Trans-endocardial delivery catheter

Abstract

To provide a trans-endocardial delivery catheter.SOLUTION: A needle-injection catheter includes a catheter body having a distal end, a proximal end, a stiff proximal portion, a flexible distal portion, and a delivery lumen extending therethrough. In a first embodiment, a straight injection needle extends coaxially from a distal tip of the flexible portion of the catheter body, and a plurality of penetration limiting elements are positioned circumferentially about a base of the straight injection needle and configured to fold radially inwardly against a shaft of the needle when constrained in a tubular lumen and to extend radially outwardly when unconstrained. In a second embodiment, a helical needle extends from the distal tip of the flexible portion of the catheter body. The helical needle has at least one helical delivery lumen connected to receive an injectable substance from the delivery lumen of the catheter body.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Application No. 61 / 884,834, filed Sep. 30, 2013 (Attorney Docket No. 29181-706.101), the entire contents of which are incorporated herein by reference.

[0002] BACKGROUND OF THEINVENTION 1. Field of the invention The present invention relates generally to medical methods and systems, and more particularly to medical methods and systems suitable for material delivery to the heart via the radial artery, and for intracardiac delivery of cellular aggregates and other aggregated materials. [Background technology]

[0003] Localized biotherapeutic delivery to the heart is currently under clinical investigation for the treatment of acute myocardial infarction, chronic myocardial ischemia, ischemic heart failure, and non-ischemic heart failure. The primary paradigm for intramyocardial delivery is transendocardial delivery.

[0004] Currently available delivery systems include the Myostar® catheter manufactured by Johnson and Johnson Biological Delivery Systems, Diamond Bar, California, and the BioCardia® spiral injection system manufactured by BioCardia, Inc., San Carlos, California, the assignee of the present invention. Both of these systems utilize an 8 French introducer placed through the femoral artery. Both systems have a flexible distal portion that is deflectable (steerable) from a proximal handle location, and the BioCardia system includes a centrally located catheter that can be advanced from the introducer to extend to the heart wall and provide improved access for the operator.

[0005] Typically, it is desirable to use the smallest puncture site and the smallest equipment that meets the requirements of the intervention. The smaller the puncture site, the easier it is for the entry point to heal without complications and the lower the requirements for closure devices. This can result in significant cost and reduced mortality for a particular interventional procedure.

[0006] Smaller devices that allow the vasculature to be accessed from the radial artery in the arm (as opposed to the femoral artery in the groin) have enormous advantages from a cost standpoint, since the patient is ambulatory immediately after the procedure. Reducing the amount of time the patient must spend recovering on a gurney or in bed has additional patient quality of life benefits in addition to the economic benefits of a reduced hospital stay. Radial artery access requires smaller equipment, as has been extensively detailed in the literature. 7F guides and 6F sheaths (1 French (Fr) equals 0.33 mm) are the largest devices recommended for such procedures, and outcomes improve when smaller guides and sheaths are used. Entire academic publications, such as Cardiac Interventions Today April 2011, Volume 5, No 2, are devoted to radial artery access for procedures, and are incorporated herein by reference. The diameter of the radial artery is such that 95% of all patients have a radial artery larger than 2.2 mm in diameter and can accommodate a 5 French sheath (typical outer diameter of 6.5 French) or a 6.5 French guide, 60% have a radial artery larger than 2.6 mm in diameter and can accommodate a 6 French sheath (outer diameter 7.5 French) or a 7.5 French guide, 40% have a radial artery larger than 2.95 mm that can accommodate a 7 French sheath (outer diameter 8.5 French) or an 8.5 French guide, and only 20% have a radial artery larger than 3.3 mm in diameter that can accommodate an 8F sheath (outer diameter 9.5 French) or a 9.5 French guide. Saito S et al Catheter Cardiovas Interve 1999;46:173-178. Typically, the sheath size refers to the size of the guiding catheter that can fit through it.

[0007] A particular challenge with transradial access is to provide a guiding catheter that can be advanced straight over a guidewire in an atraumatic manner through the vasculature with a small profile while minimizing the possibility of damaging the vasculature during advancement into the heart and perforating the heart due to the small diameter of the catheter shaft and the stiffness of the distal region of the catheter, and that can be used to guide a transendocardial delivery catheter traversing small diameters within the heart and around bends involving angles greater than 70 degrees (preferably 90 degrees or even greater) from the axis of the catheter.

[0008] In some cases, a "sheathless" guiding catheter can be used without a sheath so that the majority of patients can be treated. The use of a 5.5F or 6.5F sheathless guiding catheter can provide a smaller pathway through the radial artery by eliminating the use of a sheath.

[0009] Once in the heart, stem cells and other therapeutic agents can be injected transendocardially using straight, spiral, or other injection needles. While spiral needles typically have a small bore, straight needle bores are frequently larger. Larger straight needles are typically used to deliver large agents such as stem cells and other cells, cell aggregates, microspheres, extracellular matrix (ECM) slurries, particles, and other high viscosity therapeutic agents such as cardiospheres with diameters of 60-150 um, with effective diameters as large as 80 um and 150 um, and the like. Spiral and other small bore needles can typically have difficulty passing such large agents, even when the internal diameter is larger than the agent. This is especially true for aggregated agents, which can result in increased viscosity that inhibits delivery. While straight, large bore needles are capable of delivering such agents, after injection, stem cells and other large aggregates are often expelled back into the heart chambers upon contraction of the myocardium, which can result in loss of injectable material and, in the case of larger aggregates and particles, risk of embolism.

[0010] For these reasons, it would be desirable to provide improved systems and methods for intracardiac delivery of cells, drugs, and other therapeutic agents. It would be particularly desirable to provide improved systems and methods for facilitating the introduction of needle-based delivery catheters via the radial artery approach, such systems preferably including a distal perforation protection system with minimal space requirements that is passive, operates without active actuation, and provides robust perforation protection capabilities. Furthermore, it would be desirable to provide improved systems and methods for using needle-based delivery catheters to deliver cells, drugs, and other therapeutic agents with reduced risk of loss of injected material back into the heart chamber as a result of cardiac contraction. At least some of these objectives may be met by the present invention, as described below.

[0011] 2. Description of Background Technology In recent years, steerable guides and sheaths have been developed that enable significant advantages for transendocardial delivery and other cardiovascular procedures. See U.S. Patent Nos. 7,840,261, 7,402,151, and U.S. Patent Application Publication Nos. 2012 / 0123327 and 2008 / 0287918, the entire disclosures of which are incorporated herein by reference. Steerable guides and sheaths typically have a wall thickness that is 1 French (1 French (Fr) equals 0.33 mm), while standard fixed guides and sheaths typically have a wall thickness of about 0.5 Fr.

[0012] U.S. Patent Application No. 2012 / 0123327 (Miller) describes how a 5Fr or 6Fr steerable sheath can be used to enter the heart via the radial artery using a guiding catheter with a flexible distal end, such as the BioCardia spiral injection system. For such a system, the 5F steerable sheath would have an inner diameter of 5.5 French and an outer diameter of just over 2.2 mm, allowing easy passage of a 5.2 French spiral injection catheter system (BioCardia, Inc.) and essentially act as a transradial steerable sheath for transendocardial delivery using the spiral injection system, enabling a steerable transendocardial delivery platform that is useful in close to 95% of all patients.

[0013] Published U.S. Patent Applications Nos. 2007 / 0005018 and 2010 / 0168713 each discuss the potential advantages of transradial access for transendocardial delivery.

