Patent Application
20150105764
The present invention is related to systems and methods for improving cardiac and/or renal function through neuromodulation, including disruption and termination of renal sympathetic nerve activity.
The kidneys are instrumental in a number of body processes, including blood filtration, regulation of fluid balance, blood pressure control, electrolyte balance, and hormone production. One primary function of the kidneys is to remove toxins, mineral salts, and water from the blood to form urine. The kidneys receive about 20-25% of cardiac output through the renal arteries that branch left and right from the abdominal aorta, entering each kidney at the concave surface of the kidneys, the renal hilum.
Blood flows into the kidneys through the renal artery and the afferent arteriole, entering the filtration portion of the kidney, the renal corpuscle. The renal corpuscle is composed of the glomerulus, a thicket of capillaries, surrounded by a fluid-filled, cup-like sac called Bowman's capsule. Solutes in the blood are filtered through the very thin capillary walls of the glomerulus due to the pressure gradient that exists between the blood in the capillaries and the fluid in the Bowman's capsule. The pressure gradient is controlled by the contraction or dilation of the arterioles. After filtration occurs, the filtered blood moves through the efferent arteriole and the peritubular capillaries, converging in the interlobular veins, and finally exiting the kidney through the renal vein.
Particles and fluid filtered from the blood move from the Bowman's capsule through a number of tubules to a collecting duct. Urine is formed in the collecting duct and then exits through the ureter and bladder. The tubules are surrounded by the peritubular capillaries (containing the filtered blood). As the filtrate moves through the tubules and toward the collecting duct, nutrients, water, and electrolytes, such as sodium and chloride, are reabsorbed into the blood.
The kidneys are innervated by the renal plexus which emanates primarily from the aorticorenal ganglion. Renal ganglia are formed by the nerves of the renal plexus as the nerves follow along the course of the renal artery and into the kidney. The renal nerves are part of the autonomic nervous system which includes sympathetic and parasympathetic components. The sympathetic nervous system is known to be the system that provides the bodies “fight or flight” response, whereas the parasympathetic nervous system provides the “rest and digest” response. Stimulation of sympathetic nerve activity triggers the sympathetic response which causes the kidneys to increase production of hormones that increase vasoconstriction and fluid retention. This process is referred to as the renin-angiotensin-aldosterone-system (RAAS) response to increased renal sympathetic nerve activity.
In response to a reduction in blood volume, the kidneys secrete renin, which stimulates the production of angiotensin. Angiotensin causes blood vessels to constrict, resulting in increased blood pressure, and also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water, which increases the volume of fluid in the body and blood pressure.
Congestive heart failure (CHF) is a condition that has been linked to kidney function. CHF occurs when the heart is unable to pump blood effectively throughout the body. When blood flow drops, renal function degrades because of insufficient perfusion of the blood within the renal corpuscles. The decreased blood flow to the kidneys triggers an increase in sympathetic nervous system activity (i.e., the RAAS becomes too active) that causes the kidneys to secrete hormones that increase fluid retention and vasorestriction. Fluid retention and vasorestriction in turn increases the peripheral resistance of the circulatory system, placing an even greater load on the heart, which diminishes blood flow further. If the deterioration in cardiac and renal functioning continues, eventually the body becomes overwhelmed, and an episode of heart failure decompensation occurs, often leading to hospitalization of the patient.
Hypertension is a chronic medical condition in which the blood pressure is elevated. Persistent hypertension is a significant risk factor associated with a variety of adverse medical conditions, including heart attacks, heart failure, arterial aneurysms, and strokes. Persistent hypertension is a leading cause of chronic renal failure. Hyperactivity of the sympathetic nervous system serving the kidneys is associated with hypertension and its progression. Deactivation of nerves in the kidneys via renal denervation can reduce blood pressure, and may be a viable treatment option for many patients with hypertension who do not respond to conventional drugs.
Devices, systems, and methods of the present invention are directed to modifying renal sympathetic nerve activity using cryotherapy. Embodiments of the present invention are directed to a cryotherapy balloon catheter apparatus that includes a flexible shaft comprising a proximal end, a distal end, and a lumen arrangement extending between the proximal and distal ends. A compliant balloon is provided at the distal end of the shaft and fluidly coupled to the lumen arrangement. The compliant balloon is arranged generally lengthwise along a longitudinal section of the distal end of the shaft and adapted to inflate in response to receiving pressurized cryogenic fluid and to deflate in response to removal of the cryogenic fluid. A hinge mechanism is provided on the flexible shaft proximal of the compliant balloon. The hinge mechanism is configured to facilitate preferential bending at the distal end of the shaft to aid in directing the compliant balloon into the renal artery from the abdominal aorta.
A compliant cryotherapy balloon of the present invention preferably comprises a distal balloon section dimensioned for placement within a renal artery and a proximal balloon section dimensioned to abut against an ostium of the renal artery and extend into at least a portion of the abdominal aorta. The compliant balloon preferably has a diameter that varies non-uniformly along a length of the compliant balloon, such that a diameter at the proximal balloon section is larger than a diameter of the distal balloon section.
Embodiments of a cryotherapy balloon catheter apparatus of the present invention may be configured to deliver cryogenic therapy to at least the ostium of the renal artery sufficient to terminate renal sympathetic nerve activity along at least the renal artery ostium. Embodiments of a cryotherapy balloon catheter apparatus may be configured to deliver cryogenic therapy to at least the ostium of the renal artery sufficient to cause neurotmesis of renal nerve fibers and ganglia at the ostium.
The above summary of the present invention is not intended to describe each embodiment or every implementation of the present invention. Advantages and attainments, together with a more complete understanding of the invention, will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.
While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It is to be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.
In the following description, references are made to the accompanying drawings which illustrate various embodiments of the invention. It is to be understood that other embodiments may be utilized, and structural and functional changes may be made to these embodiments without departing from the scope of the present invention.
The right and left kidneys are supplied with blood from the right and left renal arteries that branch from respective right and left lateral surfaces of the abdominal aorta 20. Each of the right and left renal arteries is directed across the crus of the diaphragm, so as to form nearly a right angle with the abdominal aorta 20. The right and left renal arteries extend generally from the abdominal aorta 20 to respective renal sinuses proximate the hilum 17 of the kidneys, and branch into segmental arteries and then interlobular arteries within the kidney 10. The interlobular arteries radiate outward, penetrating the renal capsule and extending through the renal columns between the renal pyramids. Typically, the kidneys receive about 20% of total cardiac output which, for normal persons, represents about 1200 mL of blood flow through the kidneys per minute.
The primary function of the kidneys is to maintain water and electrolyte balance for the body by controlling the production and concentration of urine. In producing urine, the kidneys excrete wastes such as urea and ammonium. The kidneys also control reabsorption of glucose and amino acids, and are important in the production of hormones including vitamin D, renin and erythropoietin.
