Systems and methods for treating cardiovascular tissue

Abstract

A system is provided for imparting pulsatile energy to cardiovascular tissue. Aspects of the system include a console assembly having a potential source, a manifold assembly operably connected to the output of the console assembly and including an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, and a catheter assembly operably connected to the output of the manifold assembly. The catheter assembly of the present invention includes a connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy, a catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy, and a heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to the cardiovascular tissue. Also provided is a method of imparting pulsatile energy to cardiovascular tissue, for example, deploying the system such that a heart tissue conforming element of the system is adjacent to the cardiovascular tissue and engaging the system in a manner such that the heart tissue conforming element imparts energy to the cardiovascular tissue. Additionally, a stand-alone catheter assembly and a kit comprising the components of the system described herein are provided. The system, assembly, method, and kit are utilized in a variety of different applications including balloon angioplasty applications or other catheter-based therapies or treatments.

Description

Background Art

[0001] Cardiovascular tissues including heart valve tissues are prone to the accumulation of atherosclerotic plaques through a mechanism called atherosclerosis. The accumulation of atherosclerotic plaques is the accumulation of fatty and calcified substances that cause stenosis, narrowing of the arterial lumen, or heart valve insufficiency. Calcific aortic valve stenosis is a common cause of aortic valve disease, leading to syncope (fainting), dyspnea (shortness of breath), heart failure, and ultimately death. The prevalence of aortic stenosis increases rapidly with age.

[0002] It has been demonstrated that up to one-third of elderly patients have some form of evidence of calcific aortic valve stenosis, with a prevalence of 25% in people over 65 years old and nearly 50% in people over 85 years old. In a normal state, the aortic valve is composed of three valve leaflets, each of which is thin (e.g., less than 1 mm), smooth, and has a flexible and movable structure. In aortic stenosis, these valve leaflets thicken, fibrose, and calcify, resulting in a decrease in the mobility of the valve leaflets and progressive valve occlusion. The deposition of calcium increases the stress on the valve leaflets, which leads to more damage to the blood vessels and thereby increases the deposition of calcium.

[0003] Existing treatment options include catheter-based valvuloplasty. However, the typical catheter balloon shape tends to block blood flow through the heart during inflation, for example, limiting the treatment time. Furthermore, overexpansion of balloon aortic valvuloplasty can sometimes cause aortic annulus rupture. The aortic valve area of diseased patients can be 0.1 - 1.5 cm 2 and balloon aortic valvuloplasty provides an averaging effect of balloon pressure across such tissue areas. That is, instead of delivering concentrated pressure to, for example, the commissures of the valve, it relies on the compression of the valve leaflets between the annulus and the balloon.

[0004] Balloon aortic valvuloplasty is currently known as a bridge to transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), or as a means of providing palliative care to patients who are not candidates for TAVR or SAVR, or as part of TAVR to facilitate the delivery of transcatheter valves. Balloon aortic valvuloplasty alone is associated with high morbidity and has a high restenosis rate. To the inventors' knowledge, existing perfusion catheters used in such procedures lack stability and the radial force necessary to modify calcified valves and separate commissures. Further, to the inventors' knowledge, current treatments provide a solution for balloon aortic valvuloplasty that applies local or concentrated stress points to cardiac valve features such as commissures or leaflets while also enabling perfusion, and further do not provide a mechanism for identifying the location of features of cardiovascular tissue such as valve commissures during treatment.

Summary of the Invention

[0005] Accordingly, there remains a need for improved systems and methods for successfully imparting pulsatile energy to cardiovascular tissue, such as a cardiac valve, such as the aortic valve, including providing perfusion across the cardiovascular tissue. For example, a more consistent balloon aortic valvuloplasty that requires minimal rapid pacing and a longer treatment period can improve the preparation for transcatheter aortic valve replacement (TAVR) or the potential long-term treatment of calcific aortic stenosis. Improved systems and methods for successfully imparting pulsatile energy to cardiovascular tissue can also result in a more durable valvuloplasty, obviating the need for TAVR or SAVR, or significantly delaying the time when TAVR or SAVR is required.

[0006] As described herein, the present invention is a system and method for imparting pulsatile energy to cardiovascular tissue, including a system and method that includes imparting such pulsatile energy in the context of balloon valvuloplasty treatment. Specifically, the systems and methods of the present invention facilitate providing local stress points or concentrated stress points to cardiovascular tissue, such as cardiovascular tissue in the form of a heart valve, such as commissures or leaflets, while allowing blood to continue to perfuse distal tissue, for example, by providing perfusion to the distal vasculature such that concentrated forces on the commissures and leaflets are maintained. Such embodiments allow for longer treatment periods that promote the occurrence of calcium fatigue fractures in cardiovascular tissue, such as valve commissures and leaflets.

[0007] Embodiments of the system of the present invention provide a mechanism for identifying the location of the commissure during treatment by providing an outer balloon configured to vibrate, for example, prior to full valvuloplasty balloon dilation, such that the balloon identifies the location of the least resistant path (i.e., the commissure). The location and proper alignment of the pulsatile device (i.e., the heart tissue conforming element) of embodiments of the system of the present invention can be confirmed using, for example, radiopaque markings on such pulsatile devices (e.g., on the balloon), or in some cases other identification markers that may also be able to verify commissure alignment. When properly positioned against the cardiovascular tissue, additional pulsations can be generated within the commissure to effect calcium fractures and tissue separation (e.g., heart valve leaflets).

[0008] A system for imparting pulsatile energy to cardiovascular tissue is provided. Aspects of the system include a console assembly comprising a potential source, a manifold assembly operably connected to the output of the console assembly and comprising an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, and a catheter assembly operably connected to the output of the manifold assembly. The catheter assembly of the present invention includes a connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy, a catheter comprising a fluid passageway operably connected to the output of the connector and configured to transmit the second pulsed energy, and a heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passageway of the catheter and apply pulsatile energy to the cardiovascular tissue. Also provided is a method for imparting pulsatile energy to cardiovascular tissue, for example, deploying the system such that the heart tissue conforming element of the system is adjacent to the cardiovascular tissue and engaging the system such that the heart tissue conforming element imparts energy to the cardiovascular tissue. Additionally, a stand-alone catheter assembly and a kit comprising the components of the system described herein are provided. The system, assembly, method, and kit are utilized in a variety of different applications including balloon angioplasty or other catheter-based therapies or treatments. BRIEF DESCRIPTION OF THE DRAWINGS

[0009]

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DETAILED DESCRIPTION OF THE INVENTION

[0010] A system is provided for imparting pulsatile energy to cardiovascular tissue. Aspects of the system include a console assembly having a potential source, a manifold assembly operably connected to the output of the console assembly and having an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, and a catheter assembly operably connected to the output of the manifold assembly. The catheter assembly of the present invention includes a connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy, a catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy, and a heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to the cardiovascular tissue. Also provided is a method of imparting pulsatile energy to cardiovascular tissue, for example, deploying the system such that the heart tissue conforming element of the system is adjacent to the cardiovascular tissue and engaging the system such that the heart tissue conforming element imparts energy to the cardiovascular tissue. Additionally, a stand-alone catheter assembly and a kit comprising the components of the system described herein are provided. The system, assembly, method, and kit are used in a variety of different applications, including angioplasty applications or other catheter-based therapies or procedures, such as treatment of cardiac valve calcifications.

[0011] Before the present invention is described in greater detail, it is to be understood that the invention is not limited to the particular embodiments described, and accordingly, of course, may vary. Also, it is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting, as the scope of the present invention will be limited only by the appended claims.

[0012] When a range of values is provided, unless the context clearly indicates otherwise, each intermediate value between the upper and lower limits of that range, to one tenth of the unit of the lower limit, as well as any other recited value or intermediate value within the recited range of this description, is understood to be encompassed within the present invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the present invention, subject to any specific excluded limitations within the recited range. When the recited range includes one or both of the limitations, ranges excluding either or both of those included limitations are likewise included in the present invention.

[0013] In this specification, the term "about" is prefixed to a numerical value to present a specific range. The term "about" is used in this specification to provide literal support for the exact number that it precedes, as well as for a number that is close to or approximately the number that the term precedes. When determining whether a number is close to or approximately a specifically recited number, a number that is close to or approximately a number not recited may be a number that provides substantial equivalence to the specifically recited number in the presented context.

[0014] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Also, any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of the present invention, but representative exemplary methods and materials are described below.

[0015] All publications and patents cited in this specification are hereby incorporated by reference as if each individual publication or patent were specifically and individually indicated as being incorporated by reference, and by such incorporation by reference, such publications disclose and describe the relevant methods and / or materials by which they are cited. Any citation of a publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention has no right to antedate such publication by virtue of the features of the prior invention. Further, the dates of the publications provided may be different from the actual publication dates which may need to be independently verified.

[0016] It should be noted that, as used in this specification and the appended claims, the articles “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. It should further be noted that the claims may be drafted to exclude any optional element. Accordingly, this description is intended to serve as antecedent basis for the use of such exclusive terms as “solely,” “only,” etc. in connection with the recitation of claim elements, or the use of “negative” limitations.

[0017] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein may be readily separated from, or combined with, any of the features of some other embodiments without departing from the scope or spirit of the present invention. Any recited method may be performed in the order of recited events or in any other order that is logically possible.

[0018] Devices and methods have been, or may be, described with functional descriptions for grammatical fluidity, but unless expressly recited in accordance with 35 U.S.C. § 112, claim terms should not be construed to be limited by means or step limitations, but should be accorded the full scope of the meaning ascribed by the claim terms and all equivalents under the doctrine of equivalents, and it should be clearly understood that where claim terms are expressly recited in accordance with 35 U.S.C. § 112, full statutory equivalents under 35 U.S.C. § 112 should be accorded.

[0019] In further describing various aspects of the invention, the system and its components will first be described in more detail, followed by a discussion of the method of using the system, and a kit for practicing the subject method.

[0020] A system for treating cardiovascular tissue As summarized above, a system for applying pulsatile energy to cardiovascular tissue is provided. The system of embodiments of the invention is configured to generate pulsatile energy and transmit it to a heart tissue conforming element for applying the pulsatile energy to the cardiovascular tissue. In some instances, the heart tissue conforming element is used to apply pulsatile energy to a heart valve or a feature thereof, or to tissue supporting a heart valve. In an embodiment, the heart tissue conforming element may be configured to concentrate the pulsatile energy on a particular region or feature or aspect of the cardiovascular tissue. For example, the heart tissue conforming element may be configured to deliver the concentrated pulsatile energy to a heart valve commissure or a heart valve leaflet tip.

[0021] The catheter assembly and the heart tissue conforming element can be configured such that fluid can perfuse across the heart tissue conforming element while the heart tissue conforming element applies pulsatile energy to the cardiovascular tissue. In an embodiment, a catheter assembly including the heart tissue conforming element is configured such that when deployed adjacent to the cardiovascular tissue, blood can perfuse across the heart tissue conforming element through an active or passive perfusion mechanism that is part of the catheter assembly and the heart tissue conforming element. Such a configuration facilitates an extended treatment time and increases the amount of pulsatile energy that can be applied to the cardiovascular tissue as compared to what is available with other methods.

