Multifunction catheter and method for the diagnosis and / or treatment of venous thromboembolism - Patent Application 20070123333

Abstract

Some aspects of the disclosure include a catheter having an elongate body defining one or more first ports extending through a peripheral surface of the body, a plurality of internal lumens extending longitudinally through the catheter, and one or more tubes, each having a sidewall defining a tube lumen in fluid communication with one of the first ports, and a method of operating the catheter, wherein the one or more tubes are configured to shift between a collapsed configuration and an extended configuration, the one or more tubes defining a cage shape having an unconstrained maximum transverse dimension that is greater than a corresponding maximum transverse dimension of the catheter body, and wherein in the collapsed configuration at least a portion of the tube is radially closer to the catheter body than when in the extended configuration. TIFF2024526733000002.tif106170

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 221,805, filed July 14, 2021, and U.S. Provisional Patent Application No. 63 / 345,169, filed May 24, 2022, which are incorporated by reference in their entireties.

[0002] Field of Disclosure The present disclosure relates generally to venous thromboembolism (VTE) and, more specifically, but not by way of limitation, to catheters and methods for the diagnosis and / or treatment of VTE. [Background technology]

[0003] background Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. VTE is generally an umbrella term for deep vein thrombosis (DVT) and pulmonary embolism (PE). Optimal management of these disease processes requires high-quality imaging, careful hemodynamic monitoring (in the case of pulmonary embolism), and devices designed to rapidly and effectively explore the complex anatomy of the veins. A significant proportion of intermediate- and high-risk thrombosis cases are now managed noninvasively, often with prolonged infusion of thrombolytic agents.

[0004] Current approaches to invasively manage VTE require the use of multiple catheters, and the optimal duration of thrombolytic infusion is often not individualized to the specific needs of the patient. Current workflows for catheter-based management of pulmonary embolism require multiple catheter exchanges, which can increase procedure time and corresponding radiation exposure for the patient and treatment team. First, a hemodynamic assessment of the cardiovascular system is performed, typically with a simple fluid-filled balloon catheter. This is then exchanged over the wire for a standard angiography catheter, and a diagnostic pulmonary angiogram is performed to visualize the location of the clot and determine optimal placement of the thrombolytic infusion catheter. This is followed by a further catheter exchange to place the infusion catheter, and then the thrombolytic agent is infused over an extended period of time with the goal of breaking down the clot. Importantly, current solutions generally do not allow for continuous pressure monitoring during thrombolytic infusion, and the total dose of agent and duration of infusion are often arbitrary. For example, under current approaches, thrombolytic agents are typically infused over 6-24 hours. The timing of the length of thrombolytic agent infusion is often arbitrary, and factors such as subjective improvement of symptoms, oxygen saturation by noninvasive fingertip plethysmography, and noninvasive blood pressure monitoring are often used to aid in this important decision. Prolonged infusion of thrombolytic agents may increase the risk of minor and major (i.e., intracranial) bleeding events for patients.

[0005] Pulmonary embolism (PE) is a leading cause of morbidity and mortality in the United States, accounting for as many as 600,000 cases and 100,000 deaths each year. The Centers for Disease Control and Prevention (CDC) notes that one in four patients with PE will die suddenly and without warning, making PE the third leading cause of cardiovascular death in the United States.

[0006] For patients with intermediate- and high-risk PE, catheter-based procedures have emerged as an attractive solution. The most studied minimally invasive procedure for PE is called "catheter-directed thrombolysis (CDT)." CDT typically involves placing one or more small catheters directly into the clot and infusing a thrombolytic agent, such as tissue plasminogen activator (tPA), over a 2- to 24-hour period to break down the clot. Because slower, lower-dose infusions correlate with lower rates of life-threatening bleeding, CDT is generally preferred over peripheral intravenous bolus administration of thrombolytic agents in all but the highest-risk patients. Despite the growing role of CDT for PE, some practitioners have expressed concerns regarding its safety and efficacy.

[0007] Although CDT has been shown to be effective, some experts have assessed that CDT may be associated with an approximately 2-11% risk of major adverse events, including catastrophic intracranial or intraperitoneal bleeding, and the incidence of bleeding complications correlates with the duration and dose of thrombolytic agent infusion. Therefore, to further improve the safety and efficacy of CDT, it may be desirable to infuse the lowest possible dose of thrombolytic agent for the shortest effective duration. This ideal endpoint would be the point at which complete lysis occurs, such that further thrombolytic agents would not contribute further therapeutic benefit. This endpoint is likely not the same for all patients, as chronicity, refractoriness (i.e., resistance to thrombolytic agents), and extent of thrombus vary from patient to patient. Reduction in pulmonary artery (PA) pressure during thrombolytic agent administration correlates with reduced right ventricular strain and improved cardiac output, and increased wedge pressure distal to the thrombus is a clear indicator of thrombolytic efficacy. However, current CDT devices do not allow monitoring of PA pressure during thrombolytic infusion, forcing physicians to subjectively decide when to stop thrombolytic infusion and risk unnecessary delivery of lytic agent. Summary of the Invention

[0008] overview The inventors have recognized certain promise for addressing remaining risks and limitations of existing CDT devices to reduce the risk of adverse events while improving technical ease of use. Aspects of the present catheters and methods may be configured to (1) monitor (and / or enable monitoring) the progress of thrombolysis by hemodynamic monitoring to enable an objective decision of when to terminate lytic agent delivery, and / or (2) deliver lytic agent closer to the thrombus (e.g., from a catheter structure in contact with the thrombus), thereby maximizing the effectiveness of the lytic agent and potentially reducing the amount of lytic agent required (e.g., compared to lytic agent delivered from a thinner (conventional) CDT catheter).

[0009] Some embodiments of the present catheters may be configured to provide one or more of the following advantages and features: multi-directional lytic agent delivery, advanced steerability, capability for pulmonary angiography, simultaneous distal / proximal pressure measurement, adjustable infusion length, additional mechanism for thrombolysis (surface contact), suitability for use within the pulmonary artery.

[0010] The catheters and methods allow the user to perform diagnostic pulmonary angiograms, hemodynamic monitoring, and drug infusion through a single device and eliminate at least some (e.g., all) catheter exchanges. The catheters may incorporate the functionality of hemodynamic monitoring catheters, diagnostic angiography catheters, and thrombolytic agent infusion catheters. The catheters and methods of the present invention may be configured or implemented to allow the user to perform detailed hemodynamic assessments and angiograms at the time of diagnosis, and allow for long-term infusion of drugs into the diseased vessel if the catheter is left in place. In addition, hemodynamic monitoring ports and / or microelectromechanical monitoring (MEMS) may be included to allow real-time, continuous assessment of pulmonary artery pressure and additional physiological metrics at the bedside. Such features allow the provider to more accurately determine the effectiveness of therapy over time and aid the user in determining when to discontinue thrombolytic drugs.

[0011] Although some embodiments of the present catheters and methods target emboli in the pulmonary artery, they may be suitable for other applications in other parts of the vasculature.

[0012] Additionally, clot resolution (dissolution) may be improved by maximizing exposure of the clot to thrombolytic drugs throughout its entire length and three-dimensional (3D) structure, both by improving penetration and by allowing the length of the infusion catheter to be tailored to individual patient needs to achieve more complete clot resolution (dissolution).

[0013] Some embodiments of the catheters include an elongate catheter body having a proximal end, a distal end, and a length extending from the proximal and distal ends, the catheter body defining one or more first ports extending through a peripheral surface of the body at a position along the length closer to the distal end than the proximal end, and a plurality of internal lumens extending longitudinally through the catheter along at least a portion of the length. In some such embodiments, the multiple internal lumens comprise one or more first lumens in fluid communication with the one or more first ports and one or more tubes, each having a sidewall defining a tube lumen in fluid communication with one of the first ports, the one or more tubes configured to shift between a collapsed configuration and an extended configuration, wherein the one or more tubes define a cage shape having an unconstrained maximum transverse dimension that is greater than a corresponding maximum transverse dimension of the catheter body, and in the collapsed configuration, at least a portion of the tube is radially closer to the catheter body than when in the extended configuration, and wherein at least a portion of each of the one or more tubes includes one or more openings extending through a respective sidewall in fluid communication with the respective tube lumen.

[0014] In some configurations, the one or more tubes may include a plurality of tubes. The plurality of tubes may define one or more cage shapes each having a maximum unconstrained transverse dimension greater than a corresponding maximum transverse dimension of the catheter body. In the collapsed configuration, at least a portion of the tube may be radially closer to the catheter body than when in the extended configuration. In some aspects, the maximum unconstrained transverse dimension may be at least 150%, such as at least 300%, of the corresponding maximum transverse dimension of the catheter body. In some configurations, the maximum unconstrained longitudinal dimension is at least 300% of the maximum transverse dimension of the corresponding expandable tube. The one or more openings may include a plurality of openings spaced along a longitudinal portion of the length of each tube. In some configurations, the one or more tubes include a shape memory alloy, such as Nitinol.

