US20120143294A1 - Neuromodulation cryotherapeutic devices and associated systems and methods - Google Patents

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.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)
• This application claims the benefit of the following pending applications:
• (a) U.S. Provisional Application No. 61/406,968, filed Oct. 26, 2010;
• (b) U.S. Provisional Application No. 61/528,091, filed Aug. 26, 2011;
• (c) U.S. Provisional Application No. 61/528,684, filed Aug. 29, 2011; and
• (d) U.S. Provisional Application No. 61/546,510, filed Oct. 12, 2011.
• 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
• 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
• 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
• 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.
• 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.
• 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⁺) 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
• 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.
• FIG. 1 illustrates a cryotherapeutic system in accordance with an embodiment of the present technology.
• 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.
• FIG. 2B is an enlarged cross-sectional view of the cooling assembly ofFIG. 2A in a deployed stated (e.g., expanded configuration).
• 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.
• 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.
• FIG. 3A illustrates cryogenically modulating renal nerves with a cryotherapeutic system in accordance with an embodiment of the technology.
• FIG. 3B is a block diagram illustrating a method of cryogenically modulating renal nerves in accordance with any embodiment of the present technology.
• 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.
• FIG. 5A is a partially schematic view of a cryotherapeutic system configured in accordance with another embodiment of the present technology.
• 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.
• FIG. 6A is a plan view illustrating a pre-cooling assembly configured in accordance with an embodiment of the present technology.
• FIG. 6B is a cross-sectional view illustrating the pre-cooling assembly ofFIG. 6A.
• 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.
• 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.
• FIG. 8B is a cross-sectional view illustrating the pre-cooling assembly ofFIG. 8A.
• 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.
• FIG. 9B is a cross-sectional view illustrating the pre-cooling assembly ofFIG. 9A.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• FIG. 15B is a cross-sectional view illustrating the cooling assembly ofFIG. 15A.
• 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.
• FIG. 16B is a cross-sectional view illustrating the cooling assembly ofFIG. 16A.
• 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.
• FIG. 17B is a cross-sectional view illustrating the cooling assembly ofFIG. 17A.
• 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.
• FIG. 18B is a cross-sectional view illustrating the cooling assembly ofFIG. 18A.
• 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.
• FIGS. 19B and 19C are cross-sectional views illustrating the cooling assembly ofFIG. 19A.
• 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.
• FIGS. 20B and 20C are cross-sectional views illustrating the cooling assembly ofFIG. 20A.
• 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.
• FIG. 21B is a cross-sectional view illustrating the cooling assembly ofFIG. 21A.
• FIG. 21C is a cross-sectional view illustrating the cooling assembly ofFIG. 21A in a delivery state within a delivery sheath.
• 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.
• FIG. 22B is a cross-sectional view illustrating the cooling assembly ofFIG. 22A.
• 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.
• FIG. 23B is an isometric view illustrating the cooling assembly ofFIG. 23A.
• 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.
• FIG. 24B is an isometric view illustrating the cooling assembly ofFIG. 24A.
• FIG. 25 is a profile view illustrating a cooling assembly having a helical recess configured in accordance with an embodiment of the present technology.
• FIG. 26 is a profile view illustrating a cooling assembly having spaced apart recesses configured in accordance with an embodiment of the present technology.
• FIG. 27A is a profile view illustrating a cooling assembly having spaced apart recesses configured in accordance with another embodiment of the present technology.
• FIG. 27B is a cross-sectional view illustrating the cooling assembly ofFIG. 27A.
• FIG. 27C is an isometric view illustrating the cooling assembly ofFIG. 27A.
• FIG. 28 is a profile view illustrating a cooling assembly having spaced apart protrusions configured in accordance with an embodiment of the present technology.
• 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.
• 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.
• 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.
• 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.
• FIG. 32B is a cross-sectional view illustrating the cooling assembly ofFIG. 32A.
• 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.
• FIGS. 33B and 33C are cross-sectional views illustrating the cooling assembly ofFIG. 33A.
• FIG. 33D is a cross-sectional view illustrating the cooling assembly ofFIG. 33A in a delivery state within a delivery sheath.
• 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.
• 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.
• FIG. 35B is a cross-sectional view illustrating the cooling assembly ofFIG. 35A.
• 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.
• FIG. 37 is a profile view illustrating a cooling assembly having a looped balloon configured in accordance with an embodiment of the present technology.
• FIG. 38A is a profile view illustrating a cooling assembly having multiple elongated balloons configured in accordance with an embodiment of the present technology.
• FIG. 38B is a cross-sectional view illustrating the cooling assembly ofFIG. 38A.
• FIG. 39A is a profile view illustrating a cooling assembly having multiple elongated balloons configured in accordance with another embodiment of the present technology.
• FIGS. 39B and 39C are cross-sectional views illustrating the cooling assembly ofFIG. 39A.
• 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.
• FIG. 41 is a profile view illustrating a cooling assembly having multiple helical balloons configured in accordance with an embodiment of the present technology.
• FIG. 42 is a profile view illustrating a cooling assembly having multiple helical balloons configured in accordance with another embodiment of the present technology.
• 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.
• FIG. 43B is a cross-sectional view illustrating the cooling assembly ofFIG. 43A.
• FIG. 43C is a profile view illustrating the cooling assembly ofFIG. 43A with the shaping member retracted.
• 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.
• FIG. 44B is a cross-sectional view illustrating the cooling assembly ofFIG. 44A.
• FIG. 44C is a profile view illustrating the cooling assembly ofFIG. 44A with the shaping member retracted.
• 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.
• FIG. 45B is a cross-sectional view illustrating the cooling assembly ofFIG. 45A expanded to a first cross-sectional dimension.
• FIG. 45B-1 is an enlarged cross-sectional view illustrating a partition shown inFIG. 45B.
• FIG. 45C is a cross-sectional view illustrating the cooling assembly ofFIG. 45A expanded to a second cross-sectional dimension, larger than the first cross-sectional dimension.
• 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.
• FIG. 46-1 is an enlarged cross-sectional view illustrating a partition shown inFIG. 46.
• 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.
• 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.
• FIG. 48B is a cross-sectional view illustrating the cooling assembly ofFIG. 48A.
• 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.
• 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.
• 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.
• 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.
• FIG. 52B is a cross-sectional view illustrating the distal portion ofFIG. 52A.
• 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.
• 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.
• 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.
• FIG. 56 is a conceptual illustration of the sympathetic nervous system (SNS) and how the brain communicates with the body via the SNS.
• FIG. 57 is an enlarged anatomic view of nerves innervating a left kidney to form the renal plexus surrounding the left renal artery.
• 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.
• FIGS. 59A and 59B are anatomic views of the arterial vasculature and venous vasculature, respectively, of a human.
DETAILED DESCRIPTION
• Specific details of several embodiments of the technology are described below with reference toFIGS. 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 toFIGS. 1-59B.
• 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
• 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.
• 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.
• 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.
• 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
• FIG. 1 illustrates acryotherapeutic system100 configured in accordance with several embodiments of the present technology. Thecryotherapeutic system100 can include aconsole102 and acryotherapeutic device120. In the embodiment shown inFIG. 1, theconsole102 includes asupply container104, a refrigerant106 in thesupply container104, and asupply control valve108 in fluid communication with thesupply container104. Thesupply container104 can be a single-use cartridge or a larger container that contains a sufficient volume ofrefrigerant106 to perform multiple procedures. The larger supply containers, for example, can be refillable cylinders. Thesupply container104 is configured to retain the refrigerant106 at a desired pressure. For example, in one embodiment, liquid N₂O is contained in thesupply container104 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 refrigerant106 can include carbon dioxide, a hydrofluorocarbon (“HFC”; e.g., Freon®, R-410A, etc.), and/or other suitable compressed or condensed refrigerants that can be retained in thesupply container104 at a sufficiently high pressure to maintain the refrigerant106 in at least a substantially liquid state at ambient temperatures (e.g., approximately 210 psi for R-410A).
• Thesupply control valve108 is coupled to asupply line110 configured to transport the refrigerant106 to thecryotherapeutic device120. Thesupply control valve108 can be operated manually or automatically. Theconsole102 can optionally include apump111, such as a vacuum pump or a DC power pump, and/or abackpressure control valve113 coupled to anexhaust line115 configured to receive exhausted refrigerant117 from thecryotherapeutic device120. Thepump111 can reduce the backpressure of evaporated refrigerant and, in conjunction with the supply flow rate, increase refrigeration power. In other embodiments, the expandedrefrigerant117 can exhaust to ambient pressure.
• Theconsole102 can further include anoptional controller118 that operates thesupply control valve108 and thebackpressure control valve113. Thecontroller118, for example, can be a processor or dedicated circuitry that implements a computerized algorithm for executing a procedure automatically. Theconsole102 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 thecryotherapeutic device120. In one embodiment, thecontroller118 operates thebackpressure control valve113 to control the amount of vacuum applied to theexhausted refrigerant117 returning from thecryotherapeutic device120. This modulates the backpressure of the evaporated refrigerant to control the temperature in thecryotherapeutic device120. In another embodiment, thesupply control valve108 and/or thebackpressure control valve113 can be used to increase the backpressure ofexhausted refrigerant117. Increasing the backpressure ofexhausted refrigerant117 could increase the boiling point of the refrigerant. For example, in the case of N₂O, a slight increase in backpressure from 1 atm to about 2 atm would raise the boiling point from about 88° C. to about −75° C.; an increase in backpressure to 3 atm would raise the boiling point to about −65° C.
• In certain embodiments, thecryotherapeutic system100 may also precool the refrigerant106 to provide greater refrigeration power in the refrigerant106 by the time it reaches the cooling system. Thesystem100, for example, can include a precooler119 (shown in dashed lines) in theconsole102. In other embodiments, thesystem100 can include a precooler along thesupply line110, at a handle at a proximal region of thesystem100, or elsewhere coupled to thecryotherapeutic device120.
• Thecryotherapeutic device120 includes ashaft122 that has aproximal portion124, ahandle125 at a proximal region of theproximal portion124, and adistal portion126 extending distally relative to theproximal portion124. Thecryotherapeutic device120 can further include acooling assembly130 at thedistal portion126 of theshaft122. Theshaft122 is configured to locate thedistal portion126 intravascularly at a treatment site proximate (e.g., in or near) a renal artery or renal ostium, and thecooling assembly130 is configured to provide therapeutically-effective cryogenic renal-nerve modulation.
• FIG. 2A is an enlarged cross-sectional view illustrating an embodiment of thedistal portion126 of theshaft122 and thecooling assembly130 in a delivery state (e.g., low-profile or collapsed configuration), andFIG. 2B is an enlarged cross-sectional view of the coolingassembly130 in a deployed stated (e.g., expanded configuration). In the embodiment shown inFIG. 2A, thedistal portion126 of theshaft122 can include afirst zone127aand asecond zone127b(separated by broken lines) recessed inwardly relative to thefirst zone127a. Thefirst zone127acan be demarcated from thesecond zone127bby astep128, such as a rabbet (e.g., an annular or other circumferential groove configured to be fitted with another member). Thefirst zone127acan accordingly have a first outer dimension or first cross-sectional dimension (e.g., area or diameter), and thesecond zone127bcan have a second outer dimension or second cross-sectional dimension less than the first dimension. Theshaft122 can be sized to fit within asheath150 of 8 Fr or smaller (e.g., a 6 Fr guide sheath) to accommodate small renal arteries.
• Thecryotherapeutic device120 can also include a supply tube orlumen132 and an exhaust tube orlumen134 along at least a portion of theshaft122. Thesupply lumen132 can be a small tube configured to retain the refrigerant in a liquid state at a high pressure. The inner diameter of thesupply lumen132 is selected such that at least a portion of the refrigerant reaching the coolingassembly130 is in a liquid state at adistal end135 of thesupply lumen132. Theexhaust lumen134 can be an outer tube, and thesupply lumen132 can extend within theexhaust lumen134 along at least thedistal portion126 of the shaft. As described in further detail below, several embodiments of thecryotherapeutic device120 can further include one ormore sensors138, such as a temperature sensor or pressure sensor, coupled to the controller118 (FIG. 1) by alead139. In several embodiments, thecryotherapeutic system100 can be configured to verify the proper calibration of thesensors138 before a cryotherapeutic treatment. For example, thecryotherapeutic system100 can automatically compare a measured temperature from a temperature sensor with room temperature as thecryotherapeutic system100 initiates a power up cycle to check that the temperature sensor is functioning properly.
• The embodiment of the coolingassembly130 shown inFIGS. 2A and 2B can have anapplicator140 including aballoon142 or other type of expandable member that defines an expansion chamber configured to fully occlude a renal artery or renal ostium. Theballoon142 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. Theballoon142 can comprise a compliant material, a non-compliant material, and/or a combination of compliant and non-compliant materials. In various embodiments, for example, theballoon142 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, theballoon142 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.
• In the embodiment illustrated inFIGS. 2A and 2B, the distal portion of theballoon142 is not connected to a support member (e.g., thesupply lumen132 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 theballoon142 provides a gentle surface with which to contact vessel walls so as to avoid tearing, puncturing, and/or otherwise damaging vessel walls. Additionally, the coolingassembly130 shown inFIG. 2B can have a shorter overall length than a distally connected balloon, which may facilitate positioning thecooling assembly130 in relatively short vessels (e.g., a renal artery having a length of 6 cm or less).
• The coolingassembly130 can further include anorifice144 in fluid communication with the expansion chamber. In one embodiment, theorifice144 can be defined by a distal end of acapillary tube146 inserted into thedistal end135 of thesupply lumen132. Alternatively, the opening at thedistal end135 of thesupply lumen132 can define an orifice. Thecapillary tube146 and/or theorifice144 can have a diameter less than that of thesupply lumen132 to impede the flow of refrigerant proximate the expansion chamber, thereby increasing the pressure drop of the refrigerant106 entering the expansion chamber and concentrating the refrigeration power at thecooling assembly130. In other embodiments, thesupply lumen132 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 theorifice144 has a diameter at least equal to that of thesupply lumen132. Thecryotherapeutic device120 can then further include additional hardware (e.g., valves, flow and pressure gauges, etc.) and/or software in the handle125 (FIG. 1) and/or in the console102 (FIG. 1) to control the refrigerant106 through thesupply lumen132 and focus the refrigeration power toward thedistal end portion126 of theshaft122.
• Theorifice144 can be sized relative to the area and/or length of theexhaust lumen134 at thedistal portion126 of theshaft122 to provide a sufficient flow rate of refrigerant, produce a sufficient pressure drop in the expansion chamber, and allow for sufficient venting of theexhausted refrigerant117 through theexhaust lumen134. In one embodiment, theorifice144 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 theexhaust lumen132 and the diameter and/or cross-sectional area of theorifice144 can have a ratio between approximately 4:1 and 10:1. For example, theexhaust lumen132 can have an inner diameter between approximately 0.030 inch (0.762 mm) and approximately 0.050 inch (1.27 mm), and theorifice144 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, theexhaust lumen134 and theorifice144 can have other suitable dimensions. In further embodiments, theshaft122 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 theexhaust lumen132 to the total cross-sectional dimension occupied by the supply lumen and/or other members within theshaft122 can be approximately 4:1 and 10:1.
• The flow rate of the refrigerant106 can also be manipulated by changing the lengths of thesupply lumen132 and thecapillary tube146 relative to one another. For example, in certain embodiments, thecapillary tube146 can be at most ⅓ the length of thesupply lumen132. In various embodiments, thecapillary tube146 can have a length between 2 inches (5.08 cm) and 30 inches (76.2 cm) and thesupply lumen132 can be sized accordingly. In other embodiments, thecapillary tube146 can be shorter or longer relative to thesupply lumen132 and/or thecapillary tube146 can be omitted.
• The coolingassembly130 is passed intravascularly to a target site T in a vessel V while in the delivery configuration shown inFIG. 2A. Referring toFIG. 2B, the coolingassembly130 and thesheath150 are then moved relative to each other such that the coolingassembly130 extends distally beyond thesheath150. For example, thesheath150 can be pulled proximally and/or thecooling assembly130 can be pushed distally. In operation, the refrigerant106 passes through thesupply lumen132, through theorifice144, and into the expansion chamber defined by theballoon142. As the refrigerant106 passes through theorifice144, it expands into a gaseous phase, thereby inflating the balloon and causing a significant temperature drop in the expansion chamber. The portion of theapplicator140 contacting the tissue at the target T can be a heat-transfer region149 or heat-transfer zone that, together with the refrigerant106 in the expansion chamber, causes therapeutically-effective, cryogenic renal-nerve modulation. Exhausted refrigerant117 passes in a proximal direction through theexhaust lumen134. In various embodiments, the length ofshaft122 can be minimized to decrease the losses (e.g., friction losses) of the refrigerant flowing through thesupply lumen132 and through theexhaust lumen134, thereby enhancing the refrigeration potential and the efficiency of the coolingassembly130. The additional friction losses that may be caused by longer exhaust lumens, for example, may inhibit venting of theexhausted refrigerant117, and thereby increase the pressure and temperature within theballoon142. Accordingly, theshaft122 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, theshaft122 can be longer and/or include additional features to enhance the refrigeration power at thecooling assembly130.