[0014] Penetration limiter devices on the end of transendocardial delivery catheters are known, such as those described by Eclipse Surgical Technologies in U.S. Pat. No. 6,322,548. These systems are passive systems, but require distal catheter shaft structures that consume real estate at the distal end of the catheter and would impede transradial access due to their size. U.S. Pat. Nos. 7,803,136, 8,361,039, and 8,414,558 also describe distal protection mechanisms for straight needle transendocardial delivery systems. All of these require active deployment mechanisms that increase the profile of the distal region, release at the base of the penetrating element, confirm engagement, use large diameter helical needles, which is important for the delivery of agents that are more viscous or larger or may aggregate, and use dual lumen penetrating elements, limiting space for advanced therapeutic lumen designs such as the inclusion of contrast ports and lumens. Cardiac Interventions Today April 2011, Volume 5, No 2 and Saito S et al Catheter Cardiovas Interve 1999;46:173-178 are described above. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] U.S. Patent No. 7,840,261 [Patent Document 2] U.S. Patent No. 7,402,151 [Patent Document 3] US Patent Application Publication No. 2012 / 0123327 [Patent Document 4] US Patent Application Publication No. 2008 / 0287918 [Patent Document 5] US Patent Application Publication No. 2007 / 0005018 [Patent Document 6] US Patent Application Publication No. 2010 / 0168713 [Patent Document 7] U.S. Patent No. 6,322,548 [Patent Document 8] U.S. Pat. No. 7,803,136 [Patent Document 9] U.S. Pat. No. 8,361,039 [Patent Document 10] U.S. Pat. No. 8,414,558 Summary of the Invention [Means for solving the problem]

[0016] Summary of the Invention In accordance with the present invention, methods and systems are provided for intracardiac transendocardial injection of various substances, including drugs, cells, particularly large cell aggregates, and other particulate matter. Many of these methods and systems are particularly suited for radial artery access, but may rely on femoral artery access as well. The systems of the present invention may include multiple interchangeable components, such as introducer sheaths, preformed or pre-shaped guiding catheters, steerable or deflectable guiding catheters, preformed sheathless guiding catheters, steerable sheaths or sheath guides, and sheathless steerable sheaths or sheath guides. Each of the various guiding catheters may be used for advancement of multiple types of delivery catheters, for example, with helical needles, straight needles, coaxial helical needles, coaxial straight needles, double helical needles, double curved needles, double straight needles, large bore straight needles, large bore curved needles, large bore helical needles, and the like. The delivery catheters may also include a contrast agent lumen that releases at the base of the needle or other penetrating element. These catheter systems may be configured for fluoroscopic navigation, electrical impedance navigation, electromagnetic navigation using real-time magnetic resonance imaging, 3D echo navigation, and fusion imaging systems that provide MRI, CT, or echo data and can merge it with fluoroscopic images. Additionally, these delivery systems have the capability to enable several embodiments of the disclosed wide variety of diagnostic and therapeutic agent delivery, as the inventive elements of the delivery system enable these novel treatment options.

[0017] In a first aspect, the present invention provides a method for introducing a needle injection catheter into a heart chamber via a radial artery approach. Such a method includes the step of advancing a guide catheter through the radial artery (and the intervening arterial vasculature) into a target heart chamber. The catheter may normally enter the right or left ventricle from the right side of the heart, but may be further advanced transseptally within the heart to reach the left ventricle from the right side of the heart or other heart chambers. The guide catheter is positioned to align a distal tip of the guide catheter with a target location on the endocardial wall of the heart chamber. The needle injection catheter is advanced through the lumen of the guide catheter such that a straight needle protruding coaxially from the distal tip of the needle injection catheter emerges from the distal tip, penetrates the endocardial wall, and positions an injection port at the tip of the needle into the myocardium. A number of penetration limiting elements remain constrained within the guiding catheter until the elements self-deploy radially outward from the base of the needle to limit needle penetration into the myocardium to reduce the risk of endocardial wall perforation, and a straight needle typically emerges from the distal tip, at which point the elements resiliently deploy as a result of their own spring force upon release of the constraint.

[0018] In an exemplary embodiment, the positioning step may include rotating and / or axially translating a guiding catheter having a preformed deflection at its distal end. In an alternative exemplary embodiment, the positioning step may include deflecting or "steering" the distal tip of the guiding catheter while it is within the heart chamber. In all cases, the guiding catheter may be introduced into the heart chamber, typically in a conventional manner, over a guidewire placed prior to the radial artery.

[0019] In a further exemplary embodiment, the step of advancing the needle injection catheter may include constraining the penetration limiting element within an introducer sleeve, a distal end of the sleeve being engaged against a proximal hub of the guiding catheter, and the distal end of the needle injection catheter being advanced into a proximal portion of the guiding catheter while the penetration limiting element remains constrained.

[0020] In still further exemplary embodiments, the penetration limiting element may comprise elastic petals having a base attached to the catheter body at the base of the straight needle. The petals may be shaped to curve outward from the catheter body when unconstrained. The petals may be wire loops folded over a continuous length of shape memory wire, and platinum wire may be wrapped over the shape memory wire to provide radiopacity. Alternatively, the petals may comprise solid leaves or other structures that overlap when folded inwardly relative to the needle shaft. Typically, in all such embodiments, the catheter includes 2-6 petals, most typically 3.

[0021] In a second aspect, the present invention provides a needle injection catheter comprising a catheter body having a distal end, a proximal end, a rigid proximal portion, a flexible distal portion, and a delivery lumen extending therethrough. By rigid, it is meant that the proximal portion of the catheter body may have sufficient column strength and pushability to be advanced through relatively non-tortuous regions of the vasculature, specifically from the radial artery, to the heart. By flexible, it is meant that the distal portion may be advanced across small radius curves to allow positioning within a heart chamber through pre-shaped or deflected regions of the guiding catheter. The catheter further includes a straight injection needle extending coaxially from the distal tip of the flexible portion of the catheter body. A plurality of penetration limiting elements are positioned circumferentially around the base of the straight injection needle and are configured to fold radially inward relative to the needle shaft when constrained within the tubular lumen, and to extend radially outward when unconstrained.

[0022] The penetration limiting element of the needle injection catheter may comprise elastic petals having a base attached to the catheter body at the base of the straight needle. The petals may be shaped to curve outward from the catheter body when unconstrained. The petals may be wire loops folded over a continuous length of shape memory wire, and platinum wire may be wrapped over the shape memory wire to provide radiopacity. Alternatively, the petals may comprise solid leaves or other structures that overlap when folded inwardly relative to the needle shaft. Typically, in all such embodiments, the catheter comprises 2 to 6 petals, most typically 3.

[0023] In an exemplary embodiment, the rigid proximal portion of the catheter body of the needle injection catheter may comprise a braided polymer tube, and the flexible distal portion may comprise a helical metal coil. The catheter body may typically have a first lumen for delivering the injectable composition to the needle and a second lumen for delivering contrast to the base of the needle. The needle injection catheter may further comprise a handle or hub (collectively referred to as the handle) on the proximal end of the catheter body, which may include valves, luers, and other fillers and components as necessary for connection to a source of the substance to be delivered, contrast, guidewire, and the like. The catheter body may be preferably configured to be delivered through a 6.5 Fr or smaller guide catheter.

[0024] In a further embodiment of the invention, a catheter system includes a needle injection catheter as described above in combination with a guide catheter having a lumen configured to receive the needle injection catheter and to radially constrain the plurality of penetration limiting elements when the needle injection catheter is therein. The guide catheter of such a system may have a preformed bend near its distal end so that the guide catheter can be rotated to align its distal end with a target location on the endocardial wall when the guide catheter is in the heart chamber. Alternatively, the guide catheter may have a deflectable (also referred to as steerable) distal end to allow the guide catheter to align its distal end with a target location on the endocardial wall when the guide catheter is in the heart chamber.

[0025] In a third aspect, the present invention provides a large-bore needle injection catheter comprising a catheter body having a distal end, a proximal end, and a delivery lumen therethrough. The helical needle extends from the distal end of the catheter body and has at least one helical delivery lumen connected to receive an injectable substance from the delivery lumen of the catheter body. The delivery lumen and the at least one helical lumen are sufficiently large to allow the passage and injection of a drug or biological substance having an average diameter of at least 100 μm. The catheter body delivery lumen usually has a diameter of at least 0.50 mm, typically 0.71 mm at its non-circular major axis, and the helical lumen usually has a diameter of at least 0.2 mm, typically about 0.43 mm.

