Spiral balloon catheter for renal nerve ablation

[0001] This application claims the benefit of U.S. Provisional Patent Application Ser. Nos. 61/369,447 filed Jul. 30, 2010 and 61/423,436 filed Dec. 15, 2010, to which priority is claimed pursuant to 35 U.S.C. §119(e) and which are hereby incorporated herein by reference in their entirety.

[0002] Embodiments of the disclosure are generally directed to apparatuses and methods for ablating target tissue of the body from within a vessel. Embodiments are directed to high frequency AC (e.g., radiofrequency (RF)) ablation catheters, systems, and methods that employ an ablation balloon catheter and a cooling arrangement that provides cooling to an inner wall of a target vessel during ablation. Various embodiments of the disclosure are directed to apparatuses and methods for ablating perivascular renal nerves, such as for treatment of hypertension.

[0003] Apparatuses, according to various embodiments, include a catheter comprising a flexible shaft having a lumen arrangement, a proximal end, a distal end, and a length sufficient to access at least the renal artery from a percutaneous access location of a patient. A balloon arrangement, which is dimensioned for deployment within the renal artery, is provided at the distal end of the shaft and fluidly coupled to the lumen arrangement. The balloon arrangement includes an elongated balloon body configured to complete at least one revolution of the shaft's distal end to form a spiral configuration thereabout. A mounting arrangement is provided at the distal end of the shaft and configured to maintain the balloon body in the spiral configuration during expansion and contraction of the balloon body.

[0004] An electrode arrangement is provided on the balloon body and defines one or more electrode contact regions of the balloon body. The electrode arrangement is configured to ablate perivascular nerves of the renal artery in a substantially spiral pattern. An optional cooling arrangement is configured to provide cooling to at least the electrode contact regions during ablation. At least the distal end of the shaft has a stiffness sufficient to oppose a force produced by the balloon body when inflated that tends to contort the shaft's distal end and to maintain a substantially constant apposition force between the electrode contact regions and an inner wall of the renal artery.

[0005] According to some embodiments, a catheter comprises a flexible shaft having a lumen arrangement, a proximal end, a distal end, and a length sufficient to access at least a target vessel within the body from a percutaneous access location of a patient. A balloon arrangement, dimensioned for deployment within the target vessel, is provided at the distal end of the shaft and fluidly coupled to the lumen arrangement. The balloon arrangement includes an elongated balloon body configured to complete at least one revolution of the shaft's distal end to form a spiral configuration thereabout. A mounting arrangement is provided at the distal end of the shaft and configured to maintain the balloon body in the spiral configuration during expansion and contraction of the balloon body.

[0006] An electrode arrangement is provided on the balloon body and defines one or more electrode contact regions of the balloon body. The electrode arrangement is configured to ablate target tissue of or adjacent the target vessel in a substantially spiral pattern. An optional cooling arrangement is configured to provide cooling to at least the electrode contact regions during ablation. In some configurations, at least the distal end of the shaft has a stiffness sufficient to oppose a force produced by the balloon body when inflated that tends to contort the shaft's distal end and to maintain a substantially constant apposition force between the electrode contact regions and an inner wall of the target vessel.

[0007] In other configurations, apparatuses include a flexible elongated member having a proximal end, a distal end, and a length sufficient to access at least the balloon arrangement. The elongated member is dimensioned for displacement within a lumen of the lumen arrangement and extendable to at least a portion of the shaft that includes the balloon body. At least the respective distal ends of the shaft and the elongated member have a combined stiffness sufficient to oppose a force produced by the balloon body when inflated that tends to contort the respective distal ends and to maintain a substantially constant apposition force between the electrode contact regions and an inner wall of the target vessel.

[0008] These and other features can be understood in view of the following detailed discussion and the accompanying drawings.

[0024] Embodiments of the disclosure are directed to apparatuses and methods for ablating perivascular renal nerves, such as for the treatment of hypertension. Embodiments of the disclosure are directed to improved cooled RF balloon ablation catheters and systems, and methods using same.

[0025] It has been difficult to effectively ablate perivascular renal sympathetic nerves by access from the renal artery, without causing injury to the renal artery wall. To reduce concern for potential stenotic narrowing of the renal artery after the ablation procedure, minimizing arterial injury during such an ablation procedure is important. Maintaining good contact with the artery wall during ablation of perivascular renal nerves has been difficult. If electrode-arterial wall tissue contact is variable, the tissue temperatures are not well controlled.

[0026] Consequently, an ablative temperature may not be achieved in the target tissue, while temperature in other areas, such as portions of the artery wall, may deviate enough to cause unwanted arterial tissue injury. For tortuous or diseased renal arteries in particular, there can be very poor electrode-arterial wall tissue contact to effectively and predictably transfer heat (for protective cooling of the artery wall) or electrical current (for ablation of the perivascular nerves) between an ablation device and the arterial tissue.