• The embodiment of the coolingassembly130 illustrated inFIGS. 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 region149 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 controller118 (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 handle125 (FIG. 1) or other portion of thecryotherapeutic device120. If present, thesensor138 may provide feedback to thecontroller118 to regulate or control thesystem100. 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 thesupply container104. As described in greater detail below, in other embodiments, the coolingassembly130 can be configured to partially occlude blood flow.
• In various embodiments, thesensor138 can be a thermocouple positioned on an outer surface of theballoon142 and configured to provide a real-time temperature reading of the external temperature of theballoon142. As such, thecryotherapeutic system100 can be regulated via the controller118 (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° C., −60° C., etc.). For example, the cooling power output can be regulated by switching valves (e.g., thesupply control valve108 and/or the backpressure control valve113) 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 refrigerant106 and/or the flow rate of thevacuum pump111 can be varied in response to the measured external balloon temperature. Accordingly, the external thermocouple allows thecryotherapeutic system100 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.
• FIGS. 2C-2E are enlarged cross-sectional views illustrating thedistal portion126 of thecryotherapeutic device120 configured in accordance with other embodiments of the present technology. Referring toFIG. 2C, adistal portion152 of theballoon142 can be connected to adistal connector162 via thermal bonding, adhesives, and/or other suitable attachment mechanisms. Thedistal connector162 can have a curved, bullet-like tip as shown inFIG. 2C or can be otherwise configured to provide an atraumatic tip for navigation through the vasculature.
• Thecryotherapeutic device120 further includes aguide wire lumen133athrough which aguide wire133bcan be received to guide thedistal portion126 of theshaft122 through the vasculature. In the embodiment illustrated inFIG. 2C, theguide wire lumen133aextends completely through theshaft122 from the proximal opening of theshaft122 at an adaptor201 (e.g., at thehandle125 shown inFIG. 1) to beyond the distal opening of theshaft122 in an over-the-wire (OTW) configuration, whereas in the embodiment illustrated inFIG. 2E, theguide wire lumen133aextends through only a portion of theshaft122 in a rapid exchange (RX) configuration. Although the proximal end of theguide wire lumen133ais shown inFIG. 2E extending through the sidewall of theshaft122 at thedistal portion126, in other embodiments, the proximal end of theguide wire lumen133acan be accessible anywhere between the proximal and distal ends of theshaft122. Theguide wire lumen133ashown inFIGS. 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.
• FIG. 3A illustrates cryogenically modulating renal nerves with an embodiment of thesystem100. Thecryotherapeutic device120 provides access to the renal plexus through an intravascular path P that leads to a respective renal artery RA. As illustrated, a section of theproximal portion124 of theshaft122 is exposed externally of the patient. By manipulating theproximal portion124 of theshaft122 from outside the intravascular path P, the caregiver may advance theshaft122 through the tortuous intravascular path P (e.g., via the femoral artery or a radial artery) and remotely manipulate the distal portion126 (e.g., with an actuator in the handle125). For example, theshaft122 may further include one or more pull-wires or other guidance devices to direct thedistal portion126 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 thecooling applicator140 is adequately positioned in the renal artery RA or at the renal ostium, it can be expanded or otherwise deployed using the console102 (FIG. 1), the handle125 (FIG. 1), and/or another means until theapplicator140 contacts the inner wall of the renal artery RA. The purposeful application of cooling power from theapplicator140 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.
• The neuromodulating effects are generally a function of, at least in part, the temperature of theapplicator140, contact between theapplicator140 and vessel wall, dwell time of theapplicator140 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 theapplicator140 can be cooled to a temperature of about −88° C. to about −60° C., or in other embodiments the gas in theapplicator140 can have a temperature of about −80° C. to about −40° C.
• In various embodiments, neuromodulating effects can occur within 100 seconds (e.g., 90 seconds, 75 seconds, 60 seconds, 30 seconds, etc.) of applying the cooledapplicator140 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 assembly130 (e.g., as shown inFIG. 2B) to retraction of the cooling assembly to the delivery state (e.g., as shown inFIG. 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 coolingassembly130 in the first renal artery RA, to repositioning, deployment, and retraction of the coolingassembly130 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 theapplicator140 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, theapplicator140 can be applied to less than a full circumference of the renal artery RA and/or in more than one application.
• FIG. 3B is a block diagram illustrating amethod300 of cryogenically modulating renal nerves using thesystem100 described above with reference toFIGS. 1-3A or another suitable system in accordance with an embodiment of the present technology described below. Referring toFIGS. 1-3B together, themethod300 can include intravascularly locating the coolingassembly130 in the delivery state (e.g., as shown inFIG. 2A) in a renal artery or renal ostium (block305). Thecryotherapeutic device120 and/or portions thereof (e.g., the cooling assembly130) can be inserted into a guide catheter (e.g., thesheath150 shown inFIGS. 2A-2C) to facilitate intravascular delivery of the coolingassembly130. In certain embodiments, for example, thecryotherapeutic device120 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 theshaft122 and thecooling assembly130.
• Themethod300 can further include connecting thecryotherapeutic device120 to the console102 (block310), and partially or fully inflating an expandable member of the cooling assembly130 (e.g., the balloon142) to determine whether the coolingassembly130 is in the correct position at the target site (blocks315 and320). The expandable member can be inflated via thesupply lumen132 with refrigerant from thesupply container104 at theconsole102 and/or with other suitable fluids (e.g., air) from a secondary fluid supply reservoir in fluid communication the expandable member. If thecooling assembly130 is not in the desired location, at least some of the pressure in the expandable member can be released (block325). In certain embodiments, for example, the expandable member can be fully deflated by disconnecting thecryotherapeutic device120 from theconsole102 and using a syringe to manually deflate the expandable member via a proximal end portion of theshaft122. In other embodiments, thecryotherapeutic device120 can remain attached to theconsole102, and a syringe can be connected along the length of the shaft122 (e.g., a stopcock syringe) to deflate the expandable member. In further embodiments, thecontroller118 at theconsole102 can include algorithms for partially or fully deflating the expandable member. In still further embodiments, the coolingassembly130 can be positioned at the target site using radiopaque markers and/or markings.
• Once the coolingassembly130 is properly located within the first renal artery or ostium thereof, theconsole102 can be manipulated to initiate cooling at thecooling assembly130 that modulates the renal nerves to cause partial or full denervation of the kidney (block330). 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 coolingassembly130 at the target site between cooling cycles.
• After renal-neuromodulation at the first renal artery, themethod300 can further include deflating the expandable member and retracting the coolingassembly130 into the delivery state (block335). The expandable member can be deflated manually by detaching thecryotherapeutic device120 from theconsole102 and connecting a syringe or other suitable evacuation device to the proximal end of theshaft122. In other embodiments, a syringe can be connected along the length of theshaft122 without detaching thecryotherapeutic device120 from theconsole102, or the expandable member can be deflated automatically (e.g., via the controller118). In certain embodiments, the coolingassembly130 can be withdrawn back into the guide catheter after the expandable member is deflated. Optionally, the coolingassembly130 can be removed from the guide catheter during repositioning and temporarily stored in a sterile location (e.g., in a saline solution).
• The coolingassembly130 can then be located in a second renal artery or second renal ostium (block340), and the expandable member can be expanded to confirm the position of the cooling assembly130 (block345). In selected embodiments, a contrast material can be delivered distally beyond the coolingassembly130 and fluoroscopy and/or other suitable imaging techniques can be used to locate the second renal artery. If necessary, the usedsupply container104 in theconsole102 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 theconsole102 was detached from thecryotherapeutic device120 during repositioning of the coolingassembly130, theconsole102 can be reconnected to thecryotherapeutic device120 such that themethod300 continues by applying cryogenic cooling to effectuate renal-neuromodulation at the second renal artery or second renal ostium (block350).
• In other embodiments, various steps in themethod300 can be modified, omitted, and/or additional steps may be added. For example, theconsole102 can be turned on and loaded with thesupply container104 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 thesupply container104 must be reloaded or refilled during cryotherapy, theconsole102 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, theempty supply container104 can be removed from theconsole102 and deposited within a sterile bag or housing surrounding theconsole102, and a new supply container can be attached to theconsole102 within the sterile bag or housing such that theconsole102 does not leave the sterile field during treatment. In further embodiments, theconsole102 can remain outside the sterile field and operated remotely.
• FIG. 4A is an enlarged cross-sectional view of a distal portion426 of acryotherapeutic device420 configured in accordance with another embodiment of the present technology. Thecryotherapeutic device420 includes features generally similar to the features of thecryotherapeutic device120 described above with reference toFIGS. 1-3B. For example, thecryotherapeutic device420 includes theelongated shaft122, the supply andexhaust lumens132 and134 extending along at least a portion of theshaft122, and thecooling assembly130 at the distal portion426 of theshaft102. The coolingassembly130 includes an expandable member, such as theballoon142 or other suitable expandable member, that defines at least a portion of the expansion chamber and receives the refrigerant106 in an at least substantially gas phase via theorifice144.
• In the illustrated embodiment, thedistal end135 of thesupply lumen132 is coupled to adistal portion452 of theballoon142 to provide additional support and/or control for thecooling assembly130, and theorifice144 is an opening positioned along the length of the supply lumen132 (e.g., rather than at thedistal end135 of thesupply lumen132 or at the end of a capillary tube). Thesupply lumen132 and thedistal portion452 of theballoon142 can be attached together using adhesives (e.g., thermal bonds), fasteners, and/or other suitable attachment mechanisms known in the art. In other embodiments, thesupply lumen132 can terminate at or in the expansion chamber, and/or thecryotherapeutic device420 can further include a support member (not shown) that extends from theshaft122 to at least thedistal portion452 of theballoon142.
• As shown inFIG. 4A, thecryotherapeutic device420 can further include aconnector454 at the proximal portion of theballoon142 that can be attached over the distal portion426 of theshaft122 and thereby couple theballoon142 to theshaft122. Theconnector454 can be defined by a proximal portion of the balloon142 (e.g., the neck of the balloon142) that is integral with the expandable portion as shown inFIG. 4A, or theconnector454 can be a separate and distinct component from theballoon142, such as a collar or other suitable retainer. Theconnector454 can be attached to the distal portion426 of theshaft122 using thermal bonds, adhesives, interlocking surfaces (e.g., threads), friction fit, snap fit, suction, and/or other suitable attachment mechanisms, or theconnector454 can be formed integrally with the distal portion426.
• In the illustrated embodiment, theconnector454 is positioned proximate thestep128 over thesecond zone127bof the distal portion426 of theshaft122. As shown inFIG. 4A, thefirst zone127aof the distal portion426 can have a first outer cross-sectional dimension or diameter OD₁and thesecond zone127bdistal to thestep128 can have a second outer cross-sectional dimension or diameter OD₂less than the first outer cross-sectional dimension OD₁. The reduction in the outer dimension of the distal portion426 at thestep128 forms an inward recess relative to thefirst zone127ain which at least a portion of theconnector454 and the proximal region of the expandable portion of theballoon142 can sit, and thereby reduces the profile of the distal portion426 of theshaft122. In certain embodiments, thestep128 can be dimensioned such that anouter surface455 of thefirst zone127ais at least substantially flush with anouter surface457 of theconnector454. Accordingly, the outer diameter OD₂of thesecond zone127bcan be equivalent to the outer diameter OD₁of thefirst zone127aless twice the thickness of theconnector454. In other embodiments, the outer diameter OD₂of thesecond zone127bcan be greater than or less than twice the thickness of theconnector454.
• In selected embodiments, theconnector454 is non-expandable such that it remains within the recess and/or substantially flush with theouter surface455 of thefirst zone127awhen the coolingassembly130 moves to the deployed state (e.g., as shown inFIG. 4A). In other embodiments, theconnector454 may be expandable and increase in cross-sectional area as the coolingassembly130 moves to the deployed state.
• In the embodiment shown inFIG. 4A, the cross-sectional area of the exhaust lumen (e.g., defined by the inner surface(s) of the shaft122) also decreases at the transition between thefirst zone127aand thesecond zone127bsuch that the distal portion426 of theshaft122 has a first inner cross-sectional dimension or diameter ID₁at thefirst zone127aand a lesser second inner cross-sectional dimension or diameter ID₂at thesecond zone127b. To avoid a build up of pressure in the expansion chamber that may be caused by insufficient venting through the necked-downexhaust lumen134, thesecond zone127bcan be positioned only at the distal-most end of theshaft122 proximate the expansion chamber where the density of theexhausted refrigerant117 is the highest. For example, thesecond zone127bcan have a length of less than 4 cm (e.g., 2 cm, 1 cm, etc.). Theexhausted refrigerant117 also vents adequately through the smaller inner diameter ID₂of thesecond zone127bwithout undue restriction because the length of thesecond zone127balong the longitudinal axis of theshaft122 can be relatively short. For example, the length of thesecond zone127bcan be minimized to sufficiently accommodate theconnector454. Accordingly, thesmaller exhaust lumen134 at thesecond zone127bcan transport primarily high densityexhausted refrigerant117 and can expel theexhausted refrigerant117 into thelarger exhaust lumen134 at thefirst zone127aas theexhausted refrigerant117 decreases in density, thereby facilitating adequate venting through the smaller second inner diameter ID₂of thesecond zone127b.
• In operation, the inwardly recessedsecond zone127bcan reduce the profile of the distal portion426 of theshaft122 and/or provide a substantially smooth transition from theshaft122 to theconnector454 without jeopardizing the venting characteristics of theexhaust lumen134. The low-profile distal portion426 of theshaft122 can also facilitate the delivery of a fluidic contrast material between theshaft122 and thesheath150 from the proximal portion124 (FIG. 1) of theshaft122 to the distal portion426 and around the coolingassembly130 in the delivery state (e.g., as shown inFIG. 2A) to image and locate (e.g., using fluoroscopy) a target in the vasculature. As shown inFIG. 4A, for example, the recessedsecond zone127bprovides one or more passageways or channels C around the distal portion426 of theshaft122 that are large enough to deliver contrast material distally beyond the coolingassembly130 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 OD₁and the second outer diameter OD₂of the corresponding first andsecond zones127aand127bis less than 0.01 inch (0.254 mm). In other embodiments, the difference between the outer dimensions OD₁and OD₂of the first andsecond zones127aand127bmay be greater or smaller. When used during renal-neuromodulation, a first renal artery can be located by delivering contrast material distally beyond the coolingassembly130 in the delivery state via the channel C. After renal-neuromodulation at the first renal artery, the coolingassembly130 can be retracted back from the deployed state to the delivery state wherein additional contrast material can be delivered distally beyond the coolingassembly130 via the channel C to locate a second renal artery.
• In other embodiments, the distal portion426 of theshaft122 does not include the stepped-downexhaust lumen134 shown inFIG. 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 inFIGS. 2C-2E) through which a guide wire can be extended to locate thecooling assembly130 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.
• FIG. 4B is an enlarged cross-sectional view of a distal portion456 of acryotherapeutic device460 configured in accordance with another embodiment of the present technology. Thecryotherapeutic device460 includes features generally similar to the features of thecryotherapeutic device420 described above with reference toFIG. 4A. For example, the distal portion456 of theshaft122 has thestep128 that demarcates thefirst zone127afrom the smallersecond zone127b. However, in the embodiment shown inFIG. 4B, thesecond zone127bis defined by aseparate tube459 that protrudes from theshaft122. Thetube459 decreases the cross-sectional area of theexhaust lumen134 at thesecond zone127bsimilar to the inwardly stepped portion of theshaft122 shown inFIG. 4A.
• As shown inFIG. 4B, thecryotherapeutic device460 can further include aproximal connector458 that attaches theballoon142 to the distal portion456 of theshaft122. Unlike the connector456 ofFIG. 4A that sits substantially within the recess formed by thestep128, theproximal connector458 shown inFIG. 4B extends over thesecond zone127bonto theouter surface455 of thefirst zone127a. By extending the proximal connector456 over thefirst zone127a, a larger surface area is made available for attaching theballoon142 to the distal portion456 of theshaft122. Accordingly, the length of thesecond zone127bcan be reduced to facilitate adequate venting of the refrigerant117 through the necked-down exhaust lumen134 (e.g., as shown inFIGS. 4A and 4B).
• In certain embodiments, theproximal connector458 is non-expandable such that it maintains a substantially low profile against theouter surface455 of thefirst zone127ain both the deployed and delivery states. This can reduce or prevent theproximal connector458 from catching on thesheath150 as it is retracted from the deployed to the delivery configuration. In other embodiments, at least a portion of theproximal connector458 can be expandable, but configured to maintain the low profile of the distal portion456 while the coolingassembly130 is in the delivery state. Accordingly, thecryotherapeutic device460 with the extendedproximal connector458 can provide a substantially low profile for intravascularly delivering the coolingassembly130 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 coolingassembly130.