[0022] The system of the present invention is used in a variety of applications, including angioplasty applications or other catheter-based therapies or treatments, such as the treatment of cardiac valve calcifications. In some examples, the system is used to disrupt hardened materials, such as calcium deposits, embedded within cardiovascular tissue, such as cardiac valve leaflets or commissures, or other cardiovascular tissue, or tissue surrounding the heart such as pericardial calcification. Specifically, the system of the present invention is used to treat cardiovascular tissue by, for example, (1) utilizing features of a cardiac tissue conforming element to seat the cardiac tissue conforming element at a desired location adjacent to cardiovascular tissue, such as a cardiac valve; (2) utilizing features of the cardiac tissue conforming element to intensively apply pulsatile energy to the cardiovascular tissue, i.e., the pulsatile energy is directed towards a particular aspect of the cardiovascular tissue (e.g., as opposed to a monolithic balloon that applies substantially equal amounts of pulsatile energy to all aspects of the cardiovascular tissue); and (3) enabling perfusion beyond the cardiac tissue conforming element by utilizing features of the catheter assembly and the cardiac tissue conforming element. The present disclosure relates to embodiments for use in the treatment of cardiovascular tissue related to calcifications and / or deposits within cardiovascular tissue, such as cardiac valves or their features, or tissue supporting the cardiac valve or tissue surrounding the heart such as pericardial calcification. However, the system and teachings are not limited to imparting pulsatile energy to cardiovascular tissue in relation to cardiovascular tissue calcifications and can generally be applied to other applications as determined by one of ordinary skill in the art.

[0023] The system can be used to impart pulsatile energy to the cardiovascular tissue of any number of different subjects. In many embodiments, the subject is a "mammal" or "mammalian," terms used to broadly describe organisms within the class of mammals, including carnivores (e.g., dogs and cats), rodents (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In some examples, the subject is a human.

[0024] The system aspects include a console assembly having a potential source, a manifold assembly operably connected to the output of the console assembly and having an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, and a catheter assembly operably connected to the output of the manifold assembly. The catheter assembly of the present invention includes a connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy, a catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy, and a heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to cardiovascular tissue. Further, in certain embodiments, the heart tissue conforming element is configured to engage heart valve tissue. In other embodiments, the heart tissue conforming element includes a plurality of distal balloons circumferentially disposed around a rigid distal region of the catheter. In some embodiments, the catheter assembly is configured to allow fluid to perfuse beyond the distal region of the catheter. These components and their configurations are described in further detail below.

[0025] Console assembly The system of the present invention includes a console assembly. The console assembly, also referred to as a console unit or console subsystem, is used in embodiments of the system according to the present invention to generate the power and control necessary for the treatment of cardiovascular tissue using the system.

[0026] An embodiment of the console assembly of the system according to the present invention includes a potential source. The potential source of an embodiment of the present invention is configured to provide energy, and the energy can be adjusted as desired by a regulator. Any convenient potential source can be used, and examples of potential sources include a voltage source, a pressure source, an electromagnetic source, an electric field source, a chemical source, a laser source, and the like. In some embodiments, the potential source is a pressure source, and examples of suitable pressure sources include, but are not limited to, compressed gas cylinders, compressors, and the like. Optionally, the potential source can be operably coupled to a regulator, and the regulator functions to modulate the energy from the potential source into a suitable form so that it can be further acted upon, for example, by an oscillator of a manifold assembly. For example, if the potential source is a high-pressure gas source, the regulator can function to adjust the pressure of the gas to a suitable value that can be input to the oscillator. In addition to a positive potential source (e.g., high-pressure gas), the potential source of interest can also include a potential source configured to provide a negative potential, such as a vacuum potential compared to a reference potential or a standard potential, for example, compared to standard atmospheric conditions.

[0027] In some embodiments, the console assembly includes a plurality of potential sources. In embodiments with a plurality of potential sources, the potentials supplied by each potential source may all be of the same type or a combination of different potential types. For example, each potential source may be a pressure source (same or different potential levels), or alternatively, one potential source may be a pressure source and another potential source may be a voltage source.

[0028] In an embodiment, the console assembly may further include one or more regulators (i.e., power regulators), an output port, and a controller. With respect to the power regulator, as described above, in an embodiment, the potential of the potential source can be adjusted from a first input potential to a second potential, for example, transmitted to an oscillator of the manifold assembly and ultimately to a potential suitable for treating cardiovascular tissue. The potential of the potential source can be adjusted to a predetermined value, a user-set value, or adjusted according to various feedback inputs that occur during treatment. In some cases, the potential of the potential source is at least partially based on a state related to a treatment involving imparting pulsatile energy to cardiovascular tissue, for example, based on a change in tissue extensibility during treatment, as described below, and can be dynamically adjusted. In some cases, the potential of the potential source can be adjusted in real time or substantially in real time. In a particular embodiment, the potential of the source can be adjusted to an optimal value for a particular treatment. For example, the potential of the potential source can be adjusted to an optimal value for treating a diseased heart valve, such as a heart valve having calcifications on or around the valvular commissure. In some cases, one or more inputs from the console assembly, the manifold assembly, the catheter assembly, or a source external to the system (e.g., other measurements regarding the subject, such as imaging of the subject) can determine optimal treatment conditions, such as the output potential of the potential source appropriate for a desired treatment, and can then be used to adjust to those conditions.

[0029] In embodiments comprising a regulator configured to adjust the potential of a potential source (i.e., a power regulator or a potential regulator), such a regulator may be a passive regulator (i.e., a pre-set regulator or a user-adjustable regulator) or an active regulator (i.e., a regulator controlled, for example, using electrical impulses or other dynamic signals from a controller). The regulators of interest may include regulators typically used for fluid regulation such as a directional valve or a diaphragm valve, electrical regulation such as a voltage regulator, optical power regulation, etc. In embodiments comprising a plurality of potential sources, the potentials of the various potential sources may be adjusted together or separately.

[0030] In embodiments, the regulated potential and / or the unregulated potential (i.e., potential energy) from the potential source is output via an output port operably coupled to the manifold assembly of the system. In embodiments, any convenient output port such as a commercially available connector such as a pneumatic connector, a hydraulic connector, an electrical connector, or an optical connector may be used. In certain examples, the unregulated potential energy or the regulated potential energy may be converted to another form of energy before the energy is passed to the manifold assembly or otherwise transmitted, or in some cases, after the energy is passed to the manifold assembly or otherwise transmitted.

[0031] In some cases, the console assembly may comprise a plurality of physically separated units or connected units that may be operably interconnected (e.g., electrically interconnected, fluidly interconnected, interconnected using radio frequency (RF), etc.), i.e., each console unit. That is, the console assembly may comprise a single assembly or two or more different, operably connected units.

[0032] In some examples, at least some of the console assembly components are handheld or manually operated and are present, for example, within a unit configured to be moved by hand. The form factor of such a unit can vary as desired, but in some examples, such a unit can be substantially configured as a rectangular box having a height in the range of 10 to 100 cm, such as 20 cm to 30 cm, a width in the range of 5 to 100 cm, such as 10 to 20 cm, and a depth in the range of 10 to 100 cm, such as 20 to 30 cm, and a mass in the range of 1 to 20 kg, such as 5 to 8 kg.

[0033] In one embodiment, the console assembly can include a first console component that houses a potential source and a regulator and an actuator for a pressure source, such as an operable button. The console assembly can optionally include an electrical connector for providing an electrical connection to various other components of the system. For example, the electrical connector can be used to provide power to a sensor configured to receive data regarding the location and / or configuration of a cardiac tissue conforming element, such as the location or orientation of a heart valve undergoing treatment or pressure or volume measurement, and to collect such data regarding treatment using the system.

[0034] In some examples, at least some of the console assembly components are present in an attachable unit configured to be positioned or secured on or near an operating table near the subject, i.e., the patient, such that an operator, e.g., a physician, does not need to physically interact with the console assembly to treat the subject (e.g., the operator does not need to be physically present in the operating room and can communicate with the system via remote operation from a remote location). In such examples, the attachable unit is designed to be easily clamped, secured, or self-stabilize on the operating table or secured proximate to the operating table and can be operated by a distal control unit (described below in connection with the robotic control unit depicted in FIG. 16). In such examples, the attachable unit may include a communicator that provides communication between the console assembly and the distal control unit, and the communicator may be implemented by any desired hardware and / or software configuration and may be configured to communicate using a wired or wireless protocol.

[0035] The console assembly and / or its power source used in the system of the present invention can be configured to be reusable or single-use, as desired. The console assembly used in the system of the present invention can be configured to receive a sterile sleeve so that the console assembly can be used without contaminating the sterile field of the operating room. Further details regarding console units, power sources, regulators, etc. that can be used in embodiments of the present invention are provided in U.S. Patent Application Publication No. 2020 / 0046949, as well as co-pending PCT Application Serial No. PCT / US2020 / 055458, and U.S. Application No. 63274832, the disclosures of which are incorporated herein by reference.

[0036] Controller An embodiment of the console assembly of the system according to the present invention includes a control subsystem, also referred to as a controller or control assembly. Embodiments of the system may utilize the controller to control the amount and duration of energy transmitted to tissue, i.e., cardiovascular tissue such as a heart valve. In some examples, embodiments of the system may utilize the controller to measure the effect of treatment on cardiovascular tissue, such as the degree of fragmentation of calcified tissue, e.g., cardiovascular tissue extensibility, as described in detail below. In still other examples, embodiments of the system may utilize the controller to measure or control a perfusion mechanism to control perfusion of a fluid, e.g., blood, beyond a heart tissue conforming element present in a subject.

[0037] In an embodiment, the control subsystem is connected to and may receive information from and / or adjust (i.e., control) one or more aspects of a console assembly (such as a pressure source or regulator), a manifold subsystem (such as an oscillator), or a catheter assembly (such as a heart tissue conforming element). The control subsystem may also be configured to receive information from and / or control an external system such as an electrocardiogram (ECG), an intravascular or external pressure monitor, a blood volume sensor, a patient vital sensor, or an imaging subsystem such as an imaging subsystem utilizing light, fluoroscopy, intravascular ultrasound (IVUS) or optical coherence tomography (OCT), or other available imaging techniques. In certain embodiments, such an imaging subsystem (e.g., an imaging subsystem utilizing light, fluoroscopy, intravascular ultrasound (IVUS) or optical coherence tomography (OCT), or other available imaging techniques) or an aspect thereof may be integrated into the catheter assembly, e.g., integrated into the catheter of the catheter assembly, and the control subsystem may be configured to receive information from such a catheter integrated imaging system. Further, the control subsystem may include a plurality of control units interconnected such that one or more of the units communicate with each other in synchronization.

[0038] In some cases, the control subsystem (or a control unit that constitutes the control subsystem) may be configured to communicate with the components of the system such that the energy transmitted via the catheter assembly, including being transmitted via the cardiac tissue conforming element, is appropriate, i.e., appropriate for a particular treatment involving applying pulsatile energy to cardiovascular tissue. In other embodiments, the control subsystem (or a control unit that constitutes the control subsystem) may receive, for example, data signals from sensors regarding information such as the location (e.g., the location of the replacement heart valve), the deployment rate (e.g., the deployment of the replacement heart valve), the valve opening degree, the nominal characteristics (e.g., the characteristics of the replacement heart valve), the valve eccentricity, the perivalvular leakage, the ambient pressure on the valve, the proximal and / or distal pressures, the position of the valve within the circumferential blood vessel, etc., regarding the status of a cardiovascular tissue treatment such as a heart valve delivery treatment.