[0026] In a specific embodiment, the catheter body has at least one lumen in addition to the delivery lumen, and the helical needle has at least two helical delivery lumens, one connected to at least each of the catheter body lumens. The catheter body may comprise a rigid proximal section and a flexible distal section, as described above, where the rigid proximal section of the catheter body may comprise a braided polymer tube, and the flexible distal section of the catheter body may comprise a helical metal coil. The catheter body may include a first lumen, optionally a second lumen for delivery of an injectable composition to the needle, and further optionally a second or third lumen for delivery of a contrast agent to the base of the needle, and a handle may be disposed on the proximal end of the catheter body.

[0027] In a further embodiment of the invention, a catheter system includes a large bore catheter as described above in combination with a guide catheter having a lumen configured to receive a large bore needle catheter. The guide catheter of such a system may have a preformed bend near its distal end so that the guide catheter can be rotated to align its distal end with a target location on the endocardial wall when the guide catheter is in the heart chamber. Alternatively, the guide catheter may have a deflectable (also referred to as steerable) distal end to allow the distal end to be aligned with a target location on the endocardial wall when the guide catheter is in the heart chamber.

[0028] In a fourth aspect of the invention, a method for delivering particulate matter into the endocardial wall of a chamber of a beating heart includes intravascularly introducing a large-bore needle injection catheter having a helical needle into the chamber. Particulate matter that may be delivered specifically includes cells, stem cells, stem cell aggregates, and any other therapeutic or diagnostic material that may present a risk of embolism if accidentally released into the chamber when injected, as a result of being pushed or otherwise released from the injection site as a result of contraction of the myocardium as the heart beats. The helical needle of the large-bore needle injection catheter is advanced into the endocardial wall of the chamber such that the port of the needle lies near the inner end of a helical tissue tube formed by the needle. Particulate matter, typically having an average particle size of at least 100 μm, is injected through the needle into the inner end of the helical tissue tube. Backflow of the injected material through the helical tissue tube is prevented within the helical shape of the tube even after the helical needle is withdrawn.

[0029] In a specific embodiment of the particulate matter delivery method, the catheter may have a catheter body with a delivery lumen having a diameter of at least 0.50 mm, preferably in the range of 0.50 mm to 0.80 mm. The helical needle may have a helical lumen with a diameter of at least 0.2 mm, preferably in the range of 0.21 mm to 0.56 mm. The catheter body delivery lumen usually has a diameter of at least 0.50 mm, typically 0.71 mm at its non-circular major axis, and the helical lumen usually has a diameter of at least 0.2 mm, typically about 0.43 mm. The catheter body typically has at least one lumen in addition to the delivery lumen, and the helical needle typically has at least two helical delivery lumens, one connected to at least each of the catheter body lumens. The present specification also provides, for example, the following items: (Item 1) 1. A method for introducing a needle injection catheter into a heart chamber from a radial artery, comprising: advancing a guiding catheter through the radial artery and into the heart chamber; positioning the guiding catheter such that a distal tip of the guiding catheter is aligned with a target location on an endocardial wall of the heart chamber; advancing the needle injection catheter through the lumen of the guiding catheter such that a coaxially projecting straight needle emerges from the distal tip of the needle injection catheter and penetrates the endocardial wall to position an injection port at the tip of the needle within the myocardium, wherein a plurality of penetration limiting elements remain constrained within the guiding catheter until the needle emerges from the distal tip, at which point the elements self-deploy radially outward from the base of the needle to limit penetration of the needle into the myocardium to reduce a risk of perforation of the endocardial wall; A method comprising: (Item 2) 2. The method of claim 1, wherein the positioning step includes rotating and / or axially translating a guiding catheter having a preformed deflection at its distal end. (Item 3) 2. The method of claim 1, wherein the positioning step includes deflecting the distal tip of the guiding catheter while the guiding catheter is within the heart chamber. (Item 4) 2. The method of claim 1, wherein the step of advancing the needle injection catheter includes constraining the penetration limiting element within an introducer sleeve, engaging a distal end of the sleeve against a proximal hub of the guiding catheter, and advancing the distal end of the needle injection catheter into a proximal portion of the guiding catheter while the penetration limiting element remains constrained. (Item 5) Item 13. The method of item 1, wherein the penetration limiting element comprises a resilient petal having a base attached to the catheter body at the base of the straight needle. (Item 6) 6. The method of claim 5, wherein the petals are shaped to curve outwardly from the catheter body when unconstrained. (Item 7) 7. The method of claim 6, wherein the petals are continuous lengths of shape memory wire folded over wire loops. (Item 8) 8. The method of claim 7, wherein a platinum wire is wrapped over the shape memory wire to provide radiopacity. (Item 9) 7. The method of claim 6, wherein the petals are solid leaves that overlap when folded inwardly against the needle shaft. (Item 10) 6. The method according to claim 5, wherein the catheter comprises 2 to 6 petals. (Item 11) a catheter body having a distal end, a proximal end, a rigid proximal section, a flexible distal section, and a delivery lumen extending therethrough; a straight injection needle extending coaxially from the distal tip of the flexible section of the catheter body; a plurality of penetration limiting elements positioned circumferentially around the base of the straight injection needle and configured to fold radially inward relative to the needle shaft when constrained within a tubular lumen and to extend radially outward when unconstrained; A needle injection catheter comprising: (Item 12) Item 12. The catheter of item 11, wherein the penetration limiting element comprises a resilient petal having a base attached to the catheter body at the base of the straight needle. (Item 13) Item 13. The catheter of item 12, wherein the petals are shaped to curve outwardly from the catheter body when unconstrained. (Item 14) 14. The catheter of claim 13, wherein the petals are folded wire loops of a continuous length of shape memory wire. (Item 15) 15. The catheter of item 14, wherein a platinum wire is wrapped over the shape memory wire to provide radiopacity. (Item 16) Item 14. The catheter of item 13, wherein the petals are solid leaves that overlap when folded inwardly relative to the needle shaft. (Item 17) Item 13. The catheter according to item 12, wherein the catheter comprises 2 to 6 petal-shaped portions. (Item 18) Item 12. The catheter of item 11, wherein the stiff proximal portion of the catheter body comprises a braided polymer tube and the flexible distal portion of the catheter body comprises a helical metal coil. (Item 19) 12. The catheter of claim 11, wherein the catheter body has a first lumen for delivery of an injectable composition to the needle and a second lumen for delivery of a contrast agent to the base of the needle. (Item 20) Item 12. The catheter of item 11, further comprising a handle on the proximal end of the catheter body. (Item 21) Item 12. The catheter of item 11, wherein the catheter body is configured to be delivered through a 6.5 Fr guiding catheter. (Item 22) Item 12. A needle injection catheter according to item 11; a guide catheter having a lumen configured to receive the needle injection catheter and to radially constrain a plurality of penetration limiting elements when the needle injection catheter is located therein; A catheter system comprising: (Item 23) 23. The catheter system of claim 22, wherein the guiding catheter has a preformed bend near its distal end such that the guiding catheter can be rotated to align the distal end with a target location on an endocardial wall when the guiding catheter is in a heart chamber. (Item 24) 23. The catheter system of claim 22, wherein the guiding catheter has a deflectable distal end to align the distal end with a target location on an endocardial wall when the guiding catheter is within a heart chamber. (Item 25) a catheter body having a distal end, a proximal end and a delivery lumen therethrough; a helical needle having at least one helical delivery lumen extending from the distal end of the catheter body and connected to receive an injectable substance from the delivery lumen of the catheter body, the delivery lumen and the at least one helical lumen being large enough to permit the passage and injection of a pharmaceutical or biological substance having an average diameter of at least 50 μm; A large bore needle injection catheter comprising: (Item 26) 26. The catheter of claim 25, wherein the delivery lumen has a diameter of at least 0.5 mm. (Item 27) 27. The catheter of claim 26, wherein the helical lumen has a diameter of at least 0.2 mm. (Item 28) 28. The catheter of claim 27, wherein the catheter body has at least one lumen in addition to the delivery lumen, and the helical needle has at least two helical delivery lumens, one connected to at least each of the catheter body lumens. (Item 29) Item 26. The catheter of item 25, wherein the catheter body comprises a rigid proximal section and a flexible distal section. (Item 30) 28. The catheter of claim 27, wherein the stiff proximal portion of the catheter body comprises a braided polymer tube and the flexible distal portion of the catheter body comprises a helical metal coil. (Item 31) 26. The catheter of claim 25, wherein the catheter body has a first lumen for delivery of an injectable composition to the needle and a second lumen for delivery of a contrast agent to the base of the needle. (Item 32) Item 26. The catheter of item 25, further comprising a handle on the proximal end of the catheter body. (Item 33) 26. The large-bore needle catheter according to item 25, a guide catheter having a lumen configured to receive the large bore needle catheter; A catheter system comprising: (Item 34) Item 34. The catheter system of item 33, wherein the guiding catheter has a preformed bend near its distal end such that the guiding catheter can be rotated to align the distal end with a target location on an endocardial wall when the guiding catheter is within a heart chamber. (Item 35) 34. The catheter system of claim 33, wherein the guiding catheter has a deflectable distal end to align the distal end with a target location on an endocardial wall when the guiding catheter is within a heart chamber. (Item 36) 1. A method for delivering particulate matter into an endocardial wall of a chamber of a beating heart, comprising: intravascularly introducing a large bore needle injection catheter having a helical needle into a chamber of the heart; rotating and advancing the helical needle of the large bore needle injection catheter into the endocardial wall of the heart chamber so that the needle port lies adjacent an interior end of a helical tissue tube formed by the needle; injecting particulate matter having an average particle size of at least 50 μm through the needle into the inner end of the spiral tissue tube, wherein backflow of injected material through the spiral tissue tube is prevented within the spiral shape of the tube even after the spiral needle is withdrawn; A method comprising: (Item 37) 37. The method of claim 36, wherein the catheter has a catheter body with a delivery lumen having a diameter of at least 0.5 mm. (Item 38) 38. The method of claim 37, wherein the helical needle has a helical lumen with a diameter of at least 0.2 mm. (Item 39) Item 39. The method of item 38, wherein the catheter body has at least one lumen in addition to the delivery lumen, and the helical needle has at least two helical delivery lumens, one connected to at least each of the catheter body lumens. [Brief description of the drawings]