• As further shown inFIG. 4B, thecryotherapeutic device460 also includes adistal connector462 that retains thedistal portion452 of theballoon142 and asupport member433 extending through theballoon142 that braces theballoon142 in both the delivery and deployed states. Thedistal connector462 can also be attached to (e.g., by thermal bonding) or formed integrally with anatraumatic tip464 that extends distally therefrom. Theatraumatic tip464 can extend approximately 0.5 cm to 5 cm (e.g., approximately 1-2 cm) from thedistal connector462 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, theatraumatic tip464 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, theatraumatic tip464 can have other suitable lengths and/or outer diameters. Theatraumatic tip464 can serve as a fixed guide to facilitate navigation through the vasculature. In several embodiments, the angle and/or rotational orientation of theatraumatic tip464 can be adjusted by a control wire467 (e.g., a pull-wire) that extends through at least a portion of theshaft122. A user can manipulate thecontrol wire467 to torsionally deflect or otherwise move theatraumatic tip464 to steer the distal portion456 of theshaft122 to the target site T. In other embodiments, theatraumatic tip464 can be defined by a distal end portion of a guide wire (e.g., theguide wire133bshown inFIG. 2C) that extends through theshaft122 and beyond thedistal connector462.
• Theatraumatic tip464 can be made from substantially smooth and flexible materials or structures such that it can gently contact and deflect off of vessel walls as thecryotherapeutic device460 navigates the vasculature, and therefore avoids perforation and/or other trauma to the vessels through which it navigates. For example, theatraumatic tip464 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 aproximal portion469aof theatraumatic tip464 to adistal portion469bof theatraumatic tip464. A tapered wire, for example, can be generally round at theproximal portion469ahaving 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 thedistal portion469bto 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 ⅓ to ½ of the length of theatraumatic tip464 from the proximal terminus. In other embodiments, theatraumatic tip464 can have a tapered or non-tapered generally circular cross-section throughout. In several embodiments, at least a portion of the atraumatic tip464 (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 thecryotherapeutic device460 through the vasculature using imaging techniques known in the art. In certain aspects of the technology, theballoon142 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, theatraumatic tip464 can be made from other deflectable and gentle materials and structures, such as a polymer material (e.g., Pebax® polymer, nylon, etc.), a polymer material over a metallic wire (e.g., a stainless steel wire), and/or other suitable materials.
• In the embodiment illustrated inFIG. 4B, theatraumatic tip464 is shaped and/or otherwise formed into a curve or angled portion. When theatraumatic tip464 is made from a shapeable material (e.g., stainless steel, platinum, etc.), theatraumatic tip464 can be formed and/or reformed into the desired curvature. In other embodiments, theatraumatic tip464 can be pre-formed from a non-shapeable material such that it has a non-adjustable, set curve. The curve in theatraumatic tip464 can further aid in navigation of the vasculature. For example, the curve can aid in keeping the coolingassembly130 within a desired vessel (e.g., a renal artery) and avoiding side branches thereof.
Pressure Monitoring in Cryotherapeutic Systems
• FIG. 5A is a partially schematic view of acryotherapeutic system500 configured in accordance with another embodiment of the present technology, andFIG. 5B is an enlarged cross-sectional view of a distal end portion of thesystem500 ofFIG. 5A. Thecryotherapeutic system500 can include features generally similar to the features of thecryotherapeutic system100 described above with reference toFIGS. 1-3B. Referring toFIG. 5A, for example, thecryotherapeutic system500 can include acryotherapeutic device520 and aconsole502. Theconsole502 can include arefrigerant supply container504 and asupply control valve508 that are coupled to asupply line510 configured to transport the refrigerant506 to thecryotherapeutic device520. Theconsole502 can also optionally include apump511 and/or abackpressure control valve513 that are coupled to anexhaust line515 configured to receive evaporated refrigerant517 from thecryotherapeutic device520. Acontroller518 can be operably coupled to thesupply control valve508 and/or thebackpressure control valve513 to regulate refrigerant flow through thecryotherapeutic device520. In the illustrated embodiment, thecryotherapeutic device520 includes ashaft522, ahandle525 at a proximal region of aproximal portion524 of theshaft522, and adistal portion526 having a coolingassembly530 at a distal end region of adistal portion526 of theshaft522.
• As further shown inFIG. 5A, theconsole502 can also include a pressure transducer or sensor570 (e.g., a PX209-100G5V pressure transducer made by Omega Engineering of Stamford, Conn.) coupled to apressure line571 to monitor pressure within a portion of the cooling assembly530 (e.g., an expansion chamber) during cryotherapy. In various embodiments, thepressure sensor570 can be coupled to thecontroller518 to serve as a feedback mechanism that controls thesupply control valve508 and/or thebackpressure control valve513, and thereby regulates refrigerant flow to and/or from the coolingassembly530 in response to a pressure sensed at thecooling assembly530. For example, thepressure sensor570 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, thecontroller518 can decrease or terminate refrigerant flow by at least partially closing thesupply control valve508 and/or increasing refrigerant flow from the coolingassembly530 by decreasing the backpressure in the exhaust line515 (e.g., using the vacuum pump511). In other embodiments, thepressure sensor570 can be coupled directly to thesupply control valve508 and/or thebackpressure control valve513 to automatically regulate thevalves508 and513 on and/or off in response to a sensed pressure. In several embodiments, thecryotherapeutic system500 can be configured to verify that thepressure sensor570 is calibrated properly before cryotherapy. For example, thesystem500 can automatically check the functionality of thepressure sensor570 as thesystem500 powers on by comparing a pressure reading from thepressure sensor570 with the ambient pressure.
• Referring now toFIG. 5B, the distal region of thecryotherapeutic device520 can include features generally similar to the features of thecryotherapeutic device120 described above with reference toFIGS. 2A-2E. For example, thecryotherapeutic device520 includes thesupply lumen132 coupled to the supply line510 (FIG. 5A), theexhaust lumen134 coupled to the exhaust line515 (FIG. 5A), and theapplicator140 including theballoon142 or other type of expandable member that defines the expansion chamber.
• As shown inFIG. 5B, thecryotherapeutic device520 can further include apressure monitoring lumen572 coupled to the pressure sensor570 (FIG. 5A) via the pressure line571 (FIG. 5A). Thepressure monitoring lumen572 can extend through theshaft522 and have adistal opening574 in fluid communication with the expansion chamber (e.g., defined by the balloon142). The dimensions (e.g., cross-sectional area, inner diameter, and/or outer diameter) of thepressure monitoring lumen572 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 theexhaust lumen134. For example, thesupply lumen132 and thepressure monitoring lumen572 together can have a first cross-sectional dimension (e.g., a first cross-sectional area) and theexhaust lumen134 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, thepressure monitoring lumen572 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 theexhaust lumen134 can be sized accordingly. In the embodiment illustrated inFIG. 5B, thepressure monitoring lumen572 terminates in theshaft522 before the outer diameter necks down at thesecond zone127bof thedistal portion520. This configuration may be used in embodiments where the inner diameter of theshaft522 necks down (e.g., as shown inFIGS. 4A and 4B) so as not to restrict the venting of the expandedrefrigerant517 at the smallersecond zone127b. In other embodiments, theopening574 of thepressure monitoring lumen572 can be at or in the balloon542.
• Thepressure monitoring lumen572 can also have a length sufficient to intravascularly locate theopening574 along with the coolingassembly530 at the target site T (e.g., a renal artery or renal ostium via a femoral artery or a radial artery). For example, thepressure monitoring lumen572 can have a length equivalent to the full length of the shaft522 (e.g., at least 48 inches (122 cm)). In other embodiments, thepressure monitoring lumen572 can have other suitable different lengths and/or dimensions. For example, thepressure monitoring lumen572 can have a first length and thepressure line571 attached thereto can have a second length (e.g., 48 inches (122 cm), 30 inches (76 cm), 12 inches (30 cm), etc.) to extend thepressure monitoring lumen572 to thepressure sensor570, thereby allowing theconsole502 to be positioned in a desired location (e.g., on a table) during cryotherapeutic treatments.
• During cryotherapeutic treatments, thepressure monitoring lumen572 and the pressure sensor570 (FIG. 5A) may be configured to provide a signal indicating a change in pressure within the expansion chamber. For example, thepressure sensor570 can be configured to indicate a threshold pressure below the rupture pressure of theballoon142 to reduce the likelihood that theballoon142 bursts during cryotherapy. Theballoon142 may have a burst pressure dependent at least in part on the material from which theballoon142 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. Thepressure sensor570 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 theballoon142 ruptures. In other embodiments, thepressure sensor570 can be configured to indicate when theballoon142 operates outside its desired operating pressure (e.g., 20-60 psi).
• The time delay between the pressure at theopening574 of thepressure monitoring lumen572 at the expansion chamber and the pressure reading at thepressure sensor570 may depend on the volume of thepressure monitoring lumen572. As such, thepressure monitoring lumen572 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 balloon142). In certain embodiments, for example, thepressure sensor570 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 thepressure sensor570, the length of thepressure monitoring lumen572 can be shortened and significant increases in volume in thepressure monitoring lumen572 before connecting to thepressure sensor570 can be reduced. For example, thepressure monitoring lumen572 can be coupled to thepressure line571 at the proximal portion524 (FIG. 5A) of the shaft522 (e.g., at the handle525), and thepressure line571 can have a cross-sectional area similar to that of thepressure monitoring lumen572. In other embodiments, thepressure monitoring lumen572 can be coupled to thepressure sensor570 at the handle525 (e.g., omitting the pressure line571) to shorten the total length of the pressure tube to thepressure sensor570, and electrical wires can be coupled to thepressure sensor570 to carry a signal to theconsole502.
• Referring toFIGS. 5A and 5B together, in certain embodiments, thepressure line571 and/or thepressure monitoring lumen572 can be coupled to thepressure sensor570 using a fitting or adaptor576 (e.g., a quick connect adapter). In the embodiment illustrated inFIG. 5A, for example, theadaptor576 includes an internal reservoir orchannel578 that fluidly connects thepressure line571 with thepressure sensor570. Thechannel578 can have a substantially small volume so as not to disrupt the pressure differential from thepressure line571 to thepressure sensor570 and enhance the accuracy of the pressure measurement. For example, in one embodiment, thechannel578 has an internal volume of no more than 0.1 cc. In other embodiments, thechannel578 can have a larger internal volume. In further embodiments, theadaptor576 can couple thepressure monitoring lumen572 to thepressure line571 at thehandle525 or other position proximate theproximal portion524 of theshaft522. Theadaptor576, therefore, allows thepressure monitoring lumen572 and/or thepressure line571 to be detached from thepressure transducer570 after a cryotherapeutic treatment such that thepressure monitoring lumen572 can be discarded and thepressure transducer570 can be stored (e.g., along with thehandle525 and/or the console502) for subsequent cryotherapy treatments without disrupting the accuracy of the pressure reading at thepressure sensor570.
• Referring back toFIG. 5B, in various other embodiments, thecryotherapeutic device520 can further include an additionalgas supply lumen579 coupled to the supply container504 (FIG. 5A) or other gas supply reservoir to deliver additional gas to the expansion chamber and thereby modulate the temperature of theapplicator140. For example, thegas supply lumen579 can deliver the refrigerant506 (e.g., nitrous oxide) and/or other pressurized or non-pressurized gas (e.g., air) into theballoon142 before or during delivery of the refrigerant506 via theorifice144 to increase the pressure within the balloon142 (e.g., from approximately 5 psi to approximately 60 psi). The additional gas in theballoon142 decreases the pressure drop of the refrigerant506 in the expansion chamber, and thereby increases the temperature within theballoon142. As such, thegas supply lumen579 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 theballoon142 without requiring complex components in the console502 (e.g., a pressure regulator, a sub-cooler, etc.) to change the pressure drop within theballoon142. Additionally, when thegas supply lumen579 is coupled to a separate gas reservoir (e.g., an air supply), thegas supply lumen579 can be used to deliver a gas into theballoon142 before delivering the refrigerant506 into theballoon142 to monitor the position of theapplicator140 at the target site T.
• In further embodiments, a pressure regulator (not shown; e.g., a pressure relief valve) can be added to theexhaust lumen134 to trap the evaporated refrigerant517 from exiting theballoon142 and/or in theexhaust lumen134 until the pressure within theballoon142 is at a predetermined value (e.g., as sensed using the pressure monitoring lumen572). In still further embodiments, thecryotherapeutic device520 can include both a pressure regulator for theexhaust lumen134 and thegas supply lumen579 such that the pressure within theballoon142 can be modulated during cryotherapeutic treatment.
Pre-Cooling in Cryotherapeutic Systems
• 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.
• 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° C.) passes through the vasculature at body temperature (e.g., about 37° C.), the temperature of the pressurized refrigerant can increase to about 25° C. to 37° 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° C. or less than about 10° 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.
• FIGS. 6A-6B illustrate a portion of acryotherapeutic device600 including apre-cooling assembly602, anelongated shaft604 defining an exhaust passage, and ahub606 between the pre-cooling assembly and the shaft. Thepre-cooling assembly602 includes a flexibletubular member608 extending between thehub606 and anadapter610 configured to connect to a pressurized-refrigerant source (not shown). Thehub606 can include aprimary connector612 attached to theshaft604, anexhaust portal614 venting to the atmosphere, afirst branch616 attached to thetubular member608, and asecond branch618 attached to a control-wire conduit620. In several embodiments, thehub606 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.
• With reference again toFIGS. 6A-6B, two control wires621 (FIG. 6B) can extend from the control-wire conduit620, through thehub606, and into theshaft604. Thehub606 can define a generally straight primary-exhaust flow path from theshaft604 to the atmosphere through theexhaust portal614. Thetubular member608 includes a tubularproximal portion622 at theadapter610 and a tubulardistal portion624 at thefirst branch616. As most clearly shown inFIG. 6B, the tubularproximal portion622 can include afirst plug626 and asecond plug628, and theadapter610 can include anopening630 proximate thesecond plug628. Theadapter610 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.
• In the embodiment shown inFIG. 6B, thedevice600 includes a primary-supply tube632 defining a primary-supply lumen, and thepre-cooling assembly602 includes apre-cooling supply tube634 defining a pre-cooling supply lumen. The primary-supply tube632 and thepre-cooling supply tube634 can include a primary-supplyproximal opening636 and a pre-cooling supplyproximal opening638, respectively, at thesecond plug628. The primary-supplyproximal opening636 and the pre-cooling supplyproximal opening638 fluidly connect the primary-supply tube632 and thepre-cooling supply tube634, respectively, to a passage defined by theopening630. From thesecond plug628, the primary-supply tube632 and thepre-cooling supply tube634 extend through the tubularproximal portion622 and through thefirst plug626. The tubulardistal portion624 defines a pre-cooling expansion chamber extending from thefirst plug626 to the primary exhaust flow path. Thepre-cooling supply tube634 extends slightly past thefirst plug626 and terminates at a pre-coolingdistal opening640 within the pre-cooling expansion chamber. The pre-cooling expansion chamber is accordingly in fluid connection with a flow of refrigerant through thepre-cooling supply tube634 such that a pre-cooling exhaust flow path extends from the pre-coolingdistal opening640 to the primary exhaust flow path. The primary-supply tube632 extends through the pre-cooling expansion chamber, through thehub606 and into theshaft604. The portion of the primary-supply tube632 extending from primary-supplyproximal opening636 to the shaft is a first portion of the primary-supply tube632. A second portion (not shown) of the primary-supply tube632 is proximate a cooling assembly (not shown) configured to be within the vasculature.
• Expanding pressurized refrigerant into the pre-cooling expansion chamber from thepre-cooling supply tube634 can cool the pre-cooling expansion chamber and thereby cool the primary-supply tube632 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.
• After cooling the primary-supply tube632, refrigerant from the pre-cooling expansion chamber can join a flow of refrigerant from the exhaust passage and vent out theexhaust portal614 to the atmosphere.FIG. 6B shows afirst arrow642 indicating a flow direction of refrigerant through theexhaust portal614 and asecond arrow644 indicating a flow direction of refrigerant through the pre-cooling expansion chamber. The flow direction of refrigerant through theexhaust portal614 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 theexhaust portal614.
• FIG. 7 illustrates a portion of acryotherapeutic device700 similar to thecryotherapeutic device600 ofFIGS. 6A-6B, except that thedevice700 has a pre-cooling expansion chamber fluidly separate from the exhaust passage. Thecryotherapeutic device700, for example, includes apre-cooling assembly702 including avalve704 and athird plug706 fluidly separating the pre-cooling expansion chamber from internal portions of theshaft604 and thehub606. The primary-supply tube632 extends through thethird plug706 and into theshaft604.