[0027] Embodiments of the disclosure are directed to an ablation catheter having a balloon arrangement that provides electrical isolation for an RF electrode arrangement and also provides for enhanced electrode contact with the renal artery wall. Embodiments described herein are directed to a vascular catheter with a helical balloon arrangement which provides for improved renal artery wall apposition for effective ablation while facilitating blood perfusion to the kidney.

[0028] In accordance with various embodiments, a helical balloon catheter includes a shaft having a dedicated lumen that extends along the catheter's length. The dedicated lumen of catheter's shaft is configured to receive a flexible elongated member, such as a guide wire, stylet, or similar member. In some embodiments, the portion of the catheter's shaft on which the helical balloon is attached can include a fixed wire. In such embodiments, the shaft proximal to the fixed wire can include a lumen dimensioned to receive a guide wire or stylet. The respective distal ends of the catheter's shaft and elongated member (or fixed wire) preferably have a combined stiffness sufficient to oppose a force produced by the balloon when inflated that tends to contort the respective distal ends of the shaft and elongated member/fixe wire and to maintain a substantially constant apposition force between the electrode contact regions and an inner wall of the renal artery.

[0029] According to some embodiments, the helical balloon can be attached to the catheter's shaft along the length of the balloon. For example, the helical balloon can be attached to the catheter's shaft using a continuous or non-continuous seam or web. The seam or web can have properties, such as thickness, dimensions, and/or stiffness, that vary along the length of the balloon which influences the configuration of the balloon as it is inflated and deflated (e.g., provide for a degree of circumferential and axial shifting of the balloon during inflation and deflation).

[0030] In other embodiments, the helical balloon can be attached to the catheter's shaft using intermittent “curtain ring” arrangements which allow the balloon to slide around the circumference and along a length of the shaft by a small amount as needed as the balloon configuration changes during inflation and deflation. In further embodiments, multiple non-sliding flexing tethers can be used to attach the balloon to the catheter's shaft to form a helix thereabout. The flexing tethers facilitate a degree of circumferential and longitudinal shifting of the balloon as the balloon configuration changes during inflation and deflation. According to various embodiments, the balloon is configured and/or attached to the catheter's shaft in a manner that facilitates a change in the coil pitch of the balloon during inflation to accommodate varying sizes and irregularities in renal artery diameter.

[0031] In some embodiments, the balloon can be constructed to have a pre-formed helical shape using appropriate fabrication techniques. Constructing a balloon to have a pre-formed helical shape provides for tuning of the mechanical properties of the balloon prior to attachment to the shaft of the catheter. For example, the balloon can be formed with portions of the balloon wall having varying thickness, which influences the deformation profile of the balloon as it is pressurized. In other embodiments, a generally cylindrical balloon can be attached to the catheter's shaft so that the balloon, when inflated, completes at least one complete revolution of the shaft. Multiple RF electrodes attached to the outer surface of the balloon are oriented towards the artery wall when deployed. The balloon can be used for cooling of the artery wall to reduce injury during RF ablation of the perivascular nerves.

[0032] A catheter, according to some embodiments, can include more than one helical balloon, with one balloon configured for cooling while the other is configured for RF ablation. In other embodiments, a balloon can be used for cooling media infusion, and another balloon used for removal of spent cooling media. Suitable cooling arrangements include relatively simple implementations that use a cooling fluid that passes through a recirculation path or a pass-through path into the arterial blood stream. In various pass-through cooling path configurations, the balloon catheter can include a distal protection filter to capture debris that may be produced or dislodged during a renal denervation procedure. Suitable cooling arrangements include relatively complex implementations that use a cryothermal phase-change mechanism.

[0033] A catheter employing a spiral RF ablation balloon in accordance with embodiments of the disclosure provides a single device that can accommodate a wide range of artery sizes and tortuosity. A helical ablation balloon as disclosed herein can provide for improved self-positioning and orientation. A helical ablation balloon of the present disclosure can provide more reliable geometry for improved impedance measurements or directional electrodes.

[0034] Embodiments disclosed herein are particularly well suited for use in the treatment of hypertension. 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.

[0035] 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.

[0036] 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.

[0037] 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.

[0038] 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.

[0039] 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.

[0040] 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.