An important secondary function of the kidneys is to control metabolic homeostasis of the body. Controlling hemostatic functions include regulating electrolytes, acid-base balance, and blood pressure. For example, the kidneys are responsible for regulating blood volume and pressure by adjusting volume of water lost in the urine and releasing erythropoietin and renin, for example. The kidneys also regulate plasma ion concentrations (e.g., sodium, potassium, chloride ions, and calcium ion levels) by controlling the quantities lost in the urine and the synthesis of calcitrol. Other hemostatic functions controlled by the kidneys include stabilizing blood pH by controlling loss of hydrogen and bicarbonate ions in the urine, conserving valuable nutrients by preventing their excretion, and assisting the liver with detoxification.
Also shown in
The autonomic nervous system of the body controls involuntary actions of the smooth muscles in blood vessels, the digestive system, heart, and glands. The autonomic nervous system is divided into the sympathetic nervous system and the parasympathetic nervous system. In general terms, the parasympathetic nervous system prepares the body for rest by lowering heart rate, lowering blood pressure, and stimulating digestion. The sympathetic nervous system effectuates the body's fight-or-flight response by increasing heart rate, increasing blood pressure, and increasing metabolism.
In the autonomic nervous system, fibers originating from the central nervous system and extending to the various ganglia are referred to as preganglionic fibers, while those extending from the ganglia to the effector organ are referred to as postganglionic fibers. Activation of the sympathetic nervous system is effected through the release of adrenaline (epinephrine) and to a lesser extent norepinephrine from the suprarenal glands 11. This release of adrenaline is triggered by the neurotransmitter acetylcholine released from preganglionic sympathetic nerves.
The kidneys and ureters (not shown) are innervated by the renal nerves 14. FIGS. 1 and 2A-2B illustrate sympathetic innervation of the renal vasculature, primarily innervation of the renal artery 12. The primary functions of sympathetic innervation of the renal vasculature include regulation of renal blood flow and pressure, stimulation of renin release, and direct stimulation of water and sodium ion reabsorption.
Most of the nerves innervating the renal vasculature are sympathetic postganglionic fibers arising from the superior mesenteric ganglion 26. The renal nerves 14 extend generally axially along the renal arteries 12, enter the kidneys 10 at the hilum 17, follow the branches of the renal arteries 12 within the kidney 10, and extend to individual nephrons. Other renal ganglia, such as the renal ganglia 24, superior mesenteric ganglion 26, the left and right aorticorenal ganglia 22, and celiac ganglia 28 also innervate the renal vasculature. The celiac ganglion 28 is joined by the greater thoracic splanchnic nerve (greater TSN). The aorticorenal ganglia 26 is joined by the lesser thoracic splanchnic nerve (lesser TSN) and innervates the greater part of the renal plexus.
A focal location for renal innervation is the ostia 19 of the renal arteries 12. The ostium 19 of the right renal artery 12 is shown generally in
Sympathetic signals to the kidney 10 are communicated via innervated renal vasculature that originates primarily at spinal segments T10-T12 and L1. Parasympathetic signals originate primarily at spinal segments S2-S4 and from the medulla oblongata of the lower brain. Sympathetic nerve traffic travels through the sympathetic trunk ganglia, where some may synapse, while others synapse at the aorticorenal ganglion 22 (via the lesser thoracic splanchnic nerve, i.e., lesser TSN) and the renal ganglion 24 (via the least thoracic splanchnic nerve, i.e., least TSN). The postsynaptic sympathetic signals then travel along nerves 14 of the renal artery 12 to the kidney 10. Presynaptic parasympathetic signals travel to sites near the kidney 10 before they synapse on or near the kidney 10.
With particular reference to
Smooth muscle cells can be stimulated to contract or relax by the autonomic nervous system, but can also react on stimuli from neighboring cells and in response to hormones and blood borne electrolytes and agents (e.g., vasodilators or vasoconstrictors). Specialized smooth muscle cells within the afferent arteriole of the juxtaglomerular apparatus of kidney 10, for example, produces renin which activates the angiotension II system.
The renal nerves 14 innervate the smooth muscle 34 of the renal artery wall 15 and extend lengthwise in a generally axial or longitudinal manner from the ostium 19 along the renal artery wall 15. The smooth muscle 34 surrounds the renal artery circumferentially, and extends lengthwise in a direction generally transverse to the longitudinal orientation of the renal nerves 14, as is depicted in
The smooth muscle 34 of the renal artery 12 is under involuntary control of the autonomic nervous system. An increase in sympathetic activity, for example, tends to contract the smooth muscle 34, which reduces the diameter of the renal artery lumen 13 and decreases blood perfusion. A decrease in sympathetic activity tends to cause the smooth muscle 34 to relax, resulting in vessel dilation and an increase in the renal artery lumen diameter and blood perfusion. Conversely, increased parasympathetic activity tends to relax the smooth muscle 34, while decreased parasympathetic activity tends to cause smooth muscle contraction.
Adjacent the intima 32 is the media 33, which is the middle layer of the renal artery 12. The media is made up of smooth muscle 34 and elastic tissue. The media 33 can be readily identified by its color and by the transverse arrangement of its fibers. More particularly, the media 33 consists principally of bundles of smooth muscle fibers 34 arranged in a thin plate-like manner or lamellae and disposed circularly around the arterial wall 15. The outermost layer of the renal artery wall 15 is the adventitia 36, which is made up of connective tissue. The adventitia 36 includes fibroblast cells 38 that play an important role in wound healing. A renal nerve 14 is shown proximate the adventitia 36, passing into the renal artery 12 via the ostium 19, and extending longitudinally along the renal artery wall. The main trunk of the renal nerves 14 generally lies in or on the adventitia of the renal artery, with certain branches coursing into the media to enervate the renal artery smooth muscle.
Embodiments of the present invention are directed to apparatuses and methods for delivering a cryogen primarily to an ostium of a renal artery in order to modify, disrupt, or terminate renal sympathetic nerve activity. Other embodiments are directed to apparatuses and methods for delivering a cryogen primarily to an ostium of a renal artery and secondarily to a portion of the renal artery wall in order to modify, disrupt, or terminate renal sympathetic nerve activity. Preferred embodiments are those that deliver a cryogen to the ostium of a renal artery and optionally also to a renal artery wall that irreversibly terminates renal sympathetic nerve activity.