[0015] Some aspects of the catheter may include an elongate sheath having a proximal end, a distal end, and a length extending from the proximal and distal ends, the sheath defining a sheath lumen. In some such configurations, the sheath is configured to extend over the catheter body such that the distal end of the sheath can be moved proximally relative to the catheter body to allow the one or more tubes to transition from a collapsed configuration to an extended configuration.

[0016] Some embodiments of the method include inserting a distal end of one of the catheters through a clot in a blood vessel (e.g., a pulmonary vessel) of a patient such that a second port of the catheter body is distal to the clot; and retracting the sheath relative to the catheter body such that a distal end of the sheath is proximal to the clot. In some such embodiments, the method further includes injecting a lytic agent into the blood vessel through the one or more first lumens and openings in the one or more tubes; measuring distal pressure in the blood vessel distal to the clot through the second lumen and second port; and / or measuring proximal pressure in the blood vessel proximal to the clot through the sheath lumen. In some configurations, based on either a reduction / improvement or normalization of proximal pressure and / or based on an equalization of proximal and distal pressures with a pressure waveform that looks similar to a standard pulmonary artery pressure waveform, the user may choose to modify the flow rate of the lytic agent in at least one of the openings in the one or more tubes. Some methods may include displaying the proximal and distal pressures, comparing the proximal and distal pressures, displaying changes in the proximal and distal pressures, and stopping infusion of the dissolution agent based on the comparisons.

[0017] In some aspects, the catheter may include an elongate catheter body having a proximal end, a distal end, and a length extending from the proximal and distal ends. The body may define one or more first ports extending through a peripheral surface of the body at a position along the length closer to the distal end than the proximal end, one or more second ports extending through a peripheral surface of the body at a position along the length closer to the distal end than the proximal end, and a plurality of internal lumens extending longitudinally through the catheter along at least a portion of the length. In some configurations, the plurality of internal lumens may include a first lumen in fluid communication with the one or more first ports, a second lumen in fluid communication with the one or more second ports, and a third lumen extending through a distal end of the body and defining a third port through the distal end.

[0018] Some of the present catheters may include a balloon coupled to the peripheral surface of the body at a longitudinal position between the distal end and the first and second ports. In some such configurations, the plurality of internal lumens may include a fourth lumen in fluid communication with the balloon such that the balloon may be inflated via a port coupled to and in fluid communication with the fourth lumen. In some configurations, the body includes a steerable tip extending from the distal end of the body toward the proximal end, and the plurality of internal lumens includes a fourth lumen extending into the steerable tip to allow a user to change the orientation of the distal end relative to at least a portion of the body proximal to the steerable tip. In some aspects, each of the plurality of lumens has a circular cross-section. Alternatively, the third lumen may have a circular cross-section, and each of the first and second lumens have a non-circular cross-section. In such configurations, the third lumen may have a minimum internal transverse dimension that is greater than the minimum internal transverse dimension of either of the first and second lumens. The first lumen may have an inner diameter larger than the inner diameter of either the second or third lumen. In some configurations, the one or more first ports may include a plurality of first ports spanning a first area or first longitudinal range of at least 2 centimeters (cm). The first longitudinal range may have a length of between 3 cm and 5 cm.

[0019] In some configurations, the plurality of first ports are linearly disposed along the first longitudinal range. In some configurations, the plurality of first ports are helically disposed around the body along the first longitudinal range. In some aspects, the one or more second ports include a plurality of second ports spanning a second longitudinal range of at least 5 cm. The second longitudinal range may have a length of 10 cm to 15 cm. The plurality of second ports may be linearly disposed along the second longitudinal range or helically disposed around the body along the second longitudinal range. In some configurations, the second longitudinal range may overlap the first longitudinal range. In some such configurations, the entirety of the first longitudinal range is within the second longitudinal range. The second longitudinal range may have a first end and a second end, and the first longitudinal range is longitudinally spaced from each of the first and second ends of the second longitudinal range. Some of the present catheters may include a plurality of conduits or fittings, such as luer fittings, each in fluid communication with a respective one of the lumens.

[0020] Some of the methods may include inserting a distal end of a catheter through a clot in a patient's blood vessel (e.g., a pulmonary blood vessel) such that the third port is distal to the clot and the one or more first ports are proximal to the clot. The catheter may be inserted over a guidewire extending through the third lumen, and some methods may include removing the guidewire from the third lumen. In some aspects, the methods may include measuring a distal pressure in the blood vessel distal to the clot through the third lumen and the third port; measuring a proximal pressure in the blood vessel proximal to the clot through the first lumen and the one or more first ports; or both. Some methods may include injecting a contrast agent into the blood vessel through the first lumen and the one or more first ports. Some methods may include injecting a dissolving agent into the blood vessel via the second lumen and the one or more second ports. Some such methods may include measuring proximal pressure in the blood vessel through a first lumen and the one or more first ports while injecting the lytic agent; measuring distal pressure in the blood vessel through a third lumen and a third port while injecting the lytic agent; or both.

[0021] The term "coupled" is defined as connected, but not necessarily directly, and not necessarily mechanically; two items that are "coupled" may be integral with one another. The terms "a" and "an" are defined as one or more, unless the disclosure expressly requires otherwise. The term "substantially" is defined as largely as specified, but not necessarily wholly as specified (and includes what is specified, as will be understood by those of skill in the art; e.g., substantially 90 degrees includes 90 degrees, and substantially parallel includes parallel). In any embodiment of the devices, kits, and methods of the present invention, the term "substantially" is interchangeable with "within [a percentage] of" what is specified, including 0.1, 1, 5, and / or 10 percent.

[0022] The terms "comprise" (and any variation of comprise, such as "comprises" and "comprising"), "have" (and any variation of have, such as "has" and "having"), "include" (and any variation of include, such as "includes" and "including"), and "contain" (and any variation of contain, such as "contains" and "containing") are open-ended linking verbs. As a result, a device or kit that "comprises," "has," "includes," or "contains" one or more elements is not limited to having only those elements, although it possesses those one or more elements. Similarly, a method that "comprises," "has," "includes," or "contains" one or more steps is not limited to having only those one or more steps, although it has those one or more steps.

[0023] In common usage, a "thrombus" is a blood clot that forms inside a blood vessel, and an "embolus" is a portion of a thrombus that breaks free and becomes lodged at some point in the downstream vasculature. The invention of this disclosure interacts similarly with both thrombus and embolus, and therefore the terms are used interchangeably herein. Unless specifically indicated otherwise, all references to "thrombus" or "embolus" (as well as thrombi, emboli, and embolism) apply to all structures related to thrombus and embolus.

[0024] Throughout this disclosure, the terms "proximal" and "distal" refer to the catheters of the present invention; that is, the catheter handle and user controls are on the proximal end and the portion that enters the target embolus is the distal end. Furthermore, an apparatus, device, or system that is configured in a particular manner is configured in at least that manner, but may also be configured in other manners than specifically described.

[0025] Any aspect of any of the present apparatus and methods may consist of or consist essentially of - rather than comprise / include / contain / have - any of the described steps, elements, and / or features. Thus, the terms "consisting of" or "consisting essentially of" may be used in place of any open-ended linking verb in any claim to modify the scope of that claim from the scope that would result from the use of that open-ended linking verb.

[0026] Some details relating to aspects of the disclosure are described above, and other details are described below. Other embodiments, advantages, and features of the disclosure will become apparent after reviewing the entire application, including the Brief Description of the Drawings, the Detailed Description, and the Claims. [Brief description of the drawings]

[0027] The following drawings are illustrative by way of example and not by way of limitation. For simplicity and clarity, not all features of a given structure are necessarily labeled in every drawing in which that structure appears. The same label or number does not necessarily refer to the same structure. Rather, the same number may be used to refer to similar features or features with similar functionality, as well as non-identical numbers. Dimensional drawings are drawn to scale (unless otherwise noted), and thus the sizes of the depicted elements are accurate relative to one another, at least for the aspects depicted in the drawing.