[0041] FIG. 1 is an illustration of a right kidney 10 and renal vasculature including a renal artery 12 branching laterally from the abdominal aorta 20. In FIG. 1, only the right kidney 10 is shown for purposes of simplicity of explanation, but reference will be made herein to both right and left kidneys and associated renal vasculature and nervous system structures, all of which are contemplated within the context of embodiments of the disclosure. The renal artery 12 is purposefully shown to be disproportionately larger than the right kidney 10 and abdominal aorta 20 in order to facilitate discussion of various features and embodiments of the present disclosure.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] Also shown in FIG. 1 is the right suprarenal gland 11, commonly referred to as the right adrenal gland. The suprarenal gland 11 is a star-shaped endocrine gland that rests on top of the kidney 10. The primary function of the suprarenal glands (left and right) is to regulate the stress response of the body through the synthesis of corticosteroids and catecholamines, including cortisol and adrenaline (epinephrine), respectively. Encompassing the kidneys 10, suprarenal glands 11, renal vessels 12, and adjacent perirenal fat is the renal fascia, e.g., Gerota's fascia, (not shown), which is a fascial pouch derived from extraperitoneal connective tissue.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] With particular reference to FIG. 2A, the renal artery 12, as with most arteries and arterioles, is lined with smooth muscle 34 that controls the diameter of the renal artery lumen 13. Smooth muscle, in general, is an involuntary non-striated muscle found within the media layer of large and small arteries and veins, as well as various organs. The glomeruli of the kidneys, for example, contain a smooth muscle-like cell called the mesangial cell. Smooth muscle is fundamentally different from skeletal muscle and cardiac muscle in terms of structure, function, excitation-contraction coupling, and mechanism of contraction.

[0052] 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.

[0053] 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 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 FIG. 2B.

[0054] 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.

[0055] FIG. 3A shows a segment of a longitudinal cross-section through a renal artery, and illustrates various tissue layers of the wall 15 of the renal artery 12. The innermost layer of the renal artery 12 is the endothelium 30, which is the innermost layer of the intima 32 and is supported by an internal elastic membrane. The endothelium 30 is a single layer of cells that contacts the blood flowing though the vessel lumen 13. Endothelium cells are typically polygonal, oval, or fusiform, and have very distinct round or oval nuclei. Cells of the endothelium 30 are involved in several vascular functions, including control of blood pressure by way of vasoconstriction and vasodilation, blood clotting, and acting as a barrier layer between contents within the lumen 13 and surrounding tissue, such as the membrane of the intima 32 separating the intima 32 from the media 34, and the adventitia 36. The membrane or maceration of the intima 32 is a fine, transparent, colorless structure which is highly elastic, and commonly has a longitudinal corrugated pattern.

[0056] 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.

[0057] A perivascular region 37 is shown adjacent and peripheral to the adventitia 36 of the renal artery wall 15. A renal nerve 14 is shown proximate the adventitia 36 and passing through a portion of the perivascular region 37. The renal nerve 14 is shown extending substantially longitudinally along the outer wall 15 of the renal artery 12. The main trunk of the renal nerves 14 generally lies in or on the adventitia 36 of the renal artery 12, often passing through the perivascular region 37, with certain branches coursing into the media 33 to enervate the renal artery smooth muscle 34.

[0058] Embodiments of the disclosure may be implemented to provide varying degrees of denervation therapy to innervated renal vasculature. For example, embodiments of the disclosure may provide for control of the extent and relative permanency of renal nerve impulse transmission interruption achieved by denervation therapy delivered using a treatment apparatus of the disclosure. 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).

[0059] Returning to FIGS. 3B and 3C, the portion of the renal nerve 14 shown in FIGS. 3B and 3C includes bundles 14a of nerve fibers 14b each comprising axons or dendrites that originate or terminate on cell bodies or neurons located in ganglia or on the spinal cord, or in the brain. Supporting tissue structures 14c of the nerve 14 include the endoneurium (surrounding nerve axon fibers), perineurium (surrounds fiber groups to form a fascicle), and epineurium (binds fascicles into nerves), which serve to separate and support nerve fibers 14b and bundles 14a. In particular, the endoneurium, also referred to as the endoneurium tube or tubule, is a layer of delicate connective tissue that encloses the myelin sheath of a nerve fiber 14b within a fasciculus.

[0060] Major components of a neuron include the soma, which is the central part of the neuron that includes the nucleus, cellular extensions called dendrites, and axons, which are cable-like projections that carry nerve signals. The axon terminal contains synapses, which are specialized structures where neurotransmitter chemicals are released in order to communicate with target tissues. The axons of many neurons of the peripheral nervous system are sheathed in myelin, which is formed by a type of glial cell known as Schwann cells. The myelinating Schwann cells are wrapped around the axon, leaving the axolemma relatively uncovered at regularly spaced nodes, called nodes of Ranvier. Myelination of axons enables an especially rapid mode of electrical impulse propagation called saltation.

