre-cooling supply lumen. The primary-supply tube 632
and the pre-cooling supply tube 634 can include a primary-supply
proximal opening 636 and a pre-cooling supply proximal opening 638,
respectively, at the second plug 628. The primary-supply proximal
opening 636 and the pre-cooling supply proximal opening 638 fluidly
connect the primary-supply tube 632 and the pre-cooling supply tube
634, respectively, to a passage defined by the opening 630. From
the second plug 628, the primary-supply tube 632 and the
pre-cooling supply tube 634 extend through the tubular proximal
portion 622 and through the first plug 626. The tubular distal
portion 624 defines a pre-cooling expansion chamber extending from
the first plug 626 to the primary exhaust flow path. The
pre-cooling supply tube 634 extends slightly past the first plug
626 and terminates at a pre-cooling distal opening 640 within the
pre-cooling expansion chamber. The pre-cooling expansion chamber is
accordingly in fluid connection with a flow of refrigerant through
the pre-cooling supply tube 634 such that a pre-cooling exhaust
flow path extends from the pre-cooling distal opening 640 to the
primary exhaust flow path. The primary-supply tube 632 extends
through the pre-cooling expansion chamber, through the hub 606 and
into the shaft 604. The portion of the primary-supply tube 632
extending from primary-supply proximal opening 636 to the shaft is
a first portion of the primary-supply tube 632. A second portion
(not shown) of the primary-supply tube 632 is proximate a cooling
assembly (not shown) configured to be within the vasculature.
[0170] Expanding pressurized refrigerant into the pre-cooling
expansion chamber from the pre-cooling supply tube 634 can cool the
pre-cooling expansion chamber and thereby cool the primary-supply
tube 632 and liquid refrigerant within the primary-supply tube. If
pre-cooling is performed distant from an entry point into the
vasculature (e.g., if pressurized refrigerant is cooled in a
console before being transported to an entry point into the
vasculature), heat from the atmosphere can cause undesirable
warming of the pre-cooled pressurized refrigerant. Positioning the
pre-cooling expansion chamber proximate the hub can reduce such
undesirable warming. A pre-cooling assembly configured in
accordance with several embodiments of the present technology can
have a length sufficient to allow heat-transfer between expanded
refrigerant within a pre-cooling expansion chamber and pressurized
refrigerant within a portion of a primary-supply tube within the
pre-cooling expansion chamber. For example, a pre-cooling chamber
configured in accordance with several embodiments of the present
technology can have a length greater than about 10 cm, such as
greater than about 15 cm, or greater than about 25 cm. A
pre-cooling chamber configured in accordance with several
embodiments of the present technology has a length from about 20 cm
to about 30 cm.
[0171] After cooling the primary-supply tube 632, refrigerant from
the pre-cooling expansion chamber can join a flow of refrigerant
from the exhaust passage and vent out the exhaust portal 614 to the
atmosphere. FIG. 6B shows a first arrow 642 indicating a flow
direction of refrigerant through the exhaust portal 614 and a
second arrow 644 indicating a flow direction of refrigerant through
the pre-cooling expansion chamber. The flow direction of
refrigerant through the exhaust portal 614 is generally aligned
with the exhaust passage. In contrast, the flow direction of
refrigerant through the pre-cooling expansion chamber is not
aligned with the exhaust passage or the flow direction of
refrigerant through the exhaust portal 614.
[0172] FIG. 7 illustrates a portion of a cryotherapeutic device 700
similar to the cryotherapeutic device 600 of FIGS. 6A-6B, except
that the device 700 has a pre-cooling expansion chamber fluidly
separate from the exhaust passage. The cryotherapeutic device 700,
for example, includes a pre-cooling assembly 702 including a valve
704 and a third plug 706 fluidly separating the pre-cooling
expansion chamber from internal portions of the shaft 604 and the
hub 606. The primary-supply tube 632 extends through the third plug
706 and into the shaft 604.
[0173] An arrow 708 indicates a flow direction of refrigerant
through the pre-cooling expansion chamber when the valve 704 is
open. When the valve 704 is closed, pressure within the pre-cooling
expansion chamber can increase until it equilibrates with the
pre-cooling supply tube 634, thereby causing flow through the
pre-cooling supply tube to stop. In this way, opening and closing
the valve 704 can turn pre-cooling on or off. Partially opening the
valve 704 can regulate pressure within the pre-cooling expansion
chamber and thereby regulate refrigerant flow through the
pre-cooling supply tube 634 and an associated pre-cooling
temperature. For example, an actuator 710 can be operably connected
to the valve 704 and be configured to receive a signal from a
processor 712. The processor 712 can be configured to receive a
signal from a user interface 714 and/or a sensor 716 to direct the
actuator 710 to open or close the valve fully or incrementally. The
sensor 716, for example, can be a temperature sensor of an
associated cooling assembly. In one embodiment, the temperature
sensor can send a signal to the processor 712 causing the valve 704
to (a) open and pre-cooling to increase if a detected temperature
of the cooling assembly or tissue proximate the cooling assembly is
higher than a desired value, or to (b) close and pre-cooling to
decrease if a detected temperature of the cooling assembly or
tissue proximate the cooling assembly is lower than a desired
value.
[0174] FIGS. 8A-8B illustrate a portion of a cryotherapeutic device
800 with a pre-cooler 802 configured in accordance with another
embodiment of the present technology. Accessing an internal portion
of the tubular member 608 to form the first plug 626 of the
pre-cooling assembly 602 (FIGS. 6A-6B) can be challenging. Instead
of the first plug 626 and the pre-cooling supply tube 634 (FIG.
6B), the pre-cooler 802 can include a flow separator attached to a
primary-supply tube. For example, the pre-cooler 802 can include a
flow separator 804 attached to a primary-supply tube 806 and a
container 808 having a container proximal portion 810 and a
container distal portion 812. In this embodiment, the flow
separator 804 divides the container 802 into the container proximal
portion 810 and the container distal portion 812. The container
proximal portion 810 defines a proximal chamber or a combined
supply lumen between the opening 630 and the flow separator 804 and
the container distal portion 812 defines a pre-cooling expansion
chamber. As most clearly shown in FIG. 8B, the flow separator 804
defines a primary passage 814 fluidly connected to the
primary-supply tube 806 and a pre-cooling passage 816 along a
periphery of the flow separator 804.
[0175] Referring still to FIG. 8B, the pre-cooling passage 816 is
sized to cause a pressure drop sufficient to expand refrigerant and
cool the pre-cooling expansion chamber. The flow separator 804
includes a tubular segment 818 and a flow-separator plug 820. The
flow-separator plug 820 is positioned between an outer surface of
the primary-supply tube 806 and an inner surface of the container
808. The tubular segment 818 can be selected to have an outer
cross-sectional dimension (e.g., diameter) slightly smaller than an
inner cross-sectional dimension (e.g., diameter) of the container
808. The flow-separator plug 820 can include, for example, an
adhesive material configured to bond to the outer surface of the
primary-supply tube 806 and the inner surface of the container
808.
[0176] In one embodiment, the flow separator 804 floats in the
container 808 (i.e., it is not fixed within the container 808) such
that the pre-cooling passage 816 is an annular space between the
flow separator 804 and an inner surface of the container 808. In
other embodiments, flow separators can have different
configurations. For example, a flow separator can be fixed to the
container and a pre-cooling passage can extend through the flow
separator around only a portion of the periphery of the flow
separator, such as a curved portion. In still other embodiments,
the flow separator can be attached to the container around
generally its entire circumference and the flow separator can
include an opening spaced inwardly apart from the periphery of the
flow separator. For example, a flow separator can include an
internal opening configured to expand refrigerant into the
pre-cooling expansion chamber.
[0177] FIGS. 9A-9B illustrate a portion of a cryotherapeutic device
900 similar to the cryotherapeutic device 800 of FIGS. 8A-8B,
except having different flow-separator and primary-supply tube
configurations. The cryotherapeutic device 900 includes a primary
supply tube 902 and a pre-cooler 904 including a flow separator 906
attached to the primary-supply tube 902. The pre-cooler 904 can
also include a container 908 having a container proximal portion
910 and a container distal portion 912 on opposite sides of the
flow separator 906. In this embodiment, the flow separator 906 does
not include a tubular segment and can be constructed, for example,
from a cylindrical block of material (e.g., rubber, polymer, metal,
or another material) having a hole through which the primary-supply
tube 902 can be threaded or otherwise attached. As most clearly
shown in FIG. 9B, the flow separator 906 can define a pre-cooling
passage 914 along a periphery of the flow separator 906. The
primary-supply tube 902 can extend through the flow separator 906
and can be attached to an inner surface of the container proximal
portion 910 proximate the opening 630. Attaching the primary-supply
tube 906 to an accessible portion of the container proximal portion
910 can be useful to prevent undesirable longitudinal movement of
the flow separator 906 and the primary-supply tube 902 when the
proximal chamber is at high pressure.
[0178] A pre-cooling assembly configured in accordance with several
embodiments of the present technology can be arranged in a compact
configuration. For example, at least a portion of such a
pre-cooling assembly can be within a handle of a cryotherapeutic
device. FIG. 10 illustrates a portion of a cryotherapeutic device
1000 including a pre-cooling assembly 1002 and a hub 1004 within a
handle 1006. The pre-cooling assembly 1002 includes a flexible
tubular member 1008 extending from the hub 1004, through a bottom
portion 1010 of the handle 1008, and to an adapter 1012 configured
to connect to a pressurized-refrigerant source (not shown). The hub
1004 can include an elongated exhaust portal 1014 extending through
the bottom portion 1010, and a control-wire conduit 1016 can extend
from the hub 1004 through the bottom portion 1010. In one
embodiment, the tubular member 1008 is coiled around the exhaust
portal 1014. The handle 1006 also can be insulated to prevent heat
loss to the atmosphere and improve pre-cooling efficiency.
[0179] FIG. 11 illustrates a portion of a cryotherapeutic device
1100 having an alternative configuration within and around a
handle. The cryotherapeutic device 1100 includes a pre-cooling
assembly 1102 and a hub 1104 within a handle 1106. The pre-cooling
assembly 1102 includes a flexible tubular member 1108 extending
from the hub 1104 and through a bottom portion 1110 of the handle
1106. The hub 1104 can include an elongated exhaust portal 1112
extending through the bottom portion 1110, and a control-wire
conduit 1114 can extend from the hub 1104 through the bottom
portion 1110. In one embodiment, the tubular member 1108 includes a
helical portion 1116 spaced apart from the exhaust portal 1112. The
handle 1106 also can be insulated to prevent heat loss to the
atmosphere and improve pre-cooling efficiency.
Cryotherapeutic-Device Components
[0180] Having in mind the foregoing discussion of cryotherapeutic
devices configured in accordance with several embodiments of the
present technology, a variety of different cooling assemblies,
occlusion members, and other cryotherapeutic-device components are
described below with reference to FIGS. 12-55. It will be
appreciated that the cryotherapeutic-device components described
below and/or specific features of the cryotherapeutic-device
components described below can be used with the cryotherapeutic
system 100 shown in FIG. 1, used in a standalone or self-contained
handheld device, or used with another suitable system. For ease of
reference, throughout this disclosure identical reference numbers
are used to identify similar or analogous components or features,
but the use of the same reference number does not imply that the
parts should be construed to be identical. Indeed, in many examples
described herein, the identically-numbered parts are distinct in
structure and/or function.
[0181] Several embodiments of cryotherapeutic-device components
described below can be configured to facilitate one or more
treatment objectives related to cryogenic renal-nerve modulation.
For example, several embodiments of applicators described below are
configured to apply cryogenic cooling in a desirable localized or
overall treatment pattern. A desirable localized treatment pattern
can include, for example, partially-circumferential cooling at one
or more longitudinal segments of a renal artery or a renal ostium.
A desirable overall treatment pattern can include a combination of
localized treatment patterns at a treatment site. For example, a
desirable overall treatment pattern can be a
partially-circumferential or a fully-circumferential treatment
pattern in a plane perpendicular to a renal artery or a renal
ostium. To facilitate a desirable localized or overall treatment
pattern, an applicator configured in accordance with several
embodiments of the present technology can have more than one
heat-transfer portion, such as a primary heat-transfer portion and
a secondary heat-transfer portion. When a cooling assembly
including such an applicator is operating in a deployed state, a
primary heat-transfer portion of the applicator can have a
heat-transfer rate sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation. A secondary heat-transfer portion
of the applicator can have a lower heat-transfer rate during
operation, such as a heat-transfer rate insufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation. The
positioning of the primary and secondary heat-transfer portions can
correspond to a desirable localized or overall treatment
pattern.
[0182] Several embodiments of applicators described below include
features configured to affect the positioning of primary and
secondary heat-transfer portions. Such features can include, for
example, features related to (a) differential convective
heat-transfer within an applicator, (b) differential conductive
heat-transfer through an applicator, and/or (c) differential
contact or spacing between an applicator and a renal artery or a
renal ostium at a treatment site. Features related to differential
convective heat transfer can include, for example, refrigerant
supply tubes and orifices configured to selectively direct
expansion of refrigerant toward different portions of an
applicator. Features related to differential conductive heat
transfer through an applicator can include, for example, additional
balloons (e.g., non-cooling balloons and balloons having low levels
of cooling), differential composition (e.g., low thermal
conductivity and high thermal conductivity materials), differential
thicknesses (e.g., balloon-wall thicknesses), and
thermally-insulative structures (e.g., elongated,
thermally-insulative members within balloons or attached to balloon
walls). Features related to differential contact or spacing between
an applicator and a renal artery or a renal ostium can include, for
example, additional balloons, and characteristics of complex
balloons, such as shape (e.g., helical, curved,
longitudinally-asymmetrical, and radially-asymmetrical), surface
differentiation (e.g., recesses, groves, protrusions, and
projections), and differential expansion (e.g.,
partially-constrained expansion).
[0183] Several embodiments of applicators described below are also
configured to facilitate sizing, such as delivery at a reduced
(e.g., low-profile) cross-sectional dimension and deployment at a
cross-sectional dimension suitable for providing
therapeutically-effective treatment to renal arteries and/or renal
ostiums having different sizes. For example, several embodiments of
applicators described below include a balloon that is at least
partially collapsed when an associated cooling assembly is in a
delivery state and at least partially expanded when an associated
cooling assembly is in a deployed state. Features related to sizing
can include, for example, balloon composition (e.g., compliant and
non-compliant materials), additional balloons, and characteristics
of complex balloons, such as shape (e.g., compliant and
non-compliant shapes). Non-compliant materials (e.g., polyethylene
terephthalate) can have compliance (e.g., elasticity), for example,
from about 0% to about 30%. Compliant materials (e.g., polyurethane
and other thermoplastic elastomers) can have compliance, for
example, from about 30% to about 500%. Non-compliant materials
typically have greater strength (e.g., higher pressure ratings)
than compliant materials. Several embodiments of applicators
described below can be configured to facilitate a desirable level
of occlusion of a renal artery and/or a renal ostium. For example,
several embodiments of applicators described below are configured
to be partially occlusive, such as to apply
therapeutically-effective cooling for renal nerve modulation at a
treatment site without preventing blood flow through the treatment
site. Features related to partial occlusion include, for example,
characteristics of complex balloons, such as shape (e.g., helical,
curved, longitudinally-asymmetrical, and radially-asymmetrical) and
differential expansion (e.g., partially-constrained expansion).
Full occlusion, such as complete or near-complete blockage of
blood-flow through a renal artery or a renal ostium can be
desirable with regard to certain treatments. Features related to
full occlusion can include, for example, any suitable feature
related to sizing. As described below, cryotherapeutic devices
configured in accordance with several embodiments of the present
technology can include an occlusion member, such as an expandable
member of a cooling assembly (e.g., a balloon defining an expansion
chamber) or a separate occlusion member (e.g., proximal to a
cooling assembly). An occlusion member can be combined with any
suitable applicator described herein to provide occlusion in
conjunction with features associated with the applicator.
[0184] Cooling assemblies configured in accordance with the present
technology can include structures that take advantage of frozen
and/or liquid blood proximate an applicator to facilitate one or
more treatment objectives related to cryogenic renal-nerve
modulation. Frozen and/or liquid blood proximate an applicator can
affect factors such as heat transfer, sizing, and occlusion. For
example, several embodiments can be configured to freeze blood
around an applicator to cause full or partial occlusion. In some
cases, therapeutically-effective cooling can occur through a layer
of frozen blood (e.g. a layer of frozen blood having a thickness
less than about 0.8 mm, 1 mm, or 1.2 mm). A balloon can be
configured such that frozen blood having a thickness through which
therapeutically-effective cooling can occur is formed between a
primary heat-transfer portion of the balloon and a renal artery or
a renal ostium. This layer, for example, can facilitate sizing or a
desired level of occlusion. Moreover, a balloon can be configured
such that frozen blood having a thickness through which
therapeutically-effective cooling cannot occur (e.g., a thickness
greater than about 0.8 mm, 1 mm, or 1.2 mm) is formed between a
secondary heat-transfer portion and a renal artery or a renal
ostium. Such balloons can include, for example, recessed and
non-recessed portions and other suitable structures as described in
greater detail below.