[0028] [Figure 1] 1 shows a schematic diagram of an example of a catheter of the present thrombolysis catheter system. [Figure 2A] 2A-2D illustrate various cross-sectional views of an example catheter of the present thrombolysis catheter system. [Figure 2B] See legend to Figure 2A. [Figure 2C] See legend to Figure 2A. [Figure 2D] See legend to Figure 2A. [Diagram 3] 3A-3C illustrate various examples of components that may be utilized with the catheters of the present thrombolysis catheter system. [Figure 4A] 1 shows a schematic side view of another example of a catheter of the present thrombolysis catheter system in a first state. [Figure 4B] 4B shows a schematic side view of the catheter of FIG. 4A in a second state. [Figure 4C] 4C and 4D are cross-sectional views of the catheter of FIG. 4A taken along lines AA and BB, respectively. [Figure 4D] See legend to Figure 4C. [Figure 5A] FIG. 2 shows a schematic side view of an example of a catheter of the present thrombolysis catheter system in an extended state. [Figure 5B] 1 shows an illustrative diagram of an example of a catheter during thrombolysis operation. [Figure 6] Figure 6A shows a schematic perspective view of another example of a catheter of the present thrombolysis catheter system, and Figure 6B shows a schematic side view of the catheter of Figure 6A coupled to a handle assembly. [Figure 7] 7A-7E show perspective views of the catheter of FIG. 6A in first through fifth configurations. [Figure 8] 8A and 8B are cross-sectional views of one example of a catheter of the present thrombolysis catheter system. [Figure 9]Figure 9A is a cross-sectional view of another example of a catheter of the present thrombolysis catheter system, and Figure 9B is a perspective view of the catheter of Figure 9A. [Figure 10] 1 shows an illustrative diagram of an example of a catheter during pulmonary artery thrombolysis operation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029] Detailed Description Referring now to the drawings, and more particularly to FIG. 1, one configuration of a catheter system is illustrated and designated by the numeral 10. The system 10 includes various components as described herein that are configured to facilitate thrombolysis. In the configuration shown in FIG. 1, the system 10 includes a catheter 14 having an elongated catheter body 18 configured to be placed within the human body, such as within a vein or artery. The catheter body 18 may comprise a polymer, such as PTFE, Pebax, PEEK, metal, hard plastic braid or coil, or other strong, flexible, or biocompatible material known in the art. To minimize procedure time and infusion volume of thrombolytic agent compared to conventional catheters, the catheter body 18 defines a number of ports 20 and a number of lumens 30 extending longitudinally therethrough to allow fluid communication between the catheter 14 and the bloodstream while the catheter is placed within a blood vessel. For example, catheter 14 may include a thrombolytic agent dispersion region 40 associated with one or more ports configured to deliver a thrombolytic agent to a blood vessel, a contrast agent infusion region 44 configured to deliver a contrast agent to a blood vessel, or both. In some configurations, region 40 and region 44 may overlap one another.

[0030] The catheter body 18 extends between a proximal end 48 and a distal end 52 to define the plurality of lumens 30 at positions between the proximal and distal ends. As shown in FIG. 1, the lumens 30 may, but need not, extend along the entire length defined between the proximal and distal ends. For example, one lumen (e.g., 30) may extend from the proximal end 48 to the contrast injection region 44, another lumen (e.g., 30) may extend from the proximal end to the thrombolytic agent dispersion region 40, yet another lumen (e.g., 30) may extend from the proximal end to the distal end 52, or a combination thereof. The length of the body 18 is sufficient to allow the distal end 52 to extend to an embolus anywhere within the human vasculature, while the proximal end 48 remains outside the body.

[0031] In some configurations, the contrast infusion region 44 may include ports 20 (e.g., all ports associated with the contrast infusion lumen) spaced along a 3-5 cm length of the body 18 and may be spaced 8-12 cm from the distal end 52 of the catheter 14. In some configurations, the thrombolytic agent dispersion region 40 may include ports 20 (e.g., all ports associated with the thrombolytic agent lumen) spaced along a 15-22 cm length of the body 18 and may be positioned at or near the distal end 52 of the catheter. The ports 20 may be arranged in a linear fashion along the body 18 or in other suitable patterns. In some configurations, the body 18 may include a maximum transverse dimension D1 that is less than or equal to 3 mm (9 French), such as 8 French or 7 French. Alternatively, the maximum transverse dimension D1 may be larger, such as 10 French, 18 French, or greater. In some configurations, the system 10 may include a sleeve that is movable (e.g., slidable) relative to the body. For example, the sleeve may be movable relative to the body to block or expose one or more ports 20 associated with the thrombolytic agent dispersion region 40, the contrast agent injection region 44, or both, as described in more detail below with reference to FIGS. 4A-4D.

[0032] In some configurations, each of the thrombolytic agent dispersion region 40 and the contrast agent injection region 44 is positioned closer to the distal end 52 than to the proximal end 48 to allow for the injection of an agent at or near the embolus. For example, in the illustrated configuration, the proximal end 48 branches or branches off to form a plurality of conduits 56. Each conduit 56 may be associated with (e.g., in fluid communication with) a respective one of the plurality of lumens 30 and may receive a drug or other material for dispersion within the blood vessel. The conduits 56 may include fittings or other interfaces (e.g., Luer locks, Luer slip connections, twist connect couplings, small bore connectors, Tuohy-Borst connectors, or other known connectors) that allow the conduits and associated lumens 30 to be connected to other components (e.g., external syringes, pumps, transducers, or sensors, etc.).

[0033] As shown in the close-up cutaway view of the body 18 depicted in FIG. 1, the body defines one or more ports 20 extending through a peripheral surface 60 of the body. The ports 20 may be positioned along the length of the body 18 closer to the distal end 52 than to the proximal end 48. In some configurations, the ports 20 include apertures connecting the respective lumens (e.g., 30) to the exterior of the body 18. For example, a first series of ports (e.g., 20) may be positioned within the thrombolytic agent dispersion region 40 in fluid communication with the first lumen (e.g., 30) for delivering thrombolytic agent from the proximal end 48 (e.g., via the first conduit 56) to the thrombolytic agent dispersion region. Additionally or alternatively, a second series of ports (e.g., 20) may be positioned within the contrast agent infusion region 44 in fluid communication with the second lumen (e.g., 30) for delivering contrast agent from the proximal end 48 (e.g., via the second conduit 56) to the contrast agent infusion region.

[0034] In some configurations, the system 10 may include one or more sensors 64, one or more controllers 68, or both. As shown in FIG. 1, the sensor 64 may be coupled (e.g., integrated) with the body 18. The sensor 64 may be coupled to the body 18 at any position along its length, and in some configurations may be located closer to the distal end 52 than the proximal end 48. In some configurations, the sensor 64 is configured to detect or measure clinically relevant data. For example, the sensor 64 may include or correspond to a microelectromechanical sensing (MEMS) device configured to sensitively measure pressure, an integrated oxygen sensor, a flow sensor, a pressure sensor, a blood oxygen saturation sensor, a pH sensor, a hemoglobin sensor, a chemical sensor, a strain gauge, a blood flow sensor, or a combination thereof. The sensor 64 may be associated with one or more ports 20, one or more lumens 30, or both, for detecting and transmitting information from the sensor to a device (e.g., the controller 68) that communicates the information to an operator. In an illustrative configuration, the sensor 64 may be disposed within the body 18 (e.g., in a sidewall), and wiring may extend through the body, through designated lumens (e.g., 30), and through the conduit 56. In some configurations, one or more wires may be coupled to the sensor 64 and extend through the body of the catheter 14 to connect to an external console or controller 68. In some configurations, the sensor may include an electrical sensor, such as the TiSense pressure sensor by Millar Corporation, in which a transduction element is located in situ on the catheter 14 and wires extend to the proximal end 48 to carry power and data. In some configurations, the sensor 64 may include an optical sensor, such as the RJ50 by RJ Enterprises, in which a Fabry-Perot cavity or other optical sensor is placed in situ on the catheter 14, each with an optical fiber leading to the proximal end 48.The controller 68 or sensors may be configured to model hemodynamics in real time and may be configured for high-fidelity sensing (including blood pressure, oxygen, pH, and flow), including shock conditions (such as cardiogenic, distributive, hemorrhagic, or obstructive), intraoperative monitoring, or trauma.

[0035] The controller 68 may be in wired or wireless communication with one or more other components of the system 10, such as the sensors 64, a fluid source (e.g., a pump), a pressure transducer, a monitor, medical machinery (e.g., an imaging system, or a vitals monitor), a control system, or other electrical components typically utilized during a thrombolysis procedure. The controller 68 may include a processor coupled to a memory (e.g., a computer-readable storage device). In some configurations, the controller 68 may include one or more applications that access the processor and / or memory to perform one or more operations of the system 10 as described herein. The processor may include or correspond to a microcontroller / microprocessor, a central processing unit (CPU), a field programmable gate array (FPGA) device, an application specific integrated circuit (ASIC), another hardware device, a firmware device, or any combination thereof. A memory, such as a non-transitory computer-readable storage medium, may include a volatile memory device (e.g., a random access memory (RAM) device), a non-volatile memory device (e.g., a read-only memory (ROM) device, a programmable read-only memory, and a flash memory), or both. A memory may be configured to store instructions, one or more thresholds, one or more data sets, or a combination thereof. In some configurations, the instructions (e.g., control logic), when executed by the one or more processors, may be configured to cause the processor to perform one or more operations (e.g., determine pressure at various positions along the catheter 14, transmit a prompt based on a measured parameter, display a parameter or notification on a display, or operate a fluid source). The one or more thresholds and one or more data sets may be configured to cause the processor to generate a control signal to perform an operation.As described herein, the system 10 may include real-time monitoring during thrombolysis, which may shorten treatment times and reduce the effective dose of thrombolytic drugs to improve patient safety compared to conventional catheter systems.