[0061] In some embodiments, a treatment apparatus of the disclosure may be implemented to deliver denervation therapy that causes transient and reversible injury to renal nerve fibers 14b. In other embodiments, a treatment apparatus of the disclosure may be implemented to deliver denervation therapy that causes more severe injury to renal nerve fibers 14b, which may be reversible if the therapy is terminated in a timely manner. In preferred embodiments, a treatment apparatus of the disclosure may be implemented to deliver denervation therapy that causes severe and irreversible injury to renal nerve fibers 14b, resulting in permanent cessation of renal sympathetic nerve activity. For example, a treatment apparatus may be implemented to deliver a denervation therapy that disrupts nerve fiber morphology to a degree sufficient to physically separate the endoneurium tube of the nerve fiber 14b, which can prevent regeneration and re-innervation processes.

[0062] By way of example, and in accordance with Seddon's classification as is known in the art, a treatment apparatus of the disclosure may be implemented to deliver a denervation therapy that interrupts conduction of nerve impulses along the renal nerve fibers 14b by imparting damage to the renal nerve fibers 14b consistent with neurapraxia. 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 treatment apparatus according to embodiments of the disclosure.

[0063] A treatment apparatus 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.

[0064] A treatment apparatus 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.

[0065] 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.

[0066] 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.

[0067] Turning now to FIGS. 4A and 4B, there is shown a distal portion of a catheter 100 which includes a spiral balloon 102 that supports an electrode arrangement 120 configured for ablating target tissue of the body according to various embodiments. The catheter 100 shown in FIGS. 4A and 4B is preferably implemented for intravascular delivery of a denervation therapy to a renal artery of a patient, although other vascular structures and target tissues are contemplated. The catheter 100 includes a lumen arrangement 105 and a flexible shaft 104 having a proximal end, a distal end, and a length sufficient to access at least the renal artery from a location external of the patient.

[0068] A balloon arrangement 102 is provided at the distal end of the shaft 104 and fluidly coupled to the lumen arrangement 105. In some embodiments, a proximal inlet 136 of the balloon arrangement 102 is fluidly coupled to a port arrangement provided in a sidewall of the shaft 104. In other embodiments, the proximal inlet 136 of the balloon arrangement 102 is fluidly coupled to a lumen 106 that extends along an exterior surface or side lumen of the shaft 104.

[0069] The balloon arrangement 102 shown in FIGS. 4A and 4B is preferably dimensioned for deployment within the renal artery. The balloon arrangement 102 includes an elongated balloon body 103 having a proximal end and a distal end. The balloon body 103 is arranged to complete at least one revolution of the shaft's distal end to form a spiral configuration thereabout. An attachment arrangement 140 is provided at the distal end of the shaft 104 and configured to maintain the balloon body 103 in the spiral configuration during expansion and contraction of the balloon body 103.

[0070] An electrode arrangement 120 is provided on the balloon body 103 and arranged to define one or more electrode contact regions of the balloon body 103. The electrode arrangement 120 is configured for ablation of perivascular nerves of the renal artery. In some embodiments, as shown in FIG. 4A, the electrode arrangement 120 includes a multiplicity of electrodes 120a arranged in a spaced-apart relationship to define a multiplicity of electrode contact regions of the balloon body 103. FIG. 5 is a rear view of a portion of the balloon body 103 shown in FIG. 4A.

[0071] In other embodiments, as shown in FIG. 4B, the electrode arrangement 120 includes at least one continuous ribbon electrode 120b arranged on the balloon body 103 to define one or more continuous electrode contact regions of the balloon body 103. The balloon body 103 can include electrically insulating material at or near regions of the balloon body 103 where the RF electrodes 120a/120b are situated. The electrically insulating material provides enhanced electrical isolation for the RF electrode arrangement 102.

[0072] The distal end of the shaft 104 preferably has a stiffness sufficient to oppose a force produced by the balloon body 103 when inflated that tends to contort the shaft's distal end and sufficient to maintain a substantially constant apposition force between the electrode contact region(s) of the balloon body 103 and an inner wall of the renal artery. A cooling arrangement is preferably deployed at the distal end of the catheter 100 and configured to provide cooling to at least the electrode contact region(s) during ablation.

[0073] Shaft 104 has a stiffness characterized by its section modulus defined as the product of the elastic modulus of the material (E) and the bending moment of inertial of the shaft (I). The modulus may range from a few thousand PSI for polymers or elastomers to 10 MPSI for nitinol in its linear phase and 30 MPSI for stainless steel.

[0074] Bending loads applied to the shaft 104 by the vessel, either directly or indirectly via the balloon arrangement 102, will cause a deflection of the shaft 104. The forces required to accomplish this deflection will generally be proportional to the 3^rd power of the length over which the forces are applied. Likewise, the balloon arrangement 102 will have its own characteristic stiffness. The contribution of the balloon arrangement 102 to the overall stiffness of the device depends on the pressure to which the balloon arrangement 102 is inflated and the manner in which it is attached to the shaft 104. If, for example, the balloon arrangement 102 is rigidly attached to the shaft 104, the result will be generally greater overall stiffness than if it loosely attached an allowed to move relative to the shaft 104. Likewise, if the balloon arrangement 102 is inflated to a high pressure, the balloon cross section will resist deformation under bending loads, resulting in a higher over all stiffness.