• Anarrow708 indicates a flow direction of refrigerant through the pre-cooling expansion chamber when thevalve704 is open. When thevalve704 is closed, pressure within the pre-cooling expansion chamber can increase until it equilibrates with thepre-cooling supply tube634, thereby causing flow through the pre-cooling supply tube to stop. In this way, opening and closing thevalve704 can turn pre-cooling on or off. Partially opening thevalve704 can regulate pressure within the pre-cooling expansion chamber and thereby regulate refrigerant flow through thepre-cooling supply tube634 and an associated pre-cooling temperature. For example, anactuator710 can be operably connected to thevalve704 and be configured to receive a signal from aprocessor712. Theprocessor712 can be configured to receive a signal from auser interface714 and/or asensor716 to direct theactuator710 to open or close the valve fully or incrementally. Thesensor716, for example, can be a temperature sensor of an associated cooling assembly. In one embodiment, the temperature sensor can send a signal to theprocessor712 causing thevalve704 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.
• FIGS. 8A-8B illustrate a portion of acryotherapeutic device800 with a pre-cooler802 configured in accordance with another embodiment of the present technology. Accessing an internal portion of thetubular member608 to form thefirst plug626 of the pre-cooling assembly602 (FIGS. 6A-6B) can be challenging. Instead of thefirst plug626 and the pre-cooling supply tube634 (FIG. 6B), the pre-cooler802 can include a flow separator attached to a primary-supply tube. For example, the pre-cooler802 can include aflow separator804 attached to a primary-supply tube806 and acontainer808 having a containerproximal portion810 and a containerdistal portion812. In this embodiment, theflow separator804 divides thecontainer802 into the containerproximal portion810 and the containerdistal portion812. The containerproximal portion810 defines a proximal chamber or a combined supply lumen between theopening630 and theflow separator804 and the containerdistal portion812 defines a pre-cooling expansion chamber. As most clearly shown inFIG. 8B, theflow separator804 defines aprimary passage814 fluidly connected to the primary-supply tube806 and apre-cooling passage816 along a periphery of theflow separator804.
• Referring still toFIG. 8B, thepre-cooling passage816 is sized to cause a pressure drop sufficient to expand refrigerant and cool the pre-cooling expansion chamber. Theflow separator804 includes atubular segment818 and a flow-separator plug820. The flow-separator plug820 is positioned between an outer surface of the primary-supply tube806 and an inner surface of thecontainer808. Thetubular segment818 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 thecontainer808. The flow-separator plug820 can include, for example, an adhesive material configured to bond to the outer surface of the primary-supply tube806 and the inner surface of thecontainer808.
• In one embodiment, theflow separator804 floats in the container808 (i.e., it is not fixed within the container808) such that thepre-cooling passage816 is an annular space between theflow separator804 and an inner surface of thecontainer808. 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.
• FIGS. 9A-9B illustrate a portion of acryotherapeutic device900 similar to thecryotherapeutic device800 ofFIGS. 8A-8B, except having different flow-separator and primary-supply tube configurations. Thecryotherapeutic device900 includes aprimary supply tube902 and a pre-cooler904 including aflow separator906 attached to the primary-supply tube902. The pre-cooler904 can also include acontainer908 having a containerproximal portion910 and a containerdistal portion912 on opposite sides of theflow separator906. In this embodiment, theflow separator906 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 tube902 can be threaded or otherwise attached. As most clearly shown inFIG. 9B, theflow separator906 can define apre-cooling passage914 along a periphery of theflow separator906. The primary-supply tube902 can extend through theflow separator906 and can be attached to an inner surface of the containerproximal portion910 proximate theopening630. Attaching the primary-supply tube906 to an accessible portion of the containerproximal portion910 can be useful to prevent undesirable longitudinal movement of theflow separator906 and the primary-supply tube902 when the proximal chamber is at high pressure.
• 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 acryotherapeutic device1000 including apre-cooling assembly1002 and ahub1004 within ahandle1006. Thepre-cooling assembly1002 includes aflexible tubular member1008 extending from thehub1004, through abottom portion1010 of thehandle1008, and to anadapter1012 configured to connect to a pressurized-refrigerant source (not shown). Thehub1004 can include anelongated exhaust portal1014 extending through thebottom portion1010, and a control-wire conduit1016 can extend from thehub1004 through thebottom portion1010. In one embodiment, thetubular member1008 is coiled around theexhaust portal1014. Thehandle1006 also can be insulated to prevent heat loss to the atmosphere and improve pre-cooling efficiency.
• FIG. 11 illustrates a portion of acryotherapeutic device1100 having an alternative configuration within and around a handle. Thecryotherapeutic device1100 includes apre-cooling assembly1102 and ahub1104 within ahandle1106. Thepre-cooling assembly1102 includes aflexible tubular member1108 extending from thehub1104 and through abottom portion1110 of thehandle1106. Thehub1104 can include anelongated exhaust portal1112 extending through thebottom portion1110, and a control-wire conduit1114 can extend from thehub1104 through thebottom portion1110. In one embodiment, thetubular member1108 includes ahelical portion1116 spaced apart from theexhaust portal1112. Thehandle1106 also can be insulated to prevent heat loss to the atmosphere and improve pre-cooling efficiency.
Cryotherapeutic-Device Components
• 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 toFIGS. 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 thecryotherapeutic system100 shown inFIG. 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.
• 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.
• 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).
• 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.
• 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
• 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.
• FIG. 12 illustrates a portion of acryotherapeutic device1200 including acooling assembly1202 at adistal portion1204 of anelongated shaft1206 defining an exhaust passage. As described above, thedistal portion1204 can have astep1208 and thecooling assembly1202 can include anapplicator1210 having a plurality of heat transfer portions (individually identified as1211a-d). Theapplicator1210 also can have aballoon1212 with adistal neck1214, and theballoon1212 can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice1200 can further include anelongated guide member1216a, afirst supply tube1218 defining a first supply lumen, and asecond supply tube1220 defining a second supply lumen. Theguide member1216acan define a guide-wire lumen shaped to receive aguide wire1216b, 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, theguide member1216ahas a straight end and extends to thedistal neck1214. Alternatively, theguide member1216acan include a rounded end and/or an end that extends beyond thedistal neck1214. 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.
• Thefirst supply tube1218 can include a first angleddistal portion1222, and thecooling assembly1202 can include afirst orifice1224 at the end of the first angleddistal portion1222. Similarly, thesecond supply tube1220 can include a second angleddistal portion1226, and the cooling assembly can include asecond orifice1228 at the end of the second angled distal portion. The first and second angleddistal portions1222,1226 of the illustrated embodiment are longitudinally and radially spaced apart along and about the length of thecooling assembly1202. In several other embodiments, the first and second angleddistal portions1222,1226 have the same longitudinal and/or radial position, or another configuration. When thecooling assembly1202 is in a deployed state, refrigerant can flow through the first andsecond supply tubes1218,1220, flow through the first and second angleddistal portions1222,1226, respectively, and flow out the first andsecond orifices1224,1228, respectively. The first and second angleddistal portions1222,1226 can direct expanded refrigerant toward the heat-transfer portions1211aand1211d, respectively. As a result, when refrigerant flows out of the first andsecond orifices1224,1228, the heat-transfer portions1211aand1211dcan have higher overall and particularly convective heat-transfer rates relative to other heat-transfer portions of theapplicator1210. 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 theapplicator1210. The difference in heat-transfer rate can vary depending on a distance from the heat-transfer portions1211aand1211d. A functionally significant difference in heat-transfer rate can separate the heat-transfer portion1211afrom the heat-transfer portion1211c, which is generally circumferentially opposite to the heat-transfer portion1211a. Similarly, a functionally significant difference in heat-transfer rate can separate the heat-transfer portion1211dfrom the heat-transfer portion1211b, which is generally circumferentially opposite to the heat-transfer portion1211d. In several embodiments, the heat-transfer portions1211aand1211dhave heat-transfer rates sufficient to cause therapeutically-effective renal nerve modulation, while the heat-transfer portions1211band1211chave heat-transfer rates insufficient to cause therapeutically-effective renal nerve modulation.
• The first andsecond supply tubes1218,1220 can be configured, for example, to direct expansion of refrigerant at angles about 45° offset from the length of theapplicator1210 or the length of thecooling assembly1202. In several other embodiments, one or more supply tubes are configured to direct refrigerant at an angle from about 15° to about 90° relative to a length of an applicator or a cooling assembly, such as from about 30° to about 45°, or from about 30° to about 40°. Additionally, thefirst supply tube1218 can be at a different angle than thesecond supply tube1220. The longitudinal distance between afirst orifice1224 and asecond orifice1228 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.
• 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 acryotherapeutic device1300 including acooling assembly1302 at adistal portion1304 of anelongated shaft1306 defining an exhaust passage open at the end of thedistal portion1304. Thedistal portion1304 can have astep1307 and thecooling assembly1302 can include anapplicator1308 having a first heat-transfer portion1309 and a second heat-transfer portion1310. The first and second heat-transfer portions1309,1310 are elongated and radially spaced apart around the length of thecooling assembly1302. Theapplicator1308 also can have aballoon1311 that can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice1300 can further include anelongated guide member1312 and asupply tube1313 extending along the length of theshaft1306. Within theballoon1311, thesupply tube1313 can include ahelical portion1314 that exits thedistal portion1304 and wraps around the distal portion1304 (e.g., thedistal portion1304 can define a central axis of the helical portion1314). Thecooling assembly1302 can include a plurality of orifices (individually identified as1316a-e) laterally spaced apart along thehelical portion1314. In the illustrated embodiment, if thehelical portion1314 were straightened, the orifices1316a-ewould be generally radially aligned. In this embodiment, the shape of thehelical portion1314 causes the orifices1316a-eto point in different radial directions. In other embodiments, thehelical portion1314 can have a different number and/or orientation of orifices1316a-e.
• Thehelical portion1314 locates the orifices1316a-ecloser to theballoon1311 than they would be if thesupply tube1312 were straight. This can cause refrigerant exiting the orifices1316a-eto contact theballoon1311 at higher velocities and increase the amount of convective cooling at corresponding heat-transfer portions of theballoon1311. This can also provide more control of the size and spacing of where refrigerant first contacts theballoon1311. 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.
• In the illustrated embodiment, theorifices1316a,1316c,1316epoint generally toward an upper half of theballoon1311, while theorifices1316b,1316dpoint generally toward a lower half of theballoon1311. When thecooling assembly1302 is in a deployed state, refrigerant flow throughorifices1316a,1316c,1316eproduces the first heat-transfer portion1309, while refrigerant flow throughorifices1316b,1316dproduces the second heat-transfer portion1310. As a result of the refrigerant flow, the first and second heat-transfer portions1309,1310 can have higher overall and particularly convective heat-transfer rates relative to other heat-transfer portions of theapplicator1308. 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 theapplicator1308. In several embodiments, the first and second heat-transfer portions1309,1310 have heat-transfer rates sufficient to cause therapeutically-effective renal nerve modulation, while portions of theapplicator1308 between the first and second heat-transfer portions1309,1310 have heat-transfer rates insufficient to cause therapeutically-effective renal nerve modulation.
• FIG. 14 illustrates a portion of acryotherapeutic device1400 that differs from thedevice1300 ofFIG. 13 primarily with respect to an exhaust configuration. Thedevice1400 includes acooling assembly1402 at adistal portion1404 of anelongated shaft1406 defining an exhaust passage. Thedistal portion1404 can have astep1407, a plurality ofexhaust openings1408, and arounded end1409. Thecooling assembly1402 can include anapplicator1410 with aballoon1411 having adistal neck1412 and theballoon1411 can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice1400 can further include asupply tube1413 extending along the length of theshaft1406 and into theballoon1411. Within theballoon1411, thesupply tube1413 can include ahelical portion1414 that exits thedistal portion1404 and wraps around the distal portion1404 (e.g., thedistal portion1404 can define a central axis of the helical portion1414). The helical coils of thehelical portion1414 can be located between theexhaust openings1408. Thecooling assembly1402 can include a plurality of orifices (individually identified as1416a-d) laterally spaced apart along thehelical portion1414. In the illustrated embodiment, thedistal portion1404 is sufficiently narrow to allow thehelical portion1414 to wrap around thedistal portion1404 generally without extending beyond the diameter of theshaft1406 proximal to thedistal portion1404. Accordingly, thecooling assembly1402 in a delivery state can be configured to fit within a delivery sheath sized according to theshaft1406. The plurality ofexhaust openings1408 can promote exhaust flow and mitigate any flow restriction associated with the sizing of thedistal portion1404. Thus, as discussed above, the relatively high density of expanded refrigerant entering the exhaust passage can allow thedistal portion1404 to be sized down without necessarily causing an unsuitable increase in back pressure.
• Similar to the orifices1316a-eof thedevice1300 ofFIG. 13, the orifices1416a-din the illustrated embodiment are laterally spaced apart along thehelical portion1414. However, unlike the orifices1316a-dof thedevice1300 ofFIG. 13, the orifices1416a-din the illustrated embodiment are configured to direct refrigerant flow in different radial directions around the length of thecooling assembly1402. Specifically, the orifices1416a-dare configured to direct refrigerant flow in directions radially spaced apart by increments of about 90°. The orifices1416a-dare sized to cause corresponding heat-transfer portions having circumferential arcs greater than about 90°. As a result, the projected circumference of the heat-transfer portions corresponding to the orifices1416a-dis generally fully circumferential, while being partially circumferential in particular longitudinal segments of thecooling assembly1402.
• As discussed above with reference toFIG. 13, locating primary refrigerant expansion areas closer to a balloon can facilitate convective heat transfer.FIGS. 15A-15B illustrate a portion of acryotherapeutic device1500 that also can be configured to locate primary refrigerant expansion areas closer to a balloon. Thedevice1500 includes acooling assembly1502 at adistal portion1504 of anelongated shaft1506 defining an exhaust passage. Thedistal portion1504 can have astep1507, and thecooling assembly1502 can include anapplicator1508 with anouter balloon1510 that can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice1500 can further include asupply tube1512 and aninner balloon1514. Thesupply tube1512 has arounded end1516 and can extend along the length of theshaft1506 and through a distal portion of theouter balloon1510. Theinner balloon1514 extends around a portion of thesupply tube1512 within theouter balloon1510. In several other embodiments configured in accordance with the present technology, asupply tube1512 terminates within an inner distributor, such as theinner balloon1514, and/or the device can include a guide member that can extend through theinner balloon1514 and through the distal portion of theouter balloon1510. With reference again to the embodiment of thedevice1500 shown inFIGS. 15A-15B, the portion of thesupply tube1512 within theinner balloon1514 can include supply-tube orifices1518. Thecooling assembly1502 can include inner-balloon orifices1520 distributed in a helical arrangement or other suitable arrangement on theinner balloon1514. The inner-balloon orifices1520 can be, for example, laser-cut holes in theinner balloon1514. When thecooling assembly1502 is in a delivery state, theouter balloon1510 and theinner balloon1514 can be at least partially collapsed to fit within a delivery sheath.
• When thecooling assembly1502 is in a deployed state, refrigerant can flow from thesupply tube1512, through the supply-tube orifices1518, and into theinner balloon1514. The supply-tube orifices1518 can be large enough to allow refrigerant to enter theinner balloon1514 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 theinner balloon1514 outside thesupply tube1512 can be from about 40% to about 100% of a refrigerant absolute vapor pressure within the portion of the supply tube within theinner balloon1514, 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 orifices1520 can be less than a second free-passage area equal to the total free-passage area of the supply-tube orifices1518. The size and/or number of inner-balloon orifices1520 can be selected to control the first free-passage area. Similarly, the size and/or number of supply-tube orifices1518 can be selected to control the second free-passage area. From theinner balloon1514, refrigerant can expand through the inner-balloon orifices1520 to cool one or more corresponding heat-transfer portions of theapplicator1508. In particular, the inner-balloon orifices1520 can be configured to cool a generally helical heat-transfer portion.
• FIGS. 16A-16B illustrate acryotherapeutic device1600 that differs from thecooling assembly1500 ofFIG. 15A with respect to an outer-balloon shape. Thedevice1600 includes acooling assembly1602 including anapplicator1604 with anouter balloon1606 having a raisedhelical portion1608 and a recessedportion1610. The inner surface of the raisedhelical portion1608 can be configured to receive expanded refrigerant from the inner-balloon orifices1520, and the shape of the inner surface of the raisedhelical portion1608 can help to localize increased convective cooling at the raisedhelical portion1608. The recessedportion1610 is generally configured not to contact a renal artery or a renal ostium. Localizing increased convective cooling to the raisedhelical portion1606 can promote cooling efficiency as well as cooling-location selectivity. The raisedhelical portion1608 can correspond to a heat-transfer portion having a higher heat-transfer rate than other heat-transfer portions of theapplicator1604, such as a heat-transfer portion corresponding to the recessedportion1610. For example, during operation, the raisedhelical portion1608 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 portion1610) has a heat-transfer rate insufficient to cause therapeutically-effective renal nerve modulation.
Conductive Heat Transfer
• 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).