[0036] In some configurations, the system 10 may include a user interface (UI) configured to display useful parameters such as proximal and distal pressure waveforms, pressure averages, infusion pressure and flow rate, total time of infusion, total volume of thrombolytic agent infused, as described herein. The UI may be in communication with the controller 68 and may be configured to be utilized with instructions (e.g., an algorithm) to determine when the proximal and distal waveforms are similar enough that complete thrombolysis can be assumed to have occurred. The UI may have an algorithm that monitors the infusion pressure and flow rate of the thrombolytic agent and signals the user when the embolus is likely to have been fully lysed. The controller 68 may initiate one or more prompts visible via the UI when flow rates are high, possibly indicating infusion in areas outside the embolus. In configurations where the expandable tubes (e.g., 96) are arranged such that individual tubes infuse only certain zones along the length of the catheter 14, the UI may indicate where an embolus is likely still present based on flow rates in different zones. The UI may display a graphic image of the embolus to show the current estimated shape and size of the embolus. In some configurations, the UI may alert the user when the amount or time of lytic agent exceeds a threshold, or when the amount or time of contrast agent exceeds a threshold. The UI may alert the user when the proximal pressure sensor (e.g., 64) does not show a valid pulmonary artery waveform. The UI may also monitor and provide threshold alerts for typical signs of thrombolytic agent effectiveness, such as a reduction in pulmonary artery pressure (proximal sensor) and an increase in pulmonary capillary wedge pressure (distal sensor). The UI may record data for future download / upload. The UI may utilize a learning algorithm to determine optical thrombolytic agent dose for future patients based on the outcomes of past successful patients. The UI may upload parameter data to a shared database that can form the basis of machine learning to improve thrombolytic parameter settings.

[0037] 2A-2D, cross-sectional views of various configurations of body 18 are shown and described in more detail. For example, Figures 2A and 2B depict a three-lumen configuration of body 18 having a first lumen 32, a second lumen 34, and a third lumen 36, while Figures 2C and 2B depict a three-lumen configuration of body 18 having a first lumen 32, a second lumen 34, and a third lumen 36. First lumen 32, second lumen 34, third lumen 36, and fourth lumen 38 may have a variety of geometries and are not limited to the shapes and sizes shown in Figures 2A-2D.

[0038] In some configurations, the first lumen 32 is configured to act as a guidewire lumen. In such configurations, the first lumen 32 may extend along the entire length of the catheter 14 from the proximal end 48 to the distal tip. The first lumen 32 may be sized to receive a guidewire and may have a maximum transverse dimension greater than or equal to 0.035 inches (in), such as 0.04 in, 0.05 in, or more. In some configurations, the minimum internal transverse dimension of the lumen 32 is greater than that of the second, third, or fourth lumens 34, 36, 38. The first lumen 32 may be configured to measure a distal pressure, such as the pressure distal to a thrombus. For example, the first lumen 32 may be in fluid communication with an opening at the distal end 52 (e.g., the distal tip) and may be connected to a pressure transducer to measure the pressure of the blood vessel at the distal end of the body 18. In some configurations, such as the configurations shown in FIGS. 2B and 2D, the first lumen 32 is centrally located within the body 18. In other configurations, the first lumen 32 may have a longitudinal axis that is closer to the longitudinal axis (eg, the centerline) of the body than the peripheral surface 60 .

[0039] In some configurations, the second lumen 34 may be configured to operate as a contrast injection lumen. In some configurations, such as when the second lumen 34 is circular, the second lumen may have a maximum transverse dimension greater than or equal to 1.33 mm (4 French), such as 5 French, 6 French, or more. The second lumen 34 may be in fluid communication with a series of ports 20 (second ports) disposed along the region 44 and may be configured to deliver a contrast agent into the bloodstream for diagnostic quality angiographic images. For example, the second lumen 34 may be in communication with a second conduit (e.g., 56) connected to a fluid source (e.g., a pump, syringe, or other pressurized source configured to inject a fluid into the bloodstream) having a contrast agent configured for fluoroscopy, MRI, CT, PET, or other medical imaging modality. Additionally or alternatively, the second lumen 34 may be configured to measure proximal pressure, such as pressure proximal to a thrombus. For example, the second lumen 34 may be connected (e.g., in a second conduit) to a pressure transducer to measure the pressure at the second port (e.g., 20). This connection may be made in parallel with the fluid source (e.g., a contrast injection device) using a T-piece, or optionally with a valve or manifold arrangement to isolate the fluid source and the pressure sensor.

[0040] The catheter 14 may detect pressure at two different points in the bloodstream during operation using the first and second lumens 32, 34. Sensing pressure at longitudinally spaced positions (proximal and distal to the thrombus) allows for real-time analysis of blood flow restoration in the vessel through analysis of the pressure waveform both upstream and downstream of the thrombus. For example, within and distal to the thrombus, the pressure waveform (e.g., pulmonary artery pressure waveform) becomes blunted due to lack of pulsatile flow through the thrombus. As the thrombus dissipates, such as during delivery of a lytic agent, the distal pressure waveform gradually becomes more normal. Thus, the system 10 or its operator can infer normalization of blood flow within the thrombus or in the vessel distal to it to determine when thrombolysis is complete. This capability thus allows a smaller effective amount of thrombolytic drug to be administered, thereby minimizing the patient's bleeding risk that may otherwise be increased by administration of more lytic agent than is required to restore normal blood flow.

[0041] In some configurations, the third lumen 36 may be configured to operate as a lytic agent distribution lumen. In some configurations, such as when the third lumen 36 is circular, the third lumen may have a maximum transverse dimension greater than or equal to 1.00 mm (3 French), such as 5 French, 6 French, or more. The third lumen 36 may be in fluid communication with a series of ports 20 (third ports) disposed along the region 40 and may be configured to continuously deliver a thrombolytic agent into the bloodstream to treat a thrombus. For example, the third lumen 36 may be in communication with a third conduit (e.g., 56) connected to a source of fluid having a lytic agent (e.g., a pump, syringe, or other pressurized source configured to inject a fluid into the bloodstream). The third lumen 36 is separate from the first and second lumens 32, 34, and injection of a fluid (e.g., a lytic agent) in the third lumen 36 may occur without interfering with the function (e.g., pressure sensing) of the first and second lumens.

[0042] 2C and 2D, the body 18 may include a fourth lumen 38. The fourth lumen 38 may be utilized for various functions, such as those described above with respect to the first, second, or third lumens 32, 34, 36 for redundancy. In some configurations, the fourth lumen 38 may be utilized with a balloon disposed at or near the distal end 52 (e.g., as shown in FIG. 3A). In such configurations, the fourth lumen 38 may be in fluid communication with the balloon for inflating and de-inflating the balloon to navigate the catheter through the human vasculature, such as through the heart and into the pulmonary vasculature. In other configurations, the fourth lumen 38 may be utilized with a steerable tip (e.g., so that the distal tip can be steered over a 180 degree range) to facilitate navigation and wire selection of different branches of the pulmonary arterial tree. In such configurations, the fourth lumen 38 may be used to control the steerable tip (e.g., as shown in FIG. 3B). In some configurations in which the catheter 14 includes a sleeve, the fourth lumen 38 may be utilized to move the sleeve relative to the body 18, such as via a wire extending through the fourth lumen 38.

[0043] Although the catheter 14 is described as being utilized for the treatment of pulmonary embolism, it may be utilized for other applications, such as, for example, intravascular thrombolytic therapy, and may utilize real-time hemodynamic monitoring and self-expandable cage / basket lytic agent delivery, as described herein. For example, the catheter 14 may facilitate the treatment of both arterial and venous thrombosis, including, but not limited to, deep vein thrombosis, lower limb arterial thrombosis, renal vein thrombosis, mesenteric vein thrombosis, and IVC filter-associated thrombosis. In some applications, the catheter 14 may be modified based on the treatment area. As an illustrative example, in the deep vein and mesenteric / splanchnic vein space, the catheter 14 may have a larger profile to provide greater surface contact of the lytic agent with the thrombus, along with a longer length to allow for tunable infusion. Some such examples may also include greater mechanisms for mechanical thrombus removal, along with repeated distal vena cava protection to avoid distal embolization. For example, in some configurations, the catheter may be substantially 10 French to help facilitate contrast injection, or up to substantially 18 French for thrombectomy. In other applications, the catheter may have a smaller profile to accommodate smaller vessel diameters and the need for less surface contact with the vessel wall. Distal embolic protection mechanisms may also be employed as well.

[0044] It should be understood that each of the first lumen 32, second lumen 34, third lumen 36, and fourth lumen 38 may be utilized for a different function than that described above. In some configurations, this may be alternative or additional to the functions described herein. For example, the lumens described herein may be utilized to draw blood samples for testing, such as during an index procedure or while the catheter is being used for drug infusion and / or hemodynamic monitoring.

[0045] 3A-3C, the catheter 14 may include or be operable with one or more other components to increase the functionality of the catheter. For example, FIG. 3A depicts an inflatable balloon 72 disposed on the distal end 52 of the body 18 configured to expand and contract to navigate within a blood vessel, and FIG. 3B depicts a distal end having a steerable tip configured to rotate relative to a more proximal portion of the body. The steerable tip may include wiring, such as a steering cable 76, to manipulate the distal tip. The balloon 72 may be positioned between the distal end 52 and the port 20. In some configurations, the balloon 72 and the steerable tip may be controlled at the proximal end 48, such as via a lumen (e.g., 38) or one or more conduits (e.g., 56).