Convective Heat Transfer
[0185] FIGS. 12-16B illustrate several embodiments of
cryotherapeutic devices that can use differential convective
heat-transfer to affect a treatment. Features related to convective
heat transfer within an applicator can facilitate one or more
treatment objectives of cryogenic renal-nerve modulation, such as a
desirable localized or overall treatment pattern. Such features can
include, for example, refrigerant supply tubes and orifices
configured to selectively direct expansion of refrigerant toward
different portions of an applicator.
[0186] FIG. 12 illustrates a portion of a cryotherapeutic device
1200 including a cooling assembly 1202 at a distal portion 1204 of
an elongated shaft 1206 defining an exhaust passage. As described
above, the distal portion 1204 can have a step 1208 and the cooling
assembly 1202 can include an applicator 1210 having a plurality of
heat transfer portions (individually identified as 1211a-d). The
applicator 1210 also can have a balloon 1212 with a distal neck
1214, and the balloon 1212 can define an expansion chamber
configured to generate and deliver cryogenic cooling. The device
1200 can further include an elongated guide member 1216a, a first
supply tube 1218 defining a first supply lumen, and a second supply
tube 1220 defining a second supply lumen. The guide member 1216a
can define a guide-wire lumen shaped to receive a guide wire 1216b,
as described in greater detail above. Guide members described with
respect to other cryotherapeutic-device components described herein
can be similarly configured, although for clarity of illustration,
associated guide wires typically are not shown. In the illustrated
embodiment, the guide member 1216a has a straight end and extends
to the distal neck 1214. Alternatively, the guide member 1216a can
include a rounded end and/or an end that extends beyond the distal
neck 1214. Similarly, in other cryotherapeutic-device components
described herein, illustrated ends of guide members and/or supply
tubes that exit distal portions of balloons can have various
suitable shapes (e.g., atraumatic shapes) and can extend varying
distances relative to distal necks of balloons.
[0187] The first supply tube 1218 can include a first angled distal
portion 1222, and the cooling assembly 1202 can include a first
orifice 1224 at the end of the first angled distal portion 1222.
Similarly, the second supply tube 1220 can include a second angled
distal portion 1226, and the cooling assembly can include a second
orifice 1228 at the end of the second angled distal portion. The
first and second angled distal portions 1222, 1226 of the
illustrated embodiment are longitudinally and radially spaced apart
along and about the length of the cooling assembly 1202. In several
other embodiments, the first and second angled distal portions
1222, 1226 have the same longitudinal and/or radial position, or
another configuration. When the cooling assembly 1202 is in a
deployed state, refrigerant can flow through the first and second
supply tubes 1218, 1220, flow through the first and second angled
distal portions 1222, 1226, respectively, and flow out the first
and second orifices 1224, 1228, respectively. The first and second
angled distal portions 1222, 1226 can direct expanded refrigerant
toward the heat-transfer portions 1211a and 1211d, respectively. As
a result, when refrigerant flows out of the first and second
orifices 1224, 1228, the heat-transfer portions 1211a and 1211d can
have higher overall and particularly convective heat-transfer rates
relative to other heat-transfer portions of the applicator 1210.
This variation in heat-transfer rate can correspond to a desired
cooling pattern, such as a partially-circumferential cooling
pattern at some or all longitudinal segments of the applicator
1210. The difference in heat-transfer rate can vary depending on a
distance from the heat-transfer portions 1211a and 1211d. A
functionally significant difference in heat-transfer rate can
separate the heat-transfer portion 1211a from the heat-transfer
portion 1211c, which is generally circumferentially opposite to the
heat-transfer portion 1211a. Similarly, a functionally significant
difference in heat-transfer rate can separate the heat-transfer
portion 1211d from the heat-transfer portion 1211b, which is
generally circumferentially opposite to the heat-transfer portion
1211d. In several embodiments, the heat-transfer portions 1211a and
1211d have heat-transfer rates sufficient to cause
therapeutically-effective renal nerve modulation, while the
heat-transfer portions 1211b and 1211c have heat-transfer rates
insufficient to cause therapeutically-effective renal nerve
modulation.
[0188] The first and second supply tubes 1218, 1220 can be
configured, for example, to direct expansion of refrigerant at
angles about 45.degree. offset from the length of the applicator
1210 or the length of the cooling assembly 1202. In several other
embodiments, one or more supply tubes are configured to direct
refrigerant at an angle from about 15.degree. to about 90.degree.
relative to a length of an applicator or a cooling assembly, such
as from about 30.degree. to about 45.degree., or from about
30.degree. to about 40.degree.. Additionally, the first supply tube
1218 can be at a different angle than the second supply tube 1220.
The longitudinal distance between a first orifice 1224 and a second
orifice 1228 of a cooling assembly configured in accordance with
several embodiments of the present technology can be, for example,
from about 1 mm to about 20 mm, such as from about 2 mm to about 15
mm, or from about 3 mm to about 10 mm.
[0189] Cooling assemblies configured in accordance with several
embodiments of the present technology can alternatively include a
supply tube or lumen having a curved and/or helical portion. FIG.
13 illustrates a portion of a cryotherapeutic device 1300 including
a cooling assembly 1302 at a distal portion 1304 of an elongated
shaft 1306 defining an exhaust passage open at the end of the
distal portion 1304. The distal portion 1304 can have a step 1307
and the cooling assembly 1302 can include an applicator 1308 having
a first heat-transfer portion 1309 and a second heat-transfer
portion 1310. The first and second heat-transfer portions 1309,
1310 are elongated and radially spaced apart around the length of
the cooling assembly 1302. The applicator 1308 also can have a
balloon 1311 that can define an expansion chamber configured to
generate and deliver cryogenic cooling. The device 1300 can further
include an elongated guide member 1312 and a supply tube 1313
extending along the length of the shaft 1306. Within the balloon
1311, the supply tube 1313 can include a helical portion 1314 that
exits the distal portion 1304 and wraps around the distal portion
1304 (e.g., the distal portion 1304 can define a central axis of
the helical portion 1314). The cooling assembly 1302 can include a
plurality of orifices (individually identified as 1316a-e)
laterally spaced apart along the helical portion 1314. In the
illustrated embodiment, if the helical portion 1314 were
straightened, the orifices 1316a-e would be generally radially
aligned. In this embodiment, the shape of the helical portion 1314
causes the orifices 1316a-e to point in different radial
directions. In other embodiments, the helical portion 1314 can have
a different number and/or orientation of orifices 1316a-e.
[0190] The helical portion 1314 locates the orifices 1316a-e closer
to the balloon 1311 than they would be if the supply tube 1312 were
straight. This can cause refrigerant exiting the orifices 1316a-e
to contact the balloon 1311 at higher velocities and increase the
amount of convective cooling at corresponding heat-transfer
portions of the balloon 1311. This can also provide more control of
the size and spacing of where refrigerant first contacts the
balloon 1311. Cooling assemblies configured in accordance with
several embodiments of the present technology can include orifices
spaced apart greater than about 0.01 mm (e.g., greater than about
0.1 mm, greater than about 0.5 mm, or greater than about 1 mm) from
central longitudinal axes of cooling assemblies when the cooling
assemblies are in a deployed state. For example, orifices in
several embodiments can be between about 0.01 mm and about 4 mm or
between about 0.1 mm and about 2 mm from central longitudinal axes
of cooling assemblies when the cooling assemblies are in a deployed
state. Similarly, cooling assemblies configured in accordance with
several embodiments of the present technology can include orifices
spaced apart by less than about 4 mm (e.g., less than about 2 mm,
less than about 1 mm, or less than about 0.5 mm) from balloons when
the cooling assemblies are in a deployed state. For example,
orifices in several embodiments can be between about 0.1 mm and
about 4 mm or between about 0.5 mm and about 2 mm apart from
balloons when the cooling assemblies are in a deployed state.
Furthermore, cooling assemblies configured in accordance with
several embodiments of the present technology can include an
orifice positioned such that a distance from a central longitudinal
axis of a cooling assembly to the orifice is not less than about
20% (e.g., not less than about 25%, 40%, or 60%) of a distance from
the central longitudinal axis to an inner surface of a balloon in a
plane at the orifice and perpendicular to the central longitudinal
axis.
[0191] In the illustrated embodiment, the orifices 1316a, 1316c,
1316e point generally toward an upper half of the balloon 1311,
while the orifices 1316b, 1316d point generally toward a lower half
of the balloon 1311. When the cooling assembly 1302 is in a
deployed state, refrigerant flow through orifices 1316a, 1316c,
1316e produces the first heat-transfer portion 1309, while
refrigerant flow through orifices 1316b, 1316d produces the second
heat-transfer portion 1310. As a result of the refrigerant flow,
the first and second heat-transfer portions 1309, 1310 can have
higher overall and particularly convective heat-transfer rates
relative to other heat-transfer portions of the applicator 1308.
This variation in heat-transfer rate can correspond to a desired
cooling pattern, such as a partially-circumferential cooling
pattern at some or all longitudinal segments of the applicator
1308. In several embodiments, the first and second heat-transfer
portions 1309, 1310 have heat-transfer rates sufficient to cause
therapeutically-effective renal nerve modulation, while portions of
the applicator 1308 between the first and second heat-transfer
portions 1309, 1310 have heat-transfer rates insufficient to cause
therapeutically-effective renal nerve modulation.
[0192] FIG. 14 illustrates a portion of a cryotherapeutic device
1400 that differs from the device 1300 of FIG. 13 primarily with
respect to an exhaust configuration. The device 1400 includes a
cooling assembly 1402 at a distal portion 1404 of an elongated
shaft 1406 defining an exhaust passage. The distal portion 1404 can
have a step 1407, a plurality of exhaust openings 1408, and a
rounded end 1409. The cooling assembly 1402 can include an
applicator 1410 with a balloon 1411 having a distal neck 1412 and
the balloon 1411 can define an expansion chamber configured to
generate and deliver cryogenic cooling. The device 1400 can further
include a supply tube 1413 extending along the length of the shaft
1406 and into the balloon 1411. Within the balloon 1411, the supply
tube 1413 can include a helical portion 1414 that exits the distal
portion 1404 and wraps around the distal portion 1404 (e.g., the
distal portion 1404 can define a central axis of the helical
portion 1414). The helical coils of the helical portion 1414 can be
located between the exhaust openings 1408. The cooling assembly
1402 can include a plurality of orifices (individually identified
as 1416a-d) laterally spaced apart along the helical portion 1414.
In the illustrated embodiment, the distal portion 1404 is
sufficiently narrow to allow the helical portion 1414 to wrap
around the distal portion 1404 generally without extending beyond
the diameter of the shaft 1406 proximal to the distal portion 1404.
Accordingly, the cooling assembly 1402 in a delivery state can be
configured to fit within a delivery sheath sized according to the
shaft 1406. The plurality of exhaust openings 1408 can promote
exhaust flow and mitigate any flow restriction associated with the
sizing of the distal portion 1404. Thus, as discussed above, the
relatively high density of expanded refrigerant entering the
exhaust passage can allow the distal portion 1404 to be sized down
without necessarily causing an unsuitable increase in back
pressure.
[0193] Similar to the orifices 1316a-e of the device 1300 of FIG.
13, the orifices 1416a-d in the illustrated embodiment are
laterally spaced apart along the helical portion 1414. However,
unlike the orifices 1316a-d of the device 1300 of FIG. 13, the
orifices 1416a-d in the illustrated embodiment are configured to
direct refrigerant flow in different radial directions around the
length of the cooling assembly 1402. Specifically, the orifices
1416a-d are configured to direct refrigerant flow in directions
radially spaced apart by increments of about 90.degree.. The
orifices 1416a-d are sized to cause corresponding heat-transfer
portions having circumferential arcs greater than about 90.degree..
As a result, the projected circumference of the heat-transfer
portions corresponding to the orifices 1416a-d is generally fully
circumferential, while being partially circumferential in
particular longitudinal segments of the cooling assembly 1402.
[0194] As discussed above with reference to FIG. 13, locating
primary refrigerant expansion areas closer to a balloon can
facilitate convective heat transfer. FIGS. 15A-15B illustrate a
portion of a cryotherapeutic device 1500 that also can be
configured to locate primary refrigerant expansion areas closer to
a balloon. The device 1500 includes a cooling assembly 1502 at a
distal portion 1504 of an elongated shaft 1506 defining an exhaust
passage. The distal portion 1504 can have a step 1507, and the
cooling assembly 1502 can include an applicator 1508 with an outer
balloon 1510 that can define an expansion chamber configured to
generate and deliver cryogenic cooling. The device 1500 can further
include a supply tube 1512 and an inner balloon 1514. The supply
tube 1512 has a rounded end 1516 and can extend along the length of
the shaft 1506 and through a distal portion of the outer balloon
1510. The inner balloon 1514 extends around a portion of the supply
tube 1512 within the outer balloon 1510. In several other
embodiments configured in accordance with the present technology, a
supply tube 1512 terminates within an inner distributor, such as
the inner balloon 1514, and/or the device can include a guide
member that can extend through the inner balloon 1514 and through
the distal portion of the outer balloon 1510. With reference again
to the embodiment of the device 1500 shown in FIGS. 15A-15B, the
portion of the supply tube 1512 within the inner balloon 1514 can
include supply-tube orifices 1518. The cooling assembly 1502 can
include inner-balloon orifices 1520 distributed in a helical
arrangement or other suitable arrangement on the inner balloon
1514. The inner-balloon orifices 1520 can be, for example,
laser-cut holes in the inner balloon 1514. When the cooling
assembly 1502 is in a delivery state, the outer balloon 1510 and
the inner balloon 1514 can be at least partially collapsed to fit
within a delivery sheath.
[0195] When the cooling assembly 1502 is in a deployed state,
refrigerant can flow from the supply tube 1512, through the
supply-tube orifices 1518, and into the inner balloon 1514. The
supply-tube orifices 1518 can be large enough to allow refrigerant
to enter the inner balloon 1514 without liquid-to-gas phase change
of a significant portion of liquid refrigerant (e.g., a majority of
liquid refrigerant). For example, in the deployed state, a
refrigerant absolute vapor pressure within the inner balloon 1514
outside the supply tube 1512 can be from about 40% to about 100% of
a refrigerant absolute vapor pressure within the portion of the
supply tube within the inner balloon 1514, such as from about 20%
to about 100%, or from about 33% to about 100%. A first
free-passage area equal to the total free-passage area of the
inner-balloon orifices 1520 can be less than a second free-passage
area equal to the total free-passage area of the supply-tube
orifices 1518. The size and/or number of inner-balloon orifices
1520 can be selected to control the first free-passage area.
Similarly, the size and/or number of supply-tube orifices 1518 can
be selected to control the second free-passage area. From the inner
balloon 1514, refrigerant can expand through the inner-balloon
orifices 1520 to cool one or more corresponding heat-transfer
portions of the applicator 1508. In particular, the inner-balloon
orifices 1520 can be configured to cool a generally helical
heat-transfer portion.
[0196] FIGS. 16A-16B illustrate a cryotherapeutic device 1600 that
differs from the cooling assembly 1500 of FIG. 15A with respect to
an outer-balloon shape. The device 1600 includes a cooling assembly
1602 including an applicator 1604 with an outer balloon 1606 having
a raised helical portion 1608 and a recessed portion 1610. The
inner surface of the raised helical portion 1608 can be configured
to receive expanded refrigerant from the inner-balloon orifices
1520, and the shape of the inner surface of the raised helical
portion 1608 can help to localize increased convective cooling at
the raised helical portion 1608. The recessed portion 1610 is
generally configured not to contact a renal artery or a renal
ostium. Localizing increased convective cooling to the raised
helical portion 1606 can promote cooling efficiency as well as
cooling-location selectivity. The raised helical portion 1608 can
correspond to a heat-transfer portion having a higher heat-transfer
rate than other heat-transfer portions of the applicator 1604, such
as a heat-transfer portion corresponding to the recessed portion
1610. For example, during operation, the raised helical portion
1608 can correspond to a heat-transfer portion having a
heat-transfer rate sufficient to cause therapeutically-effective
renal nerve modulation, while another heat-transfer portion of the
applicator (e.g., a heat-transfer portion corresponding to the
recessed portion 1610) has a heat-transfer rate insufficient to
cause therapeutically-effective renal nerve modulation.