[0039] In one embodiment, the controller is configured to receive a treatment plan, i.e., control instructions related to a particular treatment for a particular treatment of a subject. The treatment plan may include, for example, a specified potential amount, the frequency or duty cycle of an oscillator. Additionally, the treatment plan may include information regarding the type of cardiac tissue conforming element used, such as size or orientation. Additional details regarding the manner of the controller for implementing the treatment plan are described below in connection with the exemplary control loop depicted in FIG. 15. Further details regarding updating the behavior of a catheter-based procedure based on a treatment plan, a control system, and data collected during the procedure are described in U.S. Application No. 63346704, entitled "Systems and Methods Related to Catheter-Based Procedures", which was filed on the event date together with this specification (attorney docket number AVSI-005PRV), and the disclosure of which is incorporated herein by reference. In one embodiment, the cardiac tissue conforming element is configured to expand during the diastolic phase of the cardiovascular tissue. That is, when the cardiovascular tissue to which the cardiac tissue conforming element is applied, for example, the subject's cardiovascular tissue, enters the diastolic phase of the cardiac cycle, the cardiac tissue conforming element is expanded. In other embodiments, the cardiac tissue conforming element is configured to expand during the systolic phase of the cardiovascular tissue. That is, when the cardiovascular tissue to which the cardiac tissue conforming element is applied, for example, the subject's cardiovascular tissue, enters the systolic phase of the cardiac cycle, the cardiac tissue conforming element is expanded. By being expanded, it means that energy is transmitted to the cardiac tissue conforming element. In some cases, expanding the cardiac tissue conforming element includes expanding aspects of the cardiac tissue conforming element, such as expanding one or more intermediate radius balloons of the cardiac tissue conforming element. For example, in some cases, expanding the cardiac tissue conforming element includes applying pressure to the balloon of the cardiac tissue conforming element or injecting fluid into the balloon, and increasing its volume includes, for example, expanding the outer diameter of the cardiac tissue conforming element. Systole or the systolic phase or the systolic portion means the portion of the cardiac cycle during which the cardiovascular tissue contracts (e.g., in some cases, the ventricles contract after being replenished with blood).By "expansion" or "diastole" or "expanded portion" is meant a part of the cardiac cycle in which the cardiovascular tissue relaxes (as contrasted with contraction) (e.g., in some cases, the ventricles relax and refill with blood after emptying during systole).

[0040] In other embodiments, the cardiac tissue conforming element is further configured to relax during systole of the cardiovascular tissue. That is, when the cardiovascular tissue to which the cardiac tissue conforming element is applied, e.g., the subject's cardiovascular tissue, enters systole of the cardiac cycle, the cardiac tissue conforming element is relaxed. In other embodiments, the cardiac tissue conforming element is further configured to relax during diastole of the cardiovascular tissue. That is, when the subject's cardiovascular tissue to which the cardiac tissue conforming element is applied enters diastole of the cardiac cycle, the cardiac tissue conforming element is relaxed. By "relaxed" is meant that no energy is transmitted to the cardiac tissue conforming element. In some cases, relaxing the cardiac tissue conforming element includes collapsing the aspect of the cardiac tissue conforming element, such as relaxing or collapsing one or more intermediate radius balloons of the cardiac tissue conforming element. For example, in some cases, relaxing the cardiac tissue conforming element includes reducing the pressure of the fluid within the balloon of the cardiac tissue conforming element, or removing fluid from the balloon, or allowing fluid to exit the balloon, including reducing the volume of the cardiac tissue conforming element by reducing the outer diameter of the cardiac tissue conforming element. In some embodiments, as described above, relaxing or collapsing or contracting the cardiac tissue conforming element can reduce the radial force applied to the heart valve by the balloon.

[0041] In an embodiment, the system is configured such that when the heart tissue conforming element is expanded, the heart tissue conforming element applies pulsatile energy to the heart vascular tissue. That is, in an embodiment, the heart tissue conforming element can cycle between an expanded state and a relaxed state, and within such a cycle, the heart tissue conforming element can be further configured to apply pulsatile energy to the heart vascular tissue only when it is expanded, not when it is relaxed or crushed. In some embodiments, the heart tissue conforming element can be expanded and relaxed by periodically applying pressure to one or more intermediate radius balloons of the heart tissue conforming element, and the winged balloon (i.e., the balloon laminated on the outer surface of one or more intermediate radius balloons) can be further configured to apply pulsatile energy to the heart vascular tissue when one or more intermediate radius balloons are expanded, i.e., when expanded, and not to apply pulsatile energy to the heart vascular tissue when one or more intermediate radius balloons are reduced or depressurized.

[0042] In an embodiment, the heart tissue conforming element can be configured to expand and relax (i.e., contract) in a manner synchronized with the diastolic and systolic phases of the cardiac cycle. Such expansion and relaxation of the heart tissue conforming element can be configured to facilitate stable positioning of the heart tissue conforming element relative to the heart vascular tissue. That is, the expansion and relaxation of the heart tissue conforming element can facilitate positioning the heart tissue conforming element in a desired location relative to the heart vascular tissue, and further facilitate keeping the heart tissue conforming element relatively fixed, i.e., staying in a stable location and orientation, relative to the heart vascular tissue. In some cases, the heart tissue conforming element is configured to expand and contract in a manner that emulates the behavior of a heart valve.

[0043] In an embodiment, the expansion and / or relaxation of the cardiac tissue conforming element can be determined, i.e., controlled, based on the results of a pressure sensor that measures a pressure signal, i.e., for example, an intravascular pressure monitor or a pressure across the cardiac tissue conforming element (i.e., a pressure gradient between a proximal position and a distal position with respect to the cardiac tissue conforming element), in conjunction with the systolic and / or diastolic phases of the cardiovascular tissue, or can be determined based on the results of an electrocardiogram (ECG), i.e., the electrocardiogram of the cardiovascular tissue. In other embodiments, the expansion and / or relaxation of the cardiac tissue conforming element during the systolic or diastolic phase of the cardiovascular tissue can be determined, i.e., controlled, based on the results of a blood volume monitor or the results of an imaging system. In an embodiment, the system further comprises a controller as described above configured to expand or contract the cardiac tissue conforming element during the systolic and / or diastolic phases of the cardiovascular tissue. In such an embodiment, the controller can be configured to expand or relax the cardiac tissue conforming element based on an input from at least one of the results of an electrocardiogram, an intravascular pressure monitor, a blood volume monitor, or an imaging system. In other cases, the controller can be configured to expand or relax the cardiac tissue conforming element based on a predetermined configuration at a specific frequency, e.g., a frequency corresponding to the induced cardiac cycle. That is, the controller can be configured to expand or relax the cardiac tissue conforming element according to a specific predetermined pattern, e.g., can be pre-programmed to operate the controller. In some embodiments, the controller can be configured to expand the cardiac tissue conforming element at 40 beats per minute to 150 beats per minute over a certain period of time.

[0044] In an embodiment, the controller can be configured to provide feedback to an operator of the system of the present invention in any convenient manner. In some cases, the controller is configured to provide haptic feedback to the operator, for example, by vibration. For example, the controller can be configured to vibrate a handle or other interface with the operator of the system in response to a measurement of a sensor, such as a change in the extensibility of cardiovascular tissue, or other relevant changes or decisions. Such haptic feedback can be used in connection with an instruction to the operator of an embodiment of the system to change the configuration of the system.

[0045] Manifold assembly The system of the present invention includes a manifold assembly. The manifold assembly, also referred to as a manifold unit or a manifold subsystem, receives energy transmitted from a potential source of the console assembly and is used in an embodiment of the system according to the present invention to transmit such energy to the catheter assembly. In an embodiment, the manifold assembly includes an oscillator configured to generate pulsed energy from the energy transmitted from the potential source. In such an example, the oscillator is used to modulate the magnitude and timing of the potential energy from the potential energy source to provide the desired energy for use in applying pulsatile energy to the cardiovascular tissue via the heart tissue conforming element.

[0046] In an embodiment, the manifold subsystem includes an input connection to a console assembly, one or more oscillators, and an output connection to a catheter assembly. As described above, in some embodiments where the console assembly includes one or more console units, the input connection includes an input connection to one or more console units of the console assembly. As described above, in an embodiment, the manifold subsystem is configured to receive energy from the console assembly and output energy to the catheter assembly. The manifold subsystem may be configured to receive various forms of potential energy (e.g., voltage potential, electromagnetic potential, pressure potential, etc.) from one or more console units and distribute that energy to one or more oscillators within the manifold assembly. In an embodiment, any convenient input / output connection such as a commercially available connector such as a pneumatic connector, a hydraulic connector, an electrical connector, or an optical connector may be used.

[0047] In a particular example, the manifold assembly may receive potential energy such as from one or more console units of the console assembly and distribute that potential energy to one or more oscillators of the manifold assembly. In some cases, there is a one-to-one correspondence between the console units and the oscillators within the manifold subsystem. In other cases, a single console unit may deliver energy to one or more oscillators. In still other cases, one or more console units may deliver energy to a single oscillator such that, for example, the potential energy of one or more console units is combined into a single oscillator.

[0048] In an embodiment, the energy transmitted to the manifold system oscillator includes regulated or unregulated fluid under pressure. The oscillator can be operated to output a pulsatile and / or static pressure output. In certain embodiments where the potential energy transmitted by the console assembly is a regulated or unregulated fluid under pressure, the oscillator can include a solenoid valve. Such a solenoid valve can include, for example, a two-position, three-way, normally closed solenoid valve. In such an example, the solenoid valve is configured to receive a high-pressure regulated or unregulated fluid. Such a solenoid valve can be configured to have two modes: an "on" mode and an "off" mode. Such a solenoid valve can be configured to have three ports: a port (i.e., an input port) operably connected to a high-pressure regulated or unregulated fluid, a port (i.e., a first output port) ultimately operably connected to the catheter assembly, and an exhaust port (i.e., a second output port). The solenoid valve can be configured such that when it is turned on (i.e., in the "on" mode), the valve allows a high-pressure regulated or unregulated fluid to be transmitted, i.e., transmitted downstream within the system, such as to be transmitted to the catheter assembly of the system. The valve can be further configured such that when it is off (i.e., in the "off" mode), the solenoid changes, i.e., reverses, the connected ports such that the distal side of the valve is exhausted (e.g., exhausted to the atmosphere or a vacuum). That is, in the "off" mode, the first output port can be connected to the second output port, thereby exhausting the high-pressure fluid present on the distal side of the solenoid valve.

[0049] In certain embodiments, the frequency and / or duty cycle of the oscillator can be adjusted to produce an appropriate output for treatment and for a catheter assembly that includes cardiac tissue conforming elements. In various embodiments, one or more oscillators of the manifold assembly can be configured to oscillate at one or more frequencies and / or duty cycles. In a particular example, for instance, an oscillator configured to deliver pulsatile intravascular lithotripsy to cardiovascular tissue can be configured to oscillate at a frequency of 0 - 50 Hz, such as 1 - 10 Hz or 10 - 20 Hz or 21 - 30 Hz or 31 - 40 Hz or 41 - 50 Hz, and at a duty cycle of 10% - 90%, such as 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%. In an example where the oscillator is configured to use fluid pressure to deliver a pulsatile pressure pulse for a treatment that involves enabling vascular perfusion of cardiovascular tissue, the oscillator can be oscillated at a frequency of 0.25 Hz - 5 Hz, such as 1 Hz or 2 Hz or 3 Hz or 4 Hz or 5 Hz, and at a duty cycle of 10 - 90%, such as 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%. In an example where the oscillator is configured to deliver pulsed energy that includes light or a high voltage source, the oscillator can oscillate at a frequency of 0.1 Hz - 1 GHz, such as 1 Hz or 2 Hz or 3 Hz or 4 Hz or 5 Hz or more, and at a duty cycle of 0.0001% - 90%, such as 0.0001% or 0.01% or 0.1% or 1% or 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%.

[0050] Further details regarding aspects of the manifold assembly and oscillator, and their components, that can be used in embodiments of the present invention are provided in U.S. Patent Application Publication No. 2020 / 0046949, as well as co-pending PCT Application Serial No. PCT / US2020 / 055458, and U.S. Application No. 63274832, the disclosures of which are incorporated herein by reference.