[0046] In some configurations, the system 10 may include a handle assembly 80, as shown in FIG. 3C, disposed at the proximal end 48 to facilitate control of the catheter 14 by an operator. As shown, the handle assembly 80 includes a number of fittings 84 configured to engage with respective conduits 56 or lumens 30. The illustrated handle assembly 80 includes three fittings 84. In some configurations, a first fitting (e.g., 84) is configured to provide or facilitate infusion of a dissolution agent, a second fitting (e.g., 84) is configured to provide or facilitate use with a guidewire, and a third fitting (e.g., 84) is configured to provide or facilitate use with a balloon (e.g., 72). In some such configurations, the second fitting may be connected to a distal pressure transducer, such as via a T-piece or valve assembly to enable parallel function. In some configurations, the handle assembly 80 may include additional fittings configured to provide or facilitate contrast injection, connect to a proximal pressure transducer, or both, or may be coupled to another component with additional fittings (e.g., 126 shown in FIG. 6B). In some configurations, the handle assembly 80 includes a steering mechanism 88 including a handle connected to a gear ring such that movement of the handle moves the gear ring. In such configurations, steering wires may be coupled to the steering mechanism 88 to adjust the distal end 52 of the body based on movement of the handle. The steering mechanism need not necessarily include a gear ring or handle, but may be configured to manipulate steering wires as understood in the art, such as via a simple pull wire, a push rod, a rotating knob, a motorized retraction system, or other system.

[0047] 4A-4D, a second configuration of the subject catheter of system 10 is shown and designated by the reference numeral 14a. In this configuration, components that are similar (e.g., in structure and / or function) to components discussed with respect to Figures 1-3C are labeled with the same reference numeral and the suffix "a."

[0048] FIG. 4A depicts the distal end 52 of the catheter 14a including a body 18a (e.g., an inner sheath) disposed within an outer sheath 92. The body 18a includes one or more expandable tubes 96 configured to extend radially relative to the body 18a. Although multiple "tubes" are used throughout to reflect that multiple tube segments define the overall shape of the expandable tube 96, the multiple tube segments may be part of a single continuous tube in some embodiments. The outer sheath 92 may be independently movable relative to the body 18 to selectively cover or expose portions of the body 18a. For example, as shown in FIG. 4A, the outer sheath 92 is disposed over the expandable tube 96 such that the tube is in a collapsed state. As shown in FIG. 4B, the outer sheath 92 may be moved relative to the body 18 to expose the expandable tube 96 such that the tube is in an expanded state having a maximum unconstrained transverse dimension D2 that is greater than the corresponding maximum transverse dimension of the body 18a or the outer sheath 92. While the expandable tube 96 is in the collapsed state, at least a portion of the tube is radially closer to the body 18a than in the expanded state to reduce the overall diameter of the catheter 14a (compared to the expanded state) to facilitate progression through the vasculature to the embolus. Movement of the outer sheath 92 may be controlled at the proximal end (e.g., 48) as described above. In some configurations, the outer sheath 92 and body 18a may include fluoroscopic markings to aid in navigation.

[0049] In some configurations, the expandable tube 96's maximum unconstrained transverse dimension D2 may be at least 150% (e.g., greater than any one of or between any two of 150%, 200%, 250%, 300%, 350%, 400%, 450%, and / or 500%) of the maximum transverse dimension D3 of the outer sheath 92. As shown in FIG. 4B, while in the expanded state, the expandable tube 96 may have an elongated shape. For example, the expandable tube 96 may have a maximum unconstrained longitudinal dimension D4 that is greater than the maximum unconstrained transverse dimension D2. In some configurations, the maximum unconstrained longitudinal dimension D4 may be greater than 500% of the maximum unconstrained transverse dimension D2. In other configurations, the maximum unconstrained longitudinal dimension D4 may be greater than or between any two of: 125%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, and / or 750% of the maximum unconstrained transverse dimension D2.

[0050] The expandable tube 96 may be formed of Nitinol configured to exhibit superelastic or shape memory properties. For example, the expandable tube 96 may be formed of laser cut or extruded Nitinol tubing that is wrapped around a mandrel and heat treated to the desired shape in some configurations. In some configurations, the expandable tube 96 may comprise multiple materials, such as a distal portion of the tube comprising Nitinol and a proximal portion comprising PTFE or other polymer. In some configurations, the tube 96 may be in fluid communication with the lumen of the body 18a and may be configured to deliver a fluid (e.g., a lytic agent) into the blood vessel. The expandable tube 96 may be positioned closer to the distal end 52 than the proximal end 48 and may be configured to expand into a shape conducive to uniform and isotropic infusion of a thrombolytic agent throughout the interior volume of the target embolus. Although not shown for clarity, the expandable tube 96 may include multiple ports, such as port 20, disposed along its length to allow the thrombolytic agent to enter the blood vessel. The shape of the expandable tube 96 may be configured to distribute fluid in multiple directions and may increase the surface area available for infusion compared to conventional catheters. In one illustrative configuration, the expandable tube 96 may assume the shape of a helix, spiral, spherical, cone, flower, cage, or basket while in an expanded state.

[0051] 4C and 4D, a cross-sectional view of the catheter 14a is shown. As best illustrated in FIG. 4C, the body 18a may include an outer body 100 and an inner body 104. In some configurations, the length of the outer body 100 may be shorter than the length of the inner body 104 such that the distal tip of the outer body is more proximal than the distal tip of the inner body. The outer body 100 may surround the inner body 104 and may include a channel configured to receive the inner body. The outer body 100 and the inner body may have a variety of geometric shapes (e.g., number and size of lumens or ports), such as circular, rectangular, hexagonal, curvilinear, or elliptical, and are not limited to the shapes and sizes shown in FIGS. 4A-4D.

[0052] The outer body 104 may include multiple lumens 108 configured to be in fluid communication with the expandable tube 96. In some configurations, the lumens 108 may include or correspond to the lumens 36 of the catheter 14. In some configurations, each lumen 108 is configured to be coupled to a respective tube end of the expandable tube 96, while in other configurations, a pair of lumens (e.g., 108) may be coupled to opposing ends of the expandable tube or other configurations. The lumens 108 may be coupled to the expandable tube 96 in any suitable manner to allow for fluid communication, such as via heat fitting, adhesives, molding processes, or any other process known in the art. The expandable tube 96 may be disposed within and extend partially along the lumen 108, or may extend all the way to the proximal end 48. In some configurations, the lumens 108 may be fluidly connected together near the proximal end 48 to be driven by a fluid source (e.g., a single thrombolytic agent infusion pump or syringe), or in other configurations, the lumens 108 may remain separate and be driven by separate fluid sources or by a single fluid source through a manifold or valve arrangement. Although four lumens 108 are shown in the figures with corresponding connections to the expandable tube 96, any number of lumens and corresponding connections to the expandable tube may be used. In an alternative embodiment, the expandable tube 96 may not be part of the body 18a, but may extend the length of the body and be loosely held within the outer sheath 92 and the body (e.g., inner body 104).

[0053] As shown in FIGS. 4C and 4D, the outer sheath defines a lumen 110 within which the body 18a is disposed. The inner diameter of the outer sheath 92 may be greater than the outer diameter of the outer body 100 such that the lumen 110 can function as described herein. In one illustrative example, the outer sheath 92 may include an inner diameter of substantially 2 mm and the outer body 100 may have an outer diameter of substantially 1 mm such that the lumen 110 defines an annular gap of 1 mm at line AA and a larger gap at line BB. The lumen 110 may be configured to actuate a contrast injection lumen, a proximal pressure lumen, or both. For example, during thrombolysis, the outer sleeve 92 is positioned proximal to the thrombus such that the extendable tube 96 can shift to an extended state. During actuation, a pressure transducer may be connected to the proximal end of the lumen 110 to measure pressure at the distal end of the lumen at a point proximal to the thrombus. In some configurations, the lumen 110 may include or correspond to the lumen 34 of the catheter 14 .

[0054] The inner body 104 includes multiple lumens extending along at least a portion of the length of the inner body from a proximal end (e.g., 48) to a distal end (e.g., 52). In the illustrated configuration, the inner body 104 includes a first lumen 114, a second lumen 116, and a third lumen 118. Each of the first, second, and third lumens 114, 116, 118 may include or correspond to lumens 32, 34, 36, or 38 described above. For example, the first lumen 114 may include a guidewire lumen sized to receive a guidewire (e.g., a 0.018" or 0.035" diameter guidewire) and may be configured to measure distal pressure, such as pressure distal to a thrombus. The first lumen 114 may be in fluid communication with an opening at a distal end 52 (e.g., a distal tip) of the inner body 104 and may be connected to a pressure transducer to measure vascular pressure at the distal end of the body 18a. In some configurations, the lumen 114 may include or correspond to the lumen 32 of the catheter 14. In one illustrative example, the second lumen 116 may be configured as a steering lumen and may be configured to receive a steerable wire to facilitate movement of the distal end 52 of the body 18a. Additionally or alternatively, the third lumen 118 may be configured as a balloon lumen and may be configured to inflate and deflate a balloon coupled to the distal end 52 of the catheter 14a. In some configurations, the lumens 116, 118 may include or correspond to the lumen 38 of the catheter 14. It should be understood that the catheter 14a (e.g., the body 18a) may include more or fewer lumens than depicted in the figures.