• FIGS. 17A-17B illustrate a portion of acryotherapeutic device1700 including acooling assembly1702 at adistal portion1704 of anelongated shaft1706 defining an exhaust passage. Thedistal portion1704 can have astep1707, and thecooling assembly1702 can include anapplicator1708 having aballoon1710 configured to contact a renal artery or a renal ostium. Theapplicator1708 can further include a plurality of elongated, thermally-insulative members1711 with lengths generally parallel to the length of thecooling assembly1702 and radially spaced apart around the circumference of thecooling assembly1702. Theballoon1710 can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice1700 can further include asupply tube1712 extending along the length of theshaft1706 and into theballoon1710, and thecooling assembly1702 can include anorifice1714 at the end of thesupply tube1712. During operation when thecooling assembly1702 is in a deployed state, the thermally-insulative members1711 can reduce conductive cooling through adjacent portions of theballoon1710. For example, portions of theballoon1710 between the thermally-insulative members1711 can have heat-transfer rates sufficient to cause therapeutically-effective renal nerve modulation, while portions of the balloon at the thermally-insulative members1711 can have lower heat-transfer rates, such as heat-transfer rates insufficient to cause therapeutically-effective renal nerve modulation. The thermally-insulative members1711 can be elongated and generally continuous along the length of portions of theapplicator1708. Accordingly, heat-transfer portions corresponding to portions of theballoon1710 between the thermally-insulative members1711 can be generally non-circumferential at longitudinal segments of thecooling assembly1702.
• The thermally-insulative members1711 can include a primary material having a thermal conductivity lower than or equal to a thermal conductivity of a primary material of theballoon1710. In several embodiments, the thermally-insulative members1711 have different compositions than theballoon1710 and are attached to an inner surface of theballoon1710. Several other embodiments can include thermally-insulative members1711 that are compositionally similar to (e.g., the same as) or different than theballoon1710. 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 member1711 can be integrally formed with aballoon1710 or attached to aballoon1710.
• FIGS. 18A-18B illustrate a portion of acryotherapeutic device1800 similar to thedevice1700 ofFIGS. 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. Thedevice1800 includes acooling assembly1802 having anapplicator1804 with aballoon1806 that can define an expansion chamber configured to generate and deliver cryogenic cooling. Theapplicator1804 also includes a plurality of thermally-insulative members1808. Thedevice1800 can further include afiller tube1810, and the thermally-insulative members1808 can be configured to be filled in the deployed state via thefiller tube1810. In the illustrate embodiment, thefiller tube1810 includes amain portion1812 and fourbranches1814, in which the branches fluidly connect the main portion with one of the thermally-insulative members1808. The thermally-insulative members1808 and thefiller tube1810 are fluidly separate from the expansion chamber within theballoon1806.
• Thefiller tube1810 has a proximal portion (not shown) configured to receive filler material from a filler-material source (not shown) from outside the vasculature. Thefiller tube1810 and the thermally-insulative members1808 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).
• Although four thermally-insulative members are shown inFIGS. 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.
• FIGS. 19A-19C illustrate a portion of acryotherapeutic device1900. Referring toFIG. 19A, thedevice1900 can include acooling assembly1902 at adistal portion1904 of anelongated shaft1906 defining an exhaust passage. Thedistal portion1904 can have astep1907, and thecooling assembly1902 can include anapplicator1908 with aballoon1910 that can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice1900 can further include asupply tube1912 extending along the length of theshaft1906 and into theballoon1910, and thecooling assembly1902 can include anorifice1914 at an end of thesupply tube1912. Thedevice1900 can further include a helical thermally-insulative member1916 that can be, for example, a thicker portion of theballoon1910 with the extra thickness at an inner surface of the balloon1910 (i.e., an outer surface of theballoon1910 can be generally smooth or otherwise even at the helical thermally-insulative member1916 and around the helical thermally-insulative member1916). During operation when thecooling assembly1902 is in a deployed state, the helical thermally-insulative member1916 can correspond to a heat-transfer portion of theapplicator1908 having a lower heat-transfer rate than other portions of theapplicator1908. For example, a heat-transfer rate of a portion of theapplicator1908 apart from the helical thermally-insulative member1916 can be sufficient to cause therapeutically-effective renal nerve modulation during operation, while a heat-transfer rate of a portion of theapplicator1908 at the helical thermally-insulative member1916 can be insufficient to cause therapeutically-effective renal nerve modulation.FIGS. 19B and 19C are cross-sectional views of theapplicator1908 at different longitudinal positions. As shown inFIGS. 19B and 19C, the circumferential position of the helical thermally-insulative member1916 changes along the length of thecooling assembly1902 such that the portion of theballoon1910 apart from the helical thermally-insulative member1916 is generally non-circumferential in longitudinal segments along the length of thecooling assembly1902.
• FIGS. 20A-20C illustrate a portion of acryotherapeutic device2000 similar to thedevice1900 ofFIGS. 19A-19C except with regard to a thermally-insulative member shape. Referring toFIG. 20A, thedevice2000 includes acooling assembly2002 having anapplicator2004 with aballoon2006 that can define an expansion chamber configured to generate and deliver cryogenic cooling. Theapplicator2004 also includes a thermally-insulative member2008 generally resembling an intertwined double helix (e.g., an intertwined right-handed helix and left-handed helix). A heat-transfer portion of theapplicator2004 at the thermally-insulative member2008 generally isolates heat-transfer portions of theapplicator2004 apart from the thermally-insulative member2008. The thermally-insulative member2008 can be configured to collapse and/or expand with theballoon2006 when thecooling assembly2002 moves between the delivery state and the deployed state. For example, if theballoon2006 is generally flexible and non-compliant, the thermally-insulative member2008 can be either generally flexible and compliant or non-compliant. If theballoon2006 is generally compliant, the thermally-insulative member2008 can be generally compliant so as to compliantly expand and contract in conjunction with theballoon2006. Thethermally insulative members1716,1808 shown inFIGS. 17A-18B, and the helical thermally-insulative member1916 shown inFIGS. 19A-19B, can be similarly configured relative to the correspondingballoons1710,1806,1910. 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%.
• 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 acryotherapeutic device2100 including acooling assembly2102 at adistal portion2104 of anelongated shaft2106 defining an exhaust passage. Thedistal portion2104 can have astep2107 and arounded lip2108. Thecooling assembly2102 can include anapplicator2109 with aballoon2110 having adistal neck2111 and theballoon2110 can define an expansion chamber configured to generate and deliver cryogenic cooling. Thedevice2100 can further include anelongated guide member2112 and asupply tube2114 extending along a length of theshaft2106 and into theballoon2110. Thecooling assembly2102 can include anorifice2116 at the end of the supply tube. In the illustrated embodiment, theguide member2112 extends through to thedistal neck2111. Theapplicator2109 further includes a first elongated, thermally-insulative member2118 and a second elongated, thermally-insulative member2120. The first and second elongated, thermally-insulative members2118,2120 are not attached to theballoon2110. Instead, the first and second elongated, thermally-insulative members2118,2120 are attached to an inner surface of thedistal portion2104.
• When thecooling assembly2102 is in a deployed state, the first and second thermally-insulative members2118,2120 can be movable relative to theballoon2110 in response to gravity. The first and second thermally-insulative members2118,2120 can move over therounded lip2108 as they settle within the balloon. As shown inFIG. 21A, the first and second thermally-insulative members2118,2120 can settle along a lower portion of theballoon2110. As shown inFIG. 21B, the first and second thermally-insulative members2118,2120 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 toFIG. 21C, thedevice2100 is shown in the delivery state within adelivery sheath2122. As shown inFIG. 21C, the first and second thermally-insulative members2118,2120 can collapse with theballoon2110 in the delivery state.
• FIGS. 22A-22B illustrate a portion of acryotherapeutic device2200 similar to thedevice2100 ofFIGS. 21A-21C except with regard to a configuration of thermally-insulative members. Thedevice2200 includes acooling assembly2202 having anapplicator2204 with aballoon2206 that can define an expansion chamber configured to generate and deliver cryogenic cooling. Theapplicator2204 also includes a first elongated, thermally-insulative member2208 and a second thermally-insulative member2210. Thedevice2200 can further include afiller tube2212 and the first and second thermally-insulative members2208,2210 can be configured to be filled in the deployed state via thefiller tube2212. Thefiller tube2212 can include ahub2214 where it branches into the first and second thermally-insulative members2208,2210. As discussed above with reference to the thermally-insulative members1808 of thedevice1800 shown inFIGS. 18A-18B, the first and second thermally-insulative members2208,2210 and thefiller tube2212 can be fluidly separate from theballoon2206. Thefiller tube2212 can have a proximal portion (not shown) configured to receive filler material from outside the vasculature. Thefiller tube2212 and the first and second thermally-insulative members2208,2210 can be configured to be fully, mostly, or partially collapsed when thecooling assembly2202 is in a delivery state.
• 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
• 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).
• FIGS. 23A-23B illustrate a portion of acryotherapeutic device2300 including acooling assembly2302 at adistal portion2304 of anelongated shaft2306 defining an exhaust passage. Thedistal portion2304 can have astep2307, afirst exhaust port2308, asecond exhaust port2309, and arounded end2310. Thecooling assembly2302 can include anapplicator2311 having afirst balloon2312 that defines a first expansion chamber and asecond balloon2313 that defines a second expansion chamber. Thefirst balloon2312 and thesecond balloon2313 are fluidly connected to the exhaust passage through thefirst exhaust port2308 and thesecond exhaust port2309, respectively. Thedevice2300 can further include asupply tube2314 extending along a length of theshaft2306, and thecooling assembly2302 can further include afirst orifice2316 and asecond orifice2318. Thefirst orifice2316 is aligned with thefirst exhaust port2308 such that refrigerant expands through thefirst exhaust port2308 and into thefirst balloon2312, and thesecond orifice2318 is aligned with thesecond exhaust port2309 such that refrigerant expands through thesecond exhaust port2309 and into thesecond balloon2313.
• The first andsecond balloons2312,2313 are spaced apart along the length of thecooling assembly2302 and configured to expand laterally across different partially-circumferential arcs along the length of thecooling assembly2302. When thecooling assembly2302 is in a deployed state, thefirst balloon2312 can be configured to contact a first partially-circumferential portion of an inner surface of a renal artery or a renal ostium, and thesecond balloon2313 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, thecooling assembly2302 can be configured to facilitate such a treatment without repositioning thecooling assembly2302 during the treatment.
• When the first andsecond balloons2312,2313 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, thedistal portion2304 can transfer forces between the first andsecond balloons2312,2313 while a portion of theshaft2306 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, thecooling assembly2302 can be configured to be non-occlusive (i.e., to less than fully occlude a renal artery or a renal ostium). For example, thecooling assembly2302 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).
• FIGS. 24A-24B illustrate a portion of acryotherapeutic device2400 that differs from thedevice2300 ofFIGS. 23A-23B primarily with respect to an exhaust configuration. Thedevice2400 includes acooling assembly2402 at adistal portion2404 of anelongated shaft2406 defining an exhaust passage. Thedistal portion2404 can have astep2407, afirst exhaust port2408, asecond exhaust port2409, and arounded end2410. Thecooling assembly2402 can include anapplicator2411 having afirst balloon2412 that defines a first expansion chamber and asecond balloon2413 that defines a second expansion chamber. Thefirst balloon2412 and thesecond balloon2413 are fluidly connected to the exhaust passage through thefirst exhaust port2408 and thesecond exhaust port2409, respectively. Thedevice2400 can further include asupply tube2414 extending along a length of theshaft2406 and having a firstlateral branch2416 and a secondlateral branch2418. Thecooling assembly2402 can further include afirst orifice2420 at the end of the firstlateral branch2416 open to thefirst balloon2412 and asecond orifice2422 at the end of the secondlateral branch2418 open to thesecond balloon2413. Unlike thedevice2300 shown inFIGS. 23A-23B, thedevice2400 includes refrigerant supply and refrigerant exhaust at circumferentially opposite sides of thedistal portion2404 for the first andsecond balloons2412,2413. The first andsecond balloons2412,2413 extend around fully-circumferential longitudinal segments of thedistal portion2404, but are attached to thedistal portion2404 and shaped so as to expand asymmetrically about thedistal portion2404.
• Cooling assemblies configured in accordance with several embodiments of the present technology can include a different number of partially-circumferential balloons from thecooling assemblies2302,2402 shown inFIGS. 23A-24B. For example, in several embodiments, thecooling assembly2302 can include thefirst balloon2312 or thesecond balloon2313 rather than both. Similarly, thecooling assembly2402 can include thefirst balloon2412 or thesecond balloon2413 rather than both. Thecooling assemblies2302,2402 shown inFIGS. 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 andsecond balloons2312,2313 of thecooling assembly2302 or the first andsecond balloons2412,2413 of thecooling assembly2402 are configured to provide a partially-circumferential overall cooling pattern.
• 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 acryotherapeutic device2500 including acooling assembly2502 at adistal portion2504 of anelongated shaft2506 defining an exhaust passage. Thedistal portion2504 can have astep2507, and thecooling assembly2502 can include anapplicator2508 with aballoon2510 that defines an expansion chamber and has adistal neck2511, ahelical recess2512, and anon-recessed portion2513. Thedevice2500 can further include anelongated guide member2514 that extends through thedistal neck2511, as well as asupply tube2516 that extends along the length of theshaft2506 and into theballoon2510. Thecooling assembly2502 can further include anorifice2518 at the distal end of thesupply tube2516. When thecooling assembly2502 is in a delivery state, thehelical recess2512 can correspond to a heat-transfer portion of theapplicator2508 having a lower heat-transfer rate than portions of theapplicator2508 spaced apart from thehelical recess2512.
• The space between thehelical recess2512 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 thehelical recess2512 from a cryogenic temperature within theballoon2510. For example, frozen or liquid blood within this space can provide thermal insulation. The depth of thehelical recess2512 relative to thenon-recessed portion2513 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 theballoon2510. 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.
• FIG. 26 illustrates a portion of another embodiment of acryotherapeutic device2600 including acooling assembly2602 at adistal portion2604 of anelongated shaft2606 defining an exhaust passage. Thedistal portion2604 can have astep2607, and thecooling assembly2602 can include anapplicator2608 with aballoon2610 that defines an expansion chamber and has adistal neck2611, a plurality ofrecesses2612, and anon-recessed portion2613. Therecesses2612 can be arranged in a helical pattern around the circumference of theballoon2610. Thecooling assembly2602 can further include anelongated guide member2614 that extends through thedistal neck2611. Thedevice2600 can also include asupply tube2616 that extends along the length of theshaft2606 and into theballoon2610. Thecooling assembly2602 can further include anorifice2618 at the distal end of thesupply tube2616. When thecooling assembly2602 is in a deployed state, therecesses2612 and thenon-recessed portion2613 can function similarly to thehelical recess2512 and thenon-recessed portion2513 of thedevice2500 shown inFIG. 25.
• FIGS. 27A-27C illustrate a portion of acryotherapeutic device2700 similar to thedevice2600 ofFIG. 26, but thedevice2700 is configured to be less occlusive within a renal artery or a renal ostium than thedevice2600 ofFIG. 26. Thedevice2700 includes acooling assembly2702 at adistal portion2704 of anelongated shaft2706 defining an exhaust passage. Thedistal portion2704 can have astep2707, and thecooling assembly2702 can include anapplicator2708 with aballoon2710 that defines an expansion chamber and hasproximal branches2711, a tubularmain portion2712,distal branches2713, a plurality ofrecesses2714, and anon-recessed portion2716. The plurality ofrecesses2714 can be arranged in a helical pattern around the circumference of theballoon2710. When thecooling assembly2702 is in a deployed state, therecesses2714 and thenon-recessed portion2716 can function similarly to therecesses2612 and thenon-recessed portion2613 of thedevice2600 shown inFIG. 26. Theproximal branches2711 can be configured to fluidly connect the tubularmain portion2712 to the exhaust passage. Thedevice2700 can further include anelongated guide member2718 that can extend along the length of theshaft2706 and attach to thedistal branches2713, as well as asupply tube2720 that extends along the length of theshaft2706, through one of theproximal branches2711, and into the tubularmain portion2712. Theproximal branches2711 and thedistal branches2713 can be configured to space apart the tubularmain portion2712 from theguide member2718. Thecooling assembly2702 can further include anorifice2722 at the distal end of thesupply tube2720.
• When thecooling assembly2702 is in a deployed state, thecooling assembly2702 can define a flow path (e.g., a blood flow path) between an outside surface of theguide member2718 and theballoon2710. The flow path can extend, for example, around theproximal branches2711, through the tubular main portion2712 (e.g., between theguide member2718 and an inner surface of the tubular main portion2712), and around thedistal branches2713. As shown inFIG. 27B, the tubularmain portion2712 can include a thermally-insulativeinner portion2724 around the flow path. The thermally-insulativeinner portion2724 can be configured to at least partially insulate fluid in the flow path from cryogenic cooling within the tubularmain portion2712. In the illustrated embodiment, the thermally-insulativeinner portion2724 can be a portion of theballoon2710 having a greater thickness than other portions of theballoon2710. In several other embodiments, the thermally-insulativeinner portion2724 has a different composition from other portions of theballoon2710 and/or includes one or more separate thermally-insulative structures. Alternatively, theballoon2710 can include a tubularmain portion2712 with an inner portion that is not more thermally insulative than other portions of theballoon2710.