[0030] [Figure 1] 1 and 2 illustrate prior art guide and delivery catheters that may be used in certain implementations of the present invention. [Diagram 2] 1 and 2 illustrate prior art guide and delivery catheters that may be used in certain implementations of the present invention. [Diagram 3] 3A and 3B illustrate a spiral delivery catheter implementation of the present invention. [Figure 4] 4A and 4B illustrate a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention being advanced from a guiding catheter. [Diagram 5] FIG. 5 illustrates the distal tip of a needle injection catheter having a straight needle in accordance with the present invention. [Figure 6-1] 6A-6E illustrate the retraction of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element into a guiding catheter in accordance with the present invention. [Figure 6-2] 6A-6E illustrate the retraction of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element into a guiding catheter in accordance with the present invention. [Figure 7] FIG. 7 illustrates an exemplary delivery catheter having two lumens and a handle assembly. [Figure 8A] 8A-1 through 8F-6 illustrate the design and fabrication details of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention. [Figure 8B]8A-1 through 8F-6 illustrate the design and fabrication details of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention. [Figure 8C] 8A-1 through 8F-6 illustrate the design and fabrication details of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention. [Figure 8D] 8A-1 through 8F-6 illustrate the design and fabrication details of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention. [Figure 8E] 8A-1 through 8F-6 illustrate the design and fabrication details of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention. [Figure 8F] 8A-1 through 8F-6 illustrate the design and fabrication details of a needle injection catheter having a straight injection needle surrounded at its base by a penetration limiting element according to the present invention. [Figure 9] FIG. 9 is a cross-sectional view of a handle assembly for a needle injection catheter in accordance with the present invention. [Figure 10] 10-12B show the distal tip of a three-lumen needle injection catheter having a two-lumen spiral injection needle. [Figure 11] 10-12B show the distal tip of a three-lumen needle injection catheter having a two-lumen spiral injection needle. [Figure 12] 10-12B show the distal tip of a three-lumen needle injection catheter having a two-lumen spiral injection needle. [Figure 13] 13A and 13B show the design and fabrication details of a three lumen catheter body configuration. [Figure 14] 14A-14C show the electrical connections of the delivery catheter in further detail. [Figure 15] FIG. 15 shows the internal configuration of a handle assembly for a spiral needle delivery catheter of the present invention. [Figure 16]16 and 17 show the design and fabrication details of a large diameter helical needle for the delivery catheter of the present invention. [Figure 17] 16 and 17 show the design and fabrication details of a large diameter helical needle for the delivery catheter of the present invention. [Figure 18] 18A-18C illustrate an alternative design of a penetration limiter that can utilize existing balloon technology to provide distal perforation protection when engaging cardiac tissue during transendocardial therapy delivery. [Figure 19] FIG. 19 shows the assembled system including a deflectable tip guiding catheter with a valve, a syringe attached to the side port of the valve, a helical needle delivery catheter, a syringe attached to the treatment port of the valve, and a syringe attached to the contrast port. [Figure 20] FIG. 20 illustrates a helical needle injection catheter including a helical needle, a flexible distal element, a braided shaft, a two-part strain relief, a handle, a treatment port, and a contrast port. [Figure 21] 21A-21D show a helical needle formed by wrapping a hypotube over a mandrel that supports the sides of the tube to reduce distortion (ovalization). [Figure 22] FIG. 22 shows an alternative design for terminating the contrast and treatment lumens utilized in a "Y" adapter or other handle. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] This patent application discloses each of these inventive elements, but in no way limits their use to the other elements herein.

[0032] Description of the Invention FIG. 1 (Prior Art) shows a preformed 6F Hockey Stick (HS) 90 cm guiding catheter 100, such as the Concierge® guiding catheter available from Merit Medical Systems, Inc., that can be advanced from either the femoral or radial artery, either straight or over a dilator or guidewire. Because the distal section is highly flexible, the guiding catheter may be safely advanced across the aortic valve and into the left ventricle. The guiding catheter 100 may be advanced into the femoral artery using any commercially available 6Fr sheath. For radial artery access, a longer 25 cm sheath, such as the Boston Scientific Super Sheath Catalog 16037-06B, is preferred to avoid complications with radial artery spasm, which frequently occurs in patients.

[0033] FIG. 2 (Prior Art) shows a preformed 6Fr HS 90cm guiding catheter 100 after a central straightening element such as a dilator or wire has been removed and a transendocardial infusion catheter 200 has been inserted with a highly flexible distal section 202 with a length of at least 6-10cm reaching 3.5-7cm beyond the end of the guiding catheter. Here, the penetrating element is a helical needle 204 that can be easily rotated within the fixed guide and advanced to engage the catheter into the cardiac tissue. The highly flexible distal section 202 on the transendocardial infusion catheter 200 does not straighten the highly flexible guide portion on the 6Fr guiding catheter, allowing the fixed guide to be advanced and rotated and then the helical needle 204 to be extended to the vertical wall with the transendocardial delivery system so that it can penetrate the tissue to accomplish therapeutic or diagnostic delivery. Due to the need for the guide distal end to be flexible, a slight straightening may occur as the transendocardial infusion catheter is inserted, so the preformed guide shape may typically bend at least 90 degrees. In FIG. 2, the transendocardial infusion catheter 200 is a BioCardia® spiral needle model 953L catheter, in which the highly flexible region comprises a multifilar coil design, although other flexible sections may also be used in the present invention, for example, the flexible section may be made of etched stainless steel tubing or form a wound ribbon structure, as shown in U.S. Patent Nos. 5,228,441, 5,243,167, 5,322,064, 5,329,923, 5,334,145, 5,454,787, 5,477,856, and 5,685,868. The bending stiffness of such coil designs can be easily calculated by following the efficient closed form differentiation for such complex geometries, as taught, for example, in Meagher, J., Altman, P.: Stresses from Flexure in Composite Helical Implantable Leads, Medical Engineering and Physics, Vol. 19, No. 7, pp 668-673, 1997.

[0034] The penetrating element in different aspects of the invention can be a straight needle, a curved needle, a multi-branched needle, and the like, as well as a helical needle. Because the preformed guide catheter used in the method and system of the invention can be advanced and retracted axially and rotated in the left ventricle, a static sheath can typically be placed in the first 25 cm of the radial artery to reduce the effect of radial artery spasm on the procedure and the viability of the radial artery at the end of the procedure. A long 6F sheath can also be used with the 6Fr guide to minimize the possibility that spasm will bind the inserted catheter and prevent the completion of the procedure.

[0035] In some embodiments, a 25 cm 6 Fr introducer sheath and a 110 cm preformed 6 Fr guide catheter with a preformed 100 degree hockey stick angle are used to advance a 5.2 Fr transendocardial delivery catheter with a penetrating element mounted on the end of a highly flexible coil. These catheters may have two lumens running to the distal end, one that discharges at the base of the penetrating element and one that passes through the penetrating element to discharge into the tissue being penetrated. Additionally, the catheter system, in its preferred embodiment, has a helical needle at its distal tip, eliminating the need for a perforation protection device. Specifically, eliminating the need for a 25 m 6 Fr sheath by providing a lubricious coating and allowing the 110 cm guide to be used as a sheathless guide allows the system to be used in an additional 35% of the population, being the preferred embodiment for patients with smaller radial arteries.

[0036] An alternative system may utilize a steerable 6Fr guide catheter with an outer diameter set to accommodate a 6Fr sheath (6.4Fr or smaller) and an inner diameter selected to accommodate a 4Fr infusion catheter with an inner diameter of 3.9Fr to 4.4Fr. Such steerable guide catheters are commercially available, a suitable steerable guide catheter is the General Purpose Deflectable Guide Catheter Model #1066 manufactured by BioCardia, Inc., with a 4.25Fr inner lumen and a 6Fr outer lumen. This approach has the same procedural advantages as the first embodiment disclosed herein, but also benefits from the ability to deflect the distal end of the guide to provide enhanced control options, as well as the ability to have better backup support within the ventricle. This system may also be used with a 25cm radial artery access sheath, but suffers from the challenge of being able to pass a larger diameter helical needle, and thus a straight needle system with the passive perforation protection system described is desirable.

[0037] An alternative steerable guide catheter suitable for certain embodiments of the present invention is disclosed in US Patent Application Publication No. 2012 / 0123327, the entire disclosure of which is incorporated herein by reference. The present guide catheter allows for entry with a 5 French steerable sheath (7.5 French outer diameter) without an introducer sheath. Although there is an additional risk of radial artery spasm associated with maneuvering the device within the artery, its steerable nature may significantly reduce manipulation versus that of a 6 Fr sheathless fixed guide with a 7 Fr outer diameter. Both the present sheathless guide and the present steerable sheath system would benefit from a lubricating coating along the entire length of the catheter shaft. With the caveat that larger catheters may pose additional risks to the radial artery, the possibility of using a larger steerable sheath for the procedure may be implemented to accommodate larger catheters for transendocardial delivery, with different fluid delivery, electrical mapping, ultrasound sensing, electromagnetic positioning, and other such well-understood geometric requirements. Currently, tri-lumen fluid management with bipolar sensing as disclosed in US Pat. No. 7,736,346 is realized in a 5.2 Fr envelope that fits into a 5 Fr sheath.

[0038] 3A and 3B show the distal end of two transendocardial delivery catheters, each with two lumens: one used for contrast delivery and terminating at the base of the helical needle, and one lumen extending to the distal end of the helical needle. The needles are formed with a winding fixture with a channel width specified to control the pitch and prevent flattening or excessive "ovalization" of the circular needle cross section, or unintentional deformation of the cross section from a circular geometry to an elliptical or similar non-circular geometry. The needles are made from 304 stainless steel, although other materials can also work. When attaching the helical needle to the distal end of the catheter, the needle is bonded into a dual lumen inner tube that is covered with a distal multifilar coil, a mandrel is inserted into the contrast release lumen to protect its patency, and the helix is ​​embedded in an epoxy resin such as Loctite M-31CL, where the needle is firmly affixed to the distal highly flexible coil. The smaller diameter helical needle has an inner diameter of 0.008 inches and the larger diameter helical has an inner diameter of 0.022 inches.

[0039] 4A and 4B show the distal end of a straight needle transendocardial catheter 402 system including a delivery catheter 404 having a passive perforation protection system with multiple (three) protective petals 406 surrounding the base of a straight injection needle 408. FIG. 4A shows the system as it is deployed, and FIG. 4B shows it as it is fully deployed. The system of the present invention includes a catheter of the present invention in combination with a guide catheter, which may be any one of a variety of conventional steerable or fixed guide catheters having a 5.2 Fr lumen, or in some cases a 4 Fr lumen. The system may optionally further include an introducer sleeve 817c as shown in FIG. 8E, which may be a thin-walled slit tube approximately 3-10 centimeters in length that is advanced over the proximal shaft of the needle injection catheter to retract the perforation protection device within the lumen of the sleeve. The catheter may then be advanced from the introducer sleeve into a guide catheter that is used to deliver the catheter after the introducer sleeve is removed.

[0040] FIG. 5 shows the distal end of a transendocardial delivery system compatible with a 5.5 Fr luminal catheter introducer system 500 in which a straight needle 504 is mounted on the distal end of a flexible distal region 511 of the catheter body or shaft. A contrast port 510 is located at the base of a petal 506 that is attached to the distal end of region 511. The straight needle 504 may be a 27 gauge normal wall needle with a 0.008 inch lumen and 0.016 inch outer diameter, and an exposed length of 0.160, 0.240, or 0.320. The tip 502 of the needle 504 preferably has three faces as shown, but could alternatively have one or two faces. The penetration limiting petals 506 may be formed from 0.0035 inch diameter Nitinol® wire that is provided with or covered with a single filler 0.0015 inch diameter Platinum Iridium (Pt / Ir) (90 / 10) wire coil over the top for radiopacity. The flexible region of the catheter may be formed from a five-strand filler 0.008 inch wire coil 511 with an outer diameter of 0.063 inch with a pitch of 0.046 inch, extending 10 centimeters from the more rigid catheter shaft. A dual lumen PEBAX 55D polymer tube (not shown in FIG. 5) typically extends most or the entire length of the catheter. The base of the straight needle penetration element 508 is inserted into and bonded to one of the two lumens of the dual lumen tube. The stem or base of the penetration limiting / perforation protection structure 510, into which a pentafiler coil 511 is inserted, typically leaves one of the internal lumens open to release the contrast medium when needed.

[0041] The penetration limiting / perforation protection device can be implemented in several ways. In a preferred embodiment, a monolithic structure includes multiple petals that are partially or completely covered with a Pt / Ir wire coil. The wire covering facilitates assembly and improves consistency of longitudinal and radial spacing. The covering may also increase the security of the attachment. Assembly is performed by straightening a superelastic wire (preformed or set to have a three-dimensional petal-like geometry as illustrated herein) and a Pt / Ir coil is advanced over the straightened wire. The petal-like wire is then allowed to regain its relaxed multi-petal shape and the penetration limiting / perforation protection structure is bonded into the distal end of the catheter body or shaft with epoxy as previously described. Additionally or alternatively, the penetration limiting / perforation protection structure may also be attached using brazing, soldering, or by welding to the needle and / or distal coil.

[0042] Other embodiments include the use of distinct sections for each petal in the multiple petals. Combinations of these are also possible, i.e., two petals in one monolithic structure and two petals in another monolithic structure, resulting in a four-petal configuration, etc. Additionally, there are more limited embodiments in which only one petal deploys from the catheter on one side.