[0075] In addition to bending stress described above, pressure in the balloon arrangement 102 generates both hoop stresses and axial stresses. The hoop stress will be twice the longitudinal stress. The material of the balloon arrangement 102 will deform under this load, causing the balloon arrangement 102 to increase in both diameter and length. If the ends of the balloon arrangement 102 are constrained by the shaft 104, the increase in length will urge the balloon arrangement 102 into a more helical configuration. This necessitates a change in angle between the balloon arrangement 102 and shaft 104. This can be accommodated by both the elasticity of the material and the means of attachment of the balloon arrangement 102 to the shaft 104. Alternatively, if the ends of the balloon arrangement 102 are not constrained, the overall length of the device may increase. In this case, the angle between the balloon arrangement 102 and the shaft 104 may decrease. In either case, the ends of the balloon arrangement 102 may rotate along with the elongation to accommodate the change in length of the balloon arrangement 102.

[0076] If, for example, the balloon arrangement 102 is inflated to a lower pressure, the cross-section of the balloon arrangement 102 may deform or flatten under the load into a generally elliptical or kidney shaped profile. This will reduce the effective stiffness of the balloon arrangement 102, but the surface of the balloon arrangement 102, and therefore the electrodes, will still be in contact with the vessel wall.

[0077] It is preferred for the balloon arrangement 102 to be inflated to sufficient pressure to ensure that the shaft 104 will be perturbed from its natural trajectory substantially along the entire length of the balloon arrangement 102. Likewise, it is preferred that the shaft 104 be of sufficient stiffness that it maintains contact between the balloon arrangement 102 and the vessel wall, while not as stiff as to unacceptably deform the renal vasculature.

[0078] The renal arteries 12 also exhibit resistance to bending, but are additionally constrained by surrounding connective tissue and contact with adjacent organs. When deployed in the renal artery 12, the shaft 104, balloon arrangement 102, arteries, and surrounding tissues will deform until a state of equilibrium is reached. Usually this will result in the shaft 104 taking a generally straighter path than the artery.

[0079] According to some embodiments, a flexible elongated member (e.g., guide wire 112 or a stylet) is provided that has a proximal end, a distal end, and a length sufficient to access at least the renal artery from a location external of the patient. The elongated member 112 is dimensioned for displacement within a lumen of the lumen arrangement 105 that extends between the distal and proximal ends of the shaft 104 including a portion of the shaft 104 that includes the balloon body 103. At least the respective distal ends of the shaft 104 and elongated member 112 have a combined stiffness sufficient to oppose a force produced by the balloon body 103 when inflated that tends to contort the respective distal ends of the shaft 104 and elongated member 112 and to maintain a substantially constant apposition force between the electrode contact regions and an inner wall of the renal artery. The behavior of the system will be as described above, but the stiffness of the shaft 104 will be the sum of the stiffnesses of the shaft 104 and the guide wire 112. If, instead, the wire is a fixed wire rigidly attached to the shaft 104, then the stiffness will be that of a composite beam comprising the wire and the shaft 104.

[0080] The balloon body 103 can be configured as a semi-compliant balloon in various embodiments. In other embodiments, the balloon body 103 can be configured as a non-compliant balloon. In the embodiments illustrated in FIGS. 4A and 4B, the balloon 102 is shown to have a generally planar surface profile. In certain embodiments, such as that illustrated in FIG. 4C, the balloon 102 may have an undulating profile. The balloon 102 shown in FIG. 4C can be formed to include a pre-formed undulating shape for example.

[0081] The undulating profile of the helical balloon 102 shown in FIG. 4C may be formed by constructing the helical balloon body 103 to have a fluted, wave, or other complex shape that is configured to contact a vessel's inner wall at longitudinally and, if desired, circumferentially spaced-apart locations. At least some of these contact locations of the helical balloon body 103 preferably incorporate an electrode 120, which aids in establishing an maintaining good mechanical contact between the electrodes 120 and the vessel's inner wall.

[0082] FIG. 6 illustrates an ablation balloon catheter in accordance with various embodiments. The catheter 100 shown in FIG. 6 includes a helical balloon 102 affixed to a distal end of the shaft 104 of the catheter 100. FIG. 7 shows a cross section of the shaft 104 of the balloon catheter of FIG. 6, which is shown to include a lumen arrangement 105. The lumen arrangement 105 includes a conductor lumen 113, a supply lumen 106, a return lumen 108, and a guide wire lumen 111.