[0051] In certain embodiments, the output from the oscillator of the manifold assembly, or in embodiments having two or more oscillators, the outputs from the various oscillators can be sent to one or more locations. In other embodiments including two or more oscillators, the oscillators can be synchronized with each other such that, for example, in terms of magnitude, frequency, phase, duty cycle, etc., the pulsatile energy transmitted from each oscillator is synchronized as desired. In other embodiments having one or more oscillators, the oscillator can be synchronized with an external factor such as, for example, the result of an electrocardiogram (ECG), or a system or sensor, or can be adjusted based on feedback from a controller or other subsystem (such as, for example, volume or pressure measurements resulting from a catheter assembly, such as volume or pressure measurements detected by a sensor present on a heart tissue conforming element or catheter). In other embodiments, one or more oscillators can be controlled based on signals from a heart valve delivery system (such as, for example, a transcatheter aortic valve replacement (TAVR) delivery system), such as data including position, valve deployment rate, valve opening amount, nominal characteristics, valve eccentricity, paravalvular leakage, ambient pressure and / or stress on the valve, proximal and / or distal pressures, position of the valve at the annulus, etc. That is, the controller can be configured to adjust the behavior of the oscillator based at least in part on such data.

[0052] In other embodiments, the manifold assembly can further include a plurality of inlet sources (such as, for example, a connection to a console unit), a manifold encasement (such as, for example, a housing for the manifold assembly), a number of oscillators, oscillator connection points (such as, for example, connection points for transmitting energy from the oscillator to the catheter assembly), controller connection points (such as, for example, connection points for transmitting inputs from sensors within and / or external to the system), and a user feedback and / or control area (such as, for example, a control area for the user to adjust the operation of the system).

[0053] In various embodiments described, the manifold assembly, similar to the console assembly, can be configured to be disposable or reusable. If the manifold assembly (or console assembly) is reusable and may come into contact with the patient area, such an assembly can be configured to be covered with a disposable sterile sleeve or bag. In certain embodiments, the manifold assembly can be configured as part of the console assembly (i.e., such that the components of the console assembly and the manifold assembly are held within a single common housing). In other embodiments, the manifold assembly can be configured in the form of a handle such that an operator of the system can hold the manifold assembly during use or treatment.

[0054] In some embodiments, as described above, components of the control subsystem or controller can be located within the manifold assembly housing and / or within the console assembly housing. In certain cases, the manifold assembly and / or console assembly includes a user interface configured such that an operator of the system can access the manifold assembly or console assembly to initiate or stop treatment, adjust the treatment intensity, adjust the treatment mode, or adjust other relevant aspects or configurations of the system.

[0055] Catheter assembly The system of the present invention includes a catheter assembly. The catheter assembly, also referred to as a catheter subsystem, receives energy transmitted from a manifold assembly and is used in embodiments of the system according to the present invention to apply pulsatile energy to cardiovascular tissue. Embodiments of the catheter assembly include a connector configured to operably connect the catheter assembly to the manifold assembly and convert first pulse energy generated by the manifold assembly into second pulse energy, a catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulse energy, and a heart tissue conforming element configured to receive the second pulse energy transmitted through the fluid passage of the catheter and apply pulsatile energy to cardiovascular tissue.

[0056] Connector As described above, in the system according to the present invention, the catheter assembly includes a connector, also referred to as a proximal connector. Embodiments of the connector are configured to operably connect the catheter assembly to the manifold assembly and convert first pulse energy generated by the manifold assembly into second pulse energy. In certain embodiments, one or more connectors are used to connect the catheter assembly to the manifold assembly and are configured to receive and transmit potential energy transmitted by one or more oscillators of the manifold assembly. Embodiments of the connector have a proximal connection point such that in some instances the connector can be releasably coupled or fixed to the manifold assembly. Embodiments of the connector also have a distal transmission point. The connector can be configured such that the distal transmission point delivers energy transmitted from the oscillator, for example, to the fluid passage of the catheter and ultimately to a heart tissue conforming element for applying such energy to cardiovascular tissue. In an embodiment, the connector is a component of the system disposed proximal to the assembled system, for example, near the proximal end, for example, within or near 1 m from the proximal end.

[0057] In certain examples, the energy transmitted through the connector can be in the form of a hydraulic pulse, such as a hydraulic pulse useful for pulsatile intravascular lithotripsy, or a hydraulic pulse to pulsate a heart tissue conforming element (i.e., its balloon) to enable perfusion to distal blood vessels beyond the heart tissue conforming element. In other examples, the energy transmitted through the connector can be in the form of an electrical impulse such that cavitation bubbles, ultrasound, plasma bubbles, or other high-pressure impulses are generated. In still other examples, the energy transmitted through the connector can be in the form of an optical pulse or a laser pulse such that cavitation bubbles, ultrasound, plasma bubbles, or other high-pressure impulses are generated. In still other examples, such energy transmitted through the connector can be in the form of thermal energy or energy, for example, for cryotherapy, i.e., to apply heat or cold to cardiovascular tissue.

[0058] In an embodiment, the connector comprises a proximal chamber and a distal chamber separated by a membrane. The volume of each of the proximal chamber and the distal chamber can vary in the range of 0.1 mL to 100 mL, such as 1 mL to 4 mL, and in some examples, the proximal chamber and / or the distal chamber is occupied by a liquid. In each case, the proximal chamber is operatively connected (i.e., via an oscillator) to an electrical potential source, such as a pressure source, ultimately, to convert energy (i.e., pressure) through the membrane and send it to the distal chamber. The form of the connector in such an embodiment can be deformed, but in some examples, the proximal chamber is defined by a proximal flange, the distal chamber is defined by a distal flange, the proximal and distal flanges are positioned on opposite sides of the membrane to define the proximal and distal chambers, and the proximal and distal chambers can be sealed (e.g., hermetically) from each other by the separating membrane.

[0059] The membrane moves in response to the pressure applied to the proximal chamber and is configured to generate pressure in the distal chamber of the connector based on such movement. The dimensions of the membrane can vary. In some examples, the membrane has an area in the range of 100 mm 2 ~5000 mm 2 , for example, 500 mm 2 ~2000 mm 2 . The membrane can be manufactured from any convenient elastic (e.g., flexible) material. In some examples, the material has a hardness in the range of Shore 10A to Shore 90A, for example, Shore 50A, and a thickness in the range of 0.5 mm to 5 mm, for example, 1.0 mm to 2.5 mm. Examples of suitable membrane materials include, but are not limited to, silicone, rubber, etc. In some cases, it can be strengthened by adding reinforcing components such as braiding. Optionally, a biasing component such as a spring can be provided to provide a default or baseline membrane position. For example, a spring that urges the membrane back to its initial position when the force is removed from the proximal chamber side of the membrane can be provided on the distal chamber side of the membrane.

[0060] In an embodiment, the proximal chamber of the connector finally comprises a port that operably (i.e., via an oscillator) connects the proximal chamber to a potential source, for example, a pressure source. Similarly, in an embodiment, the distal chamber of the connector finally comprises a port that operably connects the distal chamber to the fluid passage of the catheter and ultimately to a heart tissue conforming element.

[0061] Optionally, the proximal connector may include one or more sensors configured to provide data regarding one or more components of the system. Any convenient type of sensor may be included in the proximal connector, where sensors of interest include, but are not limited to, pressure sensors, position sensors, displacement sensors, proximity sensors, flow sensors, temperature sensors, etc. In some examples, the connector includes a pressure sensor operably coupled to the distal chamber. In such a case, the pressure sensor may detect pressure and changes in pressure in a fluid such as a liquid in the distal chamber. When a pressure sensor is included, any convenient type of pressure sensor may be present, and examples of pressure sensors that may be present include, but are not limited to, resistive, capacitive, piezoelectric, optical, and MEMS-based pressure sensors. In some examples, the proximal connector includes a membrane position sensor configured to provide spatial data regarding the position of the membrane at a given time, e.g., during use of the system. When a membrane position sensor is present, any convenient membrane position sensor may be used. In some examples, the membrane position sensor is a Hall sensor and may be used in conjunction with one or more magnets (e.g., one or more permanent magnets or electromagnets, or combinations thereof) present at one or more fixed locations relative to the membrane, such as at a fixed location of the proximal connector, whereby the one or more fixed magnets are positioned to modulate the voltage of the Hall sensor when the membrane moves. For example, in an embodiment, the magnets may be present on both sides of the Hall sensor with their poles facing each other. That is, in some cases, the magnets may be oriented such that their poles face each other across the Hall sensor. In some cases, one or more magnets are utilized in the position sensor of an embodiment of the invention to generate a linear voltage or current output, and in each case, such voltage or current output may be related to the position of the membrane. In other examples, the membrane position sensor may be an optical sensor, an electric field potential sensor, a resistive sensor, a magnetic sensor, an angle sensor, or an acceleration sensor. Further, any combination of these sensors may be used to collect position data of the membrane or diaphragm.When combinations of membrane position sensors are used, for example, sensor data can be combined via "sensor fusion" techniques as known in the art to ensure that the sensors provide accurate data over various conditions such as frequency. Methods of manufacturing membrane sensors can include, but are not limited to, adhesives, direct printing, welding, embedding, etc.

[0062] For example, in an example where a connector is configured to deliver a hydraulic pulse, including a hydraulic pulse useful for pulsatile intravascular lithotripsy, a connector configured to deliver a low volume, high frequency, and high pressure pulse can be used. As described above, embodiments of the connector include an entry port that receives pulsatile and / or static energy from a manifold assembly and outputs pulsatile and / or static energy at a distal transmission point of the connector. Further details regarding embodiments of the connector that can be used in connection with the systems described herein are provided in U.S. Application No. 63145641 and U.S. Application No. 63274832, the disclosures of which are incorporated herein by reference.

[0063] In an example where the connector is configured to pulsate the aspect of the heart tissue conforming element to enable perfusion, for example, into the distal blood vessel (i.e., to enable perfusion beyond the heart tissue conforming element), a connector capable of delivering a large volume, low frequency, and low pressure pulse may be used. In certain embodiments, such a connector may be in the form of a substantially barrel syringe to deliver a large volume change. The desired barrel syringe connector may include a pneumatic input port, a fluid output port, a plunger, a pneumatic chamber, and a fluid chamber. In a particular example, the plunger (i.e., piston) of the barrel syringe may be connected to a biasing spring, which enables the piston to be quickly returned to its original state. In this state, a portion or all of the fluid volume is removed from the fluidly coupled heart-tissue conforming element, i.e., its balloon. In other embodiments, the barrel syringe type connector is selectively connected to a vacuum (i.e., the proximal side of the connector) that facilitates the evacuation of the proximal side of the barrel syringe so that the piston of the barrel syringe type connector returns to its original position, i.e., the equilibrium position. In embodiments of such a connector, the fluidly coupled heart tissue conforming element positioned in the distal region of the catheter, i.e., one or more balloons of the heart tissue conforming element, can rapidly expand or contract. Embodiments of such a connector can have various sensors for monitoring the state of the heart tissue conforming element, such as pressure sensors, volume sensors, etc.

[0064] In other examples, the connector does not include a pneumatic connection or a fluid connection. Embodiments of a connector that do not include a pneumatic or fluid connection can be configured to deliver pulsatile energy, including, for example, pulsatile energy useful for intravascular lithotripsy, using any convenient technique, such techniques being known to those of ordinary skill in the art and including, for example, techniques by generating cavitation bubbles. In some cases, such embodiments of the connector are configured to utilize cavitation, plasma, voltage, light, laser, ultrasonic, or other sound wave-based techniques for delivering pulsatile energy, including techniques for delivering pulsatile energy related to the performance of intravascular lithotripsy. Such embodiments of the connector can include one or more electrical cables or optical cables that are present laterally across the length of the system and are configured to enable cavitation, ultrasonic, or laser-based therapies for treating cardiovascular tissue, such as heart valves. Embodiments of the connector can transmit light or high voltage or sound wave energy from an oscillator within the manifold subsystem through the proximal connection port of the connector to the distal transmission point of the connector. In such an example, the distal transmission point of the connector can include a series of electrodes or one or more laser targets configured to generate cavitation bubbles or plasma bubbles.