[0055] 5A and 5B, a configuration of the catheter 14a and a method of operating the catheter are shown. The catheter 14a may have an expandable tube 96 including a Nitinol tube. As shown in FIG. 5A, the expandable tube 96 may have a first end extending from the outer sheath 92 and a second end near the distal end 52. In some configurations, the second end may include or correspond to a return point at which a portion of the expandable tube 96 (e.g., a midpoint) turns. In some such configurations, the inlet and outlet of the expandable tube 96 may be positioned at the first end or closer to the first end than the second end. FIG. 5B illustrates a method of operating the catheter 14a to treat a pulmonary embolism in a pulmonary artery, although one skilled in the art will appreciate that the catheter may be otherwise utilized. In use, the catheter 14a may be inserted at a suitable venous access point, such as, for example, a femoral vein, a jugular vein, a brachial vein, or a subclavian vein. In some embodiments, the catheter 14a may be navigated to the embolus 122 by a balloon, guidewire, steering wire, or combination thereof, as understood in the art. During navigation, the outer sheath 92 may cover the body 18a and compress the expandable tube 96 until the embolus 122 is reached. The proximal end of the lumen 110 or 114 (e.g., the conduit 56) may be fluidly connected to a source of fluid containing imaging contrast agent for injecting a constriction agent by manual or mechanical means. In some configurations, the operator may inject contrast agent through the lumen 110 during entry to determine the location of the embolus 122. The contrast agent may be appropriate for fluoroscopy, MRI, CT, PET, or other medical imaging modalities.

[0056] Once the distal end 52 of the catheter 14a reaches the embolus 122, the operator may advance the distal tip through the embolus until the distal tip is just distal to the embolus, as shown in FIG. 5. In some embodiments, this position may be confirmed by injecting additional contrast through the lumen 110, by connecting a catheter pressure transducer to the proximal end (e.g., a conduit) of the lumen 110, or by doing both via a parallel connection to a contrast injection device using a T-piece or manifold arrangement. In configurations where the lumen 110 is configured to detect pressure, when the distal-most tip of the outer sheath 92 is within the pulmonary artery but proximal to the embolus 122, a typical pulmonary artery pressure waveform may be detected. In some such configurations, the waveform may be displayed on a monitor, or some other indicator of a normal pressure reading may be initiated. When the distal-most tip of the outer sheath 92 is distal to the embolus 122, a typical pulmonary capillary wedge pressure may be detected, and in some configurations may be displayed or otherwise indicated.

[0057] With both sheaths (e.g., 92, 18a) of the catheter 14a completely clear of the embolus 122, the operator may release the expandable tube 96, exposing the inner body 104, as shown in FIG. 5, and begin the infusion process. The operator may use controls at the proximal end of the catheter, such as the handle assembly (e.g., 80), to retract the outer sheath 92 while the inner body 104 remains in place. These proximal controls may consist of a simple pull wire, push rod, turn knob, motorized retraction system, or other systems that will be apparent to those skilled in the art. The expandable tube 96 may extend radially from the body 18a into an expanded state, and is fluidly connected to a lumen (e.g., 108) within the body that extends back to at least one conduit on the proximal end of the catheter 14a, which connects to a fluid source for infusion of the thrombolytic agent through a port 20a in the expandable tube 96. The infusion device may be a hand-held syringe or an infusion pump, as is well known in the art. The expandable tube 96 may be perforated at multiple points along its length, with ports (e.g., holes or skives) oriented in different directions perpendicular to the central axis of the tube (defined when the expandable tube is in a straight configuration). The ports may be drilled holes, cut skives, or chemically etched, or the expandable tube 96 may be manufactured as a mesh or porous material. In some configurations, the ports (e.g., 20) may be sized and shaped to create a desired spray pattern when combined with a pressure known within the capabilities of the fluid source. For example, it may be desirable to place a small nozzle or atomizer on each port to shape the spray pattern.

[0058] As mentioned above, the distal tips of both the outer sheath 92 and the body 18a may provide separate lumens that extend back to the proximal end of the catheter and terminate in fluid connection to a commercially available pressure transducer, such as the IP-BD-300 by Becton Dickinson. These two measurement points may be used to compare blood pressures proximal and distal to the embolus 122. For example, when the outer sheath 92 is retracted to a point where a normal pulmonary artery pressure waveform is detected, the operator knows that retraction of the outer sheath is sufficient and should be stopped. This ensures that the expandable tube 96 is only exposed inside the embolus 122 and does not extend into the more proximal, non-occluded portion of the artery. In this and other manners, the catheter 14a may minimize the area over which the thrombolytic agent is delivered and may also minimize the amount of thrombolytic agent infused to areas outside the embolus 122, thereby minimizing risk to the patient.

[0059] The distal tip of the body 18a (e.g., inner body 104) remains distal to the embolus 122 during retraction of the outer sheath 92, allowing typical capillary wedge pressure to be detected. During infusion of the thrombolytic agent, the operator may monitor both pressure waveforms to ensure proper positioning is maintained. As the thrombolytic agent gradually breaks down the embolus 122, the "distal pressure" waveform (capillary wedge pressure) changes until it is nearly identical to the "proximal pressure" waveform (normal pulmonary artery pressure waveform). At this point, the operator may stop infusion of the thrombolytic agent and complete the procedure. In this and other manners, the system 10 may perform thrombolysis with minimal infusion volume and time under anesthesia and fluoroscopy.

[0060] Additionally or alternatively, fluoroscopic markings may aid in positioning the catheter 14a. For example, the outer sheath 92 may have markings at its distal tip, and a graduated fluoroscopic ring may be provided on the body 18a (e.g., outer body 100, inner body 104) to facilitate measurement of the exposed length of the body and to indicate the axial length of the expanded portion of the expandable tube 96. Additionally, contrast may be injected into either the lumen 110 or lumen 114, allowing the operator to position the inner body 104 at the most proximal point that does not yet exhibit a blockage, and the outer sheath 92 at the most distal point that does exhibit a blockage. Positioning the two sheaths as close as possible to the end of the embolus 122 may reduce infusion of thrombolytic agents upstream or downstream of the embolus.

[0061] As a specific, non-limiting example, system 10 may include flow measurement via thermodilution. Illustratively, catheter 14a may inject a bolus of cold saline or other fluid into lumen 110, and a thermistor or other type of temperature sensor may be disposed at the distal end of the catheter. System 10 may measure the time between the cold saline and the sensing of the temperature drop by the thermistor. From this, flow rate, and potentially flow volume, may be estimated using algorithms known in the art.

[0062] Throughout the infusion period, the operator may use pressure measurements or contrast injection to reposition the two sheaths (e.g., 92, 18a) in response to changes in the size and shape of the embolus. The operator may adjust the position of the tip of either sheath to ensure that the expandable tube 96 is infusing agent only inside the embolus volume and not into the upstream or downstream spaces. The operator may move the outer sheath 92 relative to the body 18a to compress a portion of the expandable tube 96 and seal off the port associated with the compressed portion of the tube. In this manner, the operator may match the axial length of the infusion zone to the length of the embolus 122 in real time.

[0063] In some configurations, the present catheters (e.g., 14, 14a, 14b) may be utilized for thrombectomy as an addition or alternative to thrombolysis. For example, the expandable tube 96 may be configured to be positioned near a thrombus in an expanded state and transition to a collapsed state to engage the thrombus. The catheter is then retracted to remove the engaged thrombus. In some configurations, the large diameter (e.g., maximum unconstrained transverse dimension) of the expandable tube 96 may enable removal of the thrombus via direct interaction with the expandable tube. In configurations in which the body (e.g., 18, 18a) is moved over a guidewire, the catheter may be removed with the thrombus trapped within the interwoven cage formed by the expandable tube 96. Because most thrombectomy procedures are unable to remove the entire thrombus via manual or mechanical techniques, significant thrombus often remains, which increases the risk of long-term complications such as heart failure, pulmonary hypertension, or chronic thromboembolism. Thus, after an initial thrombectomy attempt, the catheter (e.g., 14, 14a, 14b, 14c, 14d) may be placed back into the region of interest and a thrombolytic agent (such as tissue plasminogen activator or "tPA") may be infused through the methods described herein. Multiple thrombolytic agent outlet holes (e.g., 20a) span the length of the catheter, allowing thrombi near or downstream of the catheter to be subjected to pharmacological thrombolysis. Thus, the catheter may allow for the combination of mechanical disruption and removal of clots (i.e., thrombectomy) and catheter thrombolytic therapy (i.e., lysis) using a single device. In this and other ways, the catheter may allow the user to more thoroughly treat patients with a wide range of thromboembolic diseases.