A representative embodiment of an apparatus configured to modify, disrupt, or terminate renal sympathetic nerve activity using a cryogen in accordance with the present invention is shown in
As a result of the phase change and the Joule-Thompson effect, heat is extracted from the surroundings of the cryoballoon 60, thereby cooling the treatment portion of the cryoballoon 60 and aortal/renal tissue that is in contact with the treatment portion of the cryoballoon 60. The gas released inside the cryoballoon 60 may be exhausted through a separate exhaust lumen provided in the catheter 51. The pressure inside the cryoballoon 60 may be controlled by regulating one or both of a rate at which cryogenic fluid is delivered and a rate at which the exhaust gas is extracted.
It has been shown experimentally that at sufficiently low temperatures, the blood in contact with the cryoballoon's treatment portion will freeze, thereby acting as a thermally conducting medium to conduct heat away from adjacent blood, and the tissue at the ostium 19 and renal artery 12. The diameters and insulating properties of the cryoballoon 60 can be designed such that the ostium 19 is the primary target for treatment, and the middle region of the renal artery 12 may be a secondary target for treatment. Cryogenically treating the middle region of the renal artery 12 reduces the adverse impact on the distal and proximal portions of the renal artery 12. For example, the ostial and arterial balloons 62, 64 can be designed such that only partial contact with the renal artery wall is permitted and insulating material is placed elsewhere in order to reduce and control the region(s) that are subject to cryotherapy. Under-sizing the cryoballoon 60 can serve to reduce physical vessel trauma, which can be achieved by use of compliant materials in the construction of the cryoballoon 60.
The alignment element 72 may be a feature integral to the cryoballoon 60 (e.g., a thickened wall section or encapsulated elastic coupling element) or a separate element that is bonded, welded or otherwise affixed at the transition region of the cryoballoon 60. In some configurations, the alignment element 72 extends circumferentially around the transition region of the cryoballoon 60. In other configurations, an alignment element 72 is situated at one or more discrete locations (e.g., discontinuous locations) at or around the transition region of the cryoballoon 60.
For example, one or more alignment elements 72 may be situated at each of an inferior (lower) portion and a superior (upper) portion of the transition region of the cryoballoon 60, so as to contact inferior and superior portions of the ostium 19 of the renal artery 12, respectively.
The alignment element 72 is preferably formed of a thermally conductive material and/or has the property of moderating thermal conduction at the ostial treatment site. In some embodiments, the alignment element 72 is configured as a primary cryotherapy delivery component for cryogenically treating the ostium 72 of the renal artery 12. The alignment element 72 may be implemented to provide a thermal conduction path between a cryogen contained within the ostial balloon 62 (or catheter 51) and ostial tissue at the renal artery 12. In other configurations, the alignment element 72 may be implemented to include one or more hollow sections that receive a cryogen contained within the ostial balloon 62 (or catheter 51), providing direct cryotherapy to ostial tissue at the renal artery 12.
As is depicted in
The cryoballoon 62 shown in
In accordance with other embodiments, both the ostial balloon 62 and the arterial balloon 64 include cryotherapy delivery elements. In some embodiments, the ostial balloon 62 and the arterial balloon 64 are constructed as compliant balloons. In other embodiments, the ostial balloon 62 is constructed as a compliant balloon and the arterial balloon 64 is constructed as a non-compliant balloon. As will be discussed hereinbelow, the ostial balloon 62 may be constructed as a single balloon or have a multiple balloon construction. In a multiple balloon implementation, an inner ostial balloon contains a cryogen and an outer ostial balloon is inflatable using a passive fluid, such as saline.
At least the ostial balloon 62 (and both ostial and arterial balloons 62 and 64 in some embodiments) is constructed as a very low pressure system and/or can be undersized in comparison to dimensions of the renal artery 12. The cryoballoon 60 is preferably constructed as a compliant balloon as is known in the art. For example, cryoballoon 60 may comprise a compliant material configured to enable the cryoballoon 60 to inflate under a very low pressure, such as about 1 to 2 pounds per square inch (PSI) or less (e.g., 0.5 PSI or less) above an ambient pressure that is adjacent to and outside the cryoballoon 60. The compliancy of cryoballoon 60 readily allows at least the ostial balloon 62 to conform to irregularities in the shape of the ostium 19 and surrounding tissue of the aortal/renal vasculature, which results in more efficient delivery of cryotherapy to the target tissue (i.e., renal nerve fibers and renal ganglia).
All or a portion of the cryoballoon 60 (e.g., at least the ostial balloon 62, or both ostial and arterial balloons 62 and 54 in some embodiments) may be made of a highly compliant material that elastically expands upon pressurization. Because the cryoballoon 60 elastically expands from a deflated state to an inflated state, the cryoballoon 60 has an extremely low profile in the deflated state when compared to non-compliant or semi-compliant balloons. Use of high compliance materials in the construction of the cryoballoon 60, in combination with a hinge mechanism 56 built into the catheter 51, provides for enhanced efficacy and safety when attempting to navigate a cryoballoon catheter 50 of the present invention through a nearly 90 degree turn from the abdominal aorta 20 into the ostium 19 of the renal artery 12.
Suitable materials for constructing all or a portion of the cryoballoon 60 include thermoplastic or thermoplastic elastomers, rubber type materials such as polyurethanes, natural rubber, or synthetic rubbers. The resulting balloon may be crosslinked or non-crosslinked. Other suitable materials for constructing all or a portion of the cryoballoon 60 include silicone, urethane polymer, low durometer PEBAX, or an extruded thermoplastic polyisoprene rubber such as a low durometer hydrogenated polyisoprene rubber. These and other suitable materials may be used individually or in combination to construct the cryoballoon 60. Details of various materials suitable for constructing a cryoballoon 60 are disclosed in commonly owned U.S. Patent Publication No. 2005/0197668, which is incorporated herein by reference.
With continued reference to
In
By way of further example, the arterial balloon 64 can be constructed to provide preferential expansion of its longitudinal dimension, LA, dimension relative to expansion of its diameter, dA. For example, the arterial balloon 64 may be configured to expand along its longitudinal dimension, LA, by up to about 400% of its original length, while the diameter, dA, remains about the same size or expands up to about 20% of its original size. This preferential longitudinal expansion profile of the arterial balloon 64 allows for a more compact delivery device which would aid in deliverability. This preferential longitudinal expansion profile of the arterial balloon 64 also serves to reduce the circumferential pressure exerted on the renal artery wall by increasing the surface area of contact between the arterial balloon 64 and the renal artery wall.
In some embodiments, the diameter, do, of the cryoballoon 60 at the balloon's proximal end is between about 10% to about 100% greater than the diameter, dA, of the cryoballoon 60 at the balloon's distal end. In other embodiments, the diameter, do, of the cryoballoon 60 at the balloon's proximal end is between about 10% to about 400% greater than the diameter, dA, of the cryoballoon 60 at the balloon's distal end. In further embodiments, the diameter, dO, of the cryoballoon 60 at the balloon's proximal end is at least 200% greater than the diameter, dA, of the cryoballoon 60 at the balloon's distal end. These representative diameter relationships may be applicable to the cryoballoon 60 in a deflated configuration or when inflated at a therapeutic pressure.