[0065] In one example, an embodiment of the connector can receive power from an oscillator mechanism to heat or cool a fluid within the distal chamber of the connector or at the distal connection of the connector such that a temperature change induces a therapeutic effect on cardiovascular tissue or, for example, dissolves an active agent present on the system, such as coating a heart tissue compatible element, such as a drug.

[0066] In other examples, the connector can be configured to collect and / or transmit information from the catheter and / or a heart tissue compatible element to the manifold subsystem. Such information can include, for example, pressure, temperature, volume, pre-loaded data (e.g., characteristics of cardiovascular tissue prior to applying pulsatile energy), the state of the heart tissue compatible element, balloon state, lesion extensibility, lesion opening, intravascular imaging data, drug delivery amount, amount of blood permeating during perfusion, and the like.

[0067] Input Signal vs. Output Signal in a Mechanical System The embodiments described are dynamic physical systems in which the output of the system (e.g., actual frequency, duty cycle, and amplitude) is controlled by the system input (e.g., desired frequency, duty cycle, and amplitude) and system characteristics (e.g., catheter length, friction, and flow path lumen diameter). Embodiments of the system are configured to generate mechanical pulses, such as fragmentation pulses, that are controlled in a heart tissue conforming element (e.g., via its balloon) such that the system output tracks the commanded input signal, or the desired input signal, with minimal attenuation in some examples. Signal attenuation is the reduction in the amplitude of the system output relative to the input due to the characteristics of the physical system. For treatment to be successful, minimal attenuation is required in that the output pulsatile energy remains substantially similar to the input pulsatile energy in terms of, for example, frequency, duty cycle, and / or amplitude as it propagates from the system input (e.g., potential source, oscillator, and / or connector) to the system output (e.g., heart tissue conforming element or one or more of its balloons). Thus, in some examples, any change in frequency is 30% or less, such as 20% or less, 10% or less, or 5% or less if present between the system input and the heart tissue conforming element (or one or more of its balloons). In some examples, any change in the amplitude of the pulsatile energy between the system input and the heart tissue conforming element (or one or more of its balloons) is 30% or less, such as 20% or less, 10% or less, or 5% or less if present. In some examples, any change in the duty cycle of the pulsatile energy between the proximal connector and the distal balloon is 30% or less, such as 20% or less, 10% or less, or 5% or less if present.

[0068] The prior art in this field (as described, for example, in WO2017 / 168145A1, US2019 / 0000491A1, US6348048B1, WO2001 / 010491A2, and US8574248B2) describes methods for generating pressure pulses within an angioplasty balloon. However, due to system characteristics, the prior art either needs to progress at a low frequency to achieve the full pressure pulse or is subject to significant signal attenuation. In the case of low-frequency pressure pulses, the balloon does not generate sufficient pulses within the blood vessel to achieve improved treatment results. In the case of high-frequency pressure pulses, the system output (i.e., the balloon pulse) does not track the system input and / or the system output is highly attenuated by the system characteristics, thereby rendering the treatment ineffective. In other cases, the system is designed such that the system input pressure itself is generated with high frictional losses (e.g., piston pump systems) such that the high-frequency input pressure pulse is attenuated before being transmitted to the proximal region of the system.

[0069] Connector catheter transition hub For example, in embodiments including embodiments that include a plurality of connectors, the various connectors converge in one or more connector catheter inter-hub regions and the connector output is coupled to transition to a flexible elongate tube such as a catheter or its fluid channel. The catheter may include one or more internal and / or external tubes (i.e., fluid channels) to which the output of the connector can connect and transmit energy. In an embodiment, the connector may be connected to transmit energy to such a tube or fluid channel of the catheter via an inflation lumen. In an embodiment, such a tube or fluid channel may traverse the entire lateral length of the catheter assembly or only a portion of the length of the catheter assembly.

[0070] The hub between the connector and the catheter can be made of any convenient material such as polyvinyl chloride (PVC) or polycarbonate (PC), and includes, for example, a strain relief element such as a flexible tube, and can provide flexibility in positioning the hub with respect to the catheter and one or more connectors.

[0071] In an embodiment, the guide wire channel can be integrated into the transition hub between the connector and the catheter to enable a standard over-the-wire technique for advancing the catheter assembly or its heart tissue conforming element to a position proximate to a desired region of the cardiovascular tissue. Embodiments of the system can be configured with respect to the guide wire and the guide wire channel such that it is a catheter system such as an over-the-wire, rapid exchange, monorail, etc.

[0072] Catheter As described above, in the system according to the present invention, the catheter assembly includes a catheter, also referred to as an elongated catheter. Embodiments of the catheter include a fluid passage operably connected to the output of the connector and are configured to transmit pulsed energy (i.e., a second pulsed energy) to the heart tissue conforming element.

[0073] In an embodiment, the catheter assembly may comprise a semi-rigid and flexible elongate catheter intended to traverse from a location remote from the cardiovascular tissue, such as a femoral artery or a radial artery location, to a treatment site, such as the aortic valve or other site proximal to the cardiovascular tissue. The dimensions of the catheter can vary, but in some examples, the catheter of the present invention may be sized to fit through, for example, a 4-26Fr introducer sheath, such as a 4Fr introducer sheath, a 10Fr introducer sheath, a 15Fr introducer sheath, a 20Fr introducer sheath, or a 25Fr introducer sheath or more, depending on the size of the relevant artery of the subject, the size of the cardiac tissue conforming element, or other factors as desired. In an embodiment, the catheter may have an outer diameter in the range of 1 mm to 8 mm, such as 1 mm or 1.3 mm or 2 mm or 3 mm or 4 mm or 5 mm or 6 mm or 7 mm or 8 mm. In some cases, it is desirable for the outer diameter to fall within the range of 6Fr to 12Fr. In some cases, it is desirable for the outer diameter to be 20Fr or less, such as 20Fr, 19Fr, 18Fr, 17Fr, 16Fr, 15Fr, 14Fr, 13Fr, 12Fr, 11Fr, 10Fr, 9Fr, 8Fr, 7Fr, 6Fr, 5Fr, 4Fr, 3Fr, 2Fr or 1Fr or less. In other cases, it is desirable for the outer diameter to fall within the range of 2 mm to 4 mm. In an embodiment, the outer diameter of the catheter can vary as needed, depending in particular on the characteristics of the cardiovascular tissue, including the diameter of the proximal lumen tissue, such as an artery or vein or other blood vessel. In other examples, the outer diameter of the catheter can vary depending on the characteristics of the cardiovascular tissue, such as the size, configuration, or degree or extent of calcification of the cardiac valve, such as the cardiac valve leaflets or cardiac valve commissures.

[0074] The outer diameter of the catheter can vary across different regions of the catheter. In some examples, the catheter can be tapered. In such examples, the catheter can include a taper in the range of 0.01° to 5°, such as 1° or 2° or 3° or 4°, across regions of the catheter. In some examples, different regions of the catheter can include different amounts of taper, including in some examples no taper. The amount of taper can vary depending on different uses of the system, including, among other things, the shape or other characteristics of the heart tissue conforming element and the different characteristics of the cardiovascular tissue to which the system is applied.

[0075] In embodiments, the length of the catheter can vary. For example, the catheter can have a length in the range of 50 cm to 300 cm, such as 50 cm or 100 cm or 145 cm or 200 cm or 250 cm or 300 cm.

[0076] The catheter can be manufactured from any suitable physiologically acceptable material, including but not limited to rubber, silicone, polyethane, polyimide such as polyimide braiding, or polyimide type materials. Embodiments of the catheter can further include a thermoplastic jacket, such as polyimide. In some examples, the catheter can include an outer coating selected based on the use of the system. For example, in some cases, embodiments of the catheter can further include a lubricated outer coating. Any convenient coating can be used that reduces friction related to the interaction between the catheter and the internal lumen tissue through which the catheter is passed. In some cases, such an outer coating can include polytetrafluoroethylene (i.e., PTFE). In embodiments, the catheter, or aspects thereof (e.g., the distal region of the catheter), can utilize stainless steel or nitinol or hypo tubes, such as laser cut hypo tubes (e.g., can be formed in whole or in part from stainless steel or nitinol or hypo tubes).

[0077] As described above, embodiments of the catheter may have one or more channels, such as fluid channels or passages, with various desired functions. For example, embodiments of the catheter may include, among other things, one or more channels for the following purposes: (1) passing at least one guide wire used to navigate the catheter assembly and / or the heart tissue conforming element proximal to a treatment site, i.e., a particular cardiovascular tissue; (2) inflating the aspect of a heart tissue conforming element, such as one or more balloons of the heart tissue conforming element, by propagating pressure along a fluid passage, for example; (3) delivering an intravascular lithotripsy pulse; (3) enabling blood perfusion (e.g., from the left ventricle to the aorta), and / or (4) performing various measurements, such as aortic or ventricular pressure, pressure of the heart tissue conforming element, such as pressure of a balloon of the heart tissue conforming element, dilation of the heart tissue conforming element, such as dilation of a balloon of the heart tissue conforming element, presence or extent of calcium cracking (i.e., fragmentation of calcifications), valve tissue impedance, valve extensibility, commissural opening volume, replacement heart valve opening, etc.

[0078] In an embodiment, the fluid passage of a catheter configured to propagate energy such as fluid pressure (i.e., a second pulse energy) extends longitudinally along the catheter, for example, from a proximal region of the catheter to a distal region of the catheter. In some embodiments, the fluid passage of the catheter is configured to receive energy converted from one or more connectors. For example, the fluid passage of the catheter can be configured to receive energy from each of a proximal connector having a barrel syringe connector and proximal and distal chambers separated by a membrane, as described above and as described in U.S. Application No. 63274832, which is incorporated herein by reference. In such embodiments, the barrel syringe and the proximal connector can be configured to operate synchronously to prime the fluid passage and generate pulse energy. In such embodiments, the barrel syringe can be used to prime the system, i.e., to apply a baseline pressure to the fluid present in the fluid passage, after which the proximal connector is used to provide pulsatile energy to the fluid present in the fluid passage at the baseline pressure. In an embodiment, the fluid passage can be connected to one or more connectors, such as one, two, three, four, five, six, seven, eight, nine, ten, twenty, fifty, or more than one hundred connectors. Such connectors, each connected to a single fluid passage, can be connectors of the same type and / or configuration, or can differ in any relevant respect. The plurality of connectors attached to a single fluid passage can be synchronized or otherwise configured to convert energy and send it to the fluid passage in any convenient manner. In other cases, the output of a single connector can be operably connected to a plurality of fluid passages. For example, in one embodiment, the output of a single barrel syringe can be operably connected to a plurality of fluid passages, whereby the barrel syringe can be used to prime the fluid present in each of the plurality of fluid passages.That is, the barrel syringe can be configured to apply a baseline pressure to the fluid present in each of the plurality of fluid passages. Since one barrel syringe is operably connected to the plurality of fluid passages, each of the fluid passages is primed simultaneously. In an embodiment, the connector can be operably connected to a single catheter or to the plurality of fluid passages of one or more catheters.