• FIG. 28 illustrates a portion of acryotherapeutic device2800 similar to thedevice2600 ofFIG. 26 except with regard to a configuration of recessed and non-recessed portions. Thedevice2800 includes acooling assembly2802 having anapplicator2804 with aballoon2806 that can define an expansion chamber. Theballoon2806 includes a plurality ofprotrusions2808 and anon-protruding portion2810. Theprotrusions2808 can be arranged in a helical pattern or other suitable pattern around the circumference of theballoon2806. When thecooling assembly2802 is in a delivery state, thenon-protruding portion2810 can correspond to a heat-transfer portion of theapplicator2804 having a lower heat-transfer rate than portions of the applicator at theprotrusions2808. The space between thenon-protruding portion2810 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 theballoon2806. For example, frozen or liquid blood within this space can provide thermally insulation.
• 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 acryotherapeutic device2900 including acooling assembly2902 at adistal portion2904 of anelongated shaft2906 defining an exhaust passage. Thedistal portion2904 can have astep2907, anexit hole2908, and anexhaust port2909. Thecooling assembly2902 can include anapplicator2910 with ahelical balloon2911 that defines an expansion chamber and has a balloonproximal portion2912 and a balloondistal portion2914. The balloonproximal portion2912 has minor fluid connection with the exhaust passage through theexit hole2908. The balloondistal portion2914 is attached to the outside surface of thedistal portion2904 around theexhaust opening2909, thereby fluidly connecting thehelical balloon2911 to the exhaust passage. Thehelical balloon2911 is wrapped around the distal portion2904 (e.g., thedistal portion2904 can define a central axis of the helical balloon2911). Thedevice2900 can further include asupply tube2916 defining a supply lumen and having amain portion2918 extending along the length of theshaft2906 and an angleddistal portion2920 exiting theshaft2906 through theexit hole2908. Thecooling assembly2902 also can include anorifice2922 at the distal end of the angleddistal portion2920. Thesupply tube2916 and theorifice2922 can be configured to direct expansion of refrigerant into the balloonproximal portion2912 in a direction generally corresponding to a longitudinal orientation of the balloonproximal portion2912. When thecooling assembly2902 is in a deployed state, refrigerant can flow from the balloonproximal portion2912 to the balloondistal portion2914 and then proximally along the exhaust passage. Upon reaching the balloondistal portion2914, the refrigerant can have exhausted some, most, or all of its capacity for cryogenic cooling.
• FIG. 30 illustrates a portion of acryotherapeutic device3000 that differs from thedevice2900 ofFIG. 29 primarily with respect to a refrigerant flow direction. Thedevice3000 includes acooling assembly3002 at adistal portion3004 of anelongated shaft3006 defining an exhaust passage. Thedistal portion3004 can have astep3007, and thecooling assembly3002 can include anapplicator3008 having ahelical balloon3014 that defines an expansion chamber and has a balloonproximal portion3016 and a balloondistal portion3018. The balloonproximal portion3016 can be attached to an outside surface of thedistal portion3004 proximate a distal end of thedistal portion3004, thereby fluidly connecting thehelical balloon3014 to the exhaust passage. Thedevice3000 can further include asupply tube3019 having a curveddistal portion3020. Thehelical balloon3014 can be wrapped around the supply tube3019 (e.g., thesupply tube3019 can define a central axis of the helical balloon3014). Thesupply tube3019 can extend along the length of theshaft3006, out of the shaft, out of the balloonproximal portion3016, along a central axis of thehelical balloon3014, and into the balloondistal portion3018. The balloondistal portion3016 can be sealed around thesupply tube3019 and at least partially attached to the curveddistal portion3020. Thecooling assembly3002 can further include anorifice3021 fluidly connecting thesupply tube3019 to the balloondistal portion3018. Thesupply tube3019 and theorifice3021 can be configured to direct expansion of refrigerant into the balloondistal portion3018 in a direction generally corresponding to a longitudinal orientation of the balloondistal portion3018. When thecooling assembly3002 is in a deployed state, refrigerant can flow from the balloondistal portion3018 to the balloonproximal portion3016 and then proximally along the exhaust passage.
• FIG. 31 illustrates a portion of acryotherapeutic device3100 similar to thedevice3000 ofFIG. 30 except with regard to a helical balloon shape. Thedevice3100 includes acooling assembly3102 at adistal portion3104 of anelongated shaft3106 defining an exhaust passage. Thedistal portion3104 can have astep3108, and thecooling assembly3102 can include anapplicator3110 having ahelical balloon3112 that defines an expansion chamber and has a balloonproximal portion3114 and a balloondistal portion3116. The balloonproximal portion3114 can be attached to an outside surface of thedistal portion3104 proximate a distal end of thedistal portion3104, thereby fluidly connecting thehelical balloon3112 to the exhaust passage. Thedevice3100 can further include asupply tube3117 having an angleddistal portion3118 Thehelical balloon3112 can be wrapped around thesupply tube3117 but also radially spaced apart from thesupply tube3117. Thesupply tube3117 can extend along the length of theshaft3106, out of theshaft3106, out of the balloonproximal portion3114, along a central axis of thehelical balloon3112, and into the balloondistal portion3116. The balloondistal portion3116 can be sealed around thesupply tube3117. The cooling assembly can further include anorifice3119 fluidly connecting thesupply tube3117 to the balloondistal portion3116. When thecooling assembly3102 is in a deployed state, refrigerant can flow from the balloondistal portion3116 to the balloonproximal portion3114 and then proximally along the exhaust passage. The wide helical diameter of thehelical balloon3112 can facilitate partial occlusion. For example, when thecooling assembly3102 is in the deployed state, thecooling assembly3102 can define a flow path (e.g., a blood flow path) between an outside surface of thesupply tube3117 and thehelical balloon3112.
• FIGS. 32A-32B illustrate a portion of acryotherapeutic device3200 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. Thecryotherapeutic device3200 shown inFIGS. 32A-32B includes acooling assembly3202 at adistal portion3204 of anelongated shaft3206 defining an exhaust passage. Thedistal portion3204 can have astep3207, and thecooling assembly3202 can include anapplicator3208. Thedevice3200 can further include anelongated shaping member3210 and asupply tube3212 having an angleddistal portion3214. Theapplicator3208 can include aballoon3216 with adistal seal3217. Theballoon3216 can extend around theelongated shaping member3210 and can define an expansion chamber. Thedistal seal3217 can be a flattened portion of theballoon3216 at which walls of theballoon3216 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.
• The shapingmember3210 can be configured to have a generally linear configuration when thecooling assembly3202 is in a delivery state and a curvilinear configuration when thecooling assembly3202 is in a deployed state. Thecooling assembly3202 can also include anorifice3218 at the distal end of the angleddistal portion3214. Thesupply tube3212 and theorifice3218 can be configured to direct expansion of refrigerant into theballoon3216 in a direction generally corresponding to a longitudinal orientation of theballoon3216 proximate theorifice3218. As shown inFIG. 32A, theballoon3216 has a shape in the deployed state at least partially corresponding to the curvilinear configuration of the shapingmember3210. The illustrated curvilinear configuration is generally helical, but also could be another shape, such as a serpentine shape. The shapingmember3210 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 shapingmember3210 and theballoon3216 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 theapplicator3208 to apply a desirable localized or overall treatment pattern. Similarly, the helical shape shown inFIG. 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 assemblies3202 configured in accordance with several embodiments of the present technology can includeballoons3216 that move into a pre-selected configuration corresponding to a shape of a shapingmember3210 before cryogenic cooling or during initial cryogenic cooling. When the cryogenic cooling causes the shapingmember3210 to lose some or all of its shaping properties, cryo-adhesion between theballoon3216 and external material (e.g., blood and/or tissue) can cause theballoon3216 to maintain its pre-selected configuration at least until the cryo-adhesion ends.
• In the embodiment illustrated inFIGS. 32A-32B, the shapingmember3210 is shown generally centered within the balloon, i.e., theballoon3216 is generally uniformly expanded around the shapingmember3210. Alternatively, the shapingmember3210 can have a different position within theballoon3216 when thecooling assembly3202 is in the deployed state. For example, the shapingmember3210 can be near an inner surface of theballoon3216. When the shapingmember3210 is spaced apart from walls of theballoon3216, theballoon3216 can dissipate pressure against a renal artery or renal ostium. As shown inFIG. 32A, the shapingmember3210 can extend through thedistal seal3217. Alternatively, the shapingmember3210 can be not attached to theballoon3216 and/or terminate at a portion of theballoon3216 proximal to thedistal seal3217. Furthermore, a distal portion of the shapingmember3210 can be configured to be spaced apart from a renal artery or renal ostium when thecooling assembly3202 is in the deployed state. In some embodiments, theballoon3216 is configured to generally uniformly expand around the shapingmember3210 without any internal support structures. Alternatively, theballoon3216 can include an internal structure (e.g., webbing) extending across an inner diameter of theballoon3216 and the shapingmember3210 can be attached to the internal structure at a position spaced apart from inner surfaces of theballoon3216. The internal structure, for example, can be a partition between separate balloons (e.g., as discussed below with reference toFIGS. 45A-46). In some embodiments, the cooling assembly includes a structure extending along a central axis of theballoon3216 in the deployed state. For example, thedistal portion3204 can extend along the central axis of theballoon3216 in the deployed state and theballoon3216 and the shapingmember3210 can connect to a lateral opening of thedistal portion3204. As another example, thedistal portion3204 can include a reduced-diameter extension extending along the central axis of theballoon3216 and another opening separate from the reduced-diameter extension fluidly connecting theballoon3216 to the exhaust passage. A structure extending along the central axis of theballoon3216 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).
• Thedevice3200 can be modified for use in non-cryotherapeutic applications. For example, thesupply tube3212 can be removed and thedevice3200 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, theballoon3216 can be non-occlusive in the deployed state, e.g., a blood flow path can be formed along a central axis of theballoon3216. In some non-cryotherapeutic applications, thedistal portion3204 can support a structure configured to execute a treatment (e.g., a thrombectomy) within a vessel while theballoon3216 anchors thedevice3200 to a vessel wall. In these and other embodiments, theballoon3216 advantageously can maintain thedistal portion3204 at a central position within a vessel.
• FIGS. 33A-33D illustrate a portion of acryotherapeutic device3300 that can have a pre-defined curved shape in a deployed configuration. Thedevice3300 includes acooling assembly3302 at adistal portion3304 of anelongated shaft3306 defining an exhaust passage. Thedistal portion3304 can have astep3307, and thecooling assembly3302 can include anapplicator3308 with aballoon3310 that can define an expansion chamber. Theballoon3310 can have a balloonproximal portion3312, a balloonmiddle portion3314, and a balloondistal portion3316. Thedevice3300 further includes asupply tube3318 extending along theshaft3306, and thecooling assembly3302 can have anorifice3320 at the distal end of thesupply tube3318 and within the balloonproximal portion3312. When thecooling assembly3302 is in a deployed state, theballoon3310 is curved along its length and has a generally concave first wall3322 (shown as a lower portion of the balloon inFIG. 33A) and a generally non-concave (e.g., convex) second wall3324 (shown as an upper portion of the balloon inFIG. 33A).
• The balloonproximal portion3312, the balloonmiddle portion3314, and the balloondistal portion3316 can be configured to contact partially circumferential portions of a renal artery or a renal ostium. For example, the balloonmiddle portion3314 can be configured to contact a renal artery or a renal ostium generally along thesecond wall3324 and generally not along thefirst wall3322 when thecooling assembly3302 is in a deployed state. The balloonproximal portion3312 and the balloondistal portion3316, for example, can be configured to contact a renal artery or a renal ostium generally along thefirst wall3322 and generally not along thesecond wall3324 when thecooling assembly3302 is in the deployed state. Due to this uneven pattern of contact, the curved shape of theballoon3310 can facilitate a desirable localized or overall treatment pattern.
• As best seen inFIGS. 33B-33C, theballoon3310 can include a reduced-elasticity portion3326 along thefirst wall3322 at the balloonmiddle portion3314. In the illustrated embodiment, the reduced-elasticity portion3326 can be a thicker portion of theballoon3310. As shown inFIG. 33D, theballoon3310 can be partially collapsed when thecooling assembly3302 is in the delivery state so as to fit within adelivery sheath3328. When thecooling assembly3302 is in the delivery state, the reduced-elasticity portion3326 can retain some curvature. Alternatively, the reduced-elasticity portion3326 can be generally flat. When thecooling assembly3302 is in a deployed state, portions of theballoon3310 other than the reducedelasticity portion3326, particularly portions of theballoon3310 along thesecond wall3324 at the balloonmiddle portion3314 can be configured to expand (e.g., compliantly expand) to a greater degree than the reduced-elasticity portion3326. In several embodiments, the reduced-elasticity portion3326 is generally non-compliant and a portion of theballoon3310 along thesecond wall3324 at the balloonmiddle portion3314 is generally compliant. Restriction associated with the reduced-elasticity portion3326 can facilitate curvature of theballoon3310 when thecooling assembly3302 is in the deployed state. The reduced-elasticity portion3326 can be configured to be recessed relative to a renal artery or a renal ostium when thecooling assembly3302 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 portion3326 can reduce its thermal conductivity, which can promote improve cooling efficiency and/or further facilitate a desirable localized or overall treatment pattern.
• FIG. 34 illustrates a portion of acryotherapeutic device3400 similar to thedevice3300 ofFIGS. 33A-33D except having a different support configuration. Thedevice3400 includes acooling assembly3402 having anapplicator3404 with aballoon3406 defining an expansion chamber. Thecooling assembly3402 also includes anelongated support member3408 having a curveddistal end3410. Theelongated support member3408 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, theelongated support member3408 can help to prevent theballoon3406 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.
• FIGS. 35A-35B illustrate a portion of acryotherapeutic device3500 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). Thedevice3500 shown inFIGS. 35A-35B includes acooling assembly3502 at adistal portion3504 of anelongated shaft3506 defining an exhaust passage. Thedevice3500 can include anelongated guide member3508 and asupply tube3512, and thecooling assembly3502 can include anorifice3514 at the distal end of thesupply tube3512. The cooling assembly can further include anapplicator3510 with aballoon3516 that can define an expansion chamber and can have a balloonproximal portion3518, a proximalintegral neck3520 attached to thedistal portion3504, and a distalintegral neck3522 attached to theguide member3508. Theballoon3516 can also have a constrained longitudinal portion3524 (FIG. 35B) and an expandable longitudinal portion3526 (FIG. 35B). The constrainedlongitudinal portion3524 can be at least partially attached to theguide member3508. For example, from the distalintegral neck3522 to the balloonproximal portion3518, an internal surface of theballoon3516 can be attached to theguide member3508. The expandablelongitudinal portion3526 can be spaced apart from theguide member3508 when thecooling assembly3502 is in a deployed state. The partially-constrained shape of theballoon3516 can be useful to facilitate a desirable localized or overall treatment pattern. Furthermore, the constrainedlongitudinal portion3524 can define at least a portion of a longitudinal flow path (e.g., a blood flow path) around theballoon3516. This can be useful, for example, to facilitate a level of occlusion at a treatment site, such as partial occlusion instead of full occlusion.
• FIG. 36 illustrates acryotherapeutic device3600 similar to thecryotherapeutic device3500 ofFIGS. 35A-35B, except having a different pattern of attachment between a balloon and a guide member.FIG. 36 can be considered as a substitute forFIG. 35B to illustrate a separate embodiment in which all elements of thecryotherapeutic device3500 shown inFIGS. 35A-35B are similar except for those shown differently inFIG. 36 relative toFIG. 35B. Thecryotherapeutic device3600 includes anelongated guide member3602 and aballoon3604 having radially spaced apart constrainedlongitudinal portions3506 and radially spaced apart expandedlongitudinal portions3508. AlthoughFIG. 36 shows two constrainedlongitudinal portions3606 and two expandedlongitudinal portions3608, a greater number of constrainedlongitudinal portions3606 and/or expandedlongitudinal portions3608 can be formed for example, by attaching theballoon3604 to theguide member3602 at a different number of radial segments of theguide member3602. Furthermore, the distribution of constrainedlongitudinal portions3606 and expandedlongitudinal portions3608 can be symmetrical or asymmetrical (e.g., along an axis parallel to the length of the guide member3602).