Conductive Heat Transfer
[0197] FIGS. 17A-22B illustrate several embodiments of
cryotherapeutic devices that can use differential conductive
heat-transfer to affect a treatment. Features related to conductive
heat transfer through an applicator can facilitate one or more
treatment objectives of cryogenic renal-nerve modulation, such as a
desirable localized or overall treatment pattern. In several
embodiments, the devices control conduction using
thermally-insulative members. Features related to differential
conductive heat transfer through an applicator can include, for
example, additional balloons (e.g., non-cooling balloons and
balloons having low levels of cooling), differential composition
(e.g., low thermal conductivity and high thermal conductivity
materials), differential thicknesses (e.g., balloon-wall
thicknesses), and thermally-insulative structures (e.g., elongated,
thermally-insulative members within balloons or attached to balloon
walls).
[0198] FIGS. 17A-17B illustrate a portion of a cryotherapeutic
device 1700 including a cooling assembly 1702 at a distal portion
1704 of an elongated shaft 1706 defining an exhaust passage. The
distal portion 1704 can have a step 1707, and the cooling assembly
1702 can include an applicator 1708 having a balloon 1710
configured to contact a renal artery or a renal ostium. The
applicator 1708 can further include a plurality of elongated,
thermally-insulative members 1711 with lengths generally parallel
to the length of the cooling assembly 1702 and radially spaced
apart around the circumference of the cooling assembly 1702. The
balloon 1710 can define an expansion chamber configured to generate
and deliver cryogenic cooling. The device 1700 can further include
a supply tube 1712 extending along the length of the shaft 1706 and
into the balloon 1710, and the cooling assembly 1702 can include an
orifice 1714 at the end of the supply tube 1712. During operation
when the cooling assembly 1702 is in a deployed state, the
thermally-insulative members 1711 can reduce conductive cooling
through adjacent portions of the balloon 1710. For example,
portions of the balloon 1710 between the thermally-insulative
members 1711 can have heat-transfer rates sufficient to cause
therapeutically-effective renal nerve modulation, while portions of
the balloon at the thermally-insulative members 1711 can have lower
heat-transfer rates, such as heat-transfer rates insufficient to
cause therapeutically-effective renal nerve modulation. The
thermally-insulative members 1711 can be elongated and generally
continuous along the length of portions of the applicator 1708.
Accordingly, heat-transfer portions corresponding to portions of
the balloon 1710 between the thermally-insulative members 1711 can
be generally non-circumferential at longitudinal segments of the
cooling assembly 1702.
[0199] The thermally-insulative members 1711 can include a primary
material having a thermal conductivity lower than or equal to a
thermal conductivity of a primary material of the balloon 1710. In
several embodiments, the thermally-insulative members 1711 have
different compositions than the balloon 1710 and are attached to an
inner surface of the balloon 1710. Several other embodiments can
include thermally-insulative members 1711 that are compositionally
similar to (e.g., the same as) or different than the balloon 1710.
Suitable primary materials for a thermally-insulative member
configured in accordance with several embodiments of the present
technology include thermally-insulative polymer foams (e.g.,
polyurethane foams). In several embodiments, a thermally-insulative
member 1711 can be integrally formed with a balloon 1710 or
attached to a balloon 1710.
[0200] FIGS. 18A-18B illustrate a portion of a cryotherapeutic
device 1800 similar to the device 1700 of FIGS. 17A-17B except with
regard to a configuration of thermally-insulative members.
Thermally-insulative members configured in accordance with several
embodiments of the present technology can have different insulative
properties in the delivery state than in deployed state. For
example, a thermally-insulative member can be configured to be
filled with a filler material in the deployed state. The device
1800 includes a cooling assembly 1802 having an applicator 1804
with a balloon 1806 that can define an expansion chamber configured
to generate and deliver cryogenic cooling. The applicator 1804 also
includes a plurality of thermally-insulative members 1808. The
device 1800 can further include a filler tube 1810, and the
thermally-insulative members 1808 can be configured to be filled in
the deployed state via the filler tube 1810. In the illustrate
embodiment, the filler tube 1810 includes a main portion 1812 and
four branches 1814, in which the branches fluidly connect the main
portion with one of the thermally-insulative members 1808. The
thermally-insulative members 1808 and the filler tube 1810 are
fluidly separate from the expansion chamber within the balloon
1806.
[0201] The filler tube 1810 has a proximal portion (not shown)
configured to receive filler material from a filler-material source
(not shown) from outside the vasculature. The filler tube 1810 and
the thermally-insulative members 1808 can be configured to be
fully, mostly, or partially collapsed in the delivery state. This
can be useful to allow the introduction of fluidic filler material
in the delivery state without the need to vent displaced gas.
Several other embodiments can include a filler tube that is
generally not collapsible and a thermally-insulative member
configured to receive displaced gas or liquid from such a filler
tube. A proximal portion of a filler tube configured in accordance
with several embodiments of the present technology can be fluidly
connected to a filler port, such as a filler port including syringe
adapter, such as a syringe adapter including a diaphragm configured
to be punctured with a needle of a syringe containing filler
material. Such a filler port can be configured, for example, to
reduce (e.g., prevent) passage of air before, during, and/or after
passage of filler material. However, in several embodiments, air
can be a suitable filler material. Other components of
cryotherapeutic devices configured in accordance with several
embodiments of the present technology including a filler tube
(including such embodiments described herein) can be similarly
configured. Suitable filler materials for use with cryotherapeutic
devices configured in accordance with several embodiments of the
present technology include liquids (e.g., saline), gases (e.g.,
air), biologically inert materials, and radiopaque materials (e.g.,
contrast agents).
[0202] Although four thermally-insulative members are shown in
FIGS. 17A-18B, cooling assemblies configured in accordance with
several embodiments of the present technology can include any
suitable number of thermally-insulative members, such as at least
one or more thermally-insulative members. Additionally,
thermally-insulative members configured in accordance with several
embodiments of the present technology can be generally separate
elements or portions of a single element and can have a variety of
suitable shapes.
[0203] FIGS. 19A-19C illustrate a portion of a cryotherapeutic
device 1900. Referring to FIG. 19A, the device 1900 can include a
cooling assembly 1902 at a distal portion 1904 of an elongated
shaft 1906 defining an exhaust passage. The distal portion 1904 can
have a step 1907, and the cooling assembly 1902 can include an
applicator 1908 with a balloon 1910 that can define an expansion
chamber configured to generate and deliver cryogenic cooling. The
device 1900 can further include a supply tube 1912 extending along
the length of the shaft 1906 and into the balloon 1910, and the
cooling assembly 1902 can include an orifice 1914 at an end of the
supply tube 1912. The device 1900 can further include a helical
thermally-insulative member 1916 that can be, for example, a
thicker portion of the balloon 1910 with the extra thickness at an
inner surface of the balloon 1910 (i.e., an outer surface of the
balloon 1910 can be generally smooth or otherwise even at the
helical thermally-insulative member 1916 and around the helical
thermally-insulative member 1916). During operation when the
cooling assembly 1902 is in a deployed state, the helical
thermally-insulative member 1916 can correspond to a heat-transfer
portion of the applicator 1908 having a lower heat-transfer rate
than other portions of the applicator 1908. For example, a
heat-transfer rate of a portion of the applicator 1908 apart from
the helical thermally-insulative member 1916 can be sufficient to
cause therapeutically-effective renal nerve modulation during
operation, while a heat-transfer rate of a portion of the
applicator 1908 at the helical thermally-insulative member 1916 can
be insufficient to cause therapeutically-effective renal nerve
modulation. FIGS. 19B and 19C are cross-sectional views of the
applicator 1908 at different longitudinal positions. As shown in
FIGS. 19B and 19C, the circumferential position of the helical
thermally-insulative member 1916 changes along the length of the
cooling assembly 1902 such that the portion of the balloon 1910
apart from the helical thermally-insulative member 1916 is
generally non-circumferential in longitudinal segments along the
length of the cooling assembly 1902.
[0204] FIGS. 20A-20C illustrate a portion of a cryotherapeutic
device 2000 similar to the device 1900 of FIGS. 19A-19C except with
regard to a thermally-insulative member shape. Referring to FIG.
20A, the device 2000 includes a cooling assembly 2002 having an
applicator 2004 with a balloon 2006 that can define an expansion
chamber configured to generate and deliver cryogenic cooling. The
applicator 2004 also includes a thermally-insulative member 2008
generally resembling an intertwined double helix (e.g., an
intertwined right-handed helix and left-handed helix). A
heat-transfer portion of the applicator 2004 at the
thermally-insulative member 2008 generally isolates heat-transfer
portions of the applicator 2004 apart from the thermally-insulative
member 2008. The thermally-insulative member 2008 can be configured
to collapse and/or expand with the balloon 2006 when the cooling
assembly 2002 moves between the delivery state and the deployed
state. For example, if the balloon 2006 is generally flexible and
non-compliant, the thermally-insulative member 2008 can be either
generally flexible and compliant or non-compliant. If the balloon
2006 is generally compliant, the thermally-insulative member 2008
can be generally compliant so as to compliantly expand and contract
in conjunction with the balloon 2006. The thermally insulative
members 1716, 1808 shown in FIGS. 17A-18B, and the helical
thermally-insulative member 1916 shown in FIGS. 19A-19B, can be
similarly configured relative to the corresponding balloons 1710,
1806, 1910. In several embodiments of the present technology, a
thermally-insulative member has a modulus of elasticity between
about 50% and about 150% of a modulus of elasticity of a
corresponding balloon, such as between about 20% and about 140%, or
between about 33% and about 130%.
[0205] Thermally-insulative members configured in accordance with
additional embodiments of the present technology can be fully or
partially attached to a corresponding balloon, or in other
embodiments, the thermally-insulative members are not attached to
the balloon. When a thermally-insulative member is only partially
attached or not attached to a corresponding balloon, expansion
and/or contraction of the corresponding balloon can be relatively
independent of the thermally-insulative member. FIGS. 21A-21C
illustrate a portion of a cryotherapeutic device 2100 including a
cooling assembly 2102 at a distal portion 2104 of an elongated
shaft 2106 defining an exhaust passage. The distal portion 2104 can
have a step 2107 and a rounded lip 2108. The cooling assembly 2102
can include an applicator 2109 with a balloon 2110 having a distal
neck 2111 and the balloon 2110 can define an expansion chamber
configured to generate and deliver cryogenic cooling. The device
2100 can further include an elongated guide member 2112 and a
supply tube 2114 extending along a length of the shaft 2106 and
into the balloon 2110. The cooling assembly 2102 can include an
orifice 2116 at the end of the supply tube. In the illustrated
embodiment, the guide member 2112 extends through to the distal
neck 2111. The applicator 2109 further includes a first elongated,
thermally-insulative member 2118 and a second elongated,
thermally-insulative member 2120. The first and second elongated,
thermally-insulative members 2118, 2120 are not attached to the
balloon 2110. Instead, the first and second elongated,
thermally-insulative members 2118, 2120 are attached to an inner
surface of the distal portion 2104.
[0206] When the cooling assembly 2102 is in a deployed state, the
first and second thermally-insulative members 2118, 2120 can be
movable relative to the balloon 2110 in response to gravity. The
first and second thermally-insulative members 2118, 2120 can move
over the rounded lip 2108 as they settle within the balloon. As
shown in FIG. 21A, the first and second thermally-insulative
members 2118, 2120 can settle along a lower portion of the balloon
2110. As shown in FIG. 21B, the first and second
thermally-insulative members 2118, 2120 have cross-sectional areas
resembling rounded triangles. In other embodiments, a similar
thermally-insulative member can have a different cross-sectional
area. A rounded triangular cross-sectional area can be particularly
useful to increase a contact area between a side of a generally
unattached thermally-insulative member and an inner surface of a
balloon while preventing multiple generally unattached
thermally-insulative members from overlapping. With reference to
FIG. 21C, the device 2100 is shown in the delivery state within a
delivery sheath 2122. As shown in FIG. 21C, the first and second
thermally-insulative members 2118, 2120 can collapse with the
balloon 2110 in the delivery state.
[0207] FIGS. 22A-22B illustrate a portion of a cryotherapeutic
device 2200 similar to the device 2100 of FIGS. 21A-21C except with
regard to a configuration of thermally-insulative members. The
device 2200 includes a cooling assembly 2202 having an applicator
2204 with a balloon 2206 that can define an expansion chamber
configured to generate and deliver cryogenic cooling. The
applicator 2204 also includes a first elongated,
thermally-insulative member 2208 and a second thermally-insulative
member 2210. The device 2200 can further include a filler tube 2212
and the first and second thermally-insulative members 2208, 2210
can be configured to be filled in the deployed state via the filler
tube 2212. The filler tube 2212 can include a hub 2214 where it
branches into the first and second thermally-insulative members
2208, 2210. As discussed above with reference to the
thermally-insulative members 1808 of the device 1800 shown in FIGS.
18A-18B, the first and second thermally-insulative members 2208,
2210 and the filler tube 2212 can be fluidly separate from the
balloon 2206. The filler tube 2212 can have a proximal portion (not
shown) configured to receive filler material from outside the
vasculature. The filler tube 2212 and the first and second
thermally-insulative members 2208, 2210 can be configured to be
fully, mostly, or partially collapsed when the cooling assembly
2202 is in a delivery state.
[0208] A cooling assembly configured in accordance with several
embodiments of the present technology can include one or more
thermally-insulative members having a variety of suitable shapes to
cause different patterns of heat-transfer portions around an
applicator. A pattern can be selected, for example, so that a
generally uninterrupted heat-transfer portion at a
thermally-insulative member can be large enough to sufficiently
localize cooling therapeutically-effective for renal nerve
modulation (e.g., such that cooling therapeutically-effective for
renal nerve modulation generally does not bridge across a
heat-transfer portion at a thermally-insulative member). In
addition or instead, a pattern can be selected, for example, so
that a heat-transfer portion spaced apart from a
thermally-insulative member is large enough to allow
therapeutically-effective cooling for renal nerve modulation. Heat
transfer is proportional to area, so if a heat-transfer portion
spaced apart from a thermally-insulative member is too small, the
total heat transfer through that part of the heat transfer portion
can be inadequate to cause therapeutically-effective cooling for
renal nerve modulation.
Complex Balloons
[0209] FIGS. 23A-37 illustrate several embodiments of
cryotherapeutic devices that include complex balloons which can
facilitate one or more treatment objectives related to cryogenic
renal-nerve modulation, such as a desirable localized or overall
treatment pattern, sizing, and partial occlusion. Complex balloons
can have a variety of suitable characteristics, such as shape
(e.g., helical, curved, longitudinally-asymmetrical, and
radially-asymmetrical), surface differentiation (e.g., recesses,
groves, protrusions, and projections), and differential expansion
(e.g., partially-constrained expansion).
[0210] FIGS. 23A-23B illustrate a portion of a cryotherapeutic
device 2300 including a cooling assembly 2302 at a distal portion
2304 of an elongated shaft 2306 defining an exhaust passage. The
distal portion 2304 can have a step 2307, a first exhaust port
2308, a second exhaust port 2309, and a rounded end 2310. The
cooling assembly 2302 can include an applicator 2311 having a first
balloon 2312 that defines a first expansion chamber and a second
balloon 2313 that defines a second expansion chamber. The first
balloon 2312 and the second balloon 2313 are fluidly connected to
the exhaust passage through the first exhaust port 2308 and the
second exhaust port 2309, respectively. The device 2300 can further
include a supply tube 2314 extending along a length of the shaft
2306, and the cooling assembly 2302 can further include a first
orifice 2316 and a second orifice 2318. The first orifice 2316 is
aligned with the first exhaust port 2308 such that refrigerant
expands through the first exhaust port 2308 and into the first
balloon 2312, and the second orifice 2318 is aligned with the
second exhaust port 2309 such that refrigerant expands through the
second exhaust port 2309 and into the second balloon 2313.
[0211] The first and second balloons 2312, 2313 are spaced apart
along the length of the cooling assembly 2302 and configured to
expand laterally across different partially-circumferential arcs
along the length of the cooling assembly 2302. When the cooling
assembly 2302 is in a deployed state, the first balloon 2312 can be
configured to contact a first partially-circumferential portion of
an inner surface of a renal artery or a renal ostium, and the
second balloon 2313 can be configured to contact a second
partially-circumferential portion of the inner surface of the renal
artery or the renal ostium. The first and second
partially-circumferential portions can have a fully-circumferential
combined projection in a plane perpendicular to a length of the
renal artery or the renal ostium. Accordingly, when a treatment
calls for partially-circumferential cooling at longitudinal
segments and a fully-circumferential overall cooling pattern, the
cooling assembly 2302 can be configured to facilitate such a
treatment without repositioning the cooling assembly 2302 during
the treatment.
[0212] When the first and second balloons 2312, 2313 are both in
the deployed state, they can urge each other toward generally
opposite sides of an inner surface of a renal artery or a renal
ostium. For example, the distal portion 2304 can transfer forces
between the first and second balloons 2312, 2313 while a portion of
the shaft 2306 proximal to the distal portion holds the distal
portion generally parallel to a length of a renal artery or a renal
ostium. During this and other operation, the cooling assembly 2302
can be configured to be non-occlusive (i.e., to less than fully
occlude a renal artery or a renal ostium). For example, the cooling
assembly 2302 can be configured to allow a percentage of normal
blood flow through a renal artery or a renal ostium (e.g., at least
about 1%, at least about 10%, or at least about 25% of normal blood
flow).