[0083] The guide wire lumen 111 is dimensioned to receive a guide wire or other elongated navigation assist member that can be used by the clinician to facilitate delivery of the balloon 102 into the renal artery. In the configuration shown in FIG. 6, the guide wire lumen 111 defines an open lumen of the shaft 104, which allows for advancement of a guide wire 112 therethrough for navigating the balloon 102 to the renal artery. After the guide wire 112 is positioned within the renal artery, the balloon catheter 100 is advanced along the guide wire 112 and delivered to the lumen of the renal artery using an over-the-wire delivery technique. In some approaches, the guide wire 112 can be retracted after balloon catheter deployment in the renal artery. In other approaches, the guide wire or a different elongated member can be used to alter the effective stiffness of the shaft 104 relative to contorting forces produced by the helical balloon 102 when inflated.

[0084] One or more electrical conductors defining a conductor arrangement 110 extend at least partially along the shaft 104 via the conductor lumen 113 and terminate proximate or within the balloon body 103. The conductor lumen 113 may include a layer of electrically insulating material and/or the one or more conductors disposed in the conductor lumen 113 may each include an insulating layer. Each of the electrodes 120 supported by the balloon body 103 is connected to the electrical conductor(s) 110 via respective electrode conductors 131. The electrical conductor(s) 110 are configured to conduct RF energy received from an external energy source (not shown) to the electrodes 120 sufficient to ablate perivascular renal nerves adjacent to and/or innervating the renal artery.

[0085] The electrodes 120 are preferably situated on the balloon body 103 so that each electrode 120 faces toward the target tissue and is moved radially outward to a tissue contacting position when the helical balloon 102 is inflated. Each electrode 120, for example, can be positioned at a mid-point location of a balloon segment defined between two adjacent and spaced-apart balloon-shaft attachment locations. Properly locating the electrodes 120 on the balloon body surface provides for establishing and maintaining a reliable electrode-tissue interface during renal nerve ablation.

[0086] A cooling arrangement of the catheter 100 is configured to receive and return a thermal transfer fluid via the lumen arrangement 105. The cooling arrangement includes supply and return lumens 106, 108 that deliver the thermal transfer fluid to the inlet 136 to the balloon 102 and remove spent thermal transfer fluid to the inlet 136 from the balloon 102, respectively. The supply and return lumens 106, 108 are respectively coupled to supply and return connectors of an external coolant source situated at the proximal end of the catheter 100.

[0087] The balloon 102 shown in FIG. 6 incorporates a supply lumen 106 fluidly coupled to an inlet 136 of the balloon 102. A return lumen 108 extends along the shaft 104 between the balloon 102 and a proximal end of the shaft 104. A thermal transfer fluid is delivered to the inlet 136 via the supply lumen 106 and enters the balloon 102. The return lumen 106 is fluidly coupled to one or more outlet ports 138 through which spent thermal transfer fluid passes and exits the balloon 102.

[0088] The supply and return lumens 106, 108 are respectively coupled to supply and return couplings of an external coolant source. The volumetric flow rate of thermal transfer fluid through the balloon 102 is regulated by the external coolant source. For example, the amount of pressurization of the balloon 102 and the rate of thermal transfer fluid through the balloon 102 can be regulated by appropriately controlling the pressure and/or flow rate of the fluid respectively delivered to the supply lumen 106 and removed from the return lumen 106 at the external coolant source.

[0089] In some embodiments, the cooling arrangement of the catheter 100 is configured to receive a thermal transfer fluid that is circulated through the balloon body 103 via the supply and return lumens 106, 108. Suitable thermal transfer fluids include cooled saline, cooled saline and ethanol mixture, or D5W, for example.

[0090] In other embodiments, the cooling arrangement of the catheter 100 can include a cryothermal phase-change mechanism. A thermal transfer fluid (e.g., a cryogen), for example, is delivered to the balloon body 103 via the supply lumen 106. When released inside the balloon body 103, the thermal transfer fluid undergoes a phase change that cools the treatment portions of the balloon body 103 by absorbing the latent heat of vaporization from the tissue surrounding the balloon 102, and by cooling of the vaporized gas as it enters a region of lower pressure inside the balloon body 103 (the Joule-Thomson effect).

[0091] As a result of the phase change and the Joule-Thompson effect, heat is extracted from the surroundings of the balloon body 103, thereby cooling the treatment portion of the balloon 102 and renal tissue that is in contact with the treatment portion of the balloon 102. The gas released inside the balloon body 103 is exhausted through the return lumen 108. The pressure inside the balloon 102 may be controlled by regulating one or both of a rate at which the thermal transfer fluid is delivered and a rate at which the exhaust gas is extracted. Suitable thermal transfer fluid include Freon or other fluorocarbon refrigerants, and nitrous oxide.

[0092] Another cooling mechanism involves the shape of the helical balloon ablation catheter 100, which allows for perfusion of blood through the renal artery during the ablation procedure. Blood passing through gaps resulting from the helical shape of the balloon 102 provides cooling at the electrode-tissue interface during renal nerve ablation.