• FIG. 37 illustrates a portion of acryotherapeutic device3700 including a balloon having a loop shape. Thedevice3700 includes acooling assembly3702 at adistal portion3704 of anelongated shaft3706 defining an exhaust passage, as well as asupply tube3708. Thecooling assembly3702 includes anorifice3710 at the distal end of thesupply tube3708, and anapplicator3712 with aballoon3714 having afirst balloon segment3716 and asecond balloon segment3718. Thefirst balloon segment3716 has a firstproximal portion3720 and a firstdistal portion3722. Thesecond balloon segment3718 has a secondproximal portion3724 and a seconddistal portion3726. The first balloondistal portion3722 is fluidly connected to the seconddistal portion3726. When thecooling assembly3702 is in the deployed state, refrigerant can flow from the firstproximal portion3720, to the firstdistal portion3722, and then to the seconddistal portion3726. Upon reaching the seconddistal portion3726, the refrigerant can have exhausted some, most, or all of its capacity for cryogenic cooling. Accordingly, thesecond balloon segment3718 can serve primarily to exhaust refrigerant from the firstdistal portion3722 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-segment3716. In several alternative embodiments, thefirst balloon segment3716 and thesecond balloon segment3718 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, thesecond balloon segment3718 can thermally insulate a portion of a renal artery or a renal ostium at a treatment site from cryogenic temperatures within thefirst balloon segment3716. This can be useful, for example, to facilitate a desirable localized or overall treatment pattern.
Multiple Balloons
• 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.
• FIGS. 38A-38B illustrate a portion of acryotherapeutic device3800 that can have multiple primary balloons. Thedevice3800 includes acooling assembly3802 at adistal portion3804 of anelongated shaft3806 defining an exhaust passage. Thedistal portion3804 can have astep3807, and thedevice3800 can include anelongated guide member3808 and asupply tube3810. Thecooling assembly3802 can include anorifice3811 at the distal end of thesupply tube3810 and anapplicator3812 having elongatedballoons3814 positioned generally parallel to a length of thecooling assembly3802. Theballoons3814 have a sharedproximal portion3816 and are otherwise circumferentially distributed around theguide member3808. Theorifice3811 is within the sharedproximal portion3816 and theballoons3814, in conjunction with the sharedproximal portion3816, can define expansion chambers. When thecooling assembly3802 is in a deployed state, refrigerant expanded from thesupply tube3810 can enter the sharedproximal portion3816 and circulate within theballoons3814 to cause expansion thereof and cooling. Refrigerant can exit theballoons3814 also through the sharedproximal portion3816 and flow proximally along the exhaust passage. Theballoons3814 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 theballoons3814 can define at least a portion of a longitudinal flow path (e.g., a blood flow path) around theballoons3814. This can be useful, for example, to facilitate a level of occlusion at a treatment site, such as partial occlusion instead of full occlusion.
• FIGS. 39A-39C illustrate a portion of acryotherapeutic device3900 that can have multiple balloons having different levels of cooling. Thedevice3900 includes acooling assembly3902 at adistal portion3904 of anelongated shaft3906, anelongated guide member3907, and a plurality of supply tubes (individually identified as3908a-d). Thecooling assembly3902 can include a plurality of orifices (individually identified as3910a-d) at the distal ends of the supply tubes3908a-d, and anapplicator3912 including a plurality of elongated balloons (individually identified as3914a-dinFIGS. 39A and 39C). The balloons3914a-dare circumferentially distributed around theguide member3907 and individually include proximal necks3916 (FIG. 39A) that can fluidly connect the balloons3914a-dto the exhaust passage. Theorifices3910a,3910dhave larger free-passage areas than theorifices3910b,3910c. Similarly, thesupply tubes3908a,3908dhave smaller free-passage areas than thesupply tubes3908b,3908d. The balloons3914a-dare 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 theballoons3914a,3914dthan for theballoons3914b,3914c. This can cause differential cooling within theballoons3914a,3914drelative to theballoons3914b,3914c. For example, theballoons3914a,3914dcan be configured to circulate gaseous refrigerant at a lower temperature than theballoons3914b,3914c. In addition or alternatively, theballoons3914a,3914dcan be configured for generally surface-area limited cooling when thecooling assembly3902 is in the deployed state, while theballoons3914b,3914care configured for generally refrigerant-limited cooling when thecooling assembly3902 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.
• FIG. 40 illustrates acryotherapeutic device4000 similar to thecryotherapeutic device3900 ofFIGS. 39A-39C, except having a different mechanism for differential cooling.FIG. 40 can be considered as a substitute forFIG. 39B to illustrate a separate embodiment in which all elements of thecryotherapeutic device3900 shown inFIGS. 39A-39C are similar except for those shown differently inFIG. 40 relative toFIG. 39B. Thecryotherapeutic device4000 includes ashaft4002 havinginternal walls4004 dividing theshaft4002 into fluidly separate exhaust passages, andsupply tubes4006 individually within the exhaust passages. Thesupply tubes4006 have generally equal sizes and can have orifices (not shown) having generally equal sizes. Thecryotherapeutic device4000 also includes a plurality of pressure regulators (individually identified as4008a-d) in fluid communication with the exhaust passages. The pressure regulators4008a-dcan 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, thepressure regulators4008a,4008dcan maintain a first back pressure in the corresponding exhaust passages and balloons, and thepressure regulators4008b,4008ccan 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 thedevice3900 shown inFIGS. 39A-39C can be achieved.
• FIG. 41 illustrates a portion of acryotherapeutic device4100 that can have multiple helical balloons. Thedevice4100 includes acooling assembly4101 at a distal portion4102 of anelongated shaft4103 defining an exhaust passage, asupply tube4104, and afiller tube4105. Thecooling assembly4101 can include afirst supply orifice4106, asecond supply orifice4107, and a filler orifice4108 at the distal end of thefiller tube4105. Thecooling assembly4101 also includes anapplicator4109 having a plurality of helical balloons. In one embodiment, theapplicator4109 includes a firsthelical balloon4110 having a firstdistal portion4112 and a firstproximal portion4114, a second helical balloon4116 (shown stippled for clarity of illustration) having a seconddistal portion4118 and a secondproximal portion4120, and a thirdhelical balloon4122 having a third distal portion4124 and a thirdproximal portion4126. The first andsecond supply orifices4106,4107 can be fluidly connected to the firstdistal portion4112 and the third distal portion4124, respectively, and the first and thirdhelical balloons4110,4122 can define expansion chambers. The second-balloonproximal portion4120 can be sealed around thefiller tube4107 and fluidly connected to the filler orifice4108 and the secondhelical balloon4116 can define a filler chamber. When thecooling assembly4101 is in the deployed state, the secondhelical balloon4116 can be configured to be filled via thefiller tube4105. Refrigerant can expand into the firstdistal portion4112 and the third distal portion4124, and the first and thirdhelical balloons4110,4122 can provide primary cooling in separate helical patterns or a combined helical pattern. The secondhelical balloon4116 can thermally insulate portions of a renal artery or a renal ostium from cryogenic cooling of the first and thirdhelical balloons4110,4122. This can be useful, for example, to facilitate a desirable localized or overall treatment pattern. Furthermore, the interior space between thesupply tube4004 and the first, second, and thirdhelical balloons4110,4116,4122 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.
• FIG. 42 illustrates a portion of acryotherapeutic device4200 similar to thedevice4100 shown inFIG. 41, but having modified supply and exhaust configurations in the helical balloons. Thedevice4200 includes acooling assembly4202 at adistal portion4203 of anelongated shaft4204 defining an exhaust passage, anelongated guide member4205, and asupply tube4206. Thecooling assembly4202 can include asupply orifice4207 at the distal end of thesupply tube4206 and anapplicator4208 having a plurality of helical balloons. In one embodiment, theapplicator4208 includes a firsthelical balloon4210 having a firstdistal portion4212 and a firstproximal portion4214, a second helical balloon4216 (shown stippled for clarity of illustration) having a seconddistal portion4218 and a secondproximal portion4220, and a thirdhelical balloon4222 having a thirddistal portion4224 and a thirdproximal portion4226. The firstdistal portion4212 and the thirddistal portion4224 are fluidly connected to each other and to the seconddistal portion4218. The firstproximal portion4214 and the thirdproximal portion4226 are fluidly connected to the exhaust passage. When thecooling assembly4202 is in the deployed state, refrigerant can expand into the secondproximal portion4220 and the secondhelical balloon4216 can provide primary cooling in a helical pattern. The first and thirdhelical balloons4210,4222 can receive refrigerant exhaust from the seconddistal portion4218 and can thermally insulate portions of a renal artery or a renal ostium from cryogenic cooling within the secondhelical balloon4216. Relative to thecryotherapeutic device4200 shown inFIG. 41, thedevice4100 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.
• FIGS. 43A-43C illustrate a portion of acryotherapeutic device4300 that can include balloons that are movable relative to other portions of a cooling assembly. Thedevice4300 includes acooling assembly4301 at adistal portion4302 of anelongated shaft4303 defining an exhaust passage, as well as anelongated shaping member4304, afirst supply tube4305, and asecond supply tube4306. Thedistal portion4302 can have astep4307, and thecooling assembly4301 can include afirst orifice4308 at the distal end of thefirst supply tube4305, and asecond orifice4309 at the distal end of thesecond supply tube4306. Thecooling assembly4301 further includes anapplicator4310 with a firstelongated balloon4311 defining a first expansion chamber and a secondelongated balloon4312 defining a second expansion chamber. Thefirst balloon4311 has a firstproximal portion4314, a firstmiddle portion4315, and a firstdistal portion4316. Thesecond balloon4312 has a secondproximal portion4318, a secondmiddle portion4319, and a seconddistal portion4320. The first andsecond balloons4311,4312 haveinner sides4322 closest to the shapingmember4304 andouter sides4324 opposite theinner sides4322. The firstdistal portion4316 and the seconddistal portion4320 are attached to the shapingmember4304. In several embodiments, the shapingmember4304 also defines a guide lumen through which a guide wire can be threaded.
• As shown inFIG. 43C, when thecooling assembly4301 is in the deployed state, retracting the shapingmember4304 relative to theshaft4303 can cause the firstmiddle portion4315 and the secondmiddle portion4319 to laterally move away from the shapingmember4304. A portion of the firstmiddle portion4315 and/or a portion of the secondmiddle portion4319 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 inFIG. 43C, after the shapingmember4304 has retracted theinner sides4322 of the firstmiddle portion4315 and the secondmiddle portion4319 are generally concave along their lengths, while theouter sides4324 of the firstmiddle portion4315 and the secondmiddle portion4319 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.
• FIGS. 44A-44C illustrate a portion of acryotherapeutic device4400 similar to thecryotherapeutic device4300 shown inFIGS. 43A-43B, but having a greater number of elongated balloons and including a secondary balloon. Thedevice4400 includes adistal portion4402 of anelongated shaft4404 having astep4405 and defining an exhaust passage, acooling assembly4406 at thedistal portion4402, and anelongated shaping member4408. The shapingmember4304 can be solid or can define a lumen, such as a guide lumen through which a guide wire can be threaded. Thedevice4400 further includes afirst supply tube4410, asecond supply tube4414, a third supply tube (not shown), and afiller tube4416. Thecooling assembly4406 can include afirst supply orifice4418 at the distal end of thefirst supply tube4410, asecond supply orifice4420 at the distal end of thesecond supply tube4414, a third orifice (not shown) at the distal end of the third supply tube, and afiller orifice4422 at the distal end of thefiller tube4416. Thecooling assembly4406 also includes anapplicator4424 with an elongatedfirst balloon4426 defining a first expansion chamber, an elongatedsecond balloon4428 defining a second expansion chamber, an elongated third balloon4430 (FIG. 44B) defining a third expansion chamber, and an elongatedfourth balloon4432 defining a filler chamber. The first, second, andthird balloons4426,4428,4430 are fluidly connected to the first, second, andthird supply orifices4418,4420. The fourth balloon is fluidly connected to thefiller orifice4422 and is sealed around thefiller tube4416. The first, second, third, andfourth balloons4426,4428,4430,4432 are attached to the shapingmember4408 such that, as shown inFIG. 44C, when thecooling assembly4406 is in a deployed state, retracting the shapingmember4408 relative to theshaft4404 causes theapplicator4424 to laterally expand. The first, second, andthird balloons4426,4428,4430 can have heat-transfer portions with heat-transfer rates sufficient to cause therapeutically-effective renal nerve modulation. The first, second, andthird balloons4426,4428,4430 can be configured to provide primary cooling. Thefourth balloon4432 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 thecryotherapeutic device4300 shown inFIGS. 43A-43B and thecryotherapeutic device4400 shown inFIGS. 44A-44C. In addition to sizing, these configurations can facilitate other treatment objectives, such as a desirable localized or overall treatment pattern
• FIGS. 45A-45B illustrate a portion of acryotherapeutic device4500 including a primary balloon and a secondary balloon that can have different compositions. Thedevice4500 includes acooling assembly4502 at adistal portion4504 of anelongated shaft4506 defining an exhaust passage, asupply tube4508, and afiller tube4509. Thecooling assembly4502 includes asupply orifice4510 at the distal end of thesupply tube4508, and afiller orifice4514 at the distal end of thefiller tube4509. Thecooling assembly4502 also includes anapplicator4516 with afirst balloon4518 that defines an expansion chamber and asecond balloon4520 that can define a filler chamber. Thefirst balloon4518 has aproximal neck4522 within thedistal portion4504 fluidly connecting thefirst balloon4518 to the exhaust passage. The second balloon is sealed around thefiller tube4509 and fluidly connected to thefiller orifice4514. When thecooling assembly4502 is in a deployed state, thefirst balloon4518 can be configured to deliver primary cooling and thesecond balloon4520 can be a secondary balloon.
• In several embodiments, thefirst balloon4518 has a lower level of compliance and/or elasticity than thesecond balloon4520. For example, thefirst balloon4518 can be generally non-compliant and the second balloon can be generally compliant. Additionally, thefirst balloon4518 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. Thedevice4500 shown inFIGS. 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 thedevice4500 sized to fit within renal arteries or renal ostiums of different cross-sectional dimensions. Thefirst balloon4518 has generally the same size in bothFIG. 45B andFIG. 45C. Thesecond balloon4520, however, is compliantly expanded to a greater degree inFIG. 45C than inFIG. 45B. Even with the generally non-compliant expansion of thefirst balloon4518, the variable, compliant expansion of thesecond balloon4520 can move the first balloon into contact with an inner surface of a renal artery or a renal ostium. Compliant expansion of thesecond balloon4520 can be carefully controlled via thefiller tube4509 to prevent excessive expansive forces on the renal artery or the renal ostium.
• The enlargement inFIG. 45B-1 shows apartition4524 that includes a layer ofnon-compliant material4526 and a layer ofcompliant material4528. The layer ofnon-compliant material4526 can be a portion of thefirst balloon4518 and the layer ofcompliant material4528 can be a portion of thesecond balloon4520. In one embodiment, thefirst balloon4518 and thesecond balloon4520 can be attached together at thepartition4524, but in other embodiments the first andsecond balloon4518 and4520 are not attached to each other.
• FIG. 46 illustrates acryotherapeutic device4600 similar to thecryotherapeutic device4500 ofFIGS. 45A-45C, except having a different partition.FIG. 46 can be considered as a substitute forFIG. 45B to illustrate a separate embodiment in which all elements of thecryotherapeutic device4500 shown inFIGS. 45A-45C are similar except for those shown differently inFIG. 46 relative toFIG. 45B. Thecryotherapeutic device4600 includes afirst balloon4602, asecond balloon4604, and apartition4606 between thefirst balloon4602 and thesecond balloon4604. As shown in the enlargement inFIG. 46-1, thepartition4606 includes a single layer, which can be a non-compliant layer of the first balloon. In another embodiment, thepartition4606 can include a single layer that is a compliant layer of thesecond balloon4604. To construct thedevice4600, 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 inFIG. 46, thefirst balloon4602 can be a generally D-shaped balloon and thesecond balloon4604 can be a generally C-shaped balloon attached to a generally D-shaped balloon.
• Cryotherapeutic devices configured in accordance with several embodiments of the present technology can include helical primary balloons and non-helical secondary balloons.
• FIG. 47 illustrates a portion of acryotherapeutic device4700 including acooling assembly4702 at adistal portion4704 of anelongated shaft4706 defining an exhaust passage. Thedevice4700 also includes asupply tube4707. Thecooling assembly4702 includes anapplicator4708 with a helicalfirst balloon4710 having a firstproximal portion4712 and a firstdistal portion4714 and defining an expansion chamber. Thesupply tube4707 can extend into the firstproximal portion4712, and thecooling assembly4702 can have anorifice4718 at the distal end of thesupply tube4707 within the firstproximal portion4712. The firstproximal portion4712 is sealed around thesupply tube4707. Thecooling assembly4702 can further include asecond balloon4720 having a secondproximal portion4722 and a seconddistal portion4724 and defining an exhaust chamber. The seconddistal portion4724 can be fluidly connected to the firstdistal portion4714, and thefirst balloon4710 can wrap around thesecond balloon4720. The secondproximal portion4722 can be fluidly connected to the exhaust passage. When thecooling assembly4702 is in a deployed state, refrigerant can flow from the firstproximal portion4712 to the firstdistal portion4714 and then proximally through thesecond balloon4720. Back pressure from the refrigerant can cause thesecond balloon4720 to expand (e.g., compliantly expand), which can cause a helical diameter of thefirst balloon4710 to increase. This can be useful, for example, to facilitate sizing. In addition, the helical shape of thefirst balloon4710 can be useful, for example, to facilitate a desirable localized or overall treatment pattern.