[0213] FIGS. 24A-24B illustrate a portion of a cryotherapeutic
device 2400 that differs from the device 2300 of FIGS. 23A-23B
primarily with respect to an exhaust configuration. The device 2400
includes a cooling assembly 2402 at a distal portion 2404 of an
elongated shaft 2406 defining an exhaust passage. The distal
portion 2404 can have a step 2407, a first exhaust port 2408, a
second exhaust port 2409, and a rounded end 2410. The cooling
assembly 2402 can include an applicator 2411 having a first balloon
2412 that defines a first expansion chamber and a second balloon
2413 that defines a second expansion chamber. The first balloon
2412 and the second balloon 2413 are fluidly connected to the
exhaust passage through the first exhaust port 2408 and the second
exhaust port 2409, respectively. The device 2400 can further
include a supply tube 2414 extending along a length of the shaft
2406 and having a first lateral branch 2416 and a second lateral
branch 2418. The cooling assembly 2402 can further include a first
orifice 2420 at the end of the first lateral branch 2416 open to
the first balloon 2412 and a second orifice 2422 at the end of the
second lateral branch 2418 open to the second balloon 2413. Unlike
the device 2300 shown in FIGS. 23A-23B, the device 2400 includes
refrigerant supply and refrigerant exhaust at circumferentially
opposite sides of the distal portion 2404 for the first and second
balloons 2412, 2413. The first and second balloons 2412, 2413
extend around fully-circumferential longitudinal segments of the
distal portion 2404, but are attached to the distal portion 2404
and shaped so as to expand asymmetrically about the distal portion
2404.
[0214] Cooling assemblies configured in accordance with several
embodiments of the present technology can include a different
number of partially-circumferential balloons from the cooling
assemblies 2302, 2402 shown in FIGS. 23A-24B. For example, in
several embodiments, the cooling assembly 2302 can include the
first balloon 2312 or the second balloon 2313 rather than both.
Similarly, the cooling assembly 2402 can include the first balloon
2412 or the second balloon 2413 rather than both. The cooling
assemblies 2302, 2402 shown in FIGS. 23A-24B also can include a
greater number of balloons, such as three or four balloons
longitudinally and radially spaced apart. Furthermore, the sizes of
the balloons can vary. For example, in several embodiments, the
first and second balloons 2312, 2313 of the cooling assembly 2302
or the first and second balloons 2412, 2413 of the cooling assembly
2402 are configured to provide a partially-circumferential overall
cooling pattern.
[0215] Cooling assemblies configured in accordance with several
embodiments of the present technology can include applicators with
balloons having a variety of suitable surface characteristics, such
as surface characteristics configured to facilitate
partially-circumferential cooling at longitudinal segments alone or
in combination with a fully-circumferential overall cooling
pattern. FIG. 25 illustrates a portion of a cryotherapeutic device
2500 including a cooling assembly 2502 at a distal portion 2504 of
an elongated shaft 2506 defining an exhaust passage. The distal
portion 2504 can have a step 2507, and the cooling assembly 2502
can include an applicator 2508 with a balloon 2510 that defines an
expansion chamber and has a distal neck 2511, a helical recess
2512, and a non-recessed portion 2513. The device 2500 can further
include an elongated guide member 2514 that extends through the
distal neck 2511, as well as a supply tube 2516 that extends along
the length of the shaft 2506 and into the balloon 2510. The cooling
assembly 2502 can further include an orifice 2518 at the distal end
of the supply tube 2516. When the cooling assembly 2502 is in a
delivery state, the helical recess 2512 can correspond to a
heat-transfer portion of the applicator 2508 having a lower
heat-transfer rate than portions of the applicator 2508 spaced
apart from the helical recess 2512.
[0216] The space between the helical recess 2512 and an inner
surface of a renal artery or a renal ostium at a treatment site can
thermally insulate portions of the renal artery or the renal ostium
closest to the helical recess 2512 from a cryogenic temperature
within the balloon 2510. For example, frozen or liquid blood within
this space can provide thermal insulation. The depth of the helical
recess 2512 relative to the non-recessed portion 2513 can be, for
example, a depth corresponding to a thickness of material (e.g.,
liquid or frozen blood) sufficient to thermally insulate a portion
of a renal artery or a renal ostium from cryogenic cooling within
the balloon 2510. For example, the depth can be between about 0.2
mm and about 2 mm, such as between about 0.3 mm and about 1.5 mm.
Recessed portions of balloons in several other embodiments of
cryotherapeutic-device components described herein can have similar
depths relative to non-recessed portions of the balloons.
[0217] FIG. 26 illustrates a portion of another embodiment of a
cryotherapeutic device 2600 including a cooling assembly 2602 at a
distal portion 2604 of an elongated shaft 2606 defining an exhaust
passage. The distal portion 2604 can have a step 2607, and the
cooling assembly 2602 can include an applicator 2608 with a balloon
2610 that defines an expansion chamber and has a distal neck 2611,
a plurality of recesses 2612, and a non-recessed portion 2613. The
recesses 2612 can be arranged in a helical pattern around the
circumference of the balloon 2610. The cooling assembly 2602 can
further include an elongated guide member 2614 that extends through
the distal neck 2611. The device 2600 can also include a supply
tube 2616 that extends along the length of the shaft 2606 and into
the balloon 2610. The cooling assembly 2602 can further include an
orifice 2618 at the distal end of the supply tube 2616. When the
cooling assembly 2602 is in a deployed state, the recesses 2612 and
the non-recessed portion 2613 can function similarly to the helical
recess 2512 and the non-recessed portion 2513 of the device 2500
shown in FIG. 25.
[0218] FIGS. 27A-27C illustrate a portion of a cryotherapeutic
device 2700 similar to the device 2600 of FIG. 26, but the device
2700 is configured to be less occlusive within a renal artery or a
renal ostium than the device 2600 of FIG. 26. The device 2700
includes a cooling assembly 2702 at a distal portion 2704 of an
elongated shaft 2706 defining an exhaust passage. The distal
portion 2704 can have a step 2707, and the cooling assembly 2702
can include an applicator 2708 with a balloon 2710 that defines an
expansion chamber and has proximal branches 2711, a tubular main
portion 2712, distal branches 2713, a plurality of recesses 2714,
and a non-recessed portion 2716. The plurality of recesses 2714 can
be arranged in a helical pattern around the circumference of the
balloon 2710. When the cooling assembly 2702 is in a deployed
state, the recesses 2714 and the non-recessed portion 2716 can
function similarly to the recesses 2612 and the non-recessed
portion 2613 of the device 2600 shown in FIG. 26. The proximal
branches 2711 can be configured to fluidly connect the tubular main
portion 2712 to the exhaust passage. The device 2700 can further
include an elongated guide member 2718 that can extend along the
length of the shaft 2706 and attach to the distal branches 2713, as
well as a supply tube 2720 that extends along the length of the
shaft 2706, through one of the proximal branches 2711, and into the
tubular main portion 2712. The proximal branches 2711 and the
distal branches 2713 can be configured to space apart the tubular
main portion 2712 from the guide member 2718. The cooling assembly
2702 can further include an orifice 2722 at the distal end of the
supply tube 2720.
[0219] When the cooling assembly 2702 is in a deployed state, the
cooling assembly 2702 can define a flow path (e.g., a blood flow
path) between an outside surface of the guide member 2718 and the
balloon 2710. The flow path can extend, for example, around the
proximal branches 2711, through the tubular main portion 2712
(e.g., between the guide member 2718 and an inner surface of the
tubular main portion 2712), and around the distal branches 2713. As
shown in FIG. 27B, the tubular main portion 2712 can include a
thermally-insulative inner portion 2724 around the flow path. The
thermally-insulative inner portion 2724 can be configured to at
least partially insulate fluid in the flow path from cryogenic
cooling within the tubular main portion 2712. In the illustrated
embodiment, the thermally-insulative inner portion 2724 can be a
portion of the balloon 2710 having a greater thickness than other
portions of the balloon 2710. In several other embodiments, the
thermally-insulative inner portion 2724 has a different composition
from other portions of the balloon 2710 and/or includes one or more
separate thermally-insulative structures. Alternatively, the
balloon 2710 can include a tubular main portion 2712 with an inner
portion that is not more thermally insulative than other portions
of the balloon 2710.
[0220] FIG. 28 illustrates a portion of a cryotherapeutic device
2800 similar to the device 2600 of FIG. 26 except with regard to a
configuration of recessed and non-recessed portions. The device
2800 includes a cooling assembly 2802 having an applicator 2804
with a balloon 2806 that can define an expansion chamber. The
balloon 2806 includes a plurality of protrusions 2808 and a
non-protruding portion 2810. The protrusions 2808 can be arranged
in a helical pattern or other suitable pattern around the
circumference of the balloon 2806. When the cooling assembly 2802
is in a delivery state, the non-protruding portion 2810 can
correspond to a heat-transfer portion of the applicator 2804 having
a lower heat-transfer rate than portions of the applicator at the
protrusions 2808. The space between the non-protruding portion 2810
and an inner surface of a renal artery or a renal ostium at a
treatment site can thermally insulate portions of the renal artery
or the renal ostium closest to the non-protruding portion from
cryogenic temperatures within the balloon 2806. For example, frozen
or liquid blood within this space can provide thermally
insulation.
[0221] Balloons having different shapes can facilitate certain
treatment objectives related to cryogenic renal-nerve modulation.
For example, helical shapes can facilitate a desirable localized or
overall treatment pattern. FIG. 29 illustrates a portion of a
cryotherapeutic device 2900 including a cooling assembly 2902 at a
distal portion 2904 of an elongated shaft 2906 defining an exhaust
passage. The distal portion 2904 can have a step 2907, an exit hole
2908, and an exhaust port 2909. The cooling assembly 2902 can
include an applicator 2910 with a helical balloon 2911 that defines
an expansion chamber and has a balloon proximal portion 2912 and a
balloon distal portion 2914. The balloon proximal portion 2912 has
minor fluid connection with the exhaust passage through the exit
hole 2908. The balloon distal portion 2914 is attached to the
outside surface of the distal portion 2904 around the exhaust
opening 2909, thereby fluidly connecting the helical balloon 2911
to the exhaust passage. The helical balloon 2911 is wrapped around
the distal portion 2904 (e.g., the distal portion 2904 can define a
central axis of the helical balloon 2911). The device 2900 can
further include a supply tube 2916 defining a supply lumen and
having a main portion 2918 extending along the length of the shaft
2906 and an angled distal portion 2920 exiting the shaft 2906
through the exit hole 2908. The cooling assembly 2902 also can
include an orifice 2922 at the distal end of the angled distal
portion 2920. The supply tube 2916 and the orifice 2922 can be
configured to direct expansion of refrigerant into the balloon
proximal portion 2912 in a direction generally corresponding to a
longitudinal orientation of the balloon proximal portion 2912. When
the cooling assembly 2902 is in a deployed state, refrigerant can
flow from the balloon proximal portion 2912 to the balloon distal
portion 2914 and then proximally along the exhaust passage. Upon
reaching the balloon distal portion 2914, the refrigerant can have
exhausted some, most, or all of its capacity for cryogenic
cooling.
[0222] FIG. 30 illustrates a portion of a cryotherapeutic device
3000 that differs from the device 2900 of FIG. 29 primarily with
respect to a refrigerant flow direction. The device 3000 includes a
cooling assembly 3002 at a distal portion 3004 of an elongated
shaft 3006 defining an exhaust passage. The distal portion 3004 can
have a step 3007, and the cooling assembly 3002 can include an
applicator 3008 having a helical balloon 3014 that defines an
expansion chamber and has a balloon proximal portion 3016 and a
balloon distal portion 3018. The balloon proximal portion 3016 can
be attached to an outside surface of the distal portion 3004
proximate a distal end of the distal portion 3004, thereby fluidly
connecting the helical balloon 3014 to the exhaust passage. The
device 3000 can further include a supply tube 3019 having a curved
distal portion 3020. The helical balloon 3014 can be wrapped around
the supply tube 3019 (e.g., the supply tube 3019 can define a
central axis of the helical balloon 3014). The supply tube 3019 can
extend along the length of the shaft 3006, out of the shaft, out of
the balloon proximal portion 3016, along a central axis of the
helical balloon 3014, and into the balloon distal portion 3018. The
balloon distal portion 3016 can be sealed around the supply tube
3019 and at least partially attached to the curved distal portion
3020. The cooling assembly 3002 can further include an orifice 3021
fluidly connecting the supply tube 3019 to the balloon distal
portion 3018. The supply tube 3019 and the orifice 3021 can be
configured to direct expansion of refrigerant into the balloon
distal portion 3018 in a direction generally corresponding to a
longitudinal orientation of the balloon distal portion 3018. When
the cooling assembly 3002 is in a deployed state, refrigerant can
flow from the balloon distal portion 3018 to the balloon proximal
portion 3016 and then proximally along the exhaust passage.
[0223] FIG. 31 illustrates a portion of a cryotherapeutic device
3100 similar to the device 3000 of FIG. 30 except with regard to a
helical balloon shape. The device 3100 includes a cooling assembly
3102 at a distal portion 3104 of an elongated shaft 3106 defining
an exhaust passage. The distal portion 3104 can have a step 3108,
and the cooling assembly 3102 can include an applicator 3110 having
a helical balloon 3112 that defines an expansion chamber and has a
balloon proximal portion 3114 and a balloon distal portion 3116.
The balloon proximal portion 3114 can be attached to an outside
surface of the distal portion 3104 proximate a distal end of the
distal portion 3104, thereby fluidly connecting the helical balloon
3112 to the exhaust passage. The device 3100 can further include a
supply tube 3117 having an angled distal portion 3118 The helical
balloon 3112 can be wrapped around the supply tube 3117 but also
radially spaced apart from the supply tube 3117. The supply tube
3117 can extend along the length of the shaft 3106, out of the
shaft 3106, out of the balloon proximal portion 3114, along a
central axis of the helical balloon 3112, and into the balloon
distal portion 3116. The balloon distal portion 3116 can be sealed
around the supply tube 3117. The cooling assembly can further
include an orifice 3119 fluidly connecting the supply tube 3117 to
the balloon distal portion 3116. When the cooling assembly 3102 is
in a deployed state, refrigerant can flow from the balloon distal
portion 3116 to the balloon proximal portion 3114 and then
proximally along the exhaust passage. The wide helical diameter of
the helical balloon 3112 can facilitate partial occlusion. For
example, when the cooling assembly 3102 is in the deployed state,
the cooling assembly 3102 can define a flow path (e.g., a blood
flow path) between an outside surface of the supply tube 3117 and
the helical balloon 3112.
[0224] FIGS. 32A-32B illustrate a portion of a cryotherapeutic
device 3200 that can have a complex shape corresponding to a
shaping member, such as a shaping member having a shape memory. As
discussed above, balloons in cryotherapeutic devices configured in
accordance with several embodiments of the present technology can
move from being at least partially collapsed when a corresponding
cooling assembly is in a delivery state, to being at least
partially expanded when the cooling assembly is in a deployed
state. When expanded in the deployed state, complex balloons can
have pre-defined shapes (e.g., integral shapes molded or otherwise
incorporated into the balloon) or shapes corresponding to separate
shaping structures. The cryotherapeutic device 3200 shown in FIGS.
32A-32B includes a cooling assembly 3202 at a distal portion 3204
of an elongated shaft 3206 defining an exhaust passage. The distal
portion 3204 can have a step 3207, and the cooling assembly 3202
can include an applicator 3208. The device 3200 can further include
an elongated shaping member 3210 and a supply tube 3212 having an
angled distal portion 3214. The applicator 3208 can include a
balloon 3216 with a distal seal 3217. The balloon 3216 can extend
around the elongated shaping member 3210 and can define an
expansion chamber. The distal seal 3217 can be a flattened portion
of the balloon 3216 at which walls of the balloon 3216 are sealed
together (e.g., thermally and/or with adhesive). Balloons
configured in accordance with several other embodiments of the
present technology can have another type of closed distal end. As
discussed above, balloons can be closed around structures, such as
guide members and/or supply tubes. Balloons also can be closed
around plugs. Furthermore, balloons can have integral closed distal
ends. For example, balloons can be molded (e.g., dip molded) with
integral closed distal ends.