[0079] The cross-sectional flow area of the internal channel (i.e., fluid passage) of the catheter can vary. In some examples, the cross-sectional flow area of the fluid passage of the catheter is from 1 mm 2 to 5 mm 2 such as in the range of 0.1 mm 2 to 50 mm 2 In an embodiment, the cross-sectional flow area can take on any convenient geometric shape, such as substantially circular or substantially elliptical or substantially triangular or substantially rectangular or substantially polygonal or combinations thereof. In some examples, the fluid passage of the catheter extends from the proximal region of the catheter to a heart tissue conforming element (e.g., a balloon of the heart tissue conforming element). In such a case, the fluid passage is configured to propagate energy, such as pressure, from the proximal region of the catheter (i.e., the output of the connector or the connector-catheter intermediate hub) to the distal region of the catheter, such as a heart tissue conforming element operably connected to the fluid passage, along the fluid passage. In one example, the fluid passage can be configured to contain a fluid. In such an example, applying pressure to the fluid enables the propagation of pressure along the fluid passage. Saline can be used, with or without any convenient fluid, such as a contrast agent fluid.

[0080] In the distal region of the catheter assembly, one or more channels of the catheter (e.g., fluid passages) that extend the length of the catheter can be split or shunted or otherwise separated such that the one or more channels are directed, i.e., routed, to their respective destinations, such as a balloon, electrode, target, sensor, port, etc.

[0081] In certain embodiments, the catheter is configured to pass over a guidewire such that the catheter assembly and its heart tissue conforming element can be guided to the correct anatomical location. The guidewire of interest can include any convenient commercially available guidewire, such as a standard 0.014 inch or 0.035 inch or other sized guidewire, as desired. Embodiments can include a guidewire lumen within the catheter configured to receive such a guidewire. The catheter assembly can be configured such that the guidewire lumen can be axially located with respect to the catheter or can be located on one side of the catheter. In embodiments, the guidewire lumen is configured such that a guidewire present within the guidewire lumen of the catheter can traverse longitudinally across the catheter, thereby guiding the catheter and the heart tissue conforming element to the treatment site. In some cases, the guidewire is configured to extend beyond the distal end of the catheter, i.e., the catheter can be configured to include both a guidewire inlet port and an outlet port.

[0082] In embodiments, the catheter assembly, in some cases, includes the catheter of the catheter assembly and comprises an integrated imaging subsystem. In some embodiments, the imaging subsystem is an imaging subsystem based on light, fluoroscopy, ultrasound, or OCT, or other available imaging technologies. The imaging subsystem of interest may utilize one or more such imaging modalities. Such an integrated imaging subsystem can be used to confirm that embodiments of the system of the present invention are applied to the desired anatomical region or feature of interest. Such an integrated imaging subsystem can be configured, for example, to generate an image of the luminal tissue of the subject. Such an integrated imaging subsystem can enable visualization of the location of aspects of the system, such as a cardiac tissue conforming element, relative to aspects of the anatomical structure of the subject. In embodiments, the integrated imaging subsystem can be further integrated with the control subsystem of the device, as described above. For example, the control subsystem of the device can receive imaging data from the imaging subsystem and / or the control subsystem can instruct the imaging subsystem to start imaging, switch the imaging subsystem between different imaging modalities (e.g., ultrasound versus OCT), or control aspects of the imaging subsystem such as directing the imaging subsystem to different fields of view. In embodiments, the imaging subsystem can comprise one or more ultrasound probes, transducers, and receivers, and associated electronics. In embodiments, the imaging subsystem can comprise a catheter assembly, e.g., a catheter or a radiopaque label present at a designated location on the cardiac tissue conforming element. In embodiments, the imaging subsystem can comprise an illumination element and a photodetector or camera, and associated electronics.

[0083] Perfusion mechanism In some embodiments, the catheter assembly can be configured to allow fluid, e.g., blood, to pass through the catheter assembly, i.e., through the heart tissue conforming element, using an active and / or passive perfusion mechanism. That is, when the catheter assembly, which includes a catheter and a heart tissue conforming element, is positioned proximal to a cardiovascular tissue, e.g., an artery of a subject, to apply treatment to the cardiovascular tissue, the catheter assembly can be configured to allow blood to perfuse beyond the heart tissue conforming element of the catheter assembly, i.e., beyond the heart tissue conforming element that could otherwise block or impede blood flow to the distal vessel. For example, the catheter assembly can be configured to allow blood to perfuse from the left ventricle to the proximal aorta of the subject when the heart tissue conforming element is located near the aortic valve.

[0084] The region of the catheter beyond the perfusion mechanism that allows blood to flow is referred to as the distal catheter perfusion section. The remaining portion of the catheter that is not part of the distal catheter perfusion section, i.e., that portion of the catheter that does not include the perfusion mechanism, is referred to as the proximal catheter section. In an embodiment, the distal catheter perfusion section can have any convenient length, such as a length of 5 mm to 150 mm, e.g., 5 mm or 10 mm or 40 mm or 100 mm or 150 mm. The length of the distal catheter perfusion section can vary, e.g., depending on the length of the heart tissue conforming element or other characteristics. In an embodiment, the distal catheter perfusion section and the proximal catheter section can comprise two separate components that are attached together to form the catheter assembly. Such a configuration can easily change the heart tissue conforming element attached to the distal catheter perfusion section for each application. In an embodiment, the catheter assembly can be configured such that the distal catheter perfusion section connects to the proximal catheter section with a non-invasive taper section or step.

[0085] Active perfusion refers to an active mechanism for pulling, pushing, or otherwise moving a fluid, such as blood, from one region to another, i.e., beyond the distal catheter perfusion section and beyond the heart tissue conforming element. Passive perfusion refers to a mechanism configured to enable perfusion of a fluid, such as blood, based on a pressure gradient, such as an existing pressure gradient generated by the pressure applied by cardiac contraction across different tissue regions, e.g., inside and outside of the ventricle. That is, a passive pressure gradient can be established by creating a fluid path between an existing high-pressure region and an existing low-pressure region and enabling fluid flow based on such a pressure difference. For example, fluid flow can be generated via a passive mechanism by utilizing an existing pressure gradient within cardiovascular tissue, such as a pressure gradient generated within the aorta by the left ventricle. Active-passive perfusion refers to a combination of an active mechanism and a passive mechanism such that a portion of the energy promoting perfusion, i.e., the flow of fluid through the heart tissue conforming element, is generated by the active mechanism and a portion is generated by the passive pressure gradient.

[0086] In an embodiment, the distal end of the catheter, i.e., the distal region of the catheter near the distal catheter perfusion section, is configured such that a portion of its internal cross-sectional area is dedicated to enabling blood to perfuse from a relatively distal position of the catheter assembly, beyond the heart tissue conforming element, to a relatively proximal location of the catheter assembly, e.g., from the left ventricle to the aorta. In such an embodiment, the cross-sectional area of the distal catheter (i.e., the distal catheter perfusion section) configured to enable blood flow is, in some cases, 1 mm 2 ~50 mm 2 , e.g., 1 mm 2 or 5 mm 2 or 12 mm 2 or 15 mm 2 or 20 mm 2 or 30 mm 2 or 40 mm 2 or 50 mm 2 and can be.

[0087] In some cases, the distal region of the catheter may comprise a tip attached to the distal region of the catheter configured to provide an opening (i.e., the distal catheter perfusion inlet port) for blood to enter the distal catheter perfusion section, and the distal catheter perfusion inlet port, as well as the catheter tip comprising the catheter and the heart tissue conforming element, may be shaped or otherwise configured to reduce trauma to the surrounding tissue when reaching a proximal location of the cardiovascular tissue being treated, for example, through a blood vessel and, for example, across a heart valve.

[0088] In an embodiment, the catheter assembly can include one or more ports (i.e., port holes) configured to allow blood to flow in and out, i.e., to perfuse, for example, from the distal region of the catheter assembly to the aorta. For example, such ports can be present in one or both of the catheter and the heart tissue conforming element. Such ports can be disposed in the perfusion inflow and outflow zones. The ports in the perfusion inflow and outflow zones can be configured uniformly across the region of the catheter assembly when the catheter assembly is positioned to apply treatment to cardiovascular tissue such as, for example, coronary ostia, or can be clustered near significant branches, i.e., near anatomical branches expected to be proximal to the catheter assembly. Embodiments can include any convenient number of ports in each of the perfusion inflow and outflow zones, and such number can vary. For example, embodiments can include from 1 to over 5,000 ports in each of the perfusion inflow and outflow zones, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 100, 200, 500, 1,000, 2,000, 3,000, 4,000, or 5,000 or more ports. In an embodiment, the number and configuration of the ports constituting the perfusion inflow and outflow zones can vary. In an embodiment, the perfusion inflow and outflow zones can include a number and / or configuration of ports such that the ports do not introduce structural weakness into the catheter assembly. The ports can be configured to have any convenient diameter, cross-sectional shape, and arrangement on the catheter or the heart tissue conforming element in some cases, and such can vary. For example, an embodiment can include ports having a substantially circular cross-section with a diameter in the range of 0.01 mm to 3 mm, such as 0.05 mm or 0.5 mm or 1 mm or 2 mm or 3 mm. In some cases, it is desirable for the ports to have a diameter of 1 mm or more to allow sufficient perfusion of fluid through the perfusion inlet and / or outflow zones. In an embodiment, the ports in the perfusion inflow zone and the outflow zone can be configured to reduce or minimize the amount of internal resistance encountered by fluid perfusion from the perfusion inflow zone to the perfusion outflow zone.In some cases, one or more ports of the perfusion outflow zone are configured such that the total flow area (i.e., the cross-sectional area available for fluid to perfuse) is equal to or exceeds the flow area of the perfusion inflow zone. The placement of the ports on the catheter and / or the heart tissue conforming element can assume any convenient pattern. The number of ports, their diameters, and their placement on the catheter assembly can be selected to ensure that the catheter retains its desired structural properties despite the presence of the ports. In some embodiments, specifically, the number of ports, their diameters, and their placement on the catheter assembly are selected to maintain sufficient rigidity for the catheter to apply pulsatile energy to the cardiovascular tissue (i.e., via the heart tissue conforming element) and to ensure that sufficient blood is perfused to adequately perfuse the distal vessels beyond the heart tissue conforming element. In an embodiment, the ports can be formed using any convenient technique capable of forming ports with the desired characteristics. For example, in some cases, the ports can be formed using a laser, i.e., the embodiment can comprise laser ports. In other cases, the ports can be skived, i.e., in an embodiment, by using skiving techniques to produce the desired ports. In still other cases, the ports can be formed using a braided configuration, i.e., the embodiment can be formed using braiding techniques in part to form the desired ports.

[0089] As described above, in an embodiment, the catheter assembly is configured such that a portion of the catheter assembly withdraws blood (e.g., from a relatively distal region of the catheter), and another portion of the catheter is configured to deliver blood (e.g., to a relatively proximal region of the catheter). In one embodiment, the continuous reciprocating motion of the barrel-shaped syringe connector can be configured to create a vacuum (or otherwise create a low-pressure region) at the inlet (i.e., blood withdrawal) port, push fluid into the port of the catheter assembly (i.e., blood perfusion), maintain blood flow, i.e., maintain blood perfusion to the distal blood vessel despite the presence of the catheter assembly. For example, in one embodiment, two one-way valves can be configured such that one full stroke of the reciprocating motion of the connector, e.g., the barrel-shaped syringe connector, draws blood from one region of the blood vessel and ensures that it is pushed into another region. In some cases, active perfusion can be performed multiple times to simulate the pumping motion of the heart, or in other cases, it can be performed once to create a pressure gradient, e.g., across a heart valve.