• FIGS. 48A-48B illustrate a portion of acryotherapeutic device4800 having a helical primary balloon and a non-helical secondary balloon in a different configuration. Thedevice4800 includes acooling assembly4802 at adistal portion4804 of anelongated shaft4806 defining an exhaust passage. Thedistal portion4804 can have astep4807, and thecooling assembly4802 can include anapplicator4808 with a helicalfirst balloon4810 that defines an expansion chamber and has a firstproximal portion4812 and a firstdistal portion4814. Thedevice4800 also can include asupply tube4816 extending into the firstproximal portion4812, and thecooling assembly4802 can have anorifice4818 at the distal end of thesupply tube4816 within the firstproximal portion4812. The firstproximal portion4812 is sealed around thesupply tube4816. Thecooling assembly4802 can further include asecond balloon4820 having an integralproximal neck4822 attached to thedistal portion4804. Thesecond balloon4820 can define an exhaust chamber configured to expand (e.g., compliantly expand) in response to back pressure from refrigerant exhausted from thefirst balloon4810. Thefirst balloon4810 can be attached to an internal surface of thesecond balloon4820. Expansion (e.g., compliant expansion) of thesecond balloon4820 can cause a helical diameter of thefirst balloon4810 to increase, such as to move a curved portion of thefirst balloon4810 closer to an inner surface of a renal artery or a renal ostium. Positioning thefirst balloon4810 within thesecond balloon4820 can be useful, for example, to provide redundant containment of refrigerant within the vasculature.
• FIG. 49 illustrates a portion of acryotherapeutic device4900 including a helical primary balloon and a non-helical secondary balloon in another configuration. Thedevice4900 includes acooling assembly4902 at adistal portion4904 of anelongated shaft4905 defining an exhaust passage. Thedistal portion4904 can have astep4906 and a plurality ofexhaust openings4907. Thecooling assembly4902 can include anapplicator4908 with a helicalfirst balloon4910 that defines an expansion chamber and has a firstproximal portion4912 and a firstdistal portion4914. Thedevice4900 also can include asupply tube4916 that extends into the firstproximal portion4912, and thecooling assembly4902 can have anorifice4918 at the distal end of thesupply tube4916. The firstproximal portion4912 can be sealed around thesupply tube4916. Thecooling assembly4902 can further include asecond balloon4920 positioned around thedistal portion4904 and having an integralproximal neck4922 attached to thedistal portion4904. Thefirst balloon4910 can wrap around thesecond balloon4920 and the firstdistal portion4914 can be fluidly connected to thedistal portion4904 distal of thesecond balloon4920. When thecooling assembly4902 is in a deployed state, thesecond balloon4920 can be configured to passively receive refrigerant from the exhaust passage through theexhaust openings4907 and can be configured to expand (e.g., compliantly expand) in response to back pressure from refrigerant exhausted from thefirst balloon4910. Expansion (e.g., compliant expansion) of thesecond balloon4920 can cause a helical diameter of thefirst balloon4910 to increase, which can cause a portion (e.g., a curved portion) of thefirst balloon4910 to move closer to an inner surface of a renal artery or a renal ostium.
• FIG. 50 illustrates a portion of acryotherapeutic device5000 including a helical primary balloon and a non-helical secondary balloon in another configuration. Thedevice5000 includes acooling assembly5002 at adistal portion5003 of an elongated shaft defining an exhaust passage, afiller tube5004, afiller orifice5005 at the distal end of thefiller tube5004, and asupply tube5006. Thecooling assembly5002 includes asupply orifice5007 at the distal end of thesupply tube5006. Thesupply tube5006 can include acorner5008, such as an elbow, near thesupply orifice5007. Thecooling assembly5002 further includes anapplicator5009 with a helicalfirst balloon5010 that defines an expansion chamber and has a firstproximal portion5011 and a firstdistal portion5012. Thecooling assembly5002 can also include asecond balloon5014 having a secondproximal portion5016 and a seconddistal portion5018. The secondproximal portion5016 can be fluidly connected to thefiller orifice5005 and sealed around thefiller tube5004. The seconddistal portion5018 can be sealed around thesupply tube5006, but fluidly separate from the supply tube5024 and thefirst balloon5010. Thefirst balloon5010 can wrap around thesecond balloon5014 and be configured to receive refrigerant from thesupply tube5006 and to exhaust the refrigerant through the firstproximal portion5011 into the exhaust passage. Thesecond balloon5014 can be configured to receive filler material from thefiller tube5004 and expand (e.g., compliantly expand) causing a helical diameter of thefirst balloon5010 to increase, which can cause a portion (e.g., a curved portion) of thefirst balloon5010 to move closer to an inner surface of a renal artery or a renal ostium.
• FIG. 51 illustrates a portion of acryotherapeutic device5100 including a helical primary balloon and a non-helical secondary balloon in another configuration. Thedevice5100 includes acooling assembly5101 at adistal portion5102 of anelongated shaft5103 defining an exhaust passage, asupply tube5106, and afiller tube5108. Thedistal portion5102 can have astep5104 and anexit hole5105. Thecooling assembly5101 can include asupply orifice5107 at the distal end of thesupply tube5106, and afiller orifice5109 at the distal end of thefiller tube5108. Thecooling assembly5101 can further include anapplicator5110 with a helicalfirst balloon5111 that defines an expansion chamber and has a firstproximal portion5112 and a firstdistal portion5114. Thesupply tube5106 can extend from theexit hole5105 and extend into the firstproximal portion5112, and the firstproximal portion5112 can be sealed around thesupply tube5106. Thecooling assembly5101 can further include asecond balloon5116 around thedistal portion5102 and having an integralproximal neck5118 attached to thedistal portion5102. Thesecond balloon5116 can be configured to receive filler material from thefiller tube5108 and expand (e.g., compliantly expand) causing a helical diameter of thefirst balloon5111 to increase, which can cause a portion (e.g., a curved portion) of thefirst balloon5111 to move closer to an inner surface of a renal artery or a renal ostium.
Proximal Secondary Balloons
• 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.
• FIGS. 52A-52B illustrate a portion of acryotherapeutic device5200 including acooling assembly5202 and anocclusion member5204 longitudinally spaced apart along anelongated shaft5206 defining an exhaust passage. Theshaft5206 can have a first stepped-downportion5208, cooling-assembly exhaust portal5209 at the first stepped-downportion5208, a second stepped-downportion5210, and occlusion-member exhaust portals5211 at the second stepped-downportion5210. Thecooling assembly5202 and theocclusion member5204 can be positioned at the first stepped-downportion5208 and the second stepped-downportion5210, respectively. Thedevice5200 can include asupply tube5212, and thecooling assembly5202 can haveorifice5213 at the distal end of thesupply tube5212. Thecooling assembly5202 also can include anapplicator5214 with afirst balloon5215 that defines an expansion chamber. Thesupply tube5212 can angle out of theshaft5206 and into thefirst balloon5215. Theocclusion member5204 can include asecond balloon5216 defining an occlusion chamber. Thesecond balloon5216 can be configured to passively receive refrigerant from the exhaust passage through the occlusion-member exhaust portal5211 and can be configured to expand (e.g., compliantly expand) in response to back pressure from refrigerant exhausted from thecooling assembly5202. Both thecooling assembly5202 and theocclusion member5204 can be at least partially collapsible in a delivery state and are shown inFIGS. 52A-52B in an expanded state and a deployed state, respectively. In the expanded state, theocclusion member5204 can have a cross-sectional dimension configured to fully occlude a renal artery and/or a renal ostium.
• As shown inFIG. 52B, thedevice5200 can further include a firstelongated control member5218, a secondelongated control member5220, and acontrol tube5222 with a firstdistal branch5224 and a seconddistal branch5226. Theshaft5206 can further include a firstdistal attachment point5228, a seconddistal attachment point5230, and a flexingportion5232 between the first stepped-downportion5208 and the second stepped-downportion5210. The firstelongated control member5218 can extend along thecontrol tube5222, along the firstdistal branch5224, and attach to the firstdistal attachment point5228. The secondelongated control member5220 can extend along thecontrol tube5222, along the seconddistal branch5226, and attach to the seconddistal attachment point5230. Thedevice5200 can be configured such that increasing or decreasing tension of thefirst control member5218 and/or thesecond control member5220 can control deflection of theshaft5206. Theshaft5206 can be flexible at the flexingportion5232 to position the first balloon against a vessel wall or ostium. In addition to or instead of fully occluding the vessel or ostium, theocclusion member5204 can be configured in the expanded state to support theshaft5206 within a renal artery or a renal ostium to provide controlled repositioning of thecooling assembly5202 within the renal artery or the renal ostium. For example, thecooling assembly5202 can be repositioned to cause therapeutically-effective, cryogenic renal-nerve modulation at different portions of a renal artery or a renal ostium.
• FIG. 53 illustrates a portion of acryotherapeutic device5300 similar to thecryotherapeutic device5200 shown inFIGS. 53A-53B, but thedevice5300 has additional distal cooling and different supply and control configurations. Thedevice5300 includes acooling assembly5302 and anocclusion member5304 longitudinally spaced apart along anelongated shaft5306 defining an exhaust passage. Theshaft5306 can have adistal attachment point5307 and adistal tip portion5308 defining a distal expansion chamber. Thecooling assembly5302 includes anapplicator5310 having afirst balloon5312 defining an expansion chamber, and theocclusion member5304 includes asecond balloon5314 defining an occlusion chamber fluidly separate from the exhaust passage. Thedevice5300 further includes afiller tube5316 extending to thesecond balloon5314 and asupply tube5318 having alateral branch5320 extending to thefirst balloon5312 and an angleddistal portion5322 extending to thedistal tip portion5308. Theocclusion member5304 further includes afiller orifice5324 through which a filler material can be supplied to thesecond balloon5314. Thecooling assembly5302 further includes afirst supply orifice5326 configured to direct refrigerant expansion into thefirst balloon5312 and a second supply orifice5328 configured to direct refrigerant expansion into thedistal tip portion5308.
• Thedevice5300 further includes anelongated control member5330 and acontrol tube5332. Thecontrol member5330 can extend along thecontrol tube5332 and be attached to thedistal attachment point5307. Thedevice5300 can be configured such that increasing or decreasing tension of thecontrol member5330 can control deflection of theshaft5306. In addition to or instead of fully occluding a vessel or ostium, theocclusion member5304 can be configured in the expanded state to support theshaft5306 within a renal artery or a renal ostium to provide controlled repositioning of thecooling assembly5302 within the renal artery or the renal ostium. For example, thecooling assembly5302 can be repositioned to cause therapeutically-effective, cryogenic renal-nerve modulation at different portions of a renal artery or a renal ostium.
Alternative Cooling
• 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.
• FIG. 54 illustrates a portion of acryotherapeutic device5400 that can be configured for convective heat transfer without refrigerant phase-change. Thedevice5400 includes acooling assembly5402 at adistal portion5404 of anelongated shaft5406 defining an exhaust passage. Thecooling assembly5402 includes anapplicator5408 with aballoon5410 that defines a circulation chamber. Thedevice5400 also includes asupply tube5412 extending along the length of theshaft5406 and into theballoon5410, and thecooling assembly5402 includes anorifice5414 at the distal end of thesupply tube5412. In several embodiments, thesupply tube5412 is relatively large and configured to transport liquid refrigerant, and theorifice5414 is not configured to cause a pressure drop sufficient to evaporate a refrigerant. When thecooling assembly5402 is in a deployed state, theballoon5410 can be configured to be filled with refrigerant in at least a substantially liquid phase. The refrigerant can circulate from thesupply tube5412 to the exhaust passage.FIG. 54 includesarrows5416 indicating a direction of refrigerant flow through theballoon5410. The refrigerant can be a liquid having a low freezing point (e.g., ethyl alcohol) and can be transported through thesupply tube5412 at a cryogenic temperature. Convective heat transfer between the refrigerant and theballoon5410 can cool a renal artery or a renal ostium to cause therapeutically-effective renal nerve modulation.
• FIG. 55 illustrates a portion of acryotherapeutic device5500 that also can be configured for convective heat transfer without refrigerant phase-change. Thedevice5500 includes acooling assembly5502 at adistal portion5504 of anelongated shaft5506 including ashaft partition5508 dividing the shaft into a firstlongitudinal portion5510 defining supply lumen and a secondlongitudinal portion5512 defining an exhaust passage. Thecooling assembly5502 includes anapplicator5514 with aballoon5516 including aballoon partition5518 that defines a U-shaped chamber within theballoon5516. Theballoon5516 can be configured to circulate liquid refrigerant from the firstlongitudinal portion5510, through the U-shaped chamber, and into the secondlongitudinal portion5512.FIG. 55 includes anarrow5520 indicating a direction of refrigerant flow through theballoon5516.
• 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
• Features of the cryotherapeutic-device components described above and illustrated inFIGS. 1-5B and12-55 can be modified to form additional embodiments configured in accordance with the present technology. For example, thecryotherapeutic device1700 illustrated inFIGS. 17A-17B and other cryotherapeutic devices described above and illustrated inFIGS. 1-5B and12-55 without guide members can include guide members that extend near or through distal portions of balloons. Similarly, the cryotherapeutic devices described above and illustrated inFIGS. 1-5B and12-55 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.
• The cryotherapeutic-device components described above and illustrated inFIGS. 1-5B and12-55 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 inFIGS. 1-5B and12-55 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 inFIGS. 1-5B and12-55. This can be useful, for example, to make the balloons more compatible with extrusion manufacturing processes.
• Features of the cryotherapeutic-device components described above also can be interchanged to form additional embodiments of the present technology. For example, theinner balloon1514 of thecooling assembly1502 illustrated inFIG. 15A can be incorporated into thecooling assembly1902 shown inFIGS. 19A-19C. As another example, thefirst supply tube1218 with the first angleddistal portion1222 of thecryotherapeutic device1200 illustrated inFIG. 12 can be incorporated into thecooling assembly1702 illustrated inFIGS. 17A-17B, with the first angleddistal portion1222 configured to direct expansion of refrigerant between the thermally-insulative members1711.
Related Anatomy and Physiology
• 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.
• 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.
• 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.
• 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.
• 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.
• 1. The Sympathetic Chain
• As shown inFIG. 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.
• 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.
• 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.
• 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).
• 2. Innervation of the Kidneys
• AsFIG. 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.
• 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.
• 3. Renal Sympathetic Neural Activity
• 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.
• 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.
• 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.
• 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.
• 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.
• (i) Renal Sympathetic Efferent Activity
• 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.
• (ii) Renal Sensory Afferent Nerve Activity
• 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 inFIGS. 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.
• 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.
• B. Additional Clinical Benefits of Renal Denervation
• 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 inFIG. 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.
• C. Achieving Intravascular Access to the Renal Artery
• 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. AsFIG. 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.
• AsFIG. 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.
• 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.
• 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.
• D. Properties and Characteristics of the Renal Vasculature
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• As noted above, an apparatus positioned within a renal artery should conform to the geometry of the artery. Renal artery vessel diameter, D_RA, typically is in a range of about 2-10 mm, with most of the patient population having a D_RAof about 4 mm to about 8 mm and an average of about 6 mm. Renal artery vessel length, L_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.
• 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°-135°.
• 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 toFIGS. 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 inseveral embodiments 4 mm to 8 mm. Additionally, in any of the embodiments shown and described above with reference toFIGS. 1-55, the balloons can individually and/or collectively have a length of about 8 mm to about 15 mm, and inseveral embodiments 10 mm. For example, several specific embodiments of the devices shown inFIGS. 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 inFIGS. 1-55 can be sized to fit within a 6 Fr sheath, such as a 4 Fr shaft size.
CONCLUSION
• The above detailed descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.
• From the foregoing, it will be appreciated that specific embodiments of the technology have been described herein for purposes of illustration, but well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the technology. Where the context permits, singular or plural terms may also include the plural or singular term, respectively.
• Moreover, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

Claims (28)

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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 1 wherein the expansion chamber comprises a compliant material having a rupture pressure of at least 300 psi.

10. The cryotherapeutic device ofclaim 1 wherein the expansion chamber comprises a compliant material having a rupture pressure of at most 200 psi.

11. The cryotherapeutic device ofclaim 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 ofclaim 12 wherein the response time is less than 0.01 second.

14. The cryotherapeutic device ofclaim 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 ofclaim 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 ofclaim 14 wherein the pressure monitoring lumen has a length of at least 48 inches (122 cm).

17. The cryotherapeutic device ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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 ofclaim 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.

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