[0225] The shaping member 3210 can be configured to have a
generally linear configuration when the cooling assembly 3202 is in
a delivery state and a curvilinear configuration when the cooling
assembly 3202 is in a deployed state. The cooling assembly 3202 can
also include an orifice 3218 at the distal end of the angled distal
portion 3214. The supply tube 3212 and the orifice 3218 can be
configured to direct expansion of refrigerant into the balloon 3216
in a direction generally corresponding to a longitudinal
orientation of the balloon 3216 proximate the orifice 3218. As
shown in FIG. 32A, the balloon 3216 has a shape in the deployed
state at least partially corresponding to the curvilinear
configuration of the shaping member 3210. The illustrated
curvilinear configuration is generally helical, but also could be
another shape, such as a serpentine shape. The shaping member 3210
can have a shape memory (e.g., a one-way shape memory or a two-way
shape memory) and can include a shape-memory material, such as a
nickel-titanium alloy (e.g., nitinol). Shape memory can allow the
shaping member 3210 and the balloon 3216 to move into a
pre-selected configuration (e.g., a curved, curvilinear, helical,
or serpentine configuration) in the deployed state. The
configuration can be selected, for example, to allow the applicator
3208 to apply a desirable localized or overall treatment pattern.
Similarly, the helical shape shown in FIG. 32A and other shapes can
be selected to provide a level of occlusion at a treatment site,
such as partial occlusion instead of full occlusion. Shape-memory
materials can lose some or all of their shaping properties when
exposed to cryogenic temperatures. Cooling assemblies 3202
configured in accordance with several embodiments of the present
technology can include balloons 3216 that move into a pre-selected
configuration corresponding to a shape of a shaping member 3210
before cryogenic cooling or during initial cryogenic cooling. When
the cryogenic cooling causes the shaping member 3210 to lose some
or all of its shaping properties, cryo-adhesion between the balloon
3216 and external material (e.g., blood and/or tissue) can cause
the balloon 3216 to maintain its pre-selected configuration at
least until the cryo-adhesion ends.
[0226] In the embodiment illustrated in FIGS. 32A-32B, the shaping
member 3210 is shown generally centered within the balloon, i.e.,
the balloon 3216 is generally uniformly expanded around the shaping
member 3210. Alternatively, the shaping member 3210 can have a
different position within the balloon 3216 when the cooling
assembly 3202 is in the deployed state. For example, the shaping
member 3210 can be near an inner surface of the balloon 3216. When
the shaping member 3210 is spaced apart from walls of the balloon
3216, the balloon 3216 can dissipate pressure against a renal
artery or renal ostium. As shown in FIG. 32A, the shaping member
3210 can extend through the distal seal 3217. Alternatively, the
shaping member 3210 can be not attached to the balloon 3216 and/or
terminate at a portion of the balloon 3216 proximal to the distal
seal 3217. Furthermore, a distal portion of the shaping member 3210
can be configured to be spaced apart from a renal artery or renal
ostium when the cooling assembly 3202 is in the deployed state. In
some embodiments, the balloon 3216 is configured to generally
uniformly expand around the shaping member 3210 without any
internal support structures. Alternatively, the balloon 3216 can
include an internal structure (e.g., webbing) extending across an
inner diameter of the balloon 3216 and the shaping member 3210 can
be attached to the internal structure at a position spaced apart
from inner surfaces of the balloon 3216. The internal structure,
for example, can be a partition between separate balloons (e.g., as
discussed below with reference to FIGS. 45A-46). In some
embodiments, the cooling assembly includes a structure extending
along a central axis of the balloon 3216 in the deployed state. For
example, the distal portion 3204 can extend along the central axis
of the balloon 3216 in the deployed state and the balloon 3216 and
the shaping member 3210 can connect to a lateral opening of the
distal portion 3204. As another example, the distal portion 3204
can include a reduced-diameter extension extending along the
central axis of the balloon 3216 and another opening separate from
the reduced-diameter extension fluidly connecting the balloon 3216
to the exhaust passage. A structure extending along the central
axis of the balloon 3216 can include a lumen (e.g., a lumen
configured to receive a guide wire or a control wire), a protection
device (e.g., a filter), and/or a monitoring device (e.g., a
thermocouple or a pressure transducer).
[0227] The device 3200 can be modified for use in
non-cryotherapeutic applications. For example, the supply tube 3212
can be removed and the device 3200 can be used in other
applications that benefit from less than full occlusion at a
treatment site. In both renal-neuromodulation applications and
other applications, the balloon 3216 can be non-occlusive in the
deployed state, e.g., a blood flow path can be formed along a
central axis of the balloon 3216. In some non-cryotherapeutic
applications, the distal portion 3204 can support a structure
configured to execute a treatment (e.g., a thrombectomy) within a
vessel while the balloon 3216 anchors the device 3200 to a vessel
wall. In these and other embodiments, the balloon 3216
advantageously can maintain the distal portion 3204 at a central
position within a vessel.
[0228] FIGS. 33A-33D illustrate a portion of a cryotherapeutic
device 3300 that can have a pre-defined curved shape in a deployed
configuration. The device 3300 includes a cooling assembly 3302 at
a distal portion 3304 of an elongated shaft 3306 defining an
exhaust passage. The distal portion 3304 can have a step 3307, and
the cooling assembly 3302 can include an applicator 3308 with a
balloon 3310 that can define an expansion chamber. The balloon 3310
can have a balloon proximal portion 3312, a balloon middle portion
3314, and a balloon distal portion 3316. The device 3300 further
includes a supply tube 3318 extending along the shaft 3306, and the
cooling assembly 3302 can have an orifice 3320 at the distal end of
the supply tube 3318 and within the balloon proximal portion 3312.
When the cooling assembly 3302 is in a deployed state, the balloon
3310 is curved along its length and has a generally concave first
wall 3322 (shown as a lower portion of the balloon in FIG. 33A) and
a generally non-concave (e.g., convex) second wall 3324 (shown as
an upper portion of the balloon in FIG. 33A).
[0229] The balloon proximal portion 3312, the balloon middle
portion 3314, and the balloon distal portion 3316 can be configured
to contact partially circumferential portions of a renal artery or
a renal ostium. For example, the balloon middle portion 3314 can be
configured to contact a renal artery or a renal ostium generally
along the second wall 3324 and generally not along the first wall
3322 when the cooling assembly 3302 is in a deployed state. The
balloon proximal portion 3312 and the balloon distal portion 3316,
for example, can be configured to contact a renal artery or a renal
ostium generally along the first wall 3322 and generally not along
the second wall 3324 when the cooling assembly 3302 is in the
deployed state. Due to this uneven pattern of contact, the curved
shape of the balloon 3310 can facilitate a desirable localized or
overall treatment pattern.
[0230] As best seen in FIGS. 33B-33C, the balloon 3310 can include
a reduced-elasticity portion 3326 along the first wall 3322 at the
balloon middle portion 3314. In the illustrated embodiment, the
reduced-elasticity portion 3326 can be a thicker portion of the
balloon 3310. As shown in FIG. 33D, the balloon 3310 can be
partially collapsed when the cooling assembly 3302 is in the
delivery state so as to fit within a delivery sheath 3328. When the
cooling assembly 3302 is in the delivery state, the
reduced-elasticity portion 3326 can retain some curvature.
Alternatively, the reduced-elasticity portion 3326 can be generally
flat. When the cooling assembly 3302 is in a deployed state,
portions of the balloon 3310 other than the reduced elasticity
portion 3326, particularly portions of the balloon 3310 along the
second wall 3324 at the balloon middle portion 3314 can be
configured to expand (e.g., compliantly expand) to a greater degree
than the reduced-elasticity portion 3326. In several embodiments,
the reduced-elasticity portion 3326 is generally non-compliant and
a portion of the balloon 3310 along the second wall 3324 at the
balloon middle portion 3314 is generally compliant. Restriction
associated with the reduced-elasticity portion 3326 can facilitate
curvature of the balloon 3310 when the cooling assembly 3302 is in
the deployed state. The reduced-elasticity portion 3326 can be
configured to be recessed relative to a renal artery or a renal
ostium when the cooling assembly 3302 is in the deployed state and,
correspondingly, not encompass a heat-transfer portion having a
heat-transfer rate sufficient to cause therapeutically-effective
renal nerve modulation. In addition to reducing elasticity, the
thickness of the reduced-elasticity portion 3326 can reduce its
thermal conductivity, which can promote improve cooling efficiency
and/or further facilitate a desirable localized or overall
treatment pattern.
[0231] FIG. 34 illustrates a portion of a cryotherapeutic device
3400 similar to the device 3300 of FIGS. 33A-33D except having a
different support configuration. The device 3400 includes a cooling
assembly 3402 having an applicator 3404 with a balloon 3406
defining an expansion chamber. The cooling assembly 3402 also
includes an elongated support member 3408 having a curved distal
end 3410. The elongated support member 3408 and other support
members described herein can help balloons move with a
corresponding cooling assembly as the cooling assembly moves
between a delivery state and a deployed state. For example, the
elongated support member 3408 can help to prevent the balloon 3406
from becoming stuck or twisted during treatment. Optionally,
elongated support members can be attached to distal portions of
corresponding balloons. This can be useful, for example, to
maintain a balloon in an elongated configuration.
[0232] FIGS. 35A-35B illustrate a portion of a cryotherapeutic
device 3500 in which interaction with a guide member at least
partially causes a complex balloon shape. In several other
embodiments, a complex balloon is at least partially shaped through
interaction with another cryotherapeutic-device component (e.g., a
shaft or a supply tube). The device 3500 shown in FIGS. 35A-35B
includes a cooling assembly 3502 at a distal portion 3504 of an
elongated shaft 3506 defining an exhaust passage. The device 3500
can include an elongated guide member 3508 and a supply tube 3512,
and the cooling assembly 3502 can include an orifice 3514 at the
distal end of the supply tube 3512. The cooling assembly can
further include an applicator 3510 with a balloon 3516 that can
define an expansion chamber and can have a balloon proximal portion
3518, a proximal integral neck 3520 attached to the distal portion
3504, and a distal integral neck 3522 attached to the guide member
3508. The balloon 3516 can also have a constrained longitudinal
portion 3524 (FIG. 35B) and an expandable longitudinal portion 3526
(FIG. 35B). The constrained longitudinal portion 3524 can be at
least partially attached to the guide member 3508. For example,
from the distal integral neck 3522 to the balloon proximal portion
3518, an internal surface of the balloon 3516 can be attached to
the guide member 3508. The expandable longitudinal portion 3526 can
be spaced apart from the guide member 3508 when the cooling
assembly 3502 is in a deployed state. The partially-constrained
shape of the balloon 3516 can be useful to facilitate a desirable
localized or overall treatment pattern. Furthermore, the
constrained longitudinal portion 3524 can define at least a portion
of a longitudinal flow path (e.g., a blood flow path) around the
balloon 3516. This can be useful, for example, to facilitate a
level of occlusion at a treatment site, such as partial occlusion
instead of full occlusion.
[0233] FIG. 36 illustrates a cryotherapeutic device 3600 similar to
the cryotherapeutic device 3500 of FIGS. 35A-35B, except having a
different pattern of attachment between a balloon and a guide
member. FIG. 36 can be considered as a substitute for FIG. 35B to
illustrate a separate embodiment in which all elements of the
cryotherapeutic device 3500 shown in FIGS. 35A-35B are similar
except for those shown differently in FIG. 36 relative to FIG. 35B.
The cryotherapeutic device 3600 includes an elongated guide member
3602 and a balloon 3604 having radially spaced apart constrained
longitudinal portions 3506 and radially spaced apart expanded
longitudinal portions 3508. Although FIG. 36 shows two constrained
longitudinal portions 3606 and two expanded longitudinal portions
3608, a greater number of constrained longitudinal portions 3606
and/or expanded longitudinal portions 3608 can be formed for
example, by attaching the balloon 3604 to the guide member 3602 at
a different number of radial segments of the guide member 3602.
Furthermore, the distribution of constrained longitudinal portions
3606 and expanded longitudinal portions 3608 can be symmetrical or
asymmetrical (e.g., along an axis parallel to the length of the
guide member 3602).
[0234] FIG. 37 illustrates a portion of a cryotherapeutic device
3700 including a balloon having a loop shape. The device 3700
includes a cooling assembly 3702 at a distal portion 3704 of an
elongated shaft 3706 defining an exhaust passage, as well as a
supply tube 3708. The cooling assembly 3702 includes an orifice
3710 at the distal end of the supply tube 3708, and an applicator
3712 with a balloon 3714 having a first balloon segment 3716 and a
second balloon segment 3718. The first balloon segment 3716 has a
first proximal portion 3720 and a first distal portion 3722. The
second balloon segment 3718 has a second proximal portion 3724 and
a second distal portion 3726. The first balloon distal portion 3722
is fluidly connected to the second distal portion 3726. When the
cooling assembly 3702 is in the deployed state, refrigerant can
flow from the first proximal portion 3720, to the first distal
portion 3722, and then to the second distal portion 3726. Upon
reaching the second distal portion 3726, the refrigerant can have
exhausted some, most, or all of its capacity for cryogenic cooling.
Accordingly, the second balloon segment 3718 can serve primarily to
exhaust refrigerant from the first distal portion 3722 and have a
heat-transfer portion with a heat-transfer rate lower than a
heat-transfer rate of a heat-transfer portion of the first
balloon-segment 3716. In several alternative embodiments, the first
balloon segment 3716 and the second balloon segment 3718 are
separate balloons with a fluid connection at their distal ends. In
another embodiment, the first and second balloon segments can be
portions of a single balloon that is folded. Similar to non-cooling
balloons discussed below, the second balloon segment 3718 can
thermally insulate a portion of a renal artery or a renal ostium at
a treatment site from cryogenic temperatures within the first
balloon segment 3716. This can be useful, for example, to
facilitate a desirable localized or overall treatment pattern.
Multiple Balloons
[0235] FIGS. 38-51 illustrate several embodiments of
cryotherapeutic devices that include multiple balloons that can
facilitate one or more treatment objectives related to cryogenic
renal-nerve modulation, such as a desirable localized or overall
treatment pattern, sizing, and full occlusion. In cryotherapeutic
devices configured in accordance with several embodiments of the
present technology, a primary balloon configured to generate or
deliver therapeutically effective cooling for renal nerve
modulation (e.g., including a primary heat-transfer portion) can be
used in conjunction with a secondary balloon configured to prevent
or inhibit therapeutically effective cooling temperatures at
selected locations. In several embodiments, a secondary balloon
includes a secondary heat-transfer portion. A secondary balloon,
for example, can be warming, thermally-insulative, non-cooling, or
have a low-level of cooling. Alternatively, several embodiments
include multiple balloons that include primary heat-transfer
portions with or without a secondary balloon.
[0236] FIGS. 38A-38B illustrate a portion of a cryotherapeutic
device 3800 that can have multiple primary balloons. The device
3800 includes a cooling assembly 3802 at a distal portion 3804 of
an elongated shaft 3806 defining an exhaust passage. The distal
portion 3804 can have a step 3807, and the device 3800 can include
an elongated guide member 3808 and a supply tube 3810. The cooling
assembly 3802 can include an orifice 3811 at the distal end of the
supply tube 3810 and an applicator 3812 having elongated balloons
3814 positioned generally parallel to a length of the cooling
assembly 3802. The balloons 3814 have a shared proximal portion
3816 and are otherwise circumferentially distributed around the
guide member 3808. The orifice 3811 is within the shared proximal
portion 3816 and the balloons 3814, in conjunction with the shared
proximal portion 3816, can define expansion chambers. When the
cooling assembly 3802 is in a deployed state, refrigerant expanded
from the supply tube 3810 can enter the shared proximal portion
3816 and circulate within the balloons 3814 to cause expansion
thereof and cooling. Refrigerant can exit the balloons 3814 also
through the shared proximal portion 3816 and flow proximally along
the exhaust passage. The balloons 3814 can be configured to contact
spaced-apart portions (e.g., spaced-apart longitudinal portions) of
a renal artery or a renal ostium at a treatment site. This can be
useful to facilitate a desirable localized or overall treatment
pattern. Furthermore, space between the balloons 3814 can define at
least a portion of a longitudinal flow path (e.g., a blood flow
path) around the balloons 3814. This can be useful, for example, to
facilitate a level of occlusion at a treatment site, such as
partial occlusion instead of full occlusion.
[0237] FIGS. 39A-39C illustrate a portion of a cryotherapeutic
device 3900 that can have multiple balloons having different levels
of cooling. The device 3900 includes a cooling assembly 3902 at a
distal portion 3904 of an elongated shaft 3906, an elongated guide
member 3907, and a plurality of supply tubes (individually
identified as 3908a-d). The cooling assembly 3902 can include a
plurality of orifices (individually identified as 3910a-d) at the
distal ends of the supply tubes 3908a-d, and an applicator 3912
including a plurality of elongated balloons (individually
identified as 3914a-d in FIGS. 39A and 39C). The balloons 3914a-d
are circumferentially distributed around the guide member 3907 and
individually include proximal necks 3916 (FIG. 39A) that can
fluidly connect the balloons 3914a-d to the exhaust passage. The
orifices 3910a, 3910d have larger free-passage areas than the
orifices 3910b, 3910c. Similarly, the supply tubes 3908a, 3908d
have smaller free-passage areas than the supply tubes 3908b, 3908d.