According to some embodiments, a traction feature may be included on the arterial balloon 64. Various fraction feature implementations are contemplated for improving the traction between the arterial balloon 64 and renal artery wall tissue. A traction feature is preferably situated on, applied to, or incorporated in the outer surface of the arterial balloon 64 to reduce slippage or undesirable movement of the arterial balloon 64 within the renal artery 12, which could otherwise result in dislodgment of the arterial balloon 64 from a desired location within the renal artery 12. For example, and assuming the cryoballoon 60 is deployed as shown in
Employment of a traction feature, such as a gripping feature shown in
The representative embodiment illustrated in
The cryoballoon catheter 50 can be designed such that pre-inflation of the cryoballoon 60 with a syringe using saline or similar media can partially inflate the proximal ostial balloon 62 in order to seat the ostial balloon 62 against the ostium 19 of the renal artery 12 prior to applying the cryotherapy. Alternatively, a small volume of cryogenic fluid may be injected into the cryoballoon 60 for pre-inflation purposes (e.g., at a rate to slightly inflate the cryoballoon 60 but insufficient to implicate Joule-Thompson effect cooling). After positioning the ostial balloon 62 against the ostium 19 of the renal artery 12, cryogenic fluid is injected into the cryoballoon 60 to controllably initiate cryotherapy, causing both the ostial balloon 62 and the distal arterial balloon 64 to inflate. This can be accomplished, for example, by constraining the region near the transition location 72 between the ostial balloon 62 and the arterial balloon 64, such as by using balloon crimping methods, manual restrictions, folding methods, and/or physical flow restrictions. In some embodiments, the cryoballoon catheter 50 may comprise multiple balloons, some of which are configured for pressurization using a cryogenic fluid, while others are configured for pressurization using saline or other passive fluid. A pre-inflation technique discussed above may be used in single- and multiple-balloon cryotherapy balloon catheters of the present invention.
Marker bands 77 can be placed on one or multiple parts of the ostial and arterial balloons 62, 64 to enable visualization during the procedure. Other portions of the cryoballoon 60, such as the alignment element 72, may include a marker band, as can one or more portions of the catheter shaft 51 (e.g., at the hinge mechanism 56). The marker bands 77 may be solid or split bands of platinum or other radiopaque metal, for example. Radiopaque materials are understood to be materials capable of producing a relatively bright image on a fluoroscopy screen or another imaging technique during a medical procedure. This relatively bright image aids the user of the cryoballoon catheter 50 in determining its location.
As was discussed previously, the alignment element 72 is preferably formed of a thermally conductive material and/or has the property of moderating thermal conduction at the ostial treatment site. In the embodiment shown in
The inlet port 92 is fluidly coupled to a supply lumen 96 of the catheter 51, and the output port 94 is fluidly coupled to an exhaust lumen 98 of the catheter 51. A cryogenic fluid is delivered to the alignment element 72 from a cryogen source via the supply lumen 92 and inlet port 92, and exhaust gas (or liquid) is removed from the alignment element 72 via the outlet port 94 and exhaust lumen 98. In this configuration, the alignment element 72 provides direct cryotherapy to ostial tissue at the renal artery 12. In some configurations, the alignment element 72 may be built into the distal portion of the ostial balloon 62 or maybe a separate component that is affixed to the balloon arrangement subsequent to fabrication of the ostial and arterial balloons 62, 64.
The arterial balloon 64 of the cryoballoon arrangement 60 may be constructed to include cryotherapy elements that are arranged in accordance with a predetermined pattern for purposes of delivering patterned cryotherapy to the inner wall of the renal artery 12.
According to some embodiments, the outer surface of the arterial balloon 64 incorporates material with a relatively low thermal conductivity (e.g., thermally insulating material) that forms the main body of the arterial balloon 64. The treatment pattern 154 or pattern segments 154 are formed from relatively high thermally conductive material. In other embodiments, an inner layer of the arterial balloon 64 may incorporate a polymeric composite material with a low thermal conductivity, and the outer portion of the arterial balloon 64 may incorporate a patterned or apertured layer comprising a polymeric composite material with a low thermal conductivity. In such embodiments, regions of the inner layer with high thermal conductivity are exposed for thermally treating renal ostial and arterial tissue through apertures of the outer layer with low thermal conductivity.
In some embodiments, the outer balloon 64b may have a generally cylindrical outer profile. In other embodiments, the profile of the outer balloon 64b may have a fluted, wave, or other complex shape that is configured to contact a vessel's inner wall at longitudinally and circumferentially spaced-apart locations. Each of these contact locations of the outer balloon 64b preferably incorporates a treatment pattern segment or segments, and the effective coverage area (e.g., area of pattern structure or void) of the treatment pattern segments preferably completes at least one revolution or turn of the outer balloon 64b.
According to other embodiments, as shown in
A cryoballoon that incorporates a predetermined pattern of thermally active material or regions encompassing at least one complete turn or revolution of the cryoballoon advantageously facilitates a “one-shot” denervation therapy of the ostium 19 and renal artery 12 in accordance with embodiments of the present invention. The term “one-shot” treatment refers to treating the entirety of a desired portion of innervated vascular tissue (e.g., ostium 19 of the renal artery, renal artery 12) without having to move the cryoballoon arrangement to other vessel locations in order to complete the treatment procedure (as is the case for a step-and-repeat denervation therapy approach).
A one-shot treatment approach of the present invention advantageously facilitates delivery of denervation therapy that treats at least one location of each nerve fiber passing through the ostium 19 of the renal artery 12 and, in some embodiments, also those extending along the renal artery 12, without having to reposition the cryoballoon catheter 50 during denervation therapy delivery. Embodiments of the present invention allow a physician to position a cryoballoon catheter 50 at a desired vessel location, and completely treat innervated renal vasculature without having to move the cryoballoon catheter 50 to a new vessel location. A one-shot treatment approach of the present invention also facilitates delivery of cryogenic denervation therapy that treats one or more ganglia proximate the ostium 19 of the renal artery 12 without having to reposition the cryoballoon catheter 50 during denervation therapy delivery. It is to be understood that devices and methods that utilize a cryoballoon catheter 50 of the present invention provide advantages and benefits other than facilitating one-shot treatment of a vessel or ganglion, and that cryoballoon patterning that enables one-shot vessel or ganglion treatment is not a required feature in all embodiments.