[0093] A further cooling mechanism involves passing a biocompatible heat transfer fluid through a cooling structure of the balloon 102 and discharging spent heat transfer fluid into the arterial blood stream. As discussed previously, the balloon catheter 100 can include a distal protection filter to capture any debris in the heat transfer fluid prior to discharging the spent heat transfer fluid into the arterial blood stream.

[0094] FIG. 8 illustrates the balloon arrangement 102 of a catheter 100 in accordance with embodiments that include a multiplicity of balloons structures dimensioned for deployment within a target vessel, such as a renal artery. The embodiment illustrated in FIG. 8 includes an outer helical balloon 151 configured for delivering RF ablation therapy to target tissue from within the target vessel, and an inner helical balloon 153 configured to provide cooling to the inner wall of the target vessel during ablation therapy delivery.

[0095] The outer helical balloon 151 of the catheter 100 supports an electrode arrangement, which is shown to include a number of discrete RF electrodes 120 arranged in a spaced-apart relationship about the periphery of the outer helical balloon 151. The electrodes are electrically coupled to a conductor arrangement in a manner previously described (but not shown in FIG. 8 for purposes of simplicity of explanation).

[0096] In some embodiments, the outer helical balloon 151 may have a generally cylindrical outer profile or an undulating profile. For example, the profile of the outer helical balloon 151 may have a fluted, wave, or other complex shape that is configured to contact a vessel's inner wall at longitudinally and, if desired, circumferentially spaced-apart locations. At least some of these contact locations of the outer helical balloon 151 preferably incorporate an electrode 120, so that effective coverage area of the electrode distribution along the outer helical balloon 151 completes at least one revolution or turn of the outer helical balloon 151.

[0097] The inner balloon 153 serves as a cooling balloon, through which a thermal transfer medium is communicated. In some embodiments, a thermal transfer fluid (e.g., cooled saline or D5W) is circulated through the inner balloon 153 via supply and return lumens (not shown for simplicity) in a manner previously described. In other embodiments, a cryothermal phase-change mechanism is employed in the cooling arrangement, which exploits the Joule-Thomson effect cooling to lower the temperature of the inner wall of the target vessel during ablation.

[0098] In accordance with other embodiments, the outer helical balloon 151 serves as both an ablation balloon and cooling balloon, through which a thermal transfer medium is communicated. In these embodiments, the outer helical balloon 151 is configured for infusion of a cooling media, and the inner helical balloon 153 is configured for exhausting spent cooling media. The outer and inner balloon 153, 151 can be fluidly coupled in various ways, including via a port arrangement within the inner balloon 153, the shaft 104, or both the inner balloon 153 and the shaft 104. A fluid circulation cooling mechanism or a cryothermal phase-change mechanism as described previously can be employed.

[0099] In embodiments that employ a fluid circulation cooling mechanism that discharges spent cooling media into the blood stream within the renal artery, a filter can be provided at or near an outlet of the helical balloon arrangement to remove particulates from the discharged cooling media. It is understood that biocompatible cooling media is to be used in cooling mechanisms that discharge spent cooling media into the blood stream. Suitable biocompatible cooling media include saline and D5W.

[0100] FIG. 9 shows a cross section of the dual balloon arrangement illustrated in FIG. 8. FIG. 9 shows the inner balloon 153 mounted to a shaft 104 of the catheter and an outer balloon 151 also mounted to the shaft 104 and encompassing the inner balloon 153. A void 154 of the inner balloon is configured to receive a thermal transfer fluid, which is also used to pressurize the inner balloon. A void 152, formed between the inner and outer balloons 153, 151, is configured to receive a pressurizing fluid that provides good thermal transfer between the cooled inner balloon 152 and the warmer outer balloon 151 during ablation. Suitable fluids for filling the void 152 and pressurizing the outer balloon 152 include saline, a mixture of saline and ethanol, D5W, Freon, radiographic contrast media, a mixture of radiographic contrast media and saline, carbon dioxide, and helium Xenon, for example. Suitable cooling mechanisms include convective heat transfer adiabatic expansion of gasses, or joule-Thompson cooling using refrigerants such as CO₂, N₂O, argon, propane, fluorocarbons, chlorofluorocarbons, and hydrogenated fluorocarbons, for example. The fluid may also be mixtures of fluids or refrigerants.

[0101] FIG. 10 shows a cross section of the shaft 104 of the balloon catheter of FIG. 8, which is shown to include a lumen arrangement 105. The lumen arrangement 105 includes a conductor lumen 113, a guide wire lumen 111, a first supply lumen 106a, a first return lumen 108a, a second supply lumen 106b, and a second return lumen 108b. The first supply lumen 106a and first return lumen 108a are fluidly coupled to the inner balloon 153, and the second supply lumen 106b and second return lumen 108b are fluidly coupled to the outer balloon 151.