The balloons 3914a-d are generally equal in size and have generally
equal internal and external surface areas. A ratio of orifice
and/or supply tube free-passage area to internal surface area can
be greater for the balloons 3914a, 3914d than for the balloons
3914b, 3914c. This can cause differential cooling within the
balloons 3914a, 3914d relative to the balloons 3914b, 3914c. For
example, the balloons 3914a, 3914d can be configured to circulate
gaseous refrigerant at a lower temperature than the balloons 3914b,
3914c. In addition or alternatively, the balloons 3914a, 3914d can
be configured for generally surface-area limited cooling when the
cooling assembly 3902 is in the deployed state, while the balloons
3914b, 3914c are configured for generally refrigerant-limited
cooling when the cooling assembly 3902 is in the deployed state.
Providing some cooling (e.g., low-level cooling, such as cooling
insufficient for cryogenic renal nerve modulation) to tissue near
an area targeted for therapeutically-effective renal nerve
modulation can be useful, for example, to reduce heat-gain from
surrounding tissue at the area targeted for
therapeutically-effective renal nerve modulation. The use of
multiple balloons also can facilitate a desirable localized or
overall treatment pattern and/or a desired level of occlusion at a
treatment site, such as partial occlusion instead of full
occlusion.
[0238] FIG. 40 illustrates a cryotherapeutic device 4000 similar to
the cryotherapeutic device 3900 of FIGS. 39A-39C, except having a
different mechanism for differential cooling. FIG. 40 can be
considered as a substitute for FIG. 39B to illustrate a separate
embodiment in which all elements of the cryotherapeutic device 3900
shown in FIGS. 39A-39C are similar except for those shown
differently in FIG. 40 relative to FIG. 39B. The cryotherapeutic
device 4000 includes a shaft 4002 having internal walls 4004
dividing the shaft 4002 into fluidly separate exhaust passages, and
supply tubes 4006 individually within the exhaust passages. The
supply tubes 4006 have generally equal sizes and can have orifices
(not shown) having generally equal sizes. The cryotherapeutic
device 4000 also includes a plurality of pressure regulators
(individually identified as 4008a-d) in fluid communication with
the exhaust passages. The pressure regulators 4008a-d can be
configured to be positioned outside the vasculature. Regulating
back pressures within the exhaust passages can cause temperatures
within corresponding balloons (not shown) to vary. For example, the
pressure regulators 4008a, 4008d can maintain a first back pressure
in the corresponding exhaust passages and balloons, and the
pressure regulators 4008b, 4008c can maintain a second, different
back pressure in the corresponding exhaust passages and balloons.
In this way, differential cooling similar to the differential
cooling described above with reference to the device 3900 shown in
FIGS. 39A-39C can be achieved.
[0239] FIG. 41 illustrates a portion of a cryotherapeutic device
4100 that can have multiple helical balloons. The device 4100
includes a cooling assembly 4101 at a distal portion 4102 of an
elongated shaft 4103 defining an exhaust passage, a supply tube
4104, and a filler tube 4105. The cooling assembly 4101 can include
a first supply orifice 4106, a second supply orifice 4107, and a
filler orifice 4108 at the distal end of the filler tube 4105. The
cooling assembly 4101 also includes an applicator 4109 having a
plurality of helical balloons. In one embodiment, the applicator
4109 includes a first helical balloon 4110 having a first distal
portion 4112 and a first proximal portion 4114, a second helical
balloon 4116 (shown stippled for clarity of illustration) having a
second distal portion 4118 and a second proximal portion 4120, and
a third helical balloon 4122 having a third distal portion 4124 and
a third proximal portion 4126. The first and second supply orifices
4106, 4107 can be fluidly connected to the first distal portion
4112 and the third distal portion 4124, respectively, and the first
and third helical balloons 4110, 4122 can define expansion
chambers. The second-balloon proximal portion 4120 can be sealed
around the filler tube 4107 and fluidly connected to the filler
orifice 4108 and the second helical balloon 4116 can define a
filler chamber. When the cooling assembly 4101 is in the deployed
state, the second helical balloon 4116 can be configured to be
filled via the filler tube 4105. Refrigerant can expand into the
first distal portion 4112 and the third distal portion 4124, and
the first and third helical balloons 4110, 4122 can provide primary
cooling in separate helical patterns or a combined helical pattern.
The second helical balloon 4116 can thermally insulate portions of
a renal artery or a renal ostium from cryogenic cooling of the
first and third helical balloons 4110, 4122. This can be useful,
for example, to facilitate a desirable localized or overall
treatment pattern. Furthermore, the interior space between the
supply tube 4004 and the first, second, and third helical balloons
4110, 4116, 4122 can define at least a portion of a longitudinal
flow path (e.g., a blood flow path). This can be useful, for
example, to facilitate a level of occlusion at a treatment site,
such as partial occlusion instead of full occlusion.
[0240] FIG. 42 illustrates a portion of a cryotherapeutic device
4200 similar to the device 4100 shown in FIG. 41, but having
modified supply and exhaust configurations in the helical balloons.
The device 4200 includes a cooling assembly 4202 at a distal
portion 4203 of an elongated shaft 4204 defining an exhaust
passage, an elongated guide member 4205, and a supply tube 4206.
The cooling assembly 4202 can include a supply orifice 4207 at the
distal end of the supply tube 4206 and an applicator 4208 having a
plurality of helical balloons. In one embodiment, the applicator
4208 includes a first helical balloon 4210 having a first distal
portion 4212 and a first proximal portion 4214, a second helical
balloon 4216 (shown stippled for clarity of illustration) having a
second distal portion 4218 and a second proximal portion 4220, and
a third helical balloon 4222 having a third distal portion 4224 and
a third proximal portion 4226. The first distal portion 4212 and
the third distal portion 4224 are fluidly connected to each other
and to the second distal portion 4218. The first proximal portion
4214 and the third proximal portion 4226 are fluidly connected to
the exhaust passage. When the cooling assembly 4202 is in the
deployed state, refrigerant can expand into the second proximal
portion 4220 and the second helical balloon 4216 can provide
primary cooling in a helical pattern. The first and third helical
balloons 4210, 4222 can receive refrigerant exhaust from the second
distal portion 4218 and can thermally insulate portions of a renal
artery or a renal ostium from cryogenic cooling within the second
helical balloon 4216. Relative to the cryotherapeutic device 4200
shown in FIG. 41, the device 4100 can be useful when less cooling
and/or greater spacing between areas of primary cooling is
desirable. In several other embodiments, different numbers of
helical balloons that are warming, thermally-insulative,
non-cooling, or have a low-level of cooling are intertwined in
various arrangements with helical balloons configured to provide
primary cooling, such as to facilitate a desirable localized or
overall treatment pattern.
[0241] FIGS. 43A-43C illustrate a portion of a cryotherapeutic
device 4300 that can include balloons that are movable relative to
other portions of a cooling assembly. The device 4300 includes a
cooling assembly 4301 at a distal portion 4302 of an elongated
shaft 4303 defining an exhaust passage, as well as an elongated
shaping member 4304, a first supply tube 4305, and a second supply
tube 4306. The distal portion 4302 can have a step 4307, and the
cooling assembly 4301 can include a first orifice 4308 at the
distal end of the first supply tube 4305, and a second orifice 4309
at the distal end of the second supply tube 4306. The cooling
assembly 4301 further includes an applicator 4310 with a first
elongated balloon 4311 defining a first expansion chamber and a
second elongated balloon 4312 defining a second expansion chamber.
The first balloon 4311 has a first proximal portion 4314, a first
middle portion 4315, and a first distal portion 4316. The second
balloon 4312 has a second proximal portion 4318, a second middle
portion 4319, and a second distal portion 4320. The first and
second balloons 4311, 4312 have inner sides 4322 closest to the
shaping member 4304 and outer sides 4324 opposite the inner sides
4322. The first distal portion 4316 and the second distal portion
4320 are attached to the shaping member 4304. In several
embodiments, the shaping member 4304 also defines a guide lumen
through which a guide wire can be threaded.
[0242] As shown in FIG. 43C, when the cooling assembly 4301 is in
the deployed state, retracting the shaping member 4304 relative to
the shaft 4303 can cause the first middle portion 4315 and the
second middle portion 4319 to laterally move away from the shaping
member 4304. A portion of the first middle portion 4315 and/or a
portion of the second middle portion 4319 can be weakened (e.g.,
creased, heat-treated to cause weakening, and/or thinned) or
otherwise configured to define a preferential bend position. As
shown in FIG. 43C, after the shaping member 4304 has retracted the
inner sides 4322 of the first middle portion 4315 and the second
middle portion 4319 are generally concave along their lengths,
while the outer sides 4324 of the first middle portion 4315 and the
second middle portion 4319 are generally convex along their
lengths. Controlled deflection of balloons can be particularly
useful, for example, to facilitate sizing with low risk of applying
excessive expansive pressure to a renal artery or a renal ostium.
Controlled deflection can be particularly useful when one or more
balloons of an applicator are generally non-compliant and/or
achieving sizing through compliant expansion is not practical.
[0243] FIGS. 44A-44C illustrate a portion of a cryotherapeutic
device 4400 similar to the cryotherapeutic device 4300 shown in
FIGS. 43A-43B, but having a greater number of elongated balloons
and including a secondary balloon. The device 4400 includes a
distal portion 4402 of an elongated shaft 4404 having a step 4405
and defining an exhaust passage, a cooling assembly 4406 at the
distal portion 4402, and an elongated shaping member 4408. The
shaping member 4304 can be solid or can define a lumen, such as a
guide lumen through which a guide wire can be threaded. The device
4400 further includes a first supply tube 4410, a second supply
tube 4414, a third supply tube (not shown), and a filler tube 4416.
The cooling assembly 4406 can include a first supply orifice 4418
at the distal end of the first supply tube 4410, a second supply
orifice 4420 at the distal end of the second supply tube 4414, a
third orifice (not shown) at the distal end of the third supply
tube, and a filler orifice 4422 at the distal end of the filler
tube 4416. The cooling assembly 4406 also includes an applicator
4424 with an elongated first balloon 4426 defining a first
expansion chamber, an elongated second balloon 4428 defining a
second expansion chamber, an elongated third balloon 4430 (FIG.
44B) defining a third expansion chamber, and an elongated fourth
balloon 4432 defining a filler chamber. The first, second, and
third balloons 4426, 4428, 4430 are fluidly connected to the first,
second, and third supply orifices 4418, 4420. The fourth balloon is
fluidly connected to the filler orifice 4422 and is sealed around
the filler tube 4416. The first, second, third, and fourth balloons
4426, 4428, 4430, 4432 are attached to the shaping member 4408 such
that, as shown in FIG. 44C, when the cooling assembly 4406 is in a
deployed state, retracting the shaping member 4408 relative to the
shaft 4404 causes the applicator 4424 to laterally expand. The
first, second, and third balloons 4426, 4428, 4430 can have
heat-transfer portions with heat-transfer rates sufficient to cause
therapeutically-effective renal nerve modulation. The first,
second, and third balloons 4426, 4428, 4430 can be configured to
provide primary cooling. The fourth balloon 4432 can be a secondary
balloon. In several other embodiments, a different number of
primary balloons with or without secondary balloons can be included
in a similar configuration to the configurations of the
cryotherapeutic device 4300 shown in FIGS. 43A-43B and the
cryotherapeutic device 4400 shown in FIGS. 44A-44C. In addition to
sizing, these configurations can facilitate other treatment
objectives, such as a desirable localized or overall treatment
pattern
[0244] FIGS. 45A-45B illustrate a portion of a cryotherapeutic
device 4500 including a primary balloon and a secondary balloon
that can have different compositions. The device 4500 includes a
cooling assembly 4502 at a distal portion 4504 of an elongated
shaft 4506 defining an exhaust passage, a supply tube 4508, and a
filler tube 4509. The cooling assembly 4502 includes a supply
orifice 4510 at the distal end of the supply tube 4508, and a
filler orifice 4514 at the distal end of the filler tube 4509. The
cooling assembly 4502 also includes an applicator 4516 with a first
balloon 4518 that defines an expansion chamber and a second balloon
4520 that can define a filler chamber. The first balloon 4518 has a
proximal neck 4522 within the distal portion 4504 fluidly
connecting the first balloon 4518 to the exhaust passage. The
second balloon is sealed around the filler tube 4509 and fluidly
connected to the filler orifice 4514. When the cooling assembly
4502 is in a deployed state, the first balloon 4518 can be
configured to deliver primary cooling and the second balloon 4520
can be a secondary balloon.
[0245] In several embodiments, the first balloon 4518 has a lower
level of compliance and/or elasticity than the second balloon 4520.
For example, the first balloon 4518 can be generally non-compliant
and the second balloon can be generally compliant. Additionally,
the first balloon 4518 can be non-compliant and the second balloon
can be compliant. Non-compliant materials typically have higher
strength (e.g., higher pressure ratings) than compliant materials.
For this and/or other reasons, generally compliant materials can be
well suited for balloons configured to receive expanded refrigerant
directly from an orifice and/or to apply therapeutically effective
cooling for renal nerve modulation. Generally compliant materials
can be well suited for expanding to different sizes to accommodate
renal arteries and renal ostiums having different cross-sectional
dimensions. The device 4500 shown in FIGS. 45A-45B and several
other cryotherapeutic-device components described herein can be
configured to take advantage of the different properties of both
non-compliant and compliant materials. FIGS. 45B and 45C are
cross-sectional views of the device 4500 sized to fit within renal
arteries or renal ostiums of different cross-sectional dimensions.
The first balloon 4518 has generally the same size in both FIG. 45B
and FIG. 45C. The second balloon 4520, however, is compliantly
expanded to a greater degree in FIG. 45C than in FIG. 45B. Even
with the generally non-compliant expansion of the first balloon
4518, the variable, compliant expansion of the second balloon 4520
can move the first balloon into contact with an inner surface of a
renal artery or a renal ostium. Compliant expansion of the second
balloon 4520 can be carefully controlled via the filler tube 4509
to prevent excessive expansive forces on the renal artery or the
renal ostium.
[0246] The enlargement in FIG. 45B-1 shows a partition 4524 that
includes a layer of non-compliant material 4526 and a layer of
compliant material 4528. The layer of non-compliant material 4526
can be a portion of the first balloon 4518 and the layer of
compliant material 4528 can be a portion of the second balloon
4520. In one embodiment, the first balloon 4518 and the second
balloon 4520 can be attached together at the partition 4524, but in
other embodiments the first and second balloon 4518 and 4520 are
not attached to each other.
[0247] FIG. 46 illustrates a cryotherapeutic device 4600 similar to
the cryotherapeutic device 4500 of FIGS. 45A-45C, except having a
different partition. FIG. 46 can be considered as a substitute for
FIG. 45B to illustrate a separate embodiment in which all elements
of the cryotherapeutic device 4500 shown in FIGS. 45A-45C are
similar except for those shown differently in FIG. 46 relative to
FIG. 45B. The cryotherapeutic device 4600 includes a first balloon
4602, a second balloon 4604, and a partition 4606 between the first
balloon 4602 and the second balloon 4604. As shown in the
enlargement in FIG. 46-1, the partition 4606 includes a single
layer, which can be a non-compliant layer of the first balloon. In
another embodiment, the partition 4606 can include a single layer
that is a compliant layer of the second balloon 4604. To construct
the device 4600, a generally compliant balloon portion (e.g., an
incomplete balloon) can be attached to a generally non-compliant
balloon so as to form a generally compliant balloon having a
chamber at least partially defined by a portion of the generally
non-compliant balloon. In cross section, as shown in FIG. 46, the
first balloon 4602 can be a generally D-shaped balloon and the
second balloon 4604 can be a generally C-shaped balloon attached to
a generally D-shaped balloon.
[0248] Cryotherapeutic devices configured in accordance with
several embodiments of the present technology can include helical
primary balloons and non-helical secondary balloons.
[0249] FIG. 47 illustrates a portion of a cryotherapeutic device
4700 including a cooling assembly 4702 at a distal portion 4704 of
an elongated shaft 4706 defining an exhaust passage. The device
4700 also includes a supply tube 4707. The cooling assembly 4702
includes an applicator 4708 with a helical first balloon 4710
having a first proximal portion 4712 and a first distal portion
4714 and defining an expansion chamber. The supply tube 4707 can
extend into the first proximal portion 4712, and the cooling
assembly 4702 can have an orifice 4718 at the distal end of the
supply tube 4707 within the first proximal portion 4712. The first
proximal portion 4712 is sealed around the supply tube 4707. The
cooling assembly 4702 can further include a second balloon 4720
having a second proximal portion 4722 and a second distal portion
4724 and defining an exhaust chamber. The second distal portion
4724 can be fluidly connected to the first distal portion 4714, and
the first balloon 4710 can wrap around the second balloon 4720. The
second proximal portion 4722 can be fluidly connected to the
exhaust passage. When the cooling assembly 4702 is in a deployed
state, refrigerant can flow from the first proximal portion 4712 to
the first distal portion 4714 and then proximally through the
second balloon 4720. Back pressure from the refrigerant can cause
the second balloon 4720 to expand (e.g., compliantly expand), which
can cause a helical diameter of the first balloon 4710 to increase.