As shown in
In this implementation, the amount of pressure necessary to achieve at least partial inflation of the distal section 64 is insufficient to fully inflate the proximal section 62, allowing for preferential expansion of the arterial balloon 64 into the renal artery 12 relative to expansion of the ostial balloon 62 within the aorta 20. Once the distal portion 64 of the cryoballoon 60 is inflated to the desired pressure or diameter, injection of additional pressurized fluid causes the pressure in the cryoballoon 60 to increase, resulting in further inflation and expansion of the proximal section 62 within the aorta 20. The dimensions of the arterial balloon 64 preferably allow for longitudinal expansion within the renal artery 12 during continued pressurization and expansion of the ostial balloon 62, with adequate space allotted for over-pressurization situations.
In other implementations, it may be desirable to provide equal or greater radial expansion of the ostial balloon 62 during balloon pressurization relative to radial and/or longitudinal expansion of the arterial balloon. This implementation may be useful in embodiments that only employ cryotherapy elements within the ostial balloon 62, with the arterial balloon 64 used primarily as positioning/stabilization element.
It is understood that differences in thickness between the distal section 64 and proximal section 62 of the cryoballoon 60 are selected to achieve desired inflation characteristics. For example, in one embodiment, the distal section 64 is about three-quarters to one-half the thickness of the proximal section 62. In another embodiment, the distal section 64 is about one-half to one-third the thickness of the proximal section 62. In other embodiments, the distal section 64 has about the same thickness of the proximal section 62. In further embodiments, at least a section of the proximal section 62 has a thickness equal to or less than at least a section of the distal section 64. Other thickness relationships between proximal and distal balloon portions 62, 64 are contemplated.
The materials used to construct the cryoballoon 60 can be selected to achieve desired expansion profiles for each of the ostial balloon 62 and the arterial balloon 64. For example, appropriate materials and thicknesses of such materials may be selected to achieve desired longitudinal and radial expansion characteristics of the ostial and arterial balloons 62, 64. It is noted that the thickness of the materials used for constructing the cryoballoon 60 may be different or the same for each material, or may vary as discussed above with reference to
The inner balloon 62a shown in
In
It will be appreciated that the embodiments shown in
A cryoballoon 60 of the present invention can be manufactured using various techniques, including molding techniques or solution casting methods, for example. According to one molding technique, gradient extruded tubes with a short transition length for two different proximal and distal material properties can be used. Cryoballoons 60 may be formed by combining materials with large differences in modulus or different levels of cross-linking Desired mechanical and thermal characteristics may be obtained by using materials with different properties (e.g., using filled or non-filled materials), or by use of tubes having different wall thicknesses.
Another molding technique involves forming balloons or portions of a balloon having different extruded tube wall thicknesses. A further approach involves forming different wall thickness tubes achieved after extrusion by removing a certain amount material from its outer diameter via a mechanical method, such as a grinding or laser abrasion process. Two or more different tubes having different wall thickness, material, and/or different inner/outer diameters, may be joined by forming a lap joint therebetween, such as by use of a melt process via thermal energy, laser energy, or ultrasonic energy. The resulting balloon tube can have different materials, and/or different wall thickness, and/or different inner/outer diameters to meet specified balloon shape requirements. Various balloon parts can be extruded or injection molded.
According to a representative solution casting technique, the balloons of a cryoballoon 60 can be manufactured with solution casting using thermoplastic or a thermoplastic elastomer, or rubbery type materials, such as polyurethanes, natural rubber, synthetic rubbers, silicone, or other appropriate material (e.g., low durometer material at least for the ostial balloon). The resulting balloon may be crosslinked or non-crosslinked. Other thin-wall fabrication techniques may be used to construct a cryoballoon 60 in accordance with embodiments of the present invention.
Turning now to
The cryoballoon 60 includes an ostial balloon 62 that has a flattened proximal section 70 relative to its distal treatment section. The flattened profile of the proximal section 70 serves to decrease the volume of the ostial balloon 62 within the lumen 21 of the aorta 20 when the cryoballoon catheter 50 is deployed and inflated at the ostium 19 of the renal artery 12, thereby reducing occlusion of the blood flowing through the aorta 20. The flattened profile of the proximal section 70 may be achieved by constructing this portion of the ostial balloon 62 with a wall thickness greater than that of the distal section, by use of a balloon construction material(s) of reduced elasticity relative to that used in the distal section, and/or by provision of thermal insulation that renders the proximal section 70 less resilient than the distal section of the ostial balloon 62.
An alignment element 72 is shown provided proximate a transition region between the ostial and arterial balloons 62, 64 of the cryoballoon 60. The alignment element 72 is preferably configured to facilitate proper positioning of the cryoballoon 60 at the renal artery during cryoballoon deployment. As was discussed previously, the alignment element 72 may be a feature integral to the cryoballoon 60 or a separate element that is bonded, welded or otherwise affixed at the transition region of the cryoballoon 60. The alignment element 72 may extend circumferentially around the transition region of the cryoballoon 60 or be situated at one or more discrete locations at or around the transition region of the cryoballoon 60. As was also discussed, the alignment element 72 is preferably formed of a thermally conductive material and/or has the property of moderating thermal conduction at the ostial treatment site. In some embodiments, the alignment element 72 is configured as a primary cryotherapy delivery component for cryogenically treating the ostium 72 of the renal artery 12, and may be constructed to facilitate flow of a cryogen therethrough.
In the cut-away portion of the cryoballoon 60 shown in
The catheter 51 may be formed to include an elongate core member 57 and a tubular member 53 disposed about a portion of the core member 57. The tubular member 53 may have a plurality of slots 61 formed therein. The slotted hinge region of the catheter 51 may be configured to have a preferential bending direction.
For example, and as shown in
A hinge arrangement 56 constructed to provide for a preferential bending direction allows a physician to more easily and safely navigate the cryoballoon catheter 50 to make the near 90 degree turn into the renal artery from the abdominal aorta 20. One or more marker bands may be incorporated at the hinge region 56 to provide visualization of this region of the catheter 51 during deployment. Details of useful hinge arrangements that can be incorporated into embodiments of a cryoballoon catheter 50 of the present invention are disclosed in U.S. Patent Publication Nos. 2008/0021408 and 2009/0043372, which are incorporated herein by reference. It is noted that the cryoballoon catheter 50 may incorporate a steering mechanism in addition to, or exclusion of, a hinge arrangement 56. Known steering mechanisms incorporated into steerable guide catheters may be incorporated in various embodiments of a cryoballoon catheter 50 of the present invention.