[0102] The first supply and return lumens 106a, 108a that deliver the thermal transfer fluid to the inner cooling balloon 153 and remove spent thermal transfer fluid therefrom are respectively coupled to supply and return connectors of an external coolant source situated at the proximal end of the catheter 100. The second supply and return lumens 106b, 108b that deliver and remove a pressurizing fluid to and from the outer ablation balloon 151 are respectively coupled to supply and return connectors of an external pressurized fluid source situated at the proximal end of the catheter 100. As described in previous embodiments, the guide wire lumen 111 of shaft 104 is dimensioned to receive a guide wire or other elongated navigation assist member that can be used by the clinician to facilitate delivery of the balloon 102 into the renal artery and, if desired, to alter the stiffness of the portion of the shaft 104 that supports the balloon 102, 151.

[0103] According to some embodiments, the helical balloons shown in various figures of the disclosure, such as balloon 102 and outer balloon 151, can be attached to the catheter's shaft 104 along the length of the helical balloon 102, 151. For example, the helical balloon 102, 151 can be attached to the catheter's shaft 104 using a continuous or non-continuous seam or web either by way of a welding or an adhesive. As previously discussed, the seam or web can have properties, such as thickness, dimensions, and/or stiffness, that vary along the length of the balloon which influences the configuration of the balloon as it is inflated and deflated (e.g., provide for a degree of circumferential and axial shifting of the balloon during inflation and deflation).

[0104] In other embodiments, the helical balloon 102, 151 can be attached to the catheter's shaft 104 using intermittent “curtain ring” arrangements which allow the balloon to slide around the circumference and along a length of the shaft by a small amount as needed as the balloon configuration changes during inflation and deflation. FIG. 11 shows a curtain ring attachment arrangement 140 in accordance with various embodiments of the disclosure.

[0105] Two curtain ring attachment arrangements 140 are illustrated in FIG. 11, it being understood that more than two (e.g., three, four or more) of such attachment arrangements 140 may be employed. Each of the curtain ring attachment arrangements 140 include a pair of stops 143 mounted on the shaft and separated by a distance, d. A ring member 142 having a diameter slightly larger than the shaft's outer diameter is situated on the shaft and captured between the pair of stops 143. In this configuration, the ring member 142 can freely move both longitudinally along and rotatably about the section of the shaft 104 defined between the pair of stops.

[0106] As is shown in FIG. 11, each pair of stops 143 can be separated by the same distance, d, or different distances, as indicated by distances d₁ and d₂. If desired, rotation of the ring member 142 can be limited, such as by using a vertical stop that penetrates a circumferential slot provided in the ring member 142. The range of rotation is limited by the length of the circumferential slot provided in the ring member 142.

[0107] A section of the helical balloon 102, 151 is attached to each ring member 142, such as by use of a suitable adhesive. In some configurations, only one end (e.g., proximal end) of the helical balloon 102, 151 is fixedly attached to the shaft 104, while other attachment sections of the balloon 102, 151 are affixed to individual ring members 142. In other configurations, the proximal and distal ends of the helical balloon 102, 151 are each fixedly attached to the shaft 104, while other attachment sections of the balloon 102, 151 are affixed to individual ring members 142.

[0108] In accordance with various embodiments, and as illustrated in FIG. 12, multiple non-sliding flexing tethers 145 can be used to attach the balloon 102, 151 to the catheter's shaft 104 to ensure that the helical shape of the balloon 102, 151 is maintained on the shaft 104 during deployment. The flexing tethers 145 can be fashioned from a variety of materials (e.g., polymers) and facilitate a degree of circumferential and longitudinal shifting of the helical balloon 102, 151 as the balloon 102, 151 configuration changes during inflation and deflation.

[0109] Employment of either or a combination of both the curtain ring attachment arrangements 142 of FIG. 11 or the flexing tethers 145 of FIG. 12 advantageously facilitates a change in the coil pitch of the helical balloon 102, 151 during inflation to accommodate varying sizes and irregularities in renal artery diameter. As such, patients having a wide range of renal artery sizes, shapes, and tortuosity can be accommodated using a common ablation balloon catheter according to various embodiments of the disclosure.

[0110] Thermocouples or other sensors can be incorporated on the balloon 102, 151, preferably at the electrode sites. Unipolar or bipolar arrangements can be utilized. Over-the-wire, fixed-wire, or no-wire systems can be used, with guiding sheaths or catheters as needed to properly position the balloon catheter.

[0111] It is to be understood that even though numerous characteristics of various embodiments have been set forth in the foregoing description, together with details of the structure and function of various embodiments, this detailed description is illustrative only, and changes may be made in detail, especially in matters of structure and arrangements of parts illustrated by the various embodiments to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed.