Transendocardial delivery catheter

Abstract

Provision of transendocardial delivery catheters. [Solution] The needle injection catheter includes a catheter body having a distal end, a proximal end, a rigid proximal portion, a flexible distal portion, and a delivery lumen through them. In the first embodiment, a straight injection needle extends coaxially from the distal end of the flexible portion of the catheter body, and a plurality of penetration limiting elements are circumferentially positioned around the base of the straight injection needle and configured to fold radially inward relative to the shaft of the needle when constrained in the tubular lumen, and to extend radially outward when unconstrained. In the second embodiment, a spiral needle extends from the distal end of the flexible portion of the catheter body. The spiral needle has at least one spiral delivery lumen connected to receive an injectable substance from the delivery lumen of the catheter body.

Description

[Technical Field]

[0001] (Cross-Reference to Related Application) This application claims the benefit of U.S. Provisional Application No. 61 / 884,834, filed on September 30, 2013 (Attorney Docket No. 29181-706.101), the entire content of which is hereby incorporated by reference into this specification.

[0002] (Background of the Invention) 1. Field of the Invention The present invention relates generally to medical methods and systems. More specifically, the present invention relates to medical methods and systems suitable for delivery of substances to the heart via the radial artery, and for intracardiac delivery of cell aggregates and other aggregated substances. [Background Art]

[0003] Currently, local biotherapeutic delivery to the heart is 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 from Johnson and Johnson Biological Delivery Systems (Diamond Bar, California), and the BioCardia® Helical Infusion System from BioCardia, Inc., (San Carlos, California), the assignee of the present invention. Both of these systems utilize an 8 French introducer deployed through the femoral artery. Both systems have a flexible distal portion that is deflectable (steerable) from a proximal handle location, and the BioCardia system comprises a centrally positioned catheter that can be advanced from the introducer to extend to the heart wall to provide enhanced access for the operator.

[0005] Typically, it is desirable to use the smallest puncture site and the smallest device 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 the closure device. This can result in a significant reduction in the cost and mortality rate for certain intervention procedures.

[0006] Smaller devices that allow access to the vascular system via the radial artery in the arm (as opposed to the femoral artery in the groin) offer enormous advantages from a cost perspective, as patients are able to walk immediately after the procedure. Reducing the amount of time patients must spend recovering on a Gurney or in bed has additional quality-of-life benefits for the patient, in addition to the economic benefit of a shorter hospital stay. Radial artery access requires smaller instruments, as is extensively detailed in the literature. A 7F guide and a 6F sheath (1 French (Fr) equals 0.33 mm) are the largest devices recommended for such procedures, and outcomes improve with the use of smaller guides and sheaths. Entire academic publications, such as Cardiac Interventions Today April 2011, Volume 5, No 2, are dedicated to radial artery access for procedures and are incorporated herein by reference. Radial artery diameters are such that 95% of all patients have radial arteries with a diameter greater than 2.2 mm and can be fitted with a 5-French sheath (typical outer diameter of 6.5 French) or a 6.5-French guide; 60% have radial arteries with a diameter greater than 2.6 mm and can be fitted with a 6-French sheath (outer diameter of 7.5 French) or a 7.5-French guide; 40% have radial arteries with a diameter greater than 2.95 mm and can be fitted with a 7-French sheath (outer diameter of 8.5 French) or an 8.5-French guide; and only 20% have radial arteries with a diameter greater than 3.3 mm and can be fitted with an 8F sheath (outer diameter of 9.5 French) or a 9.5-French guide. Saito S et al Catheter Cardiovas Interve 1999;46:173-178. Typically, sheath size refers to the size of the guide catheter that can be fitted through it.

[0007] The specific challenge with respect to transradial artery access is to provide a guide catheter that can be advanced straight through the vascular system via a guidewire in a nontraumatic manner with a small profile, while minimizing the possibility of damaging the vascular system during advancement into the heart, due to the small diameter of the catheter shaft and the rigidity of the distal region of the catheter, and can be used to guide a transendocardial delivery catheter across a small diameter, traversing a bend in the heart with an angle greater than 70 degrees (preferably 90 degrees or more) from the axis of the catheter.

[0008] In some cases, a “sheathless” guide catheter can be used without a sheath, allowing the majority of patients to be treated. The use of a 5.5F or 6.5F sheathless guide catheter can provide a smaller route through the radial artery by eliminating the need for a sheath.

[0009] Once inside the heart, stem cells and other therapeutic substances can be injected transendocardially using straight, spiral, or other injection needles. Spiral needles typically have smaller bore diameters, while straight needles frequently have larger bore diameters. Larger straight needles are typically used to deliver large active substances and particles such as stem cells and other cells, cell aggregates, microspheres, extracellular matrix (ECM) slurries, and other highly viscous therapeutics such as cardiospheries with diameters of 60–150 μm, as well as equivalents, with effective diameters as large as 80 μm and 150 μm. Spiral and other small-bore needles can typically have difficulty passing such large active substances, even when their bore diameter is larger than the active substance. This is especially true for agglutinating active substances, which can result in increased viscosity that hinders delivery. While straight, large-diameter needles can deliver such active substances, after injection, stem cells and other large aggregates are often released back into the cardiac chambers during myocardial contraction, potentially leading to loss of the injectable substance and, in the case of larger aggregates and particles, a 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 is particularly desirable to provide improved systems and methods for facilitating the introduction of needle-based delivery catheters via radial artery approaches, such systems preferably including a distal perforation protection system with minimal spatial requirements that is passive, operates without active action, and provides robust perforation protection. Furthermore, it would be desirable to provide improved systems and methods for using needle-based delivery catheters for delivering cells, drugs, and other therapeutic agents with reduced risk of loss of injected material returning to the cardiac chambers as a result of cardiac contraction. At least some of these objectives can be satisfied by the present invention as described below.

[0011] 2. Explanation of background technology In recent years, maneuverable guides and sheaths have been developed that enable significant advantages for transendocardial delivery and other cardiovascular procedures. See U.S. Patents 7,840,261, 7,402,151, and U.S. Patent Publications 2012 / 0123327 and 2008 / 0287918, whose full disclosures are incorporated herein by reference. Maneuverable guides and sheaths typically have a wall thickness of 1 French (1 French (Fr) is equal to 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 maneuverable sheath can be used to enter the heart via the radial artery using a guide catheter with a flexible distal end, such as the BioCardia spiral infusion system. For such a system, a 5Fr maneuverable sheath has an inner diameter of 5.5 French and an outer diameter of just over 2.2 mm, allowing a 5.2 French spiral infusion catheter system (BioCardia, Inc.) to pass through easily and, using the spiral infusion system, would substantially function as a transradial maneuverable sheath for transendocardial delivery, enabling a useful maneuverable transendocardial delivery platform in nearly 95% of all patients.

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

[0014] Penetration limiter devices above the end of transendocardial delivery catheters are known, such as those described by Eclipse Surgical Technologies in U.S. Patent No. 6,322,548. These systems are passive systems but require distal catheter shaft structures that consume area at the distal end of the catheter and, depending on their size, would obstruct transradial artery access. U.S. Patents No. 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 limit space for advanced therapeutic lumen designs, such as contrast agent ports and lumen inclusion, to increase the profile of the distal region and to limit space for advanced therapeutic lumen designs, such as using a large-bore spiral needle and a double-lumen penetrating element, which is important for the delivery of active materials that are of higher viscosity or larger size or may aggregate, to release at the base of the penetrating element and to ensure engagement. Cardiac Interventions Today April 2011, Volume 5, No 2 and Saito S et al Catheter Cardiovas Interve 1999;46:173-178 explains this 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] U.S. Patent Application Publication No. 2012 / 0123327 [Patent Document 4] U.S. Patent Application Publication No. 2008 / 0287918 [Patent Document 5] U.S. Patent Application Publication No. 2007 / 0005018 [Patent Document 6] U.S. Patent Application Publication No. 2010 / 0168713 [Patent Document 7] U.S. Patent No. 6,322,548 [Patent Document 8] U.S. Patent No. 7,803,136 [Patent Document 9] U.S. Patent No. 8,361,039 [Patent Document 10] U.S. Patent No. 8,414,558 [Overview of the project] [Means for solving the problem]

[0016] (Summary of the invention) The present invention provides methods and systems for intracardiac transendocardial infusion of various substances, including drugs, cells, specifically large cell aggregates, and other particulate matter. Many of these methods and systems are particularly suited to radial artery access, but can also be relied upon for femoral artery access. The systems of the present invention may include a plurality of interchangeable components, such as an introducer sheath, a pre-formed or pre-molded guide catheter, a maneuverable or deflectable guide catheter, a pre-formed sheathless guide catheter, a maneuverable sheath or sheath guide, and a sheathless maneuverable sheath or sheath guide. Each of the various guide catheters may be used for advancing a plurality of types of delivery catheters, each having, for example, a spiral needle, a straight needle, a coaxial spiral needle, a coaxial straight needle, a twin-barrel spiral needle, a twin-barrel curved needle, a twin-barrel straight needle, a large-bore straight needle, a large-bore curved needle, a large-bore spiral needle, and equivalents. The delivery catheter may also include a contrast agent lumen that is released 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, three-dimensional echo navigation, and fusion imaging systems that can deliver MRI, CT, or echo data and merge it with fluoroscopic images. Furthermore, these delivery systems have the ability to enable several embodiments of the wide variety of diagnostic and therapeutic drug delivery disclosed, as the elements of the delivery system invention enable these novel therapeutic 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 comprises advancing a guiding catheter through the radial artery (and intervening arterial vasculature) into the target heart chamber. The catheter may typically enter the right or left ventricle from the right side of the heart, but may also be further advanced transseptally within the heart to reach the left ventricle from the right side of the heart or another heart chamber. The guiding catheter is positioned to align the distal tip of the guiding catheter with a target location on the endocardial wall of the heart chamber. The needle injection catheter is advanced through the lumen of the guiding 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 within the myocardium. The plurality of penetration limiting elements remain constrained within the guiding catheter until the straight needle emerges from the distal tip, wherein the elements self-deploy radially outward from the base of the needle to limit penetration of the needle into the myocardium, so as to reduce the risk of perforation of the endocardial wall, and typically deploy elastically as a result of their own spring force upon release of constraint.

[0018] In an exemplary embodiment, the positioning step may comprise rotating and / or axially translating the guiding catheter, which has a pre-shaped deflection at its distal end. In alternative exemplary embodiments, the positioning step may comprise deflecting or "steering" the distal tip of the guiding catheter while the guiding catheter is within the heart chamber. In all cases, the guiding catheter may typically be introduced into the heart chamber over a previously placed guidewire from the radial artery in a conventional manner.

[0019] In a further exemplary embodiment, advancing the needle injection catheter may comprise constraining the penetration limiting elements within an introducer sleeve. The distal end of the sleeve is engaged against the proximal hub of the guiding catheter, and the distal end of the needle injection catheter is advanced into the proximal portion of the guiding catheter while the penetration limiting elements remain constrained.

[0020] In further exemplary embodiments, the penetration limiting element may comprise an elastic petal-shaped portion having a base attached to the catheter body at the base of a straight needle. The petal-shaped portion may be shaped to curve outward from the catheter body when unrestrained. The petal-shaped portion may be a wire loop folded over a continuous length of shape-memory wire, and a platinum wire may be wrapped around the shape-memory wire to provide radiopaqueness. Alternatively, the petal-shaped portion may comprise a solid leaf or other structure that overlaps when folded inward relative to the needle shaft. Typically, in all such embodiments, the catheter comprises 2 to 6 petal-shaped portions, 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 through them. Rigidity means that the proximal portion of the catheter body may have sufficient columnar strength and pushability to advance through relatively non-tortuotic regions of the vascular system, specifically from the radial artery to the heart. Flexible means that the distal portion may advance across small-radial curves to allow for positioning within the cardiac chambers through pre-formed or deflected regions of the guide catheter. The catheter further includes a straight injection needle extending coaxially from the distal end of the flexible portion of the catheter body. Multiple penetration limiting elements are circumferentially positioned 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.

[0022] The penetration limiting element of a needle injection catheter may comprise an elastic petal-shaped portion having a base attached to the catheter body at the base of a straight needle. The petal-shaped portion may be shaped to curve outward from the catheter body when unrestrained. The petal-shaped portion may be a wire loop folded over a continuous length of shape-memory wire, and a platinum wire may be wrapped around the shape-memory wire to provide radiopaqueness. Alternatively, the petal-shaped portion may comprise a solid leaf or other structure that overlaps when folded inward relative to the needle shaft. Typically, in all such embodiments, the catheter comprises 2 to 6 petal-shaped portions, most typically 3.

[0023] In exemplary embodiments, 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 an injectable composition to the needle and a second lumen for delivering a contrast agent 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, and the handle may optionally include valves, Luer connectors, and other fillers and components for connection to a source of the substance to be delivered, contrast agent, guidewire, and equivalents. The catheter body may preferably be configured to be delivered through a 6.5 Fr or smaller guide catheter.

[0024] In a further embodiment of the present invention, the catheter system comprises a needle injection catheter as described above, in combination with a guide catheter having a lumen configured to receive a needle injection catheter and to radially restrain a plurality of penetration limiting elements when the needle injection catheter is present therein. The guide catheter of such a system may have a pre-formed bend near its distal end so that the guide catheter can be rotated so that its distal end is aligned with a target location on the endocardial wall when the guide catheter is in a cardiac chamber. Alternatively, the guide catheter may have a deflectable (also referred to as maneuverable) distal end so that the guide catheter can be aligned with a target location on the endocardial wall when the guide catheter is in a cardiac 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 through them. The spiral needle has at least one spiral 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 at least one spiral lumen are large enough 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 typically has a diameter of at least 0.50 mm, and is typically 0.71 mm at its non-circular principal axis, and the spiral lumen typically has a diameter of at least 0.2 mm, and is typically about 0.43 mm.

[0026] In specific embodiments, 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 of which is connected to at least each of the catheter body lumens. The catheter body may comprise a rigid proximal portion and a flexible distal portion as described above, the rigid proximal portion of the catheter body may comprise a braided polymer tube, and the flexible distal portion of the catheter body may comprise a helical metal coil. The catheter body may comprise 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 located on the proximal end of the catheter body.

[0027] In a further embodiment of the present invention, the catheter system comprises 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 in such a system may have a pre-formed 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 a cardiac chamber. Alternatively, the guide catheter may have a deflectable (also referred to as maneuverable) distal end to allow the distal end to align with a target location on the endocardial wall when the guide catheter is in a cardiac chamber.

[0028] In a fourth aspect of the present invention, a method for delivering particulate matter into the endocardial wall of a beating heart chamber comprises the step of transvascularly introducing a large-bore needle injection catheter having a spiral needle into the heart chamber. The particulate matter to be delivered specifically includes cells, stem cells, stem cell aggregates, and any other therapeutic or diagnostic substances that may pose a risk of embolism if incidentally released into the heart chamber at the time of injection, either as a result of being pushed out from the injection site as a result of myocardial contraction as the heart beats, or otherwise released. The spiral needle of the large-bore needle injection catheter is advanced into the endocardial wall of the heart chamber such that the port of the needle lies near the inner end of the spiral tissue canal formed by the needle. Typically, particulate matter having an average particle size of at least 100 μm is injected through the needle into the inner end of the spiral tissue canal. Backflow of the injected material through the spiral tissue canal is prevented within the spiral shape of the canal, even after the spiral needle has been 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 spiral needle may have a spiral lumen having 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 principal axis, and the spiral 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 spiral needle typically has at least two spiral delivery lumens, one of which is connected to at least each of the catheter body lumens. This specification also provides, for example, the following items: (Item 1) A method for introducing a needle injection catheter into a cardiac chamber via the radial artery, The steps include advancing the guide catheter into the cardiac chamber through the radial artery, The steps include positioning the lead catheter so that its distal tip aligns with a target location on the endocardial wall of the cardiac chamber, Steps include: advancing the needle injection catheter through the lumen of the lead catheter such that a straight needle protruding coaxially emerges from the distal tip of the needle injection catheter, penetrates the endocardial wall, and positions the injection port at the tip of the needle within the myocardium, wherein a plurality of penetration-restricting elements are points that self-unfold radially outward from the base of the needle to restrict the needle from penetrating the myocardium in order to reduce the risk of perforation of the endocardial wall, and the elements remain constrained within the lead catheter until the needle emerges from the distal tip; and Methods that include... (Item 2) The method according to item 1, wherein the positioning step includes rotating and / or translating the guide catheter, which has a pre-formed deflection at its distal end. (Item 3) The method according to item 1, wherein the positioning step includes deflecting the distal tip of the guide catheter while the guide catheter is in the cardiac chamber. (Item 4) The method according to item 1, wherein the step of advancing the needle injection catheter includes restraining the penetration limiting element within the introducer sleeve, engaging the distal end of the sleeve with the proximal hub of the guide catheter, and advancing the distal end of the needle injection catheter into the proximal portion of the guide catheter while the penetration limiting element remains restrained. (Item 5) The method according to item 1, wherein the penetration limiting element comprises an elastic petal-shaped portion having a base attached to the catheter body at the base of the straight needle. (Item 6) The method according to item 5, wherein the petal-shaped portion is shaped to curve outward from the catheter body when not restrained. (Item 7) The method according to item 6, wherein the petal-like portion is a wire loop folded over a continuous length of shape-memory wire. (Item 8) The method according to item 7, wherein a platinum wire is wrapped around and wound over the shape memory wire to provide radiopaqueness. (Item 9) The method according to item 6, wherein the petal-like portion is a solid leaf that overlaps when folded inward relative to the needle shaft. (Item 10) The catheter is the method described in item 5, comprising 2 to 6 petal-shaped portions. (Item 11) A catheter body having a distal end, a proximal end, a rigid proximal portion, a flexible distal portion, and a delivery lumen extending through it, A straight injection needle extends coaxially from the distal end of the flexible portion of the catheter body, Multiple penetration limiting elements are positioned circumferentially around the base of the straight injection needle and are configured to fold radially inward relative to the shaft of the needle when constrained within a tubular lumen, and to extend radially outward when not constrained. A needle injection catheter equipped with a needle. (Item 12) The catheter according to item 11, wherein the penetration limiting element comprises an elastic petal-shaped portion having a base attached to the catheter body at the base of the straight needle. (Item 13) The catheter according to item 12, wherein the petal-shaped portion is shaped to curve outward from the catheter body when not restrained. (Item 14) The catheter described in item 13, wherein the petal-shaped portion is a wire loop folded over a continuous length of shape-memory wire. (Item 15) The catheter according to item 14, wherein a platinum wire is wound around the shape memory wire to provide radiopaqueness. (Item 16) The catheter according to item 13, wherein the petal-shaped portion is a solid leaf that overlaps when folded inward relative to the needle shaft. (Item 17) The catheter is the catheter described in item 12, comprising 2 to 6 petal-shaped portions. (Item 18) The catheter according to item 11, wherein the rigid 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) The catheter according to item 11, wherein the catheter body has a first lumen for delivering an injectable composition to the needle and a second lumen for delivering a contrast agent to the base of the needle. (Item 20) The catheter according to item 11, further comprising a handle on the proximal end of the catheter body. (Item 21) The catheter according to item 11, wherein the catheter body is configured to be delivered through a 6.5Fr lead catheter. (Item 22) The needle injection catheter described in item 11, A guide catheter having a lumen, configured to receive the aforementioned needle injection catheter and to radially restrain a plurality of penetration limiting elements when the needle injection catheter is therein, A catheter system equipped with the following features. (Item 23) The catheter system according to item 22, wherein the lead catheter has a pre-formed bend near its distal end so that the lead catheter can be rotated to align its distal end with a target location on the endocardial wall when the lead catheter is in a cardiac chamber. (Item 24) The catheter system according to item 22, wherein the lead catheter has a deflectable distal end so as to align the distal end with a target location on the endocardial wall when the lead catheter is in a cardiac chamber. (Item 25) A catheter body having a distal end, a proximal end, and a delivery lumen passing through them, A spiral needle having at least one spiral 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, wherein the delivery lumen and the at least one spiral lumen are large enough to allow the passage and injection of a drug or biological substance having an average diameter of at least 50 μm. A large-diameter needle injection catheter equipped with a large-bore needle. (Item 26) The catheter according to item 25, wherein the delivery lumen has a diameter of at least 0.5 mm. (Item 27) The catheter according to item 26, wherein the helical lumen has a diameter of at least 0.2 mm. (Item 28) The catheter according to item 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 of which is connected to at least each of the catheter body lumens. (Item 29) The catheter according to item 25, wherein the catheter body comprises a rigid proximal portion and a flexible distal portion. (Item 30) The catheter according to item 27, wherein the rigid 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) The catheter according to item 25, wherein the catheter body has a first lumen for delivering an injectable composition to the needle and a second lumen for delivering a contrast agent to the base of the needle. (Item 32) The catheter according to item 25, further comprising a handle on the proximal end of the catheter body. (Item 33) The large-diameter needle catheter described in item 25, A guide catheter having a lumen configured to receive the aforementioned large-diameter needle catheter, A catheter system equipped with the following features. (Item 34) The catheter system according to item 33, wherein the lead catheter has a pre-formed bend near its distal end so that the lead catheter can be rotated so that the distal end aligns with a target location on the endocardial wall when the lead catheter is in a cardiac chamber. (Item 35) The catheter system according to item 33, wherein the lead catheter has a deflectable distal end so as to align the distal end with a target location on the endocardial wall when the lead catheter is in a cardiac chamber. (Item 36) A method for delivering particulate matter into the endocardial wall of the cardiac chambers of a beating heart, The steps include introducing a large-diameter needle injection catheter with a spiral needle into the cardiac chamber via the vascular system, The steps include rotating and advancing the spiral needle of the large-diameter needle injection catheter into the endocardial wall of the cardiac chamber such that the port of the needle lies near the inner end of the spiral tissue canal formed by the needle, The steps include: injecting particulate matter having an average particle size of at least 50 μm into the inner end of the helical tissue tube through the needle, wherein backflow of the injected material through the helical tissue tube is prevented within the helical shape of the tube, even after the helical needle has been withdrawn; and Methods that include... (Item 37) The catheter according to item 36, wherein the catheter has a catheter body with a delivery lumen having a diameter of at least 0.5 mm. (Item 38) The method according to item 37, wherein the helical needle has a helical lumen with a diameter of at least 0.2 mm. (Item 39) The method according to 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 of which is connected to at least each of the catheter body lumens. [Brief explanation of the drawing]

[0030] [Figure 1] Figures 1 and 2 illustrate prior art induction and delivery catheters that may be used in a certain implementation of the present invention. [Figure 2] Figures 1 and 2 illustrate prior art induction and delivery catheters that may be used in a certain implementation of the present invention. [Figure 3] Figures 3A and 3B illustrate the spiral delivery catheter implementation of the present invention. [Figure 4] Figures 4A and 4B illustrate a needle injection catheter having a straight injection needle that is advanced from a guide catheter and surrounded at its base by a penetration limiting element according to the present invention. [Figure 5] Figure 5 illustrates the distal tip of a needle injection catheter having a straight injection needle according to the present invention. [Figure 6-1] Figures 6A to 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 guide catheter, according to the present invention. [Figure 6-2] Figures 6A to 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 guide catheter, according to the present invention. [Figure 7] Figure 7 illustrates an exemplary delivery catheter having two lumens and a handle assembly. [Figure 8A] Figures 8A-1 to 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]Figures 8A-1 to 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] Figures 8A-1 to 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] Figures 8A-1 to 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] Figures 8A-1 to 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] Figures 8A-1 to 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] Figure 9 is a cross-sectional view of a handle assembly for a needle injection catheter according to the present invention. [Figure 10] Figures 10-12B show the distal tip of a triple-lumen needle injection catheter with two lumen spiral injection needles. [Figure 11] Figures 10-12B show the distal tip of a triple-lumen needle injection catheter with two lumen spiral injection needles. [Figure 12] Figures 10-12B show the distal tip of a triple-lumen needle injection catheter with two lumen spiral injection needles. [Figure 13] Figures 13A and 13B show the design and manufacturing details of the three-lumen catheter body. [Figure 14] Figures 14A-14C show the electrical connections of the delivery catheter in more detail. [Figure 15] Figure 15 shows the internal configuration of the handle assembly for the helical needle delivery catheter of the present invention. [Figure 16]Figures 16 and 17 show the design and manufacturing details of the large-diameter spiral needle for the delivery catheter of the present invention. [Figure 17] Figures 16 and 17 show the design and manufacturing details of the large-diameter spiral needle for the delivery catheter of the present invention. [Figure 18] Figures 18A–18C illustrate alternative designs for penetration limitation that can provide distal perforation protection using existing balloon technology when engaging with cardiac tissue during transendocardial therapeutic delivery. [Figure 19] Figure 19 shows an assembled system including a deflectable tip guide catheter with a valve, a syringe attached to the side port of the valve, a spiral needle delivery catheter, a syringe attached to the therapeutic port of the valve, and a syringe attached to the contrast agent port. [Figure 20] Figure 20 illustrates a spiral needle injection catheter, which includes a spiral needle, a flexible distal element, a braided shaft, a two-part tension reliever, a handle, a treatment port, and a contrast agent port. [Figure 21] Figures 21A to 21D show a spiral needle formed by wrapping a hypo tube around a mandrel that supports the sides of the tube to reduce deformation (ellipticization). [Figure 22] Figure 22 shows alternative designs for terminating contrast agents and treatment lumens using a "Y-shaped" adapter or other handles. [Modes for carrying out the invention]

[0031] This patent application discloses elements of each of these inventions, but their uses are by no means limited to the other elements described herein.

[0032] (Description of the invention) Figure 1 (prior art) shows a pre-formed 6F Hockey Stick (HS) 90cm guide catheter 100, such as the ConcierGE® guide catheter available from Merit Medical Systems, Inc., which can be advanced straight or over either a dilator or guidewire from either the femoral or radial artery. Due to the high flexibility of the distal compartment, the guide catheter may be safely advanced across the aortic valve into the left ventricle. The guide catheter 100 may also be advanced into the femoral artery using any commercially available 6Fr sheath. For radial artery access, a longer 25cm sheath, such as the Boston Scientific Super Sheath Catalog 16037-06B, is preferred to avoid complications involving radial artery spasm, which frequently occur in patients.

[0033] Figure 2 (prior art) shows a pre-formed 6Fr HS 90cm lead catheter 100 after insertion of a transendocardial infusion catheter 200 with a highly flexible distal compartment 202 having a length of at least 6-10cm, with the central straightening element such as a dilator or wire removed and the end of the lead catheter reaching beyond 3.5cm-7cm. Here, the penetrating element is a helical needle 204 that can be easily rotated within a fixed guide and advanced to engage the catheter into cardiac tissue. The highly flexible distal compartment 202 on the transendocardial infusion catheter 200 does not straighten the highly flexible guide portion on the 6Fr lead catheter, allowing the fixed guide to advance and rotate, and then the helical needle 204 to extend to the vertical wall using the transendocardial delivery system, which allows it to penetrate the tissue and achieve therapeutic or diagnostic delivery. Due to the need for the distal end of the guide to be flexible, slight straightening may occur when the transendocardial infusion catheter is inserted, so the pre-formed guide shape can typically bend at least 90 degrees. In Figure 2, the transendocardial infusion catheter 200 is a BioCardia® spiral needle model 953L catheter with a highly flexible region featuring a multifiller coil design, but other flexible compartments can also be used in the present invention, for example, the flexible compartment can be made from an etched stainless steel tube as shown in U.S. Patents 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, or can form a coiled ribbon structure. The flexural rigidity of such coil designs can be readily calculated by following the effective closed-form derivative for such complex geometric shapes, 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, pp668-673, 1997.

[0034] In different aspects of the present invention, the penetrating element may be a straight needle, a curved needle, a multi-branched needle, and equivalents, and may also be a spiral needle. Since the pre-formed guide catheter used in the method and system of the present invention may be advanced and retracted axially and rotated within the left ventricle, a static sheath may be positioned 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 longer 6F sheath may also be used with a 6Fr guide to minimize the possibility that spasm may 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 pre-formed 6 Fr guide catheter with a pre-formed 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 that advance to the distal end, one of which exits at the base of the penetrating element and the other which passes through the penetrating element to exit into the tissue being penetrated. Furthermore, in its preferred embodiment, the catheter system has a spiral needle at its distal tip, eliminating the need for a perforation protection device. Specifically, eliminating the need for the 25 cm 6 Fr sheath by providing a lubricating 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 and is a preferred embodiment for patients with smaller radial arteries.

[0036] An alternative system may utilize a maneuverable 6Fr lead 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–4.4Fr. Such maneuverable lead catheters are commercially available, and a preferred maneuverable lead catheter is the BioCardia, Inc. general-purpose deflectable lead catheter model #1066, which has a 4.25Fr inner lumen and a 6 French 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 and the ability to have better backup support in the ventricle. This system may also be used with a 25cm radial artery access sheath, but has the challenge of the ability to pass a larger diameter spiral needle, and therefore a straight needle system with the passive perforation protection system described is desired.

[0037] An alternative maneuverable guide catheter preferred in one embodiment of the present invention is disclosed in U.S. Patent Application Publication No. 2012 / 0123327, the full disclosure of which is incorporated herein by reference. This guide catheter allows access using a 5-French maneuverable sheath (7.5-French outer diameter) without an introducer sheath. While there is an additional risk of radial artery spasm associated with manipulating the device in the artery, its maneuverability can significantly reduce manipulation compared to the nature of a 6-Fr sheathless fixed guide with a 7-Fr outer diameter. Both this sheathless guide and this maneuverable sheath system will benefit from a lubricating coating along the entire length of the catheter shaft. With caution that larger catheters may pose further risks to the radial artery, the possibility of using larger maneuverable sheaths in the procedure may be implemented to accommodate larger catheters for transendocardial delivery, which have different fluid delivery, electrical mapping, ultrasonic sensing, electromagnetic positioning, and other such well-understood geometric requirements. Currently, three-lumen fluid control with bipolar sensing, as disclosed in U.S. Patent No. 7,736,346, is implemented with a 5.2Fr envelope fitted into a 5Fr sheath.

[0038] Figures 3A and 3B show the distal ends of two transendocardial delivery catheters, each having two lumens: one lumen used for contrast agent delivery and terminating at the base of the spiral needle, and another lumen extending to the distal end of the spiral needle. These needles are formed with a winding fixture having a channel width specified to control the pitch and prevent flattening or excessive "ellipsification" of the circular needle cross-section, or unintended deformation of the cross-section from a circular geometric shape to an elliptical or similar non-circular geometric shape. The needles are made from 304 stainless steel, but other materials can also function. When attaching the spiral needle to the distal end of the catheter, the needle is coupled into a double-lumen inner tube covered with a distal multifiller coil, a mandrel is inserted into the contrast agent delivery lumen to protect its patency, and the spiral is embedded in an epoxy resin such as Loctite M-31CL, where the needle is firmly fixed to the distal, highly flexible coil. Smaller diameter spiral needles have an inner diameter of 0.008 inches, while larger diameter spirals have an inner diameter of 0.022 inches.

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

[0040] Figure 5 shows the distal end of a transendocardial delivery system compatible with a 5.5Fr lumen catheter introduction 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 agent port 510 is located at the base of a petal-shaped portion 506 that is attached to the distal end of the region 511. The straight needle 504 may be a 27-gauge conventional wall needle with a 0.008-inch lumen and a 0.016-inch outer diameter, and an exposed length of 0.160, 0.240, or 0.320 inches. The tip 502 of the needle 504 preferably has three faces as shown, but may have one or two faces instead. The penetration-limiting petal-shaped portion 506 may be formed from a 0.0035-inch diameter Nitinol® wire, provided with or covered with a coil of single filler 0.0015-inch diameter platinum-iridium (Pt / Ir)(90 / 10) wire covering the top for radiopaqueness. The flexible region of the catheter may be formed from a five-filler 0.008-inch wire coil 511 with a 0.046-inch pitch and an outer diameter of 0.063 inches, extending 10 centimeters from a more rigid catheter shaft. A double-lumen PEBAX 55D polymer tube (not shown in Figure 5) typically extends for most or the entire length of the catheter. The base of the straight needle-penetrating element 508 is inserted into and coupled to one of the two lumens of the double-lumen tube. The shank or base of the penetration restriction / perforation protection structure is inserted into the five-filler (pentafiler) coil 511, which typically leaves one of the internal lumens open to release contrast medium when needed.

[0041] Penetration restriction / perforation protection devices can be implemented in several ways. In a preferred embodiment, the monolithic structure includes multiple petal-like portions 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 enhance the security of attachment. Assembly is performed by straightening a superelastic wire (either pre-formed or set to have the three-dimensional petal-like geometry illustrated herein), and the Pt / Ir coil is advanced along the straightened wire. The petal-like wire is then restored to its relaxed multi-petal shape, and the penetration restriction / perforation protection structure is bonded into the distal end of the catheter body or shaft using epoxy, as previously described. In addition, or alternatively, the penetration restriction / perforation protection structure may also be attached by brazing, soldering, or welding to the needle and / or distal coil.

[0042] Other embodiments include the use of distinctly different parts for each petal-like portion within a plurality of petal-like portions. Combinations of these, such as two petal-like portions in one monolithic structure and two petal-like portions in another monolithic structure resulting in a four-petal-like portion configuration, are also possible. Furthermore, there are more limited embodiments in which only one petal-like portion unfolds from the catheter on one side.

[0043] The number of petal-like or lobular portions is important for determining the number of individual wires that must be anchored. Therefore, fewer lobular portions occupy less of the available space inside the catheter but may result in a thicker element. Since flexural stiffness tends to be a tertiary factor of diameter, doubling the diameter results in an 8-fold increase in stiffness. Thus, it is predicted that three loops will allow for greater stiffness (and therefore greater resistance to puncture) than four, and perhaps a more stable geometric shape than two loops. A 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 from 0.002 to 0.005 inches in diameter.

[0044] In relation to puncture resistance: perforation 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 and therefore increases the force that would be required to cause myocardial perforation.

[0045] Variable loop stiffness: The base of each loop or petal-like portion near the distal end of the catheter body is the most resistant to posterior bending (the shortest lever arm causing bending), and therefore it is also crucial to generate puncture resistance. This allows the loop to be stiffer than portions further from the catheter tip, making the system less traumatic or more sensitive to contact with fine structures within the heart. Figures 6A–6E show exemplary loop / petal-like structures suitable as penetration limiting / perforation protection elements of the present invention, which readily collapse when deployed from or retracted into the distal end of the guide catheter. Specifically, Figures 6A–6E show the penetration limiting / perforation protection system when 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 petal-like or lobular portion 506 when fully deployed. Figure 6B shows the lobular or petal-shaped portion 506 fully deployed just before entering the guide catheter 601 as the delivery catheter is retracted into the guide catheter 601; Figure 6C shows the lobular or petal-shaped portion 506 beginning to collapse around the needle 502 and into the guide catheter 601; and Figure 6D shows the lobular or petal-shaped portion 506 just before complete capture by the guide catheter 601. Figure 6E shows the perforation protection system fully retracted and almost invisible through the distal port of the guide catheter 601. This final position is referred to as the “retracted” state when the delivery catheter is protected within the guide and the guide can be manipulated to target a specific area within the ventricle. This protective device more than doubles the force required to penetrate cardiac tissue with a given 5-French straight needle catheter system. The "petal-shaped portion" passively expands / collapses when extended outward from the catheter / retracted into the catheter, and when collapsed, the tip of the loop extends past the tip of the straight needle to prevent gouging into the inner diameter of the catheter or, when partially retracted, into the tissue. In its deployed configuration, the penetration restriction / perforation protection system significantly reduces the risk of perforation by the straight needle system.

[0046] The proximal portion 700 of the delivery catheter, with two fluid lumens, is shown in Figure 7 and includes a handle assembly 701 attached to the main catheter shaft 705 by a tension relief assembly 703. The catheter shaft 705 is a flexible, torqueable composite conduit for therapeutic and contrast agent delivery lumens. The tension relief assembly 703 functions as a protective transition between the catheter shaft and the handle assembly 701. The helical needle system of the present invention may have a lower puncture potential than a straight needle embodiment, but may have the advantage of including such puncture protection embodiments for helical needle catheters, which can be easily implemented.

[0047] Figure 8A (Panels 1-4) illustrates a penetration restriction / perforation protection including exemplary leaflet or petal-shaped elements. The leaflet portion elements 801 may be independent as shown above, or may have connected legs in what we would call a “monolithic structure” 806. For example, the leaflet or petal portion may be formed from a single length of Nitinol® or other shape memory metal or polymer, which is further optionally connected at the ends to form a continuous structure with multiple loops. The legs may be linear or have certain other spiral shapes to improve bonding at adhesive joints. These loops have several radii to assist in the collapse and / or expansion of the structure during sheathing and deployment. The outer diameter 801a primarily defines the length sheathed with respect to the needle to be covered and protected. The "foldable blip" 801b is designed to prevent plastic deformation when fitted into the sheath, as its geometrically shaped section folds 180 degrees. The "root" radius 801d makes it easier to fit into the sheath because the lever arm for folding the lobular section is increased when this radius is increased. Radiopaqueness is provided by covering the lobular section with coiled platinum 801e as shown in Figure 8B (Panel 1), or can be fabricated from a drawn-filled tube (DFT) with a radiopaque center such as platinum 801f as shown in Figure 8B (Panel 2). The radiopaque coil can be attached using geometric bonding, solder, or adhesive. Panels 3 and 4 of Figure 8B show that loops are fabricated by thermosetting on a mandrel having features that create various selected radii, e.g., 809, 811, and 813.

[0048] Figure 8C shows a double-lumen tube. The double lumen 803b (panel 2) has a channel for therapeutic agents and a channel for contrast agents. The therapeutic route is connected to an injection element 808 to deliver the active ingredient into the tissue. The contrast agent lumen is open at the tip of the shaft 805, and the contrast agent is injected through it to ensure correct positioning relative to the tissue surface. Options for the double lumen include a non-circular extruded part 803b with a recess for the legs of the lobular portion to optimize the cross-sectional flow area, or a round extruded part can be blow-molded to fit around the legs of the lobular portion 803c (panel 3) to again optimize the flow area and potentially improve the safety of the lobular portion when coupled to the shaft. Tissue engagement indicators can provide additional features, and the benefit of a radiopaque loop is the possibility of having it serve as a tissue engagement indicator. The tip of the wire loop may be shaped to "lead" the tip of the catheter for a certain distance, so that as the needle punctures the tissue and the distal end of the catheter body approaches the tissue surface, the tip of the loop, which bends backward, can be visualized under fluoroscopy. A potential additional benefit of using the loop to indicate tissue engagement is the possibility of eliminating the contrast agent lumen from the shaft, which can allow for a reduction in the overall system size or adaptation to a larger therapeutic lumen that allows for the delivery of larger cells, cell aggregates, microspheres, extracellular matrix (ECM) slurries, particles, or therapeutic agents of higher viscosity. The loop can be configured to form a nearly conical, trumpet-like wide-mouthed bell shape, or a toilet plunger-like closed bell shape.