With the guide catheter 71 positioned near the ostium 19 of the renal artery 12, the cryoballoon catheter 50, in a collapsed configuration, is advanced through the lumen of the guide catheter 71. Marker bands provided on the arterial and ostial balloons 64, 62 of the cryoballoon 60 facilitates visualization of the cryoballoon catheter 50 when advancing the cryoballoon catheter 50 through the guide catheter 71. As is shown in
Further advancement of the cryoballoon catheter 50 (or retraction of the guide catheter 71) relative to the guide catheter 71 allows for an increase in bend angle at the hinge region 56, allowing the physician to safely advance the distal tip of the cryoballoon 60 into the ostium 19 of the renal artery lumen 13. As was discussed previously, the cryoballoon 60 may be slightly pressurized with saline or similar fluid to help seat the ostial balloon 62 against the ostium 19 of the renal artery 12. Pressurization of the arterial balloon 64 may also aid in cannulating the cryoballoon catheter 50 within the renal artery 12. The ostial balloon section 62 of the cryoballoon catheter 50 is preferably seated against the ostium 19, at which point cryogenic therapy may be initiated by the physician.
Embodiments of the present invention may be implemented to provide varying degrees of cryotherapy to the ostium 19 and other innervated renal vasculature. For example, embodiments provide for control of the extent and relative permanency of renal nerve impulse transmission interruption achieved by cryotherapy delivered using a cryoballoon catheter 50 of the present invention. The extent and relative permanency of renal nerve injury may be tailored to achieve a desired reduction in sympathetic nerve activity (including a partial or complete block) and to achieve a desired degree of permanency (including temporary or irreversible injury).
Returning to
Renal nerve fiber regeneration and re-innervation may be permanently compromised by applying cryogenic therapy to innervated renal vasculature, including the ostium 19 and renal ganglia, at a sufficiently low temperature to allow ice crystals to form inside nerve fibers 14b. Formation of ice crystals inside nerve fibers 14b of innervated renal arterial tissue and renal ganglia tears the nerve cells apart, and physically disrupts or separates the endoneurium tube, which can prevent regeneration and re-innervation processes. Delivery of cryogenic therapy to renal nerves 14 at a sufficiently low temperature in accordance with embodiments of the present invention can cause necrosis of renal nerve fibers 14b, resulting in a permanent and irreversible loss of the conductive function of renal nerve fibers 14b.
With continued reference to
In some embodiments, a cryoballoon catheter 50 of the present invention may be implemented to deliver a cryotherapy that causes transient and reversible injury to renal nerve fibers 14b. In other embodiments, a cryoballoon catheter 50 of the present invention may be implemented to deliver a cryotherapy that causes more severe injury to renal nerve fibers 14b, which may be reversible if cryotherapy is terminated in a timely manner. In preferred embodiments, a cryoballoon catheter 50 of the present invention may be implemented to deliver a cryotherapy that causes severe and irreversible injury to renal nerve fibers 14b, resulting in permanent cessation of renal sympathetic nerve activity. For example, a cryoballoon catheter 50 may be implemented to deliver a cryotherapy that causes formation of ice crystals sufficient to physically separate the endoneurium tube of the nerve fiber 14b, which can prevent regeneration and re-innervation processes.
By way of example, and in accordance with Seddon's classification as is known in the art, a cryoballoon catheter 50 may be implemented to deliver a cryotherapy that interrupts conduction of nerve impulses along the renal nerve fibers 14b by imparting damage to the renal nerve fibers 14b consistent with neruapraxia. Neurapraxia describes nerve damage in which there is no disruption of the nerve fiber 14b or its sheath. In this case, there is an interruption in conduction of the nerve impulse down the nerve fiber, with recovery taking place within hours to months without true regeneration, as Wallerian degeneration does not occur. Wallerian degeneration refers to a process in which the part of the axon separated from the neuron's cell nucleus degenerates. This process is also known as anterograde degeneration. Neurapraxia is the mildest form of nerve injury that may be imparted to renal nerve fibers 14b by use of a cryoballoon catheter 50 of the present invention.
A cryoballoon catheter 50 may be implemented to interrupt conduction of nerve impulses along the renal nerve fibers 14b by imparting damage to the renal nerve fibers consistent with axonotmesis. Axonotmesis involves loss of the relative continuity of the axon of a nerve fiber and its covering of myelin, but preservation of the connective tissue framework of the nerve fiber. In this case, the encapsulating support tissue 14c of the nerve fiber 14b are preserved. Because axonal continuity is lost, Wallerian degeneration occurs. Recovery from axonotmesis occurs only through regeneration of the axons, a process requiring time on the order of several weeks or months. Electrically, the nerve fiber 14b shows rapid and complete degeneration. Regeneration and re-innervation may occur as long as the endoneural tubes are intact.
A cryoballoon catheter 50 may be implemented to interrupt conduction of nerve impulses along the renal nerve fibers 14b by imparting damage to the renal nerve fibers 14b consistent with neurotmesis. Neurotmesis, according to Seddon's classification, is the most serious nerve injury in the scheme. In this type of injury, both the nerve fiber 14b and the nerve sheath are disrupted. While partial recovery may occur, complete recovery is not possible. Neurotmesis involves loss of continuity of the axon and the encapsulating connective tissue 14c, resulting in a complete loss of autonomic function, in the case of renal nerve fibers 14b. If the nerve fiber 14b has been completely divided, axonal regeneration causes a neuroma to form in the proximal stump.
A more stratified classification of neurotmesis nerve damage may be found by reference to the Sunderland System as is known in the art. The Sunderland System defines five degrees of nerve damage, the first two of which correspond closely with neurapraxia and axonotmesis of Seddon's classification. The latter three Sunderland System classifications describe different levels of neurotmesis nerve damage.
The first and second degrees of nerve injury in the Sunderland system are analogous to Seddon's neurapraxia and axonotmesis, respectively. Third degree nerve injury, according to the Sunderland System, involves disruption of the endoneurium, with the epineurium and perineurium remaining intact. Recovery may range from poor to complete depending on the degree of intrafascicular fibrosis. A fourth degree nerve injury involves interruption of all neural and supporting elements, with the epineurium remaining intact. The nerve is usually enlarged. Fifth degree nerve injury involves complete transection of the nerve fiber 14b with loss of continuity.
In some embodiments, cryotherapy delivered by a cryoballoon catheter 50 of the present invention may be controlled to achieve a desired degree of attenuation in renal nerve activity. Selecting or controlling cryotherapy delivered by the cryoballoon catheter 50 advantageously facilitates experimentation and titration of a desired degree and permanency of renal sympathetic nerve activity cessation.
In general, embodiments of a cryoballoon catheter 50 may be implemented to deliver cryogenic therapy to cause renal denervation at therapeutic temperatures ranging between approximately 0° C. and approximately −180° C. For example, embodiments of a cryoballoon catheter 50 may be implemented to deliver cryogenic therapy to cause renal denervation with temperatures at the renal nerves ranging from approximately 0° C. to approximately −30° C. at the higher end, and to about −140° C. to −180° C. at the lower end. Less robust renal nerve damage is likely for temperatures approaching and greater than 0° C., and more robust acute renal denervation is likely for temperatures approaching and less than −30° C., for example, down to −120 C. to −180 C. These therapeutic temperature ranges may be determined empirically for a patient, a patient population, or by use of human or other mammalian studies.