[0064] 6A and 6B, a third configuration of the subject catheter of system 10 is illustrated and designated 14c. In this configuration, components similar (e.g., in structure and / or function) to those discussed with respect to FIGS. 1-5 are labeled with the same reference numeral and suffix "b". Catheter 14b is similar to catheter 14a, except that expandable tube 96 is configured to form a plurality of individually spaced cages rather than a single elongated cage. As shown, one or more spherical cages are formed extending radially from body 18c while expandable tube 96 is in an expanded state. As shown in FIG. 6B, catheter 14c may be coupled to handle assembly 80c and fitting assembly 126, which may provide additional ports or conduits for connection to the lumen of the catheter.

[0065] 7A-7E, the outer sheath 92c is shown retracted relative to the body 18c to expose a series of expandable tubes 96c. Initially, the outer sheath 92c completely covers the body 18c (FIG. 7A), and the outer sheath may be retracted while the body remains in place (FIG. 7B) to uncover a first set of expandable tubes 96c, which may include a single tube or may include multiple tubes that expand radially in unison when uncovered. The outer sheath 92c may be further retracted to expose a second set of expandable tubes 96c (FIG. 7C), a third set of expandable tubes 96c (FIG. 7D), and a fourth set of expandable tubes 96c (FIG. 7E). As the outer sheath 92c is retracted or advanced, more sets of expandable tubes or cages are released or compressed, which allows the operator to adjust the effective length of the lytic agent infusion region to match the length of the embolus. In some configurations, each cage may be actuated independently of the others. By way of illustration, the operator may deploy all four expandable tube cages within the embolus and begin infusion. If each cage is attached to a separate fluid source (e.g., a lytic agent infusion source), each fluid source may monitor the pressure and flow rate of infusion into the respective expandable tube cage 96c. If one of the cages 96c shows a pressure drop or flow rate increase, this may indicate that the cage has already lysed that portion of the embolus. In this case, the operator, or an infusion source acting automatically, may stop infusion into only that cage while maintaining infusion in the other cages. In some configurations, the operator may reposition the catheter 14c based on these or other parameters. Therefore, monitoring flow and pressure at the infusion source, alone or in conjunction with contrast injection and pressure waveform analysis, may be another useful tool to detect the thrombolytic state in different parts of the embolus and to adapt the infusion to changing embolus geometry.Although Figures 7A-7E depict four spherical expandable tube cages (e.g., 96c), more or fewer cages may be implemented in catheter 14c, such as a single cage, or two, three, or five cages.

[0066] 8A and 8B show an example of a cross-sectional view of a catheter 14c. In this configuration, the catheter 14c includes an outer sheath 92c and a body 18c having multiple lumens. As shown, the body 18c may include multiple lumens 108c connected to the expandable tube 96c and configured to deliver a thrombolytic agent into the bloodstream; a lumen 114c configured to receive and pass over a guidewire; a lumen 116c configured as a steering lumen and may be configured to receive a steerable wire to facilitate movement of the distal end 52 of the body 18c; a lumen 118c configured as a balloon lumen and configured to inflate and de-inflate a balloon coupled to the distal end 52 of the catheter 14a; or a combination thereof. The outer sheath 92c includes a lumen 110c configured to actuate a contrast injection lumen, a proximal pressure lumen, or both. In some configurations, the expandable tube 96c depicted as being outside the body 18c may connect to the lumen 108c further upstream or proximally (left side in FIG. 8A ), and the expandable tube shown within the lumen 108c may exit the body 18c further downstream or distally (right side in FIG. 8A ), such as via one or more ports (e.g., 20) in the body 18c.

[0067] 9A and 9B, a fourth configuration of the subject catheter of the system 10 is illustrated and designated by the reference numeral 14d. In this configuration, components similar (e.g., in structure and / or function) to those discussed with respect to FIGS. 1-8B are labeled with the same reference numeral and suffix "d". The catheter 14d includes an outer sleeve 92d having a lumen 118d configured as a balloon lumen and configured to inflate and deflate a balloon coupled to a distal end of the catheter 14d; a lumen 116d configured as a steering lumen and may be configured to receive a steerable wire to facilitate movement of the distal end of the body 18d; and a lumen 110d in which the body 18d is disposed and configured to actuate a contrast injection lumen, a proximal pressure lumen, or both. The body 18d may include a plurality of lumens 108d connected to the expandable tube and configured to deliver a thrombolytic agent into the bloodstream. 9B, the lumen 108d may include a number of ports 20d extending through a surface of the body 18d to allow fluid communication between the lumen 108d and the blood vessel. In some configurations, an expandable tube (e.g., 96c) may be coupled to the lumen 108d and extend through the ports 20d to transition between a compressed state and an expanded state based on the relative position of the outer sheath 92d.

[0068] FIG. 10 illustrates an exemplary manner in which the present catheters (e.g., 14, 14a, 14b, 14c, 14d) may be used to treat an embolus. With respect to FIG. 10, components similar (e.g., in structure and / or function) to those described above are labeled with the subscript "d" but may include or correspond to any of the components described above (e.g., "a", "b", "c"). A first view of the artery at a first time 200 (left) shows a cutaway detail of a segment of the pulmonary artery with an embolus 122. The catheter 14d may be inserted at a suitable venous access point, such as the femoral, jugular, brachial, or subclavian vein. In some embodiments, the catheter 14d may provide a balloon to guide the blood flow to the pulmonary artery, as shown in the figure. In other embodiments, the catheter 14d may provide a lumen configured for tracking over a guidewire, as known in the art. In further embodiments, the catheter 14d may provide a steering wire to aid in tracking to the target embolus. The outer sheath 92d may cover the body 18d and compress the expandable tube 96d during entry and navigation to the embolus 122. Either the outer sheath 92d or the body 18d may be provided with fluoroscopic markings to aid in navigation. Additionally, the inner diameter of the outer sheath 92d may be relatively large compared to that of the body 18d, and the proximal end of the outer sheath may be fluidly coupled to an inlet port to allow for the injection of imaging contrast by either manual or mechanical means. The contrast inlet conduit may be connected to an external syringe or pump via a luer fitting or other means known in the art. The implanting physician may inject contrast through the outer sheath 92d during entry to determine the location of the embolus 122. In one exemplary embodiment, the outer sheath 92d may have an inner diameter of about 2 mm and the body 18d may have an outer diameter of about 1 mm. The contrast agent may be suitable for use with fluoroscopy, MRI, CT, PET, or other medical imaging modalities.

[0069] Once the distal end of the catheter 14d reaches the embolus 122, the operator advances the distal tip through the embolus until the distal tip is just distal to the embolus as shown at time 200; the left side of the figure is proximal and the right side is distal. This position may be confirmed by further contrast injection through the outer sheath 92d. Alternatively, the position may be confirmed by connecting a catheter pressure transducer to the proximal end at a port fluidly connected to the outer sheath. This connection may be made in parallel with the contrast injection device using a T-piece or, optionally, with a valve or manifold arrangement to isolate the injector and pressure sensor. When the tip of the outer sheath 92d is in the pulmonary artery but proximal to the embolus 122, as shown at time 202, a typical pulmonary artery pressure waveform 210 may be visible on the transducer output display. When the tip of the outer sheath 92d is distal to the embolus, a typical pulmonary capillary wedge pressure waveform 210 may be seen.

[0070] Body 18d may contain a relatively large lumen that opens at the distal tip of the catheter and extends back to another Luer port on the proximal end. In embodiments relating to a guidewire, this lumen may be used to hold a guidewire, e.g., a 0.018" or 0.035" diameter guidewire, and the proximal port may contain a hemostatic fitting for the guidewire, such as a Tuohy-Borst connector.

[0071] With both sheaths of the catheter completely clear of the embolus 122, the operator may expose the body 18d and begin the infusion, as shown at time 202. The operator uses controls at the proximal end of the catheter 14d to retract the outer sheath 92d while holding the body 18d in place. These proximal controls may consist of a simple pull wire, push rod, turn knob, motorized retraction system, or other systems that will be apparent to one of skill in the art. At time 202, the outer sheath 92d is pulled proximally (to the left in the frame), releasing the compressed expandable tube 96d and allowing it to extend radially from the body 18d. The inlet of the expandable tube 96d is fluidly connected to a lumen in the body 18d that extends back to at least one port on the proximal end of the catheter, which connects to a device for infusing the thrombolytic agent. The infusion device may be a hand-held syringe or an infusion pump, as is well known in the art. The expandable tube 96d is perforated at multiple points along its length with holes or skives oriented in different directions perpendicular to the long axis of the tube. The perforations may be drilled holes or cut skives, or the expandable tube 96d may be manufactured as a mesh or porous material. The holes or skives may be drilled or cut mechanically with a laser or by a chemical etching process.