[0043] The number of petals or leaflets is important as it determines the number of individual wires that must be anchored. Thus, fewer leaflets will take up less available space inside the catheter, but may result in a thicker element. Since bending stiffness tends to be a cubic factor of diameter, doubling the diameter results in eight times the stiffness. Thus, it is expected that three loops will allow for more stiffness (and therefore resistance to puncture) than four, and perhaps a more stable geometry than two loops. The preferred embodiment has three loops, but this should not limit the disclosed invention. Nitinol® wires can also be selected from a range of sizes, typically 0.002 to 0.005 inches in diameter.

[0044] Apparent Cross-Sectional Area Relates to Puncture Resistance: In the context of puncture protection, the element of interest is the distal end of the main catheter body, not the "penetrating element" or needle. The force required to cause myocardial perforation / puncture is related to the presented cross-sectional area of ​​the catheter tip. The wire loop element disclosed herein effectively increases the apparent surface area of ​​the distal end of the catheter body, thus increasing the force that would be required to cause myocardial perforation.

[0045] Variable Stiffness of Loops: The base of each loop or petal near the distal end of the catheter body is also most important for generating puncture resistance, as it is the portion of the loop / petal that is most resistant to being bent backwards (shortest lever arm to cause bending), and can be made stiffer than the portion of the loop further from the catheter tip, making the system more atraumatic or less sensitive to contact with fine structures in the heart. Figures 6A-6E show exemplary loop / petal structures suitable as penetration limiting / perforation protection elements of the present invention, which easily collapse when deployed from or retracted into the distal end of a guide catheter. Figures 6A-6E specifically show the penetration limiting / perforation protection system as the delivery catheter is being retracted back into the guide catheter, with Figure 6A showing the distal region 511 of the infusion catheter extended from the guide catheter 601, along with the protective petals or leaflets 506 at full deployment. FIG. 6B shows the leaflets or petals 506 fully deployed just prior to entering the guide catheter 601 as the delivery catheter is retracted therein, FIG. 6C shows the leaflets or petals 506 beginning to collapse around the needle 502 and into the guide catheter 601, and FIG. 6D shows the leaflets or petals 506 just prior to full capture by the guide catheter 601. FIG. 6E shows the perforation protection system fully retracted and barely visible through the distal port of the guide catheter 601. This final position is referred to as the "stored" state when the delivery catheter is protected within the guide and the guide can be manipulated to target specific areas within the ventricle. This protection device more than doubles the force of penetration of cardiac tissue with a given 5 French straight needle catheter system. The "petals" passively expand / collapse when extended out / retracted into the catheter and when collapsed the loop tips extend past the inner diameter of the catheter or the tip of the straight needle to prevent gouging tissue when partially retracted. In its deployed configuration the penetration limiting / perforation protection system significantly reduces the risk of perforation with straight needle systems.

[0046] A proximal portion 700 of a delivery catheter with two fluid lumens is shown in FIG. 7 and includes a handle assembly 701 attached to a main catheter shaft 705 by a strain relief assembly 703. The catheter shaft 705 is a flexible, torqueable composite conduit for the treatment and contrast delivery lumens. The strain relief assembly 703 serves as a protective transition between the catheter shaft and the handle assembly 701. Although the spiral needle system of the present invention may have a lower likelihood of perforation than straight needle embodiments, there may be advantages to including such a perforation protection embodiment for a spiral needle catheter that can be easily implemented.

[0047] FIG. 8A (panels 1-4) illustrates a penetration limiting / puncture protection including exemplary leaflet or petal elements. The leaflet elements 801 can be freestanding as shown above or can have legs connected in what we would call a "monolithic structure" 806, for example, the leaflets or petals may be formed from a single length of Nitinol® or other shape memory metal or polymer, which length is further optionally connected at the ends to form a continuous structure with multiple loops. The legs can be straight or have some other convoluted shape to improve bonding at the adhesive joint. These loops have several radii that aid in collapse and / or expansion of the structure during sheathing and deployment. The outer diameter 801a primarily defines the sheathed length relative to the needle that is covered and protected. The "folding blip" 801b is designed to prevent plastic distortion when sheathing, where the geometric section folds 180 degrees. The "root" radius 801d makes it easier to sheathe because the lever arm for folding the leaflets is increased when this radius is increased. Radiopacity can be provided by covering the leaflets with coiled platinum 801e as shown in FIG. 8B (panel 1) or made from a drawn filled tube (DFT) with a radiopaque center such as platinum 801f as shown in FIG. 8B (panel 2). The radiopaque coil can be attached using geometric bonding, solder, or adhesives. Panels 3 and 4 of FIG. 8B show that the loops are made by heat setting on a mandrel with features that create various selected radii, e.g., 809, 811, and 813.

[0048] FIG. 8C shows a dual lumen tube. Dual lumen 803b (panel 2) has a channel for a therapeutic agent and a channel for a contrast agent. The treatment pathway is connected to an injection element 808 to deliver the agent into the tissue. The contrast agent lumen opens at the tip of shaft 805 and contrast agent is injected through it to ensure correct positioning against the tissue surface. Options for the dual lumen include a non-circular extrusion 803b with recesses for the legs of the leaflets, optimizing the cross-sectional flow area, or a round extrusion can be blow molded to fit around the legs of the leaflets 803c (panel 3), again optimizing the flow area and also potentially improving the security of the leaflets when mated to the shaft. A tissue engagement indicator can provide an additional feature, and a benefit of the radiopaque loop is the possibility of having it act as a tissue engagement indicator. The tip of the wire loop may be shaped to "lead" the tip of the catheter a distance so that the tip of the loop can be visualized under fluoroscopy bending backwards as the needle penetrates the tissue and the distal end of the catheter body approaches the tissue surface. A potential added benefit of using a loop to indicate tissue engagement is the possibility of eliminating the contrast lumen from the shaft, which may allow for overall system size reduction or accommodate a larger treatment lumen allowing for delivery of larger cells, cell aggregates, microspheres, extracellular matrix (ECM) slurries, particles, or higher viscosity therapeutics. The loop may be configured to form a generally conical shape, a wide-mouthed bell shape like a trumpet, or a closed bell shape like a toilet plunger.

[0049] FIG. 8D shows the distal flexible element and needle. The five-filar coil 807 is a five-element coil of 0.008 inch wire with a pitch of 0.046 inch. This flexible element can optionally be made of a cut metal tube 807b (FIG. 8C) which, if thinner-walled and stiffer in the more proximal region, may have the advantage of variable flexibility along its length which can improve column support and therefore improve the ability to penetrate tough tissue in long extensions out of the steerable delivery guide catheter. The shaft typically comprises three main sections including a highly flexible distal section 807, the main length of the shaft 815, and a strain relief section 817. Note that the following items are also referred to in FIG. 7 as the main shaft 705, and the strain relief 703.

[0050] The flexible element may be fabricated with five filler coils of stainless steel round wire 807 as previously described. The main shaft consists of an outer jacket (braided polyamide) 815 and an inner dual lumen (Pebax) 803 (FIG. 8A). The strain relief 817 includes an extension of the main shaft and dual lumen 815, and also has two sections of PEEK: a smaller section 817a that fits inside the handle of the guide catheter, and a larger section 817b that can enter a rotating hemostatic valve (RHV) attached to the proximal luer of the guide catheter, but does not enter the handle of the guide. The step at the end of the larger outer diameter between the two strain relief sections is used as a reference point to be felt by the user to assess when the distal end is just "stored" within the guide catheter, while the junction is just at the proximal edge of the RHV.

[0051] Optionally, an introducer sheath can be slidably attached to the handle along the shaft, allowing the leaflets to fold forward for introduction into the guide catheter. This element can be part of the strain relief, e.g., a snap-on design 817c (panel 1, FIG. 8E). The joint between the main shaft section 815 and the distal flexible element 807 is formed of a thin-walled hypotube or "bushing" bonded in place with a cyanoacrylate adhesive. The joints from the main shaft 815 to the strain relief 817 and from the strain relief to the handle 819 may be made with an epoxy adhesive (see FIG. 8D).