[0090] In some cases, the perfusion mechanism, particularly the cross-sectional area of the perfusion mechanism as described above, comprises a valve configured such that fluid, e.g., blood, cannot flow in reverse from a proximal location (e.g., the perfusion inflow zone) to a distal location (e.g., the perfusion outflow zone). Any convenient valve may be applied and may be located in any convenient region of the perfusion mechanism, such as the perfusion inflow or outflow zone, or within a fluid passage connecting the perfusion inflow and outflow zones. In some cases, such a valve may be a passive one-way valve. Such a one-way valve may be configured to open when the pressure on the distal side of the valve (i.e., within the relatively distal region of the catheter assembly) is higher than the pressure on the proximal side of the valve (i.e., within the relatively proximal region of the catheter assembly) and to close when the pressure differential reverses (i.e., when the blood flow reverses). In other configurations, a vibrating balloon may be configured within the fluid passage or blood flow path of the perfusion mechanism of the catheter assembly (i.e., within the perfusion cross-sectional area of the perfusion mechanism) and may be used to open and close one or more ports to permit and / or block blood flow through such one or more ports.

[0091] In some configurations, the inner surface of the inner lumen of the perfusion cross-sectional area of the catheter assembly (i.e., the inner surface of the perfusion mechanism) may be coated such that it is lubricious or prevents clotting of blood passing through such area. In embodiments, the inner surface of the catheter may be coated with a hydrophilic or hydrophobic coating. In other examples, the inner surface of the catheter may be coated with an active agent, such as a heparinized coating.

[0092] In other configurations, the inner lumen of the perfusion cross-sectional area of the catheter may be fluidly coupled to an injection port such that the system is configured to inject a fluid, such as an active agent, e.g., a contrast agent, saline, or a drug, into the blood flow.

[0093] The distal region of the catheter In one example, the distal region of the catheter is configured to form a rigid structural tube that provides underlying radial support to a heart tissue conforming element or a component thereof, such as a balloon or other object fixed to and / or surrounding such a distal region of the catheter. As described above, the catheter can be manufactured from any suitable physiologically acceptable material that provides the desired structural rigidity, including but not limited to polyimide, such as a polyimide braid, or a polyimide type material. For example, in some cases, the heart tissue conforming element can include one or more, such as four or more, balloons (referred to as intermediate radius balloons, including intermediate radius balloons in a circumferentially positioned configuration) surrounding such a distal region of the catheter. When such intermediate radius balloons are inflated, the outer diameter of the catheter shaft is configured to support the opposing surfaces of the surrounding inflated intermediate radius balloons and maintain contact with the opposing surfaces without substantially deforming the outer diameter or shape of the catheter. When such intermediate radius balloons are inflated to high pressure and, for example, if they are non-stretchable balloons, these intermediate radius balloons can provide a high radial force with a diameter larger than the diameter of the distal region of the catheter itself. Such a configuration can form a stacked structure (i.e., the intermediate radius balloons are stacked around the outer periphery of the catheter or "stacked") and a foldable structure (i.e., when the intermediate radius balloons are deflated, the intermediate radius balloons collapse to a diameter substantially similar to the outer diameter of the catheter) that can pass through a narrow lumen, such as an artery. Additionally, such a multi-layer structure (i.e., a structure in which the intermediate radius balloons are arranged in layers around the outer periphery of the catheter) generates a rigid intermediate radius structure (i.e., a rigid structure around the outermost diameter of the structure formed by the inflated intermediate radius balloons), and the intermediate radius structure provides a substantial radial force to other components of the heart tissue conforming element, such as balloons, positioning knobs, or other objects, such as elements of a heart valve, etc., which are known in the art and include other elements configured to perform intravascular lithotripsy that are present on or surround such intermediate radius balloons.In an embodiment, the intermediate radius structure of rigidity comprises a distal region of the catheter and one or more intermediate radius balloons and is configured to provide sufficient structural stability and support for such elements, such as additional balloons, such as winged balloons as described herein, and, for example, apply pulsatile energy, such as apply pulsatile force to cardiovascular tissue, such as heart valve leaflets or heart valve commissures.

[0094] In some embodiments, to ensure both the rigidity and flexibility of such a distal region of the catheter, the cross-sectional shape of such a distal region of the catheter is configured to take the form of a particular geometric shape. The catheter may be configured to have a cross-section with any convenient geometric shape, and such a shape may vary, for example, according to the features of the heart tissue conforming element and the structural requirements of the catheter. For example, the catheter may be configured to have a cross-section in the form of a circle, a lobed circle, an ellipse, a triangle, a star, etc.

[0095] Heart tissue conforming element As described above, in the system according to the present invention, the catheter assembly includes a heart tissue conforming element. Embodiments of the heart tissue conforming element are configured to receive pulsed energy (i.e., the second pulsed energy) transmitted through the fluid passage of the catheter and apply pulsatile energy to cardiovascular tissue.

[0096] In an embodiment, the cardiac tissue conforming element can be configured to conform to any aspect of the cardiovascular tissue associated with a treatment involving applying pulsatile energy to the cardiovascular tissue. In some embodiments, the cardiac tissue conforming element is configured to engage cardiac valve tissue including, for example, the tissue of the mitral valve, tricuspid valve, bicuspid valve, aortic valve, or pulmonary valve. In certain embodiments, the cardiac tissue conforming element is configured to engage a cardiac valve leaflet or commissure, or a cardiac valve leaflet nodule or annulus. In an embodiment, the cardiac tissue conforming element includes a shape that engages a cardiac valve leaflet or commissure, or a cardiac valve leaflet nodule or annulus. In an embodiment, the cardiac tissue conforming element includes a shape that engages a cardiac valve leaflet or commissure, or a cardiac valve leaflet nodule, or an annulus upon inflation or pressurization of one or more balloon elements of the cardiac tissue conforming element. In some cases, the cardiac tissue conforming element is configured to engage the tissue supporting the cardiac valve. In particular, in some embodiments, the cardiac tissue conforming element is configured to engage, for example, the aortic valve including the aortic valve leaflet or commissure or aortic annulus. In other embodiments, the cardiac tissue conforming element is configured to engage the atrial septum or ventricular septum. In other embodiments, the cardiac tissue conforming element is configured to engage not only the bicuspid aortic valve but also the mitral valve. In an embodiment, the cardiac tissue conforming element includes a shape that engages the tissue supporting a cardiac valve or aortic valve, including, for example, the aortic valve leaflet or commissure, or the aortic annulus or atrial septum or ventricular septum or mitral valve or bicuspid aortic valve. In an embodiment, the cardiac tissue conforming element includes a shape that engages the tissue supporting a cardiac valve or aortic valve, including, for example, the aortic valve leaflet or commissure or aortic annulus or atrial septum or ventricular septum or mitral valve or bicuspid valve upon inflation or pressurization of one or more balloon elements of the cardiac tissue conforming element.

[0097] In an embodiment, the cardiac tissue conforming element is located, for example, within a region within 20 cm of the distal end of the catheter, such as 1 cm or less, or 2 cm or less, or 3 cm or less, or 4 cm or less, or 5 cm or less, or 6 cm or less, or 7 cm or less, or 8 cm or less, or 9 cm or less, or 10 cm or less, or 11 cm or less, or 12 cm or less, or 13 cm or less, or 14 cm or less, or 15 cm or less, or 16 cm or less, or 17 cm or less, or 18 cm or less, or 19 cm or less, or 20 cm or less from the distal end of the catheter. The cardiac tissue conforming element or an aspect thereof can be coupled to the catheter or otherwise fixed using any convenient and physiologically suitable technique, such as epoxy, cyanoacrylate, plastic cement, solvent bonding techniques, thermoplastic reflow, or combinations thereof, or any other suitable glue or adhesive or bonding technique.

[0098] Intermediate radius balloon In some embodiments, the heart tissue conforming element includes one or more distal balloons present in the rigid distal region of the catheter. Such balloons may be referred to as intermediate radius balloons and are configured to apply pulsatile energy directly by contacting the cardiovascular tissue or indirectly through the intermediate radius balloon, i.e., additional elements fixed to its outer surface, such as additional balloons like the winged balloons described below, or projections, etc., or combinations thereof. That is, the intermediate radius balloon can contact the cardiovascular tissue and apply pulsatile energy directly, and also, for example, apply pulsatile energy indirectly to the cardiovascular tissue through a winged balloon attached to the rigid surface of the intermediate radius balloon. Such balloons are called "intermediate radius" because, in part, as described below, the balloon extends radially beyond the outer periphery of the catheter but does not extend to the extent of fully engaging the cardiovascular tissue, i.e., occupies an intermediate radius position. In some embodiments, one or more intermediate radius balloons are configured to hold a radial force such that an outer element (i.e., an element attached to the outer periphery of one or more intermediate radius balloons), such as a winged balloon, can deliver a pulse, i.e., pulsatile energy, at a distance from the longitudinal axis of the catheter. That is, in such embodiments, one or more intermediate radius balloons can be configured to include a substrate on which additional elements, such as winged balloons, can deliver pulsatile energy to the cardiovascular tissue. Such an approach allows additional elements, such as winged balloons, to apply pulsatile energy to specific targeted locations around the outer surface of one or more intermediate radius balloons, such as targeting cardiac valve commissures or leaflets (i.e., such that pulsatile energy cannot be applied equally to all aspects of the cardiovascular tissue).

[0099] Embodiments may comprise 1 to 10 or more intermediate radius balloons, such as 1 intermediate radius balloon, 2 intermediate radius balloons, 3 intermediate radius balloons, 4 intermediate radius balloons, 5 intermediate radius balloons, 6 intermediate radius balloons, 7 intermediate radius balloons, 8 intermediate radius balloons, 9 intermediate radius balloons, or 10 or more intermediate radius balloons. In some cases, the heart tissue conforming element is fixed to the catheter at both the proximal and distal (with respect to the balloon), and in some cases, one or more intermediate radius balloons configured to surround or substantially surround the outer periphery of the catheter in the distal region of the catheter, including the distal end of the catheter, are included. In some cases, for example, a single intermediate radius balloon covers the distal region of the catheter such that the intermediate radius balloon and the catheter share a longitudinal axis.

[0100] Embodiments of the present invention may be configured such that a heart tissue conforming element, or one or more intermediate radius balloons thereof, may translate into and out of the lumen of a catheter assembly, such as the central lumen of a catheter present in the distal region of the catheter. That is, a heart tissue conforming element, or one or more intermediate radius balloons of a heart tissue conforming element, including any attachment to an intermediate radius balloon, such as a winged balloon, as described below, or other features attached to or present on the surface of such a balloon, may be translated into and out of the central lumen of the catheter, for example, by the control of an operator using any convenient technique. Embodiments of the present invention may be configured to allow a heart tissue conforming element, or one or more intermediate radius balloons thereof, to translate into and out of the lumen of a catheter assembly using any convenient technique, such as any convenient mechanical connection between the heart tissue conforming element and a proximal device for controlling translation of the heart tissue conforming element, etc. One or more intermediate radius balloons may be present within the catheter when the catheter is moved to a desired location within the lumen, such as a desired anatomical region of a subject, and the one or more intermediate radius balloons may be withdrawn from such a catheter lumen, for example, to engage anatomical tissue, such as a heart valve, or to disrupt calcium deposits on anatomical tissue, such as a heart valve, prior to inflating the one or more intermediate radius balloons, that is, prior to utilizing the heart tissue conforming element by inflating the one or more intermediate radius balloons or other features. Embodiments configured to allow one or more intermediate radius balloons to translate into and out of the lumen of a catheter assembly may provide certain advantages, such as easier repackaging of the one or more intermediate radius balloons and any attachments to the intermediate radius balloons, easier folding of the one or more intermediate radius balloons and any attachments to the intermediate radius balloons, easier tracking of the location of the one or more intermediate radius balloons of the heart tissue conforming element, or easier tracking of the heart tissue conforming element or its one or more intermediate radius balloons, or use of a narrower introducer to direct the heart tissue conforming element to a desired anatomical location.