[0049] Figure 8D shows the distal flexible element and needle. The five-filler coil 807 is a five-element coil of 0.008-inch wire with a pitch of 0.046 inches. The flexible element may optionally consist of a cut metal tube 807b (Figure 8C) which may have the advantage of variable flexibility along its length, which can improve support and thus improve the ability to penetrate tough tissue in the long extension outside the steering delivery guidance catheter, if it is optionally thinner-walled and more rigid in the more proximal region. The shaft typically comprises three main sections, including a highly flexible distal section 807, the main length of the shaft 815, and a tension relief section 817. Note that the following items are also referred to in Figure 7 as the main shaft 705 and tension relief 703.

[0050] The flexible element may be fabricated from a five-strand filler coil of stainless steel round wire 807, as described above. The main shaft consists of an outer jacket (braided polyamide) 815 and an inner double lumen (Pebax) 803 (Figure 8A). The tension relief 817 includes the main shaft and the extended portion of the double lumen 815, and also has two compartments of the PEEK: a smaller compartment 817a that fits inside the handle of the guide catheter, and a larger compartment 817b that can enter the rotatable 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 tension relief compartments is used as a reference point that can be touched by the user to assess that the distal end is just "retained" within the guide catheter, while its junction is just at the proximal edge of the RHV.

[0051] Optionally, the guide sheath is slidably attached to the handle along the shaft, and the lobular portion can be folded forward for introduction into the guide catheter. This element can be part of the tension relief, for example, a snap-on design 817c (Panel 1, Figure 8E). The joint between the main shaft compartment 815 and the distal flexible element 807 is formed by a thin-walled hypotube or "bushing" bonded in place using cyanoacrylate adhesive. The joints from the main shaft 815 to the tension relief 817, and from the tension relief to the handle 819, may be fabricated with epoxy adhesive (see Figure 8D).

[0052] Wire assemblies, for example, 801 and 806 in Figure 8A, may be pre-tinned with Au-Sn solder and then soldered as subassemblies to stainless steel needles and coils (or other flexible spring elements) for ease of manufacture. The radius of curvature of the wire as it exits its mounting point should not be less than 10 times the wire diameter. The minimum recommended ratio is about 5.6:1, but this is likely to deform plastically with use and have a shortened fatigue life. Monolithic sets of wire loops offer increased ease of assembly, consistency of longitudinal and radial spacing, and increased safety in mounting, in contrast to single individual lobular parts with straight "legs".

[0053] Figure 8D shows a distal flexible element and needle, including a five-element filler coil 807, which is a five-element coil of 0.008-inch wire with a 0.046-inch pitch. This flexible element may consist of a cut metal tube 807b (Figure 8C), which may have the advantage of variable flexibility along its length, which can optionally be thinner-walled and more rigid in more proximal regions, thereby improving support and thus improving the ability to penetrate tough tissue in the long extension outside the steering delivery guidance catheter. The shaft comprises three main compartments, 807, 815, and 817, including a highly flexible distal compartment 807, the main length of the shaft 815, and a tension-relaxing compartment 817 (Figure 8D).

[0054] The therapeutic lumen and contrast agent lumen typically extend uninterrupted along the entire length of the catheter shaft. The joint between the five filler coils 807 and the polyamide jacket 815 is formed by an adhesive lap joint. This is formed either by Loctite 4014, coupled to a thin-walled 304 stainless steel bushing (not shown) with an inner / outer diameter of 0.038 inches / 0.042 inches × length of 0.3 inches, or by using the outer surface of the lumen assembly as the lap joint material. Proximal to the coil-shaft joint, the main shaft outer jacket is a flexible, torqueable composite material consisting of a polyamide tube with an inner diameter of 0.042 inches × outer diameter of 0.054 inches, with a 0.0015-inch wire braid (16 carriers) encapsulated in the wall 815.

[0055] The tension relief assembly 703 functions as a protective transition between the catheter shaft and the handle assembly 701. As shown in Figure 8D, the tension relief 81 includes the main shaft and the extended portion of the double lumen 815, and also has two compartments of PEEK: a smaller compartment (0.062-inch inner diameter × 0.010-inch wall) 817a that fits inside the handle of the guide catheter, and a larger compartment (0.085-inch inner diameter × 0.010-inch wall) 817b that can enter the rotating hemostatic 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 user-touchable reference point to assess that the distal end is just "retained" within the guide catheter while its junction is just at the proximal edge of the RHV, without exposing the patient to increased radiation by using fluoroscopy to verify the needle tip position.

[0056] Panels 1 and 2 of Figure 8F show that, when the packing is slightly too tight, the loops at the tips may occupy more space than the body of the loop, so the tip positioning (in the collapsed state) may be alternated axially by alternating the root positions or by having different loop sizes (Panel 2). The leaflet sections may be fabricated to be self-reinforcing in the unfolded configuration to reduce the ease of folding. One approach is for each loop to pass through adjacent loops, as shown. Another modification shown is a “steam colander” modification 801h (Panels 3-6) with a flexible sheet or plate in a curved triangular section of a conical section. Optionally, the edges may have a folding or sliding interlocking mechanism 801i to limit “spreading”.

[0057] Figure 9 is a cross-sectional view of the handle assembly 701 from Figure 7, which may be standard for many double-lumen catheters. The handle is an ergonomic catheter control feature that includes the proximal ports of both the therapeutic and contrast agent lumens 901, 903. The catheter shaft 805 is directly fixed to the tension relief assembly using an epoxy adhesive such as Loctite M-06FL. The retaining block 913 is used to integrate the tension 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 end of the main shaft, the contrast agent lumen 907 is isolated and directed toward the proximal contrast agent lumen 901. At the end of the catheter shaft 911, the therapeutic lumen is also isolated, and a bushing 909 is used to connect the extension tube 905 to the therapeutic lumen in the main shaft. The proximal end of the extension tube is connected to the proximal therapeutic lumen 903.

[0059] An alternative version of the contrast agent lumen and treatment lumen termination, as shown in Figure 22, utilizes a "Y-shaped" adapter 2201, allowing the tubular configuration of the concentric treatment lumen 2202 and contrast agent lumen 2203 to be directly bonded to the "Y-shaped" adapter, which terminates in Luer lock fittings for the treatment port and contrast agent injection port 901 and 903.