[0052] Wire assemblies, e.g., 801 and 806 in FIG. 8A, may be pre-tinned with Au-Sn solder and then soldered to a stainless steel needle and coil (or other flexible spring element) as a subassembly for ease of manufacture. The radius of curvature of the wire as it exits its attachment point should not be less than 10 times the wire diameter. The minimum recommended ratio is about 5.6:1, but it is likely to plastically deform with use and have a shortened fatigue life. A monolithic set of wire loops, as opposed to a single individual lobe with a straight "leg", offers ease of assembly, consistency of longitudinal and radial spacing, and increased safety in attachment.

[0053] FIG. 8D shows the distal flexible element and needle including a five-filar coil 807, which is a five-element coil of 0.008 inch wire with a pitch of 0.046 inch. This flexible element can optionally be made of a cut metal tube 807b (FIG. 8C) which, if thinner-walled and stiffer in the more proximal region, may have the advantage of variable flexibility along its length which can improve column support and therefore improve the ability to penetrate tough tissue in long extensions out of the steered delivery guide catheter. The shaft comprises three main sections 807, 815, and 817, including the highly flexible distal section 807, the main length of the shaft 815, and the strain relief section 817 (FIG. 8D).

[0054] The treatment and contrast lumens typically run uninterrupted the entire length of the catheter shaft. The junction between the five filler coils 807 and the polyamide jacket 815 is formed with an adhesive lap joint. This is formed either by Loctite 4014 bonding to a thin wall 304 stainless bushing, not shown, with 0.038" ID / 0.042" OD x 0.3" length, or by using the outer surface of the lumen assembly as the lap joint material. Proximal to the coil-shaft junction, the main shaft outer jacket is a flexible torqueable composite consisting of 0.042" ID x 0.054" OD polyamide tubing with 0.0015" wire braid (16 carriers) encapsulated in the wall 815.

[0055] The strain relief assembly 703 serves as a protective transition between the catheter shaft and the handle assembly 701. As shown in FIGURE 8D, the strain relief 81 includes an extension of the main shaft and dual lumens 815 and also has two sections of PEEK: a smaller section (0.062 inch ID x 0.010 inch wall) 817a that fits inside the handle of the guide catheter, and a larger section (0.085 inch ID x 0.010 inch wall) 817b that can enter the rotating hemostasis valve (RHV) 1902 attached to the proximal luer of the guide catheter 1901, but does not enter the handle of the guide. The step between the two outer diameters can be used as a reference point to be touched by the user to assess that the junction is just at the proximal edge of the RHV while the distal end is just "stored" within the guiding catheter, without the need to expose the patient to increased radiation, by using fluoroscopy to verify needle tip position.

[0056] Panels 1 and 2 of FIG. 8F show that the tip positioning (in the collapsed state) may be staggered axially (panel 2), either by staggering root positions or by having different loop sizes, so that if the packing is slightly too tight, the loops at the tips take up more space than the body of the loop. The leaflets may be made to be self-reinforcing in the deployed configuration to reduce the tendency to collapse. One approach is for each loop to thread through the adjacent loop as shown. Another variation shown is the "steam colander" variation 801h (panels 3-6) with a flexible sheet or plate within the curved triangular section of the cone section. Optionally, the edges can have a folding or sliding interlocking mechanism 801i to limit the "spread".

[0057] FIG. 9 is a cross-sectional view of the handle assembly 701 from FIG. 7, which may now be standard for many of the dual lumen catheters. The handle is an ergonomic catheter control feature that contains proximal ports for both the treatment and contrast lumens 901, 903. The catheter shaft 805 is affixed directly to the strain relief assembly using an epoxy adhesive such as Loctite M-06FL. A retaining block 913 is used to integrate the strain relief assembly and catheter shaft with the handle assembly using Loctite 4013 cyanoacrylate adhesive. Inside the handle assembly, the catheter shaft 911 terminates just proximal to the retaining block.

[0058] At the main shaft end, the contrast lumen 907 is isolated and directed towards the contrast proximal luer 901. At the catheter shaft end 911, the treatment lumen is also isolated and a bushing 909 is used to connect an extension tube 905 to the treatment lumen in the main shaft. The proximal end of the extension tube is connected to the treatment proximal luer 903.

[0059] An alternative version of the termination of the contrast and treatment lumens utilizes a "Y" adapter 2201, as illustrated in FIG. 22, allowing the tubing configuration of the concentric treatment lumen 2202 and contrast lumen 2203 to be adhesively bonded directly to the "Y" adapter which terminates in Luer lock fittings for the treatment and contrast injection ports 901 and 903.

[0060] Current commercially available transendocardial injection systems use helical needles made from 27RW gauge 304 stainless steel hypotubes (inner diameter = 0.008 inches). The desire to pass larger sized entities led to the development of larger helically wound hypotubes. Material and design constraints (functional requirements) were used to optimize the helical parameters: pitch, helix inner diameter, helix outer diameter, hypotube inner diameter, and hypotube wall thickness. To further optimize an acceptably formed needle, various forming techniques were used, for example, to control the ovalization of the hypotube inner diameter. Figures 10-12 show the distal tip of a three lumen catheter with a two lumen delivery needle 1130, a contrast lumen 1120 terminating at the base of the needle, and a flexible distal element 1110 of a five-stranded filler coil component. All of these features are bonded together as the distal tip 1140 as shown, using two-part epoxy as the bonding material. The preferred embodiment of the helix plus needle element is a helically shaped, double stainless steel hypotube structure 1130. For the preferred embodiment, the proximal ends of both hypotubes are joined to an independent tube 1210, which serves as an axial conduit for fluid transport. An alternative embodiment includes a lumen-in-lumen design 1150, previously described by Miller in U.S. Pat. No. 7,736,346. The helical needle 1130 also serves as a distal electrode for electrophysiological sensing capabilities, connected via an electrode wire 12, and the exposed flexible distal element serves as a return electrode, also connected by a wire not shown.

[0061] 13 shows a cross-sectional view of this three lumen configuration 1340, spanning the distance of the device to the handle (electrode wires not shown). The distal and proximal electrode wires also span the length of the catheter with a three lumen bundle 1310 from their distal attachment points to the handle.

[0062] Figure 14 shows the electrical connections of the system in more detail. The preferred design of the proximal sensing electrode uses a distal flexible element formed of an exposed pentafilar coil 1110 as the proximal electrode. An electrode wire 1410 is attached to the proximal end of the flexible element. One method of wire attachment is accomplished by feeding the electrode wire through a mounting bushing 1405, winding the wire around the flexible element 1440, and then soldering in place 1420. An alternative second electrode design uses a conductive proximal ring 1430 with the electrode wire directed through the flexible element and attached to the ring.

[0063] Figure 15 shows the internal configuration of the spiral plus handle assembly. The following describes the proximal termination within the handle 1610 for the three fluid carrying lumens and the two electrode wires. A multi-channel electrical connector 1630 is incorporated into the handle, with both electrodes 1620 connected to components within the handle. All three lumens used in the preferred three lumen design are contained within the catheter shaft 1030, continue through the strain relief assembly 1040, and exit within the handle assembly. The individual lumens are then directed to and exit from proximal ports within the handle 1140, where they connect to standard luer fittings.

[0064] 16 and 17 show a large bore needle based on 23Ga tubing 1700, and a 27RW gauge helical needle 1750. The needle is secured into the tip assembly by first using an ultraviolet adhesive such as Loctite 3301 to bond it into the treatment lumen, and then secondly embedding the needle and treatment lumen into a five-strand filler coil using an epoxy such as Loctite M-31CL to form a unitary structure 1720 that captures the loops of the helix. During distal epoxy encapsulation, a ribbon of PTFE is fed between the coiled loops of the needle and into the contrast lumen (adjacent to or concentrically around the treatment lumen), which creates a flow path through the epoxy when removed after the epoxy has hardened. The contrast lumen terminates at the distal end of the embedment at the base of the exposed needle 1730. The contrast lumen can be used to assess that the tip of the shaft 805 is firmly positioned against the myocardium when the needle is threaded into the tissue by injecting contrast and observing on an x-ray the resulting flow and how it pools and hangs in a boundary layer against the myocardium or whether it simply smokes out with the cardiac output flow.