This can be useful, for example, to facilitate sizing. In addition,
the helical shape of the first balloon 4710 can be useful, for
example, to facilitate a desirable localized or overall treatment
pattern.
[0250] FIGS. 48A-48B illustrate a portion of a cryotherapeutic
device 4800 having a helical primary balloon and a non-helical
secondary balloon in a different configuration. The device 4800
includes a cooling assembly 4802 at a distal portion 4804 of an
elongated shaft 4806 defining an exhaust passage. The distal
portion 4804 can have a step 4807, and the cooling assembly 4802
can include an applicator 4808 with a helical first balloon 4810
that defines an expansion chamber and has a first proximal portion
4812 and a first distal portion 4814. The device 4800 also can
include a supply tube 4816 extending into the first proximal
portion 4812, and the cooling assembly 4802 can have an orifice
4818 at the distal end of the supply tube 4816 within the first
proximal portion 4812. The first proximal portion 4812 is sealed
around the supply tube 4816. The cooling assembly 4802 can further
include a second balloon 4820 having an integral proximal neck 4822
attached to the distal portion 4804. The second balloon 4820 can
define an exhaust chamber configured to expand (e.g., compliantly
expand) in response to back pressure from refrigerant exhausted
from the first balloon 4810. The first balloon 4810 can be attached
to an internal surface of the second balloon 4820. Expansion (e.g.,
compliant expansion) of the second balloon 4820 can cause a helical
diameter of the first balloon 4810 to increase, such as to move a
curved portion of the first balloon 4810 closer to an inner surface
of a renal artery or a renal ostium. Positioning the first balloon
4810 within the second balloon 4820 can be useful, for example, to
provide redundant containment of refrigerant within the
vasculature.
[0251] FIG. 49 illustrates a portion of a cryotherapeutic device
4900 including a helical primary balloon and a non-helical
secondary balloon in another configuration. The device 4900
includes a cooling assembly 4902 at a distal portion 4904 of an
elongated shaft 4905 defining an exhaust passage. The distal
portion 4904 can have a step 4906 and a plurality of exhaust
openings 4907. The cooling assembly 4902 can include an applicator
4908 with a helical first balloon 4910 that defines an expansion
chamber and has a first proximal portion 4912 and a first distal
portion 4914. The device 4900 also can include a supply tube 4916
that extends into the first proximal portion 4912, and the cooling
assembly 4902 can have an orifice 4918 at the distal end of the
supply tube 4916. The first proximal portion 4912 can be sealed
around the supply tube 4916. The cooling assembly 4902 can further
include a second balloon 4920 positioned around the distal portion
4904 and having an integral proximal neck 4922 attached to the
distal portion 4904. The first balloon 4910 can wrap around the
second balloon 4920 and the first distal portion 4914 can be
fluidly connected to the distal portion 4904 distal of the second
balloon 4920. When the cooling assembly 4902 is in a deployed
state, the second balloon 4920 can be configured to passively
receive refrigerant from the exhaust passage through the exhaust
openings 4907 and can be configured to expand (e.g., compliantly
expand) in response to back pressure from refrigerant exhausted
from the first balloon 4910. Expansion (e.g., compliant expansion)
of the second balloon 4920 can cause a helical diameter of the
first balloon 4910 to increase, which can cause a portion (e.g., a
curved portion) of the first balloon 4910 to move closer to an
inner surface of a renal artery or a renal ostium.
[0252] FIG. 50 illustrates a portion of a cryotherapeutic device
5000 including a helical primary balloon and a non-helical
secondary balloon in another configuration. The device 5000
includes a cooling assembly 5002 at a distal portion 5003 of an
elongated shaft defining an exhaust passage, a filler tube 5004, a
filler orifice 5005 at the distal end of the filler tube 5004, and
a supply tube 5006. The cooling assembly 5002 includes a supply
orifice 5007 at the distal end of the supply tube 5006. The supply
tube 5006 can include a corner 5008, such as an elbow, near the
supply orifice 5007. The cooling assembly 5002 further includes an
applicator 5009 with a helical first balloon 5010 that defines an
expansion chamber and has a first proximal portion 5011 and a first
distal portion 5012. The cooling assembly 5002 can also include a
second balloon 5014 having a second proximal portion 5016 and a
second distal portion 5018. The second proximal portion 5016 can be
fluidly connected to the filler orifice 5005 and sealed around the
filler tube 5004. The second distal portion 5018 can be sealed
around the supply tube 5006, but fluidly separate from the supply
tube 5024 and the first balloon 5010. The first balloon 5010 can
wrap around the second balloon 5014 and be configured to receive
refrigerant from the supply tube 5006 and to exhaust the
refrigerant through the first proximal portion 5011 into the
exhaust passage. The second balloon 5014 can be configured to
receive filler material from the filler tube 5004 and expand (e.g.,
compliantly expand) causing a helical diameter of the first balloon
5010 to increase, which can cause a portion (e.g., a curved
portion) of the first balloon 5010 to move closer to an inner
surface of a renal artery or a renal ostium.
[0253] FIG. 51 illustrates a portion of a cryotherapeutic device
5100 including a helical primary balloon and a non-helical
secondary balloon in another configuration. The device 5100
includes a cooling assembly 5101 at a distal portion 5102 of an
elongated shaft 5103 defining an exhaust passage, a supply tube
5106, and a filler tube 5108. The distal portion 5102 can have a
step 5104 and an exit hole 5105. The cooling assembly 5101 can
include a supply orifice 5107 at the distal end of the supply tube
5106, and a filler orifice 5109 at the distal end of the filler
tube 5108. The cooling assembly 5101 can further include an
applicator 5110 with a helical first balloon 5111 that defines an
expansion chamber and has a first proximal portion 5112 and a first
distal portion 5114. The supply tube 5106 can extend from the exit
hole 5105 and extend into the first proximal portion 5112, and the
first proximal portion 5112 can be sealed around the supply tube
5106. The cooling assembly 5101 can further include a second
balloon 5116 around the distal portion 5102 and having an integral
proximal neck 5118 attached to the distal portion 5102. The second
balloon 5116 can be configured to receive filler material from the
filler tube 5108 and expand (e.g., compliantly expand) causing a
helical diameter of the first balloon 5111 to increase, which can
cause a portion (e.g., a curved portion) of the first balloon 5111
to move closer to an inner surface of a renal artery or a renal
ostium.
Proximal Secondary Balloons
[0254] A primary balloon and a secondary balloon can be
longitudinally spaced apart along the length of a portion of a
cryotherapeutic device configured in accordance with several
embodiments of the present technology. For example, a secondary
balloon can be part of an occlusion member configured to fully or
partially occlude a renal artery and/or a renal ostium. FIGS.
52A-53 illustrate several embodiments of cryotherapeutic devices
that include proximal secondary balloons.
[0255] FIGS. 52A-52B illustrate a portion of a cryotherapeutic
device 5200 including a cooling assembly 5202 and an occlusion
member 5204 longitudinally spaced apart along an elongated shaft
5206 defining an exhaust passage. The shaft 5206 can have a first
stepped-down portion 5208, cooling-assembly exhaust portal 5209 at
the first stepped-down portion 5208, a second stepped-down portion
5210, and occlusion-member exhaust portals 5211 at the second
stepped-down portion 5210. The cooling assembly 5202 and the
occlusion member 5204 can be positioned at the first stepped-down
portion 5208 and the second stepped-down portion 5210,
respectively. The device 5200 can include a supply tube 5212, and
the cooling assembly 5202 can have orifice 5213 at the distal end
of the supply tube 5212. The cooling assembly 5202 also can include
an applicator 5214 with a first balloon 5215 that defines an
expansion chamber. The supply tube 5212 can angle out of the shaft
5206 and into the first balloon 5215. The occlusion member 5204 can
include a second balloon 5216 defining an occlusion chamber. The
second balloon 5216 can be configured to passively receive
refrigerant from the exhaust passage through the occlusion-member
exhaust portal 5211 and can be configured to expand (e.g.,
compliantly expand) in response to back pressure from refrigerant
exhausted from the cooling assembly 5202. Both the cooling assembly
5202 and the occlusion member 5204 can be at least partially
collapsible in a delivery state and are shown in FIGS. 52A-52B in
an expanded state and a deployed state, respectively. In the
expanded state, the occlusion member 5204 can have a
cross-sectional dimension configured to fully occlude a renal
artery and/or a renal ostium.
[0256] As shown in FIG. 52B, the device 5200 can further include a
first elongated control member 5218, a second elongated control
member 5220, and a control tube 5222 with a first distal branch
5224 and a second distal branch 5226. The shaft 5206 can further
include a first distal attachment point 5228, a second distal
attachment point 5230, and a flexing portion 5232 between the first
stepped-down portion 5208 and the second stepped-down portion 5210.
The first elongated control member 5218 can extend along the
control tube 5222, along the first distal branch 5224, and attach
to the first distal attachment point 5228. The second elongated
control member 5220 can extend along the control tube 5222, along
the second distal branch 5226, and attach to the second distal
attachment point 5230. The device 5200 can be configured such that
increasing or decreasing tension of the first control member 5218
and/or the second control member 5220 can control deflection of the
shaft 5206. The shaft 5206 can be flexible at the flexing portion
5232 to position the first balloon against a vessel wall or ostium.
In addition to or instead of fully occluding the vessel or ostium,
the occlusion member 5204 can be configured in the expanded state
to support the shaft 5206 within a renal artery or a renal ostium
to provide controlled repositioning of the cooling assembly 5202
within the renal artery or the renal ostium. For example, the
cooling assembly 5202 can be repositioned to cause
therapeutically-effective, cryogenic renal-nerve modulation at
different portions of a renal artery or a renal ostium.
[0257] FIG. 53 illustrates a portion of a cryotherapeutic device
5300 similar to the cryotherapeutic device 5200 shown in FIGS.
53A-53B, but the device 5300 has additional distal cooling and
different supply and control configurations. The device 5300
includes a cooling assembly 5302 and an occlusion member 5304
longitudinally spaced apart along an elongated shaft 5306 defining
an exhaust passage. The shaft 5306 can have a distal attachment
point 5307 and a distal tip portion 5308 defining a distal
expansion chamber. The cooling assembly 5302 includes an applicator
5310 having a first balloon 5312 defining an expansion chamber, and
the occlusion member 5304 includes a second balloon 5314 defining
an occlusion chamber fluidly separate from the exhaust passage. The
device 5300 further includes a filler tube 5316 extending to the
second balloon 5314 and a supply tube 5318 having a lateral branch
5320 extending to the first balloon 5312 and an angled distal
portion 5322 extending to the distal tip portion 5308. The
occlusion member 5304 further includes a filler orifice 5324
through which a filler material can be supplied to the second
balloon 5314. The cooling assembly 5302 further includes a first
supply orifice 5326 configured to direct refrigerant expansion into
the first balloon 5312 and a second supply orifice 5328 configured
to direct refrigerant expansion into the distal tip portion
5308.
[0258] The device 5300 further includes an elongated control member
5330 and a control tube 5332. The control member 5330 can extend
along the control tube 5332 and be attached to the distal
attachment point 5307. The device 5300 can be configured such that
increasing or decreasing tension of the control member 5330 can
control deflection of the shaft 5306. In addition to or instead of
fully occluding a vessel or ostium, the occlusion member 5304 can
be configured in the expanded state to support the shaft 5306
within a renal artery or a renal ostium to provide controlled
repositioning of the cooling assembly 5302 within the renal artery
or the renal ostium. For example, the cooling assembly 5302 can be
repositioned to cause therapeutically-effective, cryogenic
renal-nerve modulation at different portions of a renal artery or a
renal ostium.
Alternative Cooling
[0259] Cooling assemblies configured in accordance with several
embodiments of the present technology have a cooling mechanism in
the deployed state that does not involve evaporation of
refrigerant. For example, such embodiments can include cooling
assemblies configured to circulate liquid or supercritical
refrigerant at cryogenic temperatures to cause convective and
conductive cooling through a primary heat-transfer portion of an
applicator. In such applicators, the flow impedance of the supply
can be generally equal to the flow impedance of the exhaust. For
example, the cross-sectional area of a supply lumen can be
generally equal to the cross-sectional area of an exhaust passage.
In some embodiments, cryotherapeutic devices having cooling
assemblies configured to circulate refrigerant without phase change
can have features to facilitate the supply of refrigerant to the
cooling assemblies and/or the exhaust of refrigerant from the
cooling assemblies. For example, a first pump can be included to
increase the pressure of refrigerant flowing to a cooling assembly
and/or a vacuum source (e.g., a second pump) can be included to
decrease the pressure of refrigerant flowing away from a cooling
assembly. In addition to the first pump or alternatively,
refrigerant can be supplied from a pressurized source. Based on
operational considerations, e.g., refrigerant viscosity and flow
impedances of supply, exhaust, and heat-transfer portions of a
cryotherapeutic device, supply and exhaust pressures can be
selected to cause different flow rates of refrigerant. The flow
rate can be selected, for example, to correspond to a heat-transfer
rate sufficient to cause therapeutically-effective cryogenic renal
nerve modulation.
[0260] FIG. 54 illustrates a portion of a cryotherapeutic device
5400 that can be configured for convective heat transfer without
refrigerant phase-change. The device 5400 includes a cooling
assembly 5402 at a distal portion 5404 of an elongated shaft 5406
defining an exhaust passage. The cooling assembly 5402 includes an
applicator 5408 with a balloon 5410 that defines a circulation
chamber. The device 5400 also includes a supply tube 5412 extending
along the length of the shaft 5406 and into the balloon 5410, and
the cooling assembly 5402 includes an orifice 5414 at the distal
end of the supply tube 5412. In several embodiments, the supply
tube 5412 is relatively large and configured to transport liquid
refrigerant, and the orifice 5414 is not configured to cause a
pressure drop sufficient to evaporate a refrigerant. When the
cooling assembly 5402 is in a deployed state, the balloon 5410 can
be configured to be filled with refrigerant in at least a
substantially liquid phase. The refrigerant can circulate from the
supply tube 5412 to the exhaust passage. FIG. 54 includes arrows
5416 indicating a direction of refrigerant flow through the balloon
5410. The refrigerant can be a liquid having a low freezing point
(e.g., ethyl alcohol) and can be transported through the supply
tube 5412 at a cryogenic temperature. Convective heat transfer
between the refrigerant and the balloon 5410 can cool a renal
artery or a renal ostium to cause therapeutically-effective renal
nerve modulation.
[0261] FIG. 55 illustrates a portion of a cryotherapeutic device
5500 that also can be configured for convective heat transfer
without refrigerant phase-change. The device 5500 includes a
cooling assembly 5502 at a distal portion 5504 of an elongated
shaft 5506 including a shaft partition 5508 dividing the shaft into
a first longitudinal portion 5510 defining supply lumen and a
second longitudinal portion 5512 defining an exhaust passage. The
cooling assembly 5502 includes an applicator 5514 with a balloon
5516 including a balloon partition 5518 that defines a U-shaped
chamber within the balloon 5516. The balloon 5516 can be configured
to circulate liquid refrigerant from the first longitudinal portion
5510, through the U-shaped chamber, and into the second
longitudinal portion 5512. FIG. 55 includes an arrow 5520
indicating a direction of refrigerant flow through the balloon
5516.
[0262] In several embodiments, a cooling assembly is configured to
circulate a supercritical fluid (e.g., supercritical nitrogen or
water). Supercritical fluids can provide significant cooling
without phase change, but typically must be maintained at
relatively high pressures. Cooling assemblies configured to
circulate supercritical fluids can include supply, heat-transfer,
and exhaust structures having high pressure ratings. For example,
such cooling assemblies can include non-expandable applicators
(e.g., having metal walls). Such applicators can be moveable during
a treatment to contact different portions of a renal artery or a
renal ostium.
Additional Embodiments
[0263] Features of the cryotherapeutic-device components described
above and illustrated in FIGS. 1-5B and 12-55 can be modified to
form additional embodiments configured in accordance with the
present technology. For example, the cryotherapeutic device 1700
illustrated in FIGS. 17A-17B and other cryotherapeutic devices
described above and illustrated in FIGS. 1-5B and 12-55 without
guide members can include guide members that extend near or through
distal portions of balloons. Similarly, the cryotherapeutic devices
described above and illustrated in FIGS. 1-5B and 12-55 can include
control members configured to receive control wires (e.g., pull
wires). A control wire can be used, for example, to control (e.g.,
deflect, angle, position, or steer) a cooling assembly, an
applicator, or another cryotherapeutic-device component from
outside the vasculature.