[0060] Current commercially available transendocardial infusion systems use a helical needle fabricated from 27RW gauge 304 stainless steel hypotube (inner diameter = 0.008 inches). The desire to pass larger bodies led to the development of larger helical-wound hypotube. Material and design constraints (functional requirements) were used to optimize helical parameters such as pitch, helical inner diameter, helical outer diameter, hypotube inner diameter, and hypotube wall thickness. Various forming techniques were used to further optimize the acceptablely formed needle, for example, to control the ellipticization 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 agent lumen 1120 terminating at the base of the needle, and a flexible distal element 1110 of five filler coil components. All of these features are fixed together as the distal tip 1140, as shown, using two-part epoxy as the binding material. A preferred embodiment of the helical plus needle element is a helical-shaped double stainless steel hypotube structure 1130. In the preferred embodiment, the proximal ends of both hypotubes are coupled to an independent tube 1210 that 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. Patent No. 7,736,346. The helical needle 1130 also serves as a distal electrode for electrophysiological sensing ability, 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] Figure 13 shows a cross-sectional view of this three-lumen configuration 1340 extending to the device distance to the handle (electrode wires are not shown). The distal and proximal electrode wires also extend to the length of the catheter, including the 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. A preferred design for the proximal sensing electrode uses a distal flexible element formed by five exposed pentafilar coils 1110 as the proximal electrode. The electrode wire 1410 is attached to the proximal end of the flexible element. One method of wire attachment is achieved by supplying the electrode wire through a mounting bushing 1405, winding the wire onto the flexible element 1440, and then soldering it at position 1420. An alternative second electrode design uses a conductive proximal ring 1430, along with an electrode wire that is oriented through the flexible element and attached to the ring.

[0063] Figure 15 shows the internal configuration of the helical plus handle assembly. The following describes the proximal termination within the handle 1610 for the three fluid transport lumens and two electrode wires. A multi-channel electrical connector 1630 is incorporated into the handle, along 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 tension relief assembly 1040, and exit from within the handle assembly. The individual lumens are then directed towards a proximal port within the handle 1140, from which they exit and connect to a standard Luer fitting.

[0064] Figures 16 and 17 show a large-bore needle based on a 23Ga tube 1700 and a 27RW gauge helical needle 1750. The needle is fixed into the tip assembly by embedding the needle and treatment lumen within five filler coils, firstly using an ultraviolet adhesive such as Loctite 3301 to bond it into the treatment lumen, and secondly using an epoxy such as Loctite M-31CL to form a monolithic structure 1720 that captures the helical loops. During distal epoxy encapsulation, a ribbon of PTFE is supplied between the coiled loops of the needle and into the contrast agent lumen (adjacent to or concentrically around the treatment lumen), and this PTFE ribbon creates a channel through the epoxy when removed after the epoxy has cured. This contrast agent lumen terminates at the distal end of the implantation at the base of the exposed needle 1730. The contrast agent lumen can be used to assess whether the tip of shaft 805 is firmly positioned against the myocardium when the needle is screwed into the tissue. This assessment is performed by injecting the contrast agent and observing on X-ray the resulting flow and how it accumulates and adheres to the boundary layer against the myocardium, or whether it simply flows out like smoke with the flow of cardiac output.

[0065] Figure 18 shows an alternative design for distal perforation protection that utilizes existing balloon technology when engaging with cardiac tissue during transendocardial therapeutic delivery. Figure 18 shows three different views of the distally attached balloon feature, namely a side view in the uninflated state 1801, a side view in the inflated state 1802, and an isometric view in the inflated state 1803. The distally attached balloon feature provides a barrier at the proximal end of the needle 1010, as shown in 1802. A preferred deployment would involve inflating the balloon with saline or contrast agent after it has been exposed from its guide catheter and before full engagement into the cardiac wall. To inflate the balloon, fluid is injected into a handle-mounted port that extends through an internal lumen terminating below the surface of the balloon region within the distal end. A major advantage of this design is its ability to have a perforation protection system incorporated at the distal end of the helical injection catheter, which is capable of functioning when rotated during standard use with a helical needle. The use of contrast agents as balloon inflation media provides the additional benefit of a large radiopaque volume on the endocardial surface, which can further assist in assessing needle location and engagement. A suitable balloon material that fits the distal end of the catheter in its uninflated state 1810 is coupled to the base distal end structure at its distal and proximal ends. The port below the balloon structure is connected to the inflation port in the handle via a suitable conduit.

[0066] The currently available transendocardial injection system (BioCardia, Inc.) uses a helical needle fabricated from 27RW gauge 304 stainless steel hypotube (inner diameter = 0.008 inches, outer diameter = 0.016 inches). The desire to use a larger lumen to allow a wider range of therapeutic agents to pass through led to the development of helical-wound needles utilizing larger gauge tubing. Constraints of material properties and the desire to maintain a minimum profile led to the optimization of helical needle parameters such as pitch, helical inner diameter, helical outer diameter, hypotube inner diameter, and hypotube wall thickness. To further optimize the acceptablely formed needle, various forming techniques were used, for example, to control the ellipticization of the hypotube inner diameter. The mandrel size was varied to control material deformation while attempting to maintain the maximum helical diameter within constraints. Other methods to control excessive ellipticization included freezing the water in the hypotube before coiling, annealing the hypotube before coiling, and sidewall support during coiling.

[0067] Commercial pipe benders use a common rule of thumb that the bending radius of a coiled pipe should not be less than twice the pipe diameter, but a 1:1 relationship can be achieved using a method of ownership. The theoretical limit associated with material elongation was evaluated based on 60% elongation = 0.5 * pipe diameter (TD) / bending radius (RB), with an elongation limiting factor based on 304SS. The mandrel diameter (MD) is 2 * RB - TD, and the helical diameter is 2 * TD + MD.

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

[0069] The mandrel used to fabricate the 23 gauge TW large diameter needle was specified to have a small diameter of 0.018 ± 0.002 inches, resulting in a spiral outer diameter ranging from 0.071 inches to 0.074 inches with an inner diameter of approximately 0.024 inches. Thus, the "rebound" and ellipticization experienced by the spiral are demonstrated, and it is shown that a 23Ga TW spiral needle wound on a φ0.018 inch mandrel can achievably meet the maximum outer diameter specification.

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

[0071] Figure 20 shows a spiral catheter consisting of a spiral needle 1907, a flexible distal element 2001, a braided shaft 2002, a two-part tension reliever 2003, a handle 2004, a treatment port 903, and a contrast agent port 901.

[0072] Figures 21A–21D show one method of spiral needle formation, in which a hypotube is wrapped around a mandrel 2001 supporting the sides of the tube to reduce ellipsification. Needles can be formed with subcutaneous injection tubes of various sizes. A currently available repeat version is 27GA RW. It is made from 304 stainless steel. Large diameter versions are constructed using 24 and 23Ga tubing. Preferred stainless steel embodiments conform to ISO 9626 Annexes A and E. Additional methods and materials to overcome the limitations of cold working of the material may include direct forming, such as forming by electroforming nickel or other material over a chemically removable winding mandrel such as aluminum or copper. After winding, the main face is cut 2002, and then a secondary face is added 2003. Additional options may include alternative tips such as side holes, trocars, or closed forms with Tuohy tips. In a preferred embodiment, the final formed needle has a straight rear 2004 that is offset from the center by an amount equal to the lumen offset in the shaft assembly and coupled into the treatment lumen.

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

Claims

[Claim 1] The invention as described in the drawings of the present application.

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