[0065] FIG. 18 shows an alternative design for distal perforation protection that utilizes existing balloon technology when engaging cardiac tissue during transendocardial therapy delivery. FIG. 18 shows three different views of a distally mounted balloon feature: a side view in a non-inflated state 1801, a side view in an inflated state 1802, and an isometric view in an inflated state 1803. The distally mounted balloon feature provides a barrier at the proximal end of the needle 1010, as shown at 1802. A preferred deployment would involve inflating the balloon using saline or contrast after it is exposed from its guiding catheter and prior to full engagement into the heart wall. To inflate the balloon, fluid is injected into a handle-mounted port that extends through an internal lumen that terminates below the surface of the balloon region in the distal end. A major advantage of the present design is the ability to have a perforation protection system built into the distal end of the spiral infusion catheter that is capable of functioning when rotated during standard use with a spiral needle. The use of contrast as the balloon inflation medium provides the added benefit of a large amount of radiopaque volume at the endocardial surface that can further aid in assessment of needle location and engagement. A suitable balloon material that conforms to the catheter distal end in the uninflated state 1810 is bonded to a proximal distal tip structure at its distal and proximal ends. A port below the balloon structure connects via a suitable conduit to an inflation port in the handle.

[0066] Currently available transendocardial injection systems (BioCardia, Inc.) use helical needles made from 27RW gauge 304 stainless steel hypotubes (inner diameter = 0.008 inches, outer diameter = 0.016 inches). The desire to use a larger lumen to pass a wider range of therapeutic agents led to the development of helical wound needles utilizing larger gauge tubing. Material property constraints and the desire to maintain a minimum profile were evaluated to optimize the helical needle parameters of pitch, helix inner diameter, helix outer diameter, hypotube inner diameter, and hypotube wall thickness. To further optimize acceptably formed needles, various forming techniques were used, for example, to control ovalization of the hypotube inner diameter. Mandrel sizes were varied to control material deformation while attempting to maintain maximum helical diameter within constraints. Other methods of controlling excessive ovalization included freezing the water in the hypotube before coiling, annealing the hypotube before coiling, and sidewall support during winding.

[0067] Commercial tube benders use a general rule of thumb that the bend radius of coiled tubing should not be less than twice the tube diameter, but using proprietary methods, a 1:1 relationship can be achieved. Theoretical limits associated with material elongation have been estimated based on the elongation limit ratio being 60% elongation=0.5*tube diameter (TD) / bend radius (RB), based on 304SS. The mandrel diameter (MD) is 2*RB-TD, and the helix diameter is 2*TD+MD.

[0068] For example, a 23 gauge TW304SS hypotube with an OD=0.025 inch has a theoretical minimum bend radius at 60% elongation (RB=(0.5*TB) / 0.6) of 0.021 inch. The resulting theoretical minimum mandrel diameter is 0.019 inch with a helix diameter of 0.069 inch. Experimental results differed from this theory because the hypotube tended to fail via ovalization versus tensile failure and the wound helix experienced "bounce" such that the final helix diameter was larger than theoretical.

[0069] The mandrel used to fabricate the 23 Gauge TW large bore needle was specified to have a minor diameter of 0.018±0.002 inches, resulting in a helical outer diameter ranging from 0.071 inches to 0.074 inches with an inner diameter of approximately 0.024 inches. Thus, the "bounce" and ovalization experienced by the helix was evidenced, demonstrating that a 23 Ga TW helical needle wound on a φ0.018 inch mandrel can feasibly meet the maximum outer diameter specification.

[0070] 19 shows the assembled system consisting of: a Morph 895 deflectable tip catheter 1901 with an attached RHV (Merit MAP150) 1902, a syringe attached to the side port of the RHV 1903, a helical catheter 1904, a syringe attached to the treatment port 1905, and a syringe attached to the contrast port 1906. The helical needle at tip 1907 is advanced and retracted through the guide to extend past the deflectable tip of the guide 1908 controlled by the guide deflection knob 1909.

[0071] FIG. 20 shows a helical catheter consisting of a helical needle 1907, a flexible distal element 2001, a braided shaft 2002, a two-part strain relief 2003, a handle 2004, a treatment port 903, and a contrast port 901.

[0072] 21A-21D show one method of helical needle formation, where the hypotube is wrapped over a mandrel 2001 that supports the sides of the tube to reduce ovalization. The needle can be formed with hypodermic tubing of various sizes. The current commercial iteration is made from 27GA RW 304 stainless steel. Larger diameter versions are constructed using 24 and 23Ga tubing. The preferred stainless steel embodiment meets ISO 9626 appendices A and E. Additional methods and materials that overcome the limitations of material cold working may include direct forming to form using electroforming of nickel or other materials over a chemically removable wound mandrel such as aluminum or copper. After winding, the primary face is cut 2002 and then secondary faces are added 2003. Additional options may include alternative tips such as closed forms with side holes, trocars, or Tuohy tips. In a preferred embodiment, the final formed needle has a straight tail 2004 that is offset from the center by an amount equal to the lumen offset in the shaft assembly and is coupled into the treatment lumen.

[0073] While the above is a complete description of the preferred embodiments of the present invention, various alternatives, modifications, and equivalents may be used. Thus, the above description should not be taken as limiting the scope of the invention, which is defined by the appended claims.

Claims

1. A needle injection catheter system suitable for delivering an active substance to the heart, the needle injection catheter system comprising: a catheter body having a distal end, a proximal end, and a delivery tube passing therethrough, the catheter body having a flexible, elastic distal section, the delivery tube having a delivery lumen; a helical needle extending from the distal end of the catheter body, the helical needle having at least one large bore helical delivery lumen connected to receive an injectable substance from the delivery lumen of the catheter body, the at least one large bore helical delivery lumen configured to deliver particles having an average particle size of at least 100 μm; a guide catheter, the guide catheter having an angle of at least 70 degrees such that the guide catheter orients the helical needle and the catheter body as they are advanced through the guide catheter; Equipped with the catheter body and the helical portion of the helical needle are rotatable; A catheter system, wherein a center of rotation of the helical portion of the helical needle coincides with a center of rotation of the catheter body.

2. The catheter system of claim 1, wherein the delivery lumen and the at least one large diameter spiral delivery lumen are sufficiently large to allow passage and injection of a drug or biological substance.

3. The catheter system of claim 1, wherein the flexible, elastic distal section comprises a multi-filar stainless steel coil.

4. The catheter system of claim 1, wherein the guiding catheter is sufficiently small so as to be able to pass through an 8 French sheath.

5. The catheter system of claim 1, wherein the guiding catheter is sufficiently small so as to be able to pass through a 6.4 French sheath.

6. The catheter system of claim 1, wherein the catheter body has at least one tube in addition to the delivery tube, each of the at least one tube having a lumen, and the helical needle has at least two large diameter helical delivery lumens, one of the at least two large diameter helical delivery lumens connected to each lumen of at least the catheter body.

7. The catheter system of claim 1, wherein the catheter body includes a rigid proximal portion.

8. The catheter system of claim 7, wherein the rigid proximal portion of the catheter body comprises a braided polymer tube and the flexible, elastic distal section of the catheter body comprises a helical metal coil winding around the distal portion of the delivery tube.

9. The catheter system of claim 1, wherein at least a portion of the catheter body includes a helical coil that winds around a portion of the delivery tube.

10. The catheter system of claim 1, wherein the catheter body has a first tube for delivering an injectable composition to the helical needle and a second tube for delivering a contrast agent to the base of the helical needle.

11. The catheter system of claim 1, further comprising a handle on the proximal end of the catheter body.

12. The catheter system of claim 1, wherein a fixed guiding catheter having an angle of at least 90 degrees is capable of deflecting the flexible, elastic distal section of the catheter body to align the distal end with a target location on the endocardial wall when the guiding catheter is within the cardiac chamber.

13. The catheter system of claim 1, wherein the guide catheter is capable of being deflected to an angle of at least 90 degrees.

14. The catheter system of claim 1, wherein the agent is an active substance.

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