[0264] The cryotherapeutic-device components described above and
illustrated in FIGS. 1-5B and 12-55 include balloons having a
variety of features (e.g., shapes and compositions). In some cases,
manufacturing considerations and other factors can cause certain
features to be more or less desirable. For example, certain
materials can be more compatible with extrusion processes than with
molding processes or vise versa. Similarly, some balloon shapes can
be more readily formed using certain manufacturing processes than
using other manufacturing processes. For example, balloons having
integral closed distal ends, in some cases, can be difficult to
form using extrusion. The balloons and balloon features in the
cryotherapeutic-device components described above and illustrated
in FIGS. 1-5B and 12-55 can be modified or interchanged according
to such factors. For example, distal necks (e.g., sealed distal
necks) can be substituted for integral closed distal ends in the
balloons described above and illustrated in FIGS. 1-5B and 12-55.
This can be useful, for example, to make the balloons more
compatible with extrusion manufacturing processes.
[0265] Features of the cryotherapeutic-device components described
above also can be interchanged to form additional embodiments of
the present technology. For example, the inner balloon 1514 of the
cooling assembly 1502 illustrated in FIG. 15A can be incorporated
into the cooling assembly 1902 shown in FIGS. 19A-19C. As another
example, the first supply tube 1218 with the first angled distal
portion 1222 of the cryotherapeutic device 1200 illustrated in FIG.
12 can be incorporated into the cooling assembly 1702 illustrated
in FIGS. 17A-17B, with the first angled distal portion 1222
configured to direct expansion of refrigerant between the
thermally-insulative members 1711.
Related Anatomy and Physiology
[0266] 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.
[0267] 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 may elicit the release of
adrenaline from the adrenal medulla.
[0268] 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.
[0269] 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 physiological
features 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.
[0270] 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.
[0271] 1. The Sympathetic Chain
[0272] As shown in FIG. 56, 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 either the paravertebral (which lie
near the vertebral column) or prevertebral (which lie near the
aortic bifurcation) ganglia extending alongside the spinal
column.
[0273] In order to reach the target organs and glands, the axons
should 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.
[0274] In the SNS and other components of the peripheral nervous
system, these synapses are made at sites called ganglia, discussed
above. 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 (T1)
segment and third lumbar (L3) segments of the spinal cord.
Postganglionic cells have their cell bodies in the ganglia and send
their axons to target organs or glands.
[0275] 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).
[0276] 2. Innervation of the Kidneys
[0277] As FIG. 57 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 RP extends along the renal artery until it arrives
at the substance of the kidney. Fibers contributing to the renal
plexus RP 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 minimal) parasympathetic innervation of the
kidney.
[0278] 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.
[0279] 3. Renal Sympathetic Neural Activity
[0280] Messages travel through the SNS in a bidirectional flow.
Efferent messages may trigger changes in different parts of the
body simultaneously. For example, the sympathetic nervous system
may 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.
[0281] 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. Pharmaceutical management of
the renin-angiotensin-aldosterone system (RAAS) has been a
longstanding, but somewhat ineffective, approach for reducing
over-activity of the SNS.
[0282] 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.
[0283] 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.
[0284] 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 suggesting that sensory afferent signals
originating from the diseased kidneys are major contributors to
initiating and sustaining elevated central sympathetic outflow in
this patient group; this facilitates the occurrence of the well
known adverse consequences of chronic sympathetic over activity,
such as hypertension, left ventricular hypertrophy, ventricular
arrhythmias, sudden cardiac death, insulin resistance, diabetes,
and metabolic syndrome.
[0285] (i) Renal Sympathetic Efferent Activity
[0286] 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.
[0287] (ii) Renal Sensory Afferent Nerve Activity
[0288] The kidneys communicate with integral structures in the
central nervous system via renal sensory afferent nerves. Several
forms of "renal injury" may 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. 58A
and 58B, this afferent communication might be from the kidney to
the brain or might be from one kidney to the other kidney (via the
central nervous system). These afferent signals are centrally
integrated and may 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 over activity 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.
[0289] The physiology therefore suggests that (i) modulation of
tissue with efferent sympathetic nerves will reduce inappropriate
renin release, salt retention, and reduction of renal blood flow,
and that (ii) modulation of tissue with afferent sensory nerves
will reduce the systemic contribution to hypertension and other
disease states associated with increased central sympathetic tone
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.
[0290] B. Additional Clinical Benefits of Renal Denervation
[0291] 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,
insulin resistance, diabetes, left ventricular hypertrophy, chronic
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 may also
benefit other organs and bodily structures innervated by
sympathetic nerves, including those identified in FIG. 56. For
example, as previously discussed, 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 down regulation of sympathetic drive
that accompanies renal denervation.
[0292] C. Achieving Intravascular Access to the Renal Artery
[0293] In accordance with the present technology, neuromodulation
of a left and/or right renal plexus RP, which is intimately
associated with a left and/or right renal artery, may be achieved
through intravascular access. As FIG. 59A 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. 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.
[0294] As FIG. 59B shows, the blood collects in veins and returns
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. 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 oxygenated blood is conveyed into the left atrium. From the
left atrium, the oxygenated blood is conveyed by the left ventricle
back to the aorta.
[0295] As will be described in greater detail later, the femoral
artery may be accessed and cannulated at the base of the femoral
triangle just inferior to the midpoint of the inguinal ligament. A
catheter may be inserted percutaneously into the femoral artery
through this access site, passed through the iliac artery and
aorta, and placed 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.
[0296] The wrist, upper arm, and shoulder region provide other
locations for introduction of catheters into the arterial system.
For example, 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.
[0297] D. Properties and Characteristics of the Renal
Vasculature
[0298] Since neuromodulation of a left and/or right renal plexus RP
may be achieved in accordance with the present technology through
intravascular access, properties and characteristics of the renal
vasculature may impose constraints upon and/or inform the design of
apparatus, systems, and methods for achieving such renal
neuromodulation. Some of these properties and characteristics may
vary across the patient population and/or within a specific patient
across time, as well as in response to disease states, such as
hypertension, chronic kidney disease, vascular disease, end-stage
renal disease, insulin resistance, diabetes, metabolic syndrome,
etc. These properties and characteristics, as explained herein, may
have bearing on the efficacy of the procedure and the specific
design of the intravascular device. Properties of interest may
include, for example, material/mechanical, spatial, fluid
dynamic/hemodynamic and/or thermodynamic properties.
[0299] As discussed previously, a catheter may be advanced
percutaneously into either the left or right renal artery via a
minimally invasive intravascular path. However, minimally invasive
renal arterial access may be challenging, for example, because as
compared to some other arteries that are routinely accessed using
catheters, the renal arteries are often extremely tortuous, may be
of relatively small diameter, and/or may be of relatively short
length. Furthermore, renal arterial atherosclerosis is common in
many patients, particularly those with cardiovascular disease.
Renal arterial anatomy also may vary significantly from patient to
patient, which further complicates minimally invasive access.
Significant inter-patient variation may be seen, for example, in
relative tortuosity, diameter, length, and/or atherosclerotic
plaque burden, as well as in the take-off angle at which a renal
artery branches from the aorta. Apparatus, systems and methods for
achieving renal neuromodulation via intravascular access should
account for these and other aspects of renal arterial anatomy and
its variation across the patient population when minimally
invasively accessing a renal artery.
[0300] In addition to complicating renal arterial access, specifics
of the renal anatomy also complicate establishment of stable
contact between neuromodulatory apparatus and a luminal surface or
wall of a renal artery. When the neuromodulatory apparatus includes
a cryotherapeutic device, consistent positioning, appropriate
contact force applied by the cryotherapeutic device to the vessel
wall, and adhesion between the cryo-applicator and the vessel wall
are important for predictability. However, navigation is impeded by
the tight space within a renal artery, as well as tortuosity of the
artery. Furthermore, establishing consistent contact is complicated
by patient movement, respiration, and/or the cardiac cycle because
these factors may cause significant movement of the renal artery
relative to the aorta, and the cardiac cycle may transiently
distend the renal artery (i.e. cause the wall of the artery to
pulse.
[0301] Even after accessing a renal artery and facilitating stable
contact between neuromodulatory apparatus and a luminal surface of
the artery, nerves in and around the adventia of the artery should
be safely modulated via the neuromodulatory apparatus. Effectively
applying thermal treatment from within a renal artery is
non-trivial given the potential clinical complications associated
with such treatment. For example, the intima and media of the renal
artery are highly vulnerable to thermal injury. As discussed in
greater detail below, the intima-media thickness separating the
vessel lumen from its adventitia means that target renal nerves may
be multiple millimeters distant from the luminal surface of the
artery. Sufficient energy should be delivered to or heat removed
from the target renal nerves to modulate the target renal nerves
without excessively cooling or heating the vessel wall to the
extent that the wall is frozen, desiccated, or otherwise
potentially affected to an undesirable extent. A potential clinical
complication associated with excessive heating is thrombus
formation from coagulating blood flowing through the artery. Given
that this thrombus may cause a kidney infarct, thereby causing
irreversible damage to the kidney, thermal treatment from within
the renal artery should be applied carefully. Accordingly, the
complex fluid mechanics and thermodynamic conditions present in the
renal artery during treatment, particularly those that may impact
heat transfer dynamics at the treatment site, may be important in
applying energy (e.g., heating thermal energy) and/or removing heat
from the tissue (e.g., cooling thermal conditions) from within the
renal artery.
[0302] The neuromodulatory apparatus should also be configured to
allow for adjustable positioning and repositioning of the energy
delivery element within the renal artery since location of
treatment may also impact clinical efficacy. For example, it may be
tempting to apply a full circumferential treatment from within the
renal artery given that the renal nerves may be spaced
circumferentially around a renal artery. In some situations,
full-circle lesion likely resulting from a continuous
circumferential treatment may be potentially related to renal
artery stenosis. Therefore, the formation of more complex lesions
along a longitudinal dimension of the renal artery via the
cryotherapeutic devices and/or repositioning of the neuromodulatory
apparatus to multiple treatment locations may be desirable. It
should be noted, however, that a benefit of creating a
circumferential ablation may outweigh the potential of renal artery
stenosis or the risk may be mitigated with certain embodiments or
in certain patients and creating a circumferential ablation could
be a goal. Additionally, variable positioning and repositioning of
the neuromodulatory apparatus may prove to be useful in
circumstances where the renal artery is particularly tortuous or
where there are proximal branch vessels off the renal artery main
vessel, making treatment in certain locations challenging.
Manipulation of a device in a renal artery should also consider
mechanical injury imposed by the device on the renal artery. Motion
of a device in an artery, for example by inserting, manipulating,
negotiating bends and so forth, may contribute to dissection,
perforation, denuding intima, or disrupting the interior elastic
lamina.
[0303] Blood flow through a renal artery may be temporarily
occluded for a short time with minimal or no complications.
However, occlusion for a significant amount of time should be
avoided because to prevent injury to the kidney such as ischemia.
It could be beneficial to avoid occlusion all together or, if
occlusion is beneficial to the embodiment, to limit the duration of
occlusion, for example to 2-5 minutes.
[0304] Based on the above described challenges of (1) renal artery
intervention, (2) consistent and stable placement of the treatment
element against the vessel wall, (3) effective application of
treatment across the vessel wall, (4) positioning and potentially
repositioning the treatment apparatus to allow for multiple
treatment locations, and (5) avoiding or limiting duration of blood
flow occlusion, various independent and dependent properties of the
renal vasculature that may be of interest include, for example, (a)
vessel diameter, vessel length, intima-media thickness, coefficient
of friction, and tortuosity; (b) distensibility, stiffness and
modulus of elasticity of the vessel wall; (c) peak systolic,
end-diastolic blood flow velocity, as well as the mean
systolic-diastolic peak blood flow velocity, and mean/max
volumetric blood flow rate; (d) specific heat capacity of blood
and/or of the vessel wall, thermal conductivity of blood and/or of
the vessel wall, and/or thermal convectivity of blood flow past a
vessel wall treatment site and/or radiative heat transfer; (e)
renal artery motion relative to the aorta induced by respiration,
patient movement, and/or blood flow pulsatility: and (f) as well as
the take-off angle of a renal artery relative to the aorta. These
properties will be discussed in greater detail with respect to the
renal arteries. However, dependent on the apparatus, systems and
methods utilized to achieve renal neuromodulation, such properties
of the renal arteries, also may guide and/or constrain design
characteristics.
[0305] As noted above, an apparatus positioned within a renal
artery should conform to the geometry of the artery. Renal artery
vessel diameter, D.sub.RA, typically is in a range of about 2-10
mm, with most of the patient population having a D.sub.RA of about
4 mm to about 8 mm and an average of about 6 mm. Renal artery
vessel length, L.sub.RA, between its ostium at the aorta/renal
artery juncture and its distal branchings, generally is in a range
of about 5-70 mm, and a significant portion of the patient
population is in a range of about 20-50 mm. Since the target renal
plexus is embedded within the adventitia of the renal artery, the
composite Intima-Media Thickness, IMT, (i.e., the radial outward
distance from the artery's luminal surface to the adventitia
containing target neural structures) also is notable and generally
is in a range of about 0.5-2.5 mm, with an average of about 1.5 mm.
Although a certain depth of treatment is important to reach the
target neural fibers, the treatment should not be too deep (e.g.,
>5 mm from inner wall of the renal artery) to avoid non-target
tissue and anatomical structures such as the renal vein.
[0306] An additional property of the renal artery that may be of
interest is the degree of renal motion relative to the aorta
induced by respiration and/or blood flow pulsatility. A patient's
kidney, which is located at the distal end of the renal artery, may
move as much as 4'' cranially with respiratory excursion. This may
impart significant motion to the renal artery connecting the aorta
and the kidney, thereby requiring from the neuromodulatory
apparatus a unique balance of stiffness and flexibility to maintain
contact between the cryo applicator or other thermal treatment
element and the vessel wall during cycles of respiration.
Furthermore, the take-off angle between the renal artery and the
aorta may vary significantly between patients, and also may vary
dynamically within a patient, e.g., due to kidney motion. The
take-off angle generally may be in a range of about
30.degree.-135.degree..
[0307] The foregoing embodiments of cryotherapeutic devices are
configured to accurately position the cryo applicators in and/or
near the renal artery and/or renal ostium via a femoral approach,
transradial approach, or another suitable vascular approach. In any
of the foregoing embodiments described above with reference to
FIGS. 1-55, single balloons can be configured to be inflated to
diameters of about 3 mm to about 8 mm, and multiple-balloons can
collectively be configured to be inflated to diameters of about 3
mm to about 8 mm, and in several embodiments 4 mm to 8 mm.
Additionally, in any of the embodiments shown and described above
with reference to FIGS. 1-55, the balloons can individually and/or
collectively have a length of about 8 mm to about 15 mm, and in
several embodiments 10 mm. For example, several specific
embodiments of the devices shown in FIGS. 1-55 can have a 10 mm
long balloon that is configured to be inflated to a diameter of 4
mm to 8 mm. The shaft of the devices described above with reference
to any of the embodiments shown in FIGS. 1-55 can be sized to fit
within a 6 Fr sheath, such as a 4 Fr shaft size.
CONCLUSION
[0308] The above detailed descriptions of embodiments of the
technology are not intended to be exhaustive or to limit the
technology to the precise form disclosed above. Although specific
embodiments of, and examples for, the technology are described
above for illustrative purposes, various equivalent modifications
are possible within the scope of the technology, as those skilled
in the relevant art will recognize. For example, while steps are
presented in a given order, alternative embodiments may perform
steps in a different order. The various embodiments described
herein may also be combined to provide further embodiments.
[0309] From the foregoing, it will be appreciated that specific
embodiments of the technology have been described herein for
purposes of illustration, but well-known structures and functions
have not been shown or described in detail to avoid unnecessarily
obscuring the description of the embodiments of the technology.
Where the context permits, singular or plural terms may also
include the plural or singular term, respectively.
[0310] Moreover, unless the word "or" is expressly limited to mean
only a single item exclusive from the other items in reference to a
list of two or more items, then the use of "or" in such a list is
to be interpreted as including (a) any single item in the list, (b)
all of the items in the list, or (c) any combination of the items
in the list. Additionally, the term "comprising" is used throughout
to mean including at least the recited feature(s) such that any
greater number of the same feature and/or additional types of other
features are not precluded. It will also be appreciated that
specific embodiments have been described herein for purposes of
illustration, but that various modifications may be made without
deviating from the technology. Further, while advantages associated
with certain embodiments of the technology have been described in
the context of those embodiments, other embodiments may also
exhibit such advantages, and not all embodiments need necessarily
exhibit such advantages to fall within the scope of the technology.
Accordingly, the disclosure and associated technology can encompass
other embodiments not expressly shown or described herein.
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