[0101] During use of an embodiment of the heart tissue conforming element, initially, the intermediate radius balloon of the heart tissue conforming element is tightly wound around the outer surface of the catheter and / or can be folded to enable the catheter assembly or its distal region to move, for example, through an introducer sheath, to a suitable desired anatomical location, such as near the cardiovascular tissue. After being delivered to the desired anatomical location and positioned proximal (i.e., near) the desired anatomical location, the intermediate radius balloon of the heart tissue conforming element can be inflated with fluid via a fluid connection between the interior of the balloon and the fluid passage of the catheter. Such a fluid connection between the interior of the balloon and the fluid passage of the catheter can include one or more port holes configured such that the interior of the balloon is in fluid communication with the fluid passage. Any convenient number, size, and configuration of port holes can be applied to operably connect the fluid passage of the catheter to the intermediate radius balloon. In an embodiment, the port hole can be a radial hole, for example, that connects the inner wall of the fluid passage of the catheter (i.e., the surface closest to the longitudinal axis of the fluid passage) and the outer wall of the fluid passage (i.e., the surface farthest from the longitudinal axis, such as the surface to which the intermediate radius balloon is attached). The port hole can be configured to allow the passage of fluid between the fluid passage and the intermediate radius balloon. In an embodiment, the intermediate radius balloon can be inflated using fluid transferred from the fluid passage of the catheter into the interior of the balloon via the port hole of the fluid passage. That is, in some embodiments, the pressure applied at the proximal end of the fluid passage propagating along the fluid passage of the catheter can further propagate to the intermediate radius balloon via the port hole.

[0102] The number of port holes can vary in embodiments of the present invention. The port holes can be of any convenient diameter, and those diameters can vary. The arrangement of the port holes on the fluid passage can assume any convenient pattern. The number of port holes, their diameters, and their arrangement on the catheter's fluid passage can be selected to ensure that the catheter retains its desired structural properties despite the presence of the port holes. In some embodiments, specifically, the number of port holes, their diameters, and their arrangement on the catheter can be selected to ensure that the catheter maintains sufficient radial stiffness to support the expansion of an intermediate radius balloon, such as a winged balloon, and the application of pulsatile energy to cardiovascular tissue, for example, via an element attached to the intermediate radius balloon. For example, some embodiments of the catheter according to the present invention can include 1 to 5,000 port holes (such as 100 or 300 or 1,000 or 3,000) that are 0.1 mm to 0.5 mm in diameter (such as 0.1 mm or 0.25 mm or 0.4 mm) and are spaced at least 0.1 mm to 5 mm apart from each other (such as 0.5 mm or 1 mm or 5 mm).

[0103] In an embodiment, the system may be configured such that one or more intermediate radius balloons of the heart tissue conforming element are periodically inflated and deflated. In some cases, the system may be configured such that one or more intermediate radius balloons are inflated and deflated periodically to mimic the cardiac cycle, such as, for example, once per second, i.e., at 1 Hz, or at another frequency substantially synchronized with the cardiac cycle. In an embodiment, the aspects of the cardiac cycle may be determined by using a sensor to measure the pressure gradient across the heart tissue conforming element (i.e., the gradient across the proximal and distal locations of the heart tissue conforming element). As further described below, in an embodiment, during the time when one or more intermediate radius balloons are inflated (i.e., expanded to form a rigid substrate for additional elements such as, for example, a winged balloon to apply pulsatile energy to the cardiovascular tissue of the heart), additional elements such as, for example, an outer radius balloon or a winged balloon are pulsed a plurality of times at a frequency higher than the frequency of the one or more intermediate radius balloons, such as, for example, up to 15 - 20 times, i.e., at a frequency of, for example, 15 - 20 Hz. That is, in such an embodiment, the treatment (i.e., pulsatile energy) is applied when one or more intermediate radius balloons are inflated and not applied when one or more intermediate radius balloons are relaxed or deflated. Such a configuration can help prevent the occurrence of ischemia (e.g., in an embodiment, periodically shrinking or relaxing one or more intermediate radius balloons can help prevent the occurrence of ischemia because it promotes perfusion of blood across the heart tissue conforming element) and further helps ensure that appropriate treatment energy is delivered to the cardiovascular tissue such as, for example, a heart valve. In embodiments with multiple intermediate radius balloons, the intermediate radius balloons may be pressurized and depressurized synchronously, i.e., simultaneously, or independently and at different times. For example, the intermediate radius balloons may be inflated sequentially such that the intermediate shape of the heart tissue conforming element when the intermediate radius balloons are inflated conforms to a desired shape or feature of the cardiovascular tissue that promotes alignment of the heart tissue conforming element with the cardiovascular tissue of the heart.

[0104] Furthermore, in embodiments, the characteristics of the pulsatile energy applied by one or more intermediate radius balloons can change during the process of using the intermediate radius balloons in connection with applying pulsatile energy to cardiovascular tissue. Changes to the characteristics of the pulsatile energy applied by the intermediate radius balloons can be predefined, i.e., can be preprogrammed using a controller such as a preprogrammed controller, for example, or can be changed dynamically, i.e., on-the-fly, based on any convenient parameter such as sensor inputs like pressure or volume measurements (e.g., the pressure or volume of the balloon), or based on other feedback signals or user inputs, etc. For example, the pulsatile energy applied to one or more intermediate radius balloons can continuously increase or continuously decrease (i.e., the maximum or minimum or average energy applied to one or more intermediate radius balloons can continuously increase or continuously decrease), or can pause (i.e., the maximum or minimum energy applied to one or more intermediate radius balloons can be held constant, including by not applying pulsatile energy, e.g., pressure, to the balloon for a certain period of time, i.e., a relaxation period). Furthermore, in embodiments, the pulsatile energy applied to the intermediate radius balloon can decelerate or accelerate (i.e., the pulsatile energy applied to the intermediate radius balloon can be applied at a higher or lower frequency, or in other cases, the rate of change of the maximum or minimum or average energy applied to the intermediate radius balloon can be increased or decreased).

[0105] In the inflated state, the intermediate radius balloon of the heart tissue conforming element can be configured to assume any desired shape, and thus can vary depending on, for example, the intended treatment or anatomical feature of the cardiovascular tissue, or the structural requirements of the catheter assembly. For example, the intermediate radius balloon of the heart tissue conforming element can assume various shapes including, for example, spherical, yo-yo, elliptical, cylindrical, peace sign, etc. In some embodiments, the cross-sectional shape of the heart tissue conforming element, or one or more intermediate radius balloons of the heart tissue conforming element, is substantially elliptical. Such an ellipse can be advantageous for use in the mitral valve. In some cases, such an ellipse can be advantageous for use in addressing mitral valve calcification. In other cases, such an ellipse can be advantageous for use in both the mitral and tricuspid valves. In embodiments where the heart tissue conforming element includes two or more intermediate radius balloons, each intermediate radius balloon can assume the same shape or different shapes. The yo-yo shape means that when one or more intermediate radius balloons are inflated, they form lobes or hemispheres similar to the two hemispherical portions of a yo-yo, for example, the two portions of a yo-yo connected by the axis of the yo-yo, and these portions abut against each other in a manner that allows cardiovascular tissue to be present between the two lobes or hemispheres. Such a yo-yo configuration can be used to apply pulsatile energy to the cardiovascular tissue present between the two hemispheres of the intermediate radius balloons forming the yo-yo configuration. That is, the yo-yo configuration can be configured to allow, for example, cardiovascular tissue such as a heart valve leaflet to be sandwiched between the two hemispheres of the yo-yo configuration of the intermediate radius balloons, and as a result, applying pulsatile energy to the cardiovascular tissue includes squeezing the sandwich structure together and periodically compressing the cardiovascular tissue.

[0106] In an embodiment, the intermediate radius balloon of the heart tissue conforming element can be configured such that increasing the pressure applied to such a balloon (e.g., via an increase in the pressure applied to the fluid present within the balloon) results in an increase in the force applied to the cardiovascular tissue by such a balloon, i.e., an increase in the force applied to the heart valve or heart valve leaflet or heart valve commissure. That is, applying a greater pressure to the balloon of the intermediate radius portion of the heart tissue conforming element can cause such a balloon to apply a greater force to the surrounding cardiovascular tissue. In an embodiment, the intermediate radius balloon of the heart tissue conforming element can be configured such that increasing the pressure applied to such a balloon (e.g., via an increase in the pressure applied to the fluid present within the balloon) can, in some cases, result in an expansion of the volume of the balloon, including an expansion of the diameter of the intermediate radius balloon. For example, an increase in the pressure applied to the intermediate radius balloon can cause such a balloon to project a greater radial distance from the longitudinal axis of the catheter.

[0107] In a particular example, the diameter of the intermediate radius balloon of the heart tissue conforming element described above can correspond to the amount of pressure and / or volume of fluid injected into the balloon, i.e., such a balloon can be stretchable or semi-stretchable. In other examples, the diameter of the intermediate radius balloon of the heart tissue conforming element can remain substantially fixed (i.e., constant), regardless of the amount of internal pressure and / or volume of fluid injected into the balloon, e.g., additional pressure beyond a threshold amount.

[0108] Any convenient balloon can be used as an intermediate radius balloon. Suitable balloons include, but are not limited to, standard angioplasty balloons such as expandable and non-expandable angioplasty balloons. In one embodiment, the intermediate radius balloon is a composite balloon that includes two different layers, which include, for example, a non-expandable layer and an expandable layer, as further described in U.S. Application No. 63274832, the disclosure of which is incorporated herein by reference. In one embodiment of the composite angioplasty balloon, the non-expandable balloon is covered with an expandable sleeve to achieve, for example, the "pressurized stretching indicated by the arrow", as further described in the pending PCT application Serial No. PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The expandable layer can be rubber, silicone, polyurethane, or nitinol material, or another material that can be stretched up to 100-500% before breaking, can withstand thousands of cycles (i.e., expansion / relaxation cycles or application of pulsatile energy) before breaking, and minimizes plastic deformation even when plastic deformation occurs during expansion.

[0109] In embodiments, each of the intermediate radius balloons of the heart tissue conforming element, or a plurality of intermediate radius balloons, may have any convenient length and inflation diameter, such as may vary as desired, for example, according to the intended treatment or anatomical feature of the cardiovascular tissue, or the structural requirements of the catheter. In some embodiments, the intermediate radius balloon of the heart tissue conforming element may have a length of about 1.5 cm to 4 cm, or any variation in length, such as 1.5 cm or 2 cm or 3 cm or 4 cm, and when inflated, a diameter in the range of about 1.5 cm to 4 cm (i.e., an unconstrained diameter), or any variation in diameter, such as 1.5 cm or 2 cm or 3 cm or 4 cm, and for the above, for example, a balloon having a distal tip with a diameter of 1.5 cm configured to allow passage (e.g., through cardiovascular tissue, such as lumen tissue), and a smaller diameter (e.g., 1.5 cm or less) distal tip configured to reduce the risk of dilation or dissociation of the left ventricular outflow tract. In such embodiments, such balloons may extend radially from the outer surface of the catheter in various dimensions, and fix the balloon in a predetermined position prior to energy application (e.g., application of pulsatile energy). Generally, in embodiments, the balloon is, for example, 3 cm to 6 cm in length, such as 3 cm or 4 cm or 5 cm or 6 cm.

[0110] In embodiments, the distal and / or proximal regions of the intermediate radius balloon of the heart tissue conforming element may be configured to expand to a greater or lesser extent than the central region of the balloon. That is, embodiments of such balloons may take on a substantially hourglass-like shape or an oval shape, or a plurality of intermediate radius balloons may be configured to together take on such a shape. Generally, in embodiments, the intermediate radius balloon is not symmetric and may be symmetric, for example, through all planes passing through its longitudinal axis or planes perpendicular to its longitudinal axis.

[0