[0072] As mentioned above, the distal tips of both the outer sheath 92d and the body 18d may provide separate lumens that extend back to the catheter proximal end and terminate in fluid connection to a commercially available pressure transducer, such as the IP-BD-300 by Becton Dickinson. Once the guidewire is removed from the body 18d, these two measurement points may be used to compare blood pressures between the proximal and distal sides of the embolus 122, as shown at times 202 and 204. When the outer sheath 92d is retracted to the point where a normal pulmonary artery pressure waveform is displayed as "proximal pressure," the operator knows that retraction of the outer sheath 92d is sufficient and should be stopped. This ensures that the expandable tube 96d is only exposed within the volume of the embolus, and minimizes the amount of thrombolytic agent infused to areas outside the embolus, providing the patient with the greatest therapeutic benefit and the least risk.

[0073] In addition to using a pressure waveform to ensure optimal sheath retraction, fluoroscopic markings may be provided on the catheter, which, when combined with contrast injection, can aid in optimizing the position of both the other sheath 92d and the body 18d. For example, the outer sheath 92d may have markings at its distal end, and a graduated ring may be provided on the body 18d to facilitate measurement of the exposed length of the body and to indicate the axial length of the extension of the expandable tube 96d. Additionally, contrast may be injected into either the outer sheath 92d or the body 18d, allowing the operator to position the body at the most proximal point that does not yet exhibit a blockage, and the outer sheath 92d at the most distal point that does exhibit a blockage. Positioning the two sheaths as close as possible to the end of the embolus minimizes infusion of thrombolytic agents upstream or downstream of the embolus 122.

[0074] While the outer sheath 92d displays the pulmonary artery pressure waveform as the "proximal pressure", the distal tip of the body 18d remains distal to the embolus 122, displaying a typical capillary wedge pressure waveform 214 as the "distal pressure", as shown at time 202. During infusion of the thrombolytic agent, the operator may monitor both waveforms to ensure proper positioning is maintained. As the thrombolytic agent gradually breaks down the embolus 122, the "distal pressure" waveform changes until it is nearly identical to the "proximal pressure" waveform, as shown at time 204. At this point, the operator may stop infusion of the thrombolytic agent and complete the procedure, which minimizes patient risks associated with infusion volume and time under anesthesia and fluoroscopy. Similarly, multiple infusion points throughout the embolus volume ensure optimal diffusion of the thrombolytic agent, minimizing time to thrombolysis.

[0075] Throughout the infusion period, the operator may use pressure measurements or contrast injection to reposition the catheter 14d in response to changes in the size and shape of the embolus. The operator may adjust the position of the tip of either the outer sheath 92d or the body 18d to ensure that the expandable tube 96d is infusing agent only inside the embolus volume and not into the upstream or downstream spaces. As the operator retracts the body 18d back into the outer sheath 92d, a portion of the expandable tube 96d is again compressed and the infusion port is sealed off by the outer sheath 92d. In this manner, the operator can match the axial length of the infusion zone to the length of the embolus in real time. Upon completion of the procedure, the operator retracts the body 18d completely into the outer sheath 92d and removes the catheter 14d.

[0076] The above specification and examples provide a complete description of the structure and use of the exemplary embodiments. Although certain embodiments have been described above with a certain degree of specificity or with reference to one or more individual embodiments, those skilled in the art could make numerous modifications to the disclosed embodiments without departing from the scope of the present invention. As such, the various illustrative embodiments of the device are not intended to be limited to the specific forms disclosed. Rather, they include all modifications and variations that fall within the scope of the claims, and embodiments other than those shown in this disclosure may include some or all of the features of the embodiments depicted in this disclosure. For example, components may be combined into a unitary structure and / or connections may be substituted. Furthermore, where appropriate, aspects of any of the above-described examples may be combined with aspects of any other of the described examples to form further examples having comparable or different characteristics and addressing the same or different problems. Similarly, it will be understood that the benefits and advantages described above may relate to one embodiment or to multiple embodiments.

[0077] The claims are not intended to include, and should not be construed as including, means-plus-function or step-plus-function limitations unless such limitations are expressly recited in a given claim using the phrase "means for" or "step for," respectively.

Claims

1. An outer sheath (92) having a proximal end and a distal end and defining a lumen (110) extending from the proximal end to the distal end; an elongated catheter body (18a) having a proximal end (48), a distal end (52), and a length extending from the proximal end (48) and the distal end (52); The elongated catheter body (18a) is disposed within the lumen (110) of the outer sheath (92), the outer sheath (92) being independently movable relative to the elongated catheter body (18a) to selectively cover or expose portions of the elongated catheter body (18a), and the elongated catheter body (18a) is (a) an outer body (100) defining a plurality of lumens (108), wherein the inner diameter of the outer sheath (92) is greater than the outer diameter of the outer body (100), such that the lumens (110) define an annular gap between the outer sheath (92) and the outer body (100), the annular gap being configured for injection of a contrast agent therethrough; and (b) an inner body (104) having a proximal end (48) and a distal end (52) and defining a first lumen (114), a second lumen (116), and a third lumen (118); stipulates, The first lumen (114) is configured to receive a guidewire therethrough; The outer body (100) has a length that is shorter than the length of the inner body (104) such that the distal end of the outer body is more proximal than the distal end of the inner body (52). an elongated catheter body (18a); one or more expandable tubes (96) configured to expand radially relative to the elongate catheter body (18a), each expandable tube coupled to and in fluid communication with one of the plurality of lumens (108) of the outer body (100), each expandable tube comprising one or more ports (20a) configured to infuse a drug therethrough; When the outer sheath (92) is disposed over the expandable tube (96), the expandable tube (96) is constrained in a collapsed state, and the outer sheath (92) is configured to be retracted relative to the elongate catheter body (18a) to expose the inner body (104) and release the constraint on the expandable tube (96) so that the expandable tube (96) self-extends to the expanded state; when the one or more expandable tubes (96) are in an expanded state, the distal end of the outer sheath (92) is proximal to the proximal end of said expandable tubes (96), and the expandable tubes (96) have a maximum unconstrained transverse dimension that is greater than a corresponding maximum transverse dimension of the elongate catheter body (18a); While the one or more expandable tubes (96) are in the collapsed state, at least a portion of the one or more expandable tubes (96) is radially closer to the elongate catheter body (18a) than when the one or more expandable tubes (96) are in the expanded state. one or more expandable tubes (96); a controller (68) including a processor operably coupled to a memory configured to store instructions, one or more thresholds, and / or one or more data sets; one or more proximal pressure sensors (64) coupled to the elongate catheter body (18a), operatively associated with the lumen (110) defined by the outer sheath (92), operatively connected to a controller (68), and positioned proximally relative to the one or more expandable tubes; one or more distal pressure sensors (64) coupled to the distal end of the elongate catheter body (18a), operatively associated with a first lumen (114) in fluid communication with an opening at the distal end (52) of the inner body (104), and operatively connected to a controller (68); When the one or more expandable tubes (96) are in an expanded state, the one or more distal pressure sensors (64) are positioned distal to the distal end of the expandable tubes (96); one or more proximal pressure sensors (64) and one or more distal pressure sensors (64) are configured to measure pressure during the infusion of the drug when the one or more expandable tubes are in an expanded state and to communicate the measured pressure to the controller; one or more distal pressure sensors (64); a user interface display operatively connected to said controller, a controller (68) configured to generate control signals to perform operations including monitoring the measured proximal and distal pressures during the infusion of the medication, displaying the monitored proximal and distal pressures on a user interface display, displaying pressure waveforms corresponding to the measured proximal and distal pressures, displaying changes in the monitored proximal and distal pressures on a user interface display, and transmitting alerts based on changes in the monitored pressures; The flow rate of the agent may be altered based on changes in the monitored pressure. User interface display and The catheter.

2. A catheter as described in claim 1, wherein the change in the monitored proximal pressure includes a decrease in the monitored proximal pressure.

3. A catheter as described in claim 2, wherein the infusion of the drug is stopped by the user based on a comparison of the displayed monitored proximal and distal pressures.

4. A catheter as described in claim 1, wherein the user interface display is configured for use with instructions for determining when displayed pressure waveforms corresponding to measured proximal and distal pressures become sufficiently similar.

5. A catheter as described in claim 1, wherein the infusion of the drug is stopped by the user based on a comparison of the displayed pressure waveform corresponding to the measured proximal and distal pressures.

6. A catheter as described in claim 1, wherein the one or more expandable tubes (96) comprise a shape memory alloy.

7. A catheter as described in claim 6, wherein the shape memory alloy includes nitinol.

8. A catheter as described in claim 6, wherein the one or more expandable tubes (96) further comprise a polymer.

9. A catheter as described in claim 1, wherein each of the first lumen (114), the second lumen (116), and the third lumen (118) has a circular cross-section.

10. A catheter as described in claim 1, wherein the one or more extensible tubes (96) have a plurality of ports (20a), and the one or more extensible tubes (96) are configured to disperse the drug in a plurality of directions through the plurality of ports (20a).

11. A catheter as described in claim 1, wherein the one or more expandable tubes (96) have, in an expanded state, a shape selected from the group consisting of helical, spiral, spherical, conical, flower, cage, and basket shapes.

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