It has been found that delivering cryotherapy to the ostium of the renal artery and to the renal ganglia at a sufficiently low temperature with freeze/thaw cycling allows ice crystals to form inside nerve fibers 14b and disrupt renal nerve function and morphology. For example, achieving therapeutic temperatures that range from −30° C. to +10° C. at a renal nerve for treatment times of 30 seconds to 4 minutes and thaw times of about 1 to 2 minutes has been found to cause acute renal denervation in at least some of the renal nerves in a porcine model.
The representative embodiments described below are directed to cryoballoon catheters of the present invention configured for delivering cryogenic therapy to renal vasculature at specified therapeutic temperatures or temperature ranges, causing varying degrees of nerve fiber degradation. As was discussed above, therapeutic temperature ranges achieved by cryoballoon catheters of the present invention may be determined using non-human mammalian studies. The therapeutic temperatures and degrees of induced renal nerve damage described in the context of the following embodiments are based largely on cryoanalgesia studies performed on rabbits (see, e.g., L. Zhou et al., Mechanism Research of Cryoanalgesia, Neurological Research, Vol. 17, pp. 307-311 (1995)), but may generally be applicable for human renal vasculature. As is discussed below, the therapeutic temperatures and degrees of induced renal nerve damage may vary somewhat or significantly from those described in the context of the following embodiments based on a number of factors, including the design of the cryotherapy apparatus, duration of cryotherapy, and the magnitude of mechanical disruption of nerve fiber structure that can be achieved by subjecting renal nerves to freeze/thaw cycling, among others.
In accordance with various embodiments, a cryoballoon catheter 50 of the present invention may be implemented to deliver cryogenic therapy to cause a minimum level of renal nerve damage. Cooling renal nerve fibers to a therapeutic temperature ranging between about 0° C. and about −20° C. is believed sufficient to temporarily block some or all renal sympathetic nerve activity and cause a minimum degree of renal nerve damage, consistent with neurapraxia for example. Freezing renal nerves to a therapeutic temperature of −20° C. or higher may not cause a permanent change in renal nerve function or morphology. At therapeutic temperatures of −20° C. or higher, slight edema and myelin swelling may occur in some of the renal nerve fibers, but these conditions may be resolved after thawing.
In other embodiments, cooling renal nerve fibers to a therapeutic temperature ranging between about −20° C. and about −60° C. is believed sufficient to block all renal sympathetic nerve activity and cause an intermediate degree of renal nerve damage, consistent with axonotmesis (and possibly some degree of neurotmesis for lower temperatures of the −20° C. and −60° C. range), for example. Cooling renal nerves to a therapeutic temperature of −60° C. may cause freezing degeneration and loss of renal nerve conductive function, but may not result in a permanent change in renal nerve function or morphology. However, renal nerve regeneration is substantially slowed (e.g., on the order of 90 days). At a therapeutic temperature of −60° C., the frozen renal nerve is likely to demonstrate edema with thickening and loosening of the myelin sheaths and irregular swelling of axons, with Schwann cells likely remaining intact.
In further embodiments, cooling renal nerve fibers to a therapeutic temperature ranging between about −60° C. and about −100° C. is believed sufficient to block all renal sympathetic nerve activity and cause an intermediate to a high degree of renal nerve damage, consistent with neurotmesis, for example. Cooling renal nerves to a therapeutic temperature of −100° C., for example, causes swelling, thickening, and distortion in a large percentage of axons. Exposing renal nerves to a therapeutic temperature of −100° C. likely causes splitting or focal necrosis of myelin sheaths, and microfilament, microtubular, and mitochondrial edema. However, at a therapeutic temperature of −100° C., degenerated renal nerves may retain their basal membranes, allowing for complete recovery over time.
Although substantially slowed (e.g., on the order of 180 days), renal nerve regeneration may occur and be complete.
In accordance with other embodiments, cooling renal nerve fibers to a therapeutic temperature of between about −140° C. and about −180° C. is believed sufficient to block all renal sympathetic nerve activity and cause a high degree of renal nerve damage, consistent with neurotmesis for example. Application of therapeutic temperatures ranging between about −140° C. and about −180° C. to renal nerve fibers causes immediate necrosis, with destruction of basal membranes (resulting in loss of basal laminea scaffolding needed for complete regeneration). At these low temperatures, axoplasmic splitting, axoplasmic necrosis, and myelin sheath disruption and distortion is likely to occur in most renal nerve fibers. Proliferation of collagen fibers is also likely to occur, which restricts renal nerve regeneration.
It is believed that exposing renal nerves to a therapeutic temperature of about −140° C. or lower causes permanent, irreversible damage to the renal nerve fibers, thereby causing permanent and irreversible termination of renal sympathetic nerve activity. For some patients, exposing renal nerves to a therapeutic temperature ranging between about −120° C. and about −140° C. may be sufficient to provide similar permanent and irreversible damage to the renal nerve fibers, thereby causing permanent and irreversible cessation of renal sympathetic nerve activity. In other patients, it may be sufficient to expose renal nerves to a therapeutic temperature of at least −30° C. in order to provide a desired degree of renal sympathetic nerve activity cessation.
In preferred embodiments, it is desirable that the cryogen used to deliver cryotherapy to renal vasculature be capable of freezing target tissue so that nerve fibers innervating the ostium 19 and renal artery 12 are irreversibly injured, such that nerve conduction along the treated renal nerve fibers is permanently terminated. Suitable cryogens include those capable of cooling renal nerve fibers and renal ganglia to temperatures of at least about −120° C. or lower, preferably to temperatures of at least about −130° C. or lower, and more preferably to temperatures of at least about −140° C. or lower. It is understood that use of cryogens that provide for cooling of renal nerve fibers and renal ganglia to temperatures of at least about −30° C. may effect termination of renal sympathetic nerve activity with varying degrees of permanency.
The temperature ranges and associated degrees of induced renal nerve damage described herein are provided for non-limiting illustrative purposes. Actual therapeutic temperatures and magnitudes of resulting nerve injury may vary significantly from those described herein, and be impacted by a number of factors, including patient-specific factors (e.g., the patient's unique renal vasculature and sympathetic nervous system characteristics), therapy duration, frequency and duration of freeze/thaw cycling, structural characteristics of the cryotherapy balloon arrangement, type of cryogen used, and method of delivering cryotherapy, among others.
It is believed that higher degrees of renal nerve injury may be achieved by subjecting renal nerves to both cryotherapy and freeze/thaw cycling when compared to delivering cryotherapy without employing freeze/thaw cycling. Implementing freeze/thaw cycling as part of cryotherapy delivery to renal nerves may result in achieving a desired degree of renal sympathetic nerve activity attenuation (e.g., termination) and permanency (e.g., irreversible) at therapeutic temperatures higher than those discussed above. Various thermal cycling parameters may be selected for, or modified during, renal denervation cryotherapy to achieve a desired level of renal nerve damage, such parameters including the number of freeze/thaw cycles, high and low temperature limits for a given freeze/thaw cycle, the rate of temperature change for a given freeze/thaw cycle, and the duration of a given freeze/thaw cycle, for example. As was previously discussed, these therapeutic temperature ranges and associated degrees of induced renal nerve damage may be determined empirically for a particular patient or population of patients, or by use of human or other mammalian studies.
As is illustrated in
In some embodiments, the lumen arrangement includes a first lumen 166, for supplying a cryogen to the distal end of the catheter 51, and a second lumen 168, for returning the cryogen or exhaust gas to the proximal end of the catheter 51. The supply and return lumens 166, 168 are fluidly coupled to a cryoballoon 60 disposed at the distal end of the catheter 51. The cryogen may be circulated through the cryoballoon 60 via a hydraulic circuit that includes the cryogen source 142, supply and return lumens 166, 168, and the cryoballoon 60 disposed at the distal end of the catheter 51.
The supply lumen 166 may be supplied with a pressurized cryogen by the cryogen source 142 that both pressurizes the cryoballoon 60 and provides the cryogen to the cryoballoon 60. In some configurations, the catheter 51 may include one or more inflation lumens (e.g., lumens 167 and/or 169) that fluidly communicate with one or more dilation or stabilizing balloons disposed at the distal end of the catheter 51. In further embodiments, one or more cryoballoons and one or more dilation/stabilizing balloons may be incorporated at the distal end of the catheter 51, with appropriate supply, return, and pressurization lumens provided to fluidly communicate with the cryogen source 142 and an optional inflation fluid (e.g., saline) source 163. The catheter 51 may optionally include a main lumen 164 configured to receive a guide wire for embodiments that employ an over-the-wire deployment approach.
Embodiments of the present invention may incorporate selected balloon, catheter, lumen, control, and other features of the devices disclosed in the following commonly owned U.S. patents and published patent applications: U.S. Patent Publication Nos. 2009/0299356, 2009/0299355, 2009/0287202, 2009/0281533, 2009/0209951, 2009/0209949, 2009/0171333, 2009/0171333, 2008/0312644, 2008/0208182, 2008/0058791 and 2005/0197668, and U.S. Pat. Nos. 5,868,735, 6,290,696, 6,648,878, 6,666,858, 6,709,431, 6,929,639, 6,989,009, 7,022,120, 7,101,368, 7,172,589, 7,189,227, and 7,220,257, which are incorporated herein by reference. Embodiments of the present invention may incorporate selected balloon, catheter, and other features of the devices disclosed in U.S. Pat. Nos. 6,355,029, 6,428,534, 6,432,102, 6,468,297, 6,514,245, 6,602,246, 6,648,879, 6,786,900, 6,786,901, 6,811,550, 6,908,462, 6,972,015, and 7,081,112, which are incorporated herein by reference.
The catheter apparatus shown in
The following is a representative example of a cryotherapy procedure that employs a cryoballoon catheter 50 for denervating the ostium of the renal artery and, optionally, other innervated renal vasculature in accordance with embodiments of the present invention. During a first stage of the representative cryotherapy procedure, the cryoballoon catheter 50 is advanced to an aortal location proximate the ostium 19 of the renal artery 12, preferably as described previously with reference to
During a second stage of this representative example, an increased volume of cryogenic fluid can be supplied to the ostial balloon 62 in order to cool the treatment surface of the ostial balloon 62 via the Joule-Thomson effect. Cryogenic fluid may also be delivered to the arterial balloon 64 in order to cool the treatment surface of the arterial balloon 64. Alternatively, the arterial balloon 64 may be pressurized with saline or similar fluid, as discussed previously. During the second stage, the flow rate of cryogenic fluid through the cryoballoon 60 is regulated at a desired therapeutic rate, by which heat is extracted from the tissue surrounding the treatment region at a rate sufficient to cool a desired amount of ostial tissue to a therapeutically low temperature, such as a temperature between 0° C. to −180° C.
By controlling both the rate at which cryogenic fluid is delivered to the cryoballoon 60 and the rate at which exhaust gas or liquid is extracted from the cryoballoon 60, the cryogen source controller can develop and maintain a pressure inside the cryoballoon 60 at a number of different temperatures. Other useful devices and methodologies that may be implemented by a medical system 140 for controlling a cryotherapy delivered by a cryoballoon catheter 60 of the present invention are disclosed in commonly owned U.S. Published Patent No. 2009/0299356 and 2005/0197668, which are incorporated herein by reference.
Embodiments of a cryoballoon of the present invention may be implemented to incorporate features in addition to, or different from, those described hereinabove. For example, a cryoballoon may incorporate ribs, flutes, and other structural features that serve to facilitate preferential balloon expansion. Such ribbed and fluted structures may be formed by varying balloon wall thicknesses and/or incorporating different balloon materials at selected balloon locations. Ribs, flutes, and/or diversion channels or conduits may be incorporated into a cryoballoon for purposes of providing or increasing blood perfusion through or around the cryoballoon, particularly when the cryoballoon is inflated within the abdominal aorta and renal artery. Tissues in contact with flowing blood may be protected from thermal damage.
Non-uniformity of cryoballoon geometry may be achieved in various ways, including those discussed hereinabove. In some embodiments, a cryoballoon of the present invention may include an ostial balloon section having a greater circumferential surface area than an arterial balloon section. In other embodiments, the arterial balloon section may have a greater longitudinal circumferential surface area than the ostial balloon section. Embodiments of a cryoballoon of the present invention may have a generally triangular longitudinal cross-section, a generally T-shaped longitudinal cross-section, or a generally dog leg-shaped longitudinal cross-section, for example.
The foregoing description of the various embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teaching. For example, the devices and techniques disclosed herein may be employed in vasculature of the body other than renal vasculature, such as coronary and peripheral vessels and structures. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.
This application is a continuation of U.S. patent application Ser. No. 12/980,952, filed Dec. 29, 2010; which claims the benefit of Provisional Patent Application Ser. No. 61/291,476 filed on Dec. 31, 2009, to which priority is claimed under 35 U.S.C. §119(e), and which are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 61291476 | Dec 2009 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12980952 | Dec 2010 | US |
| Child | 14572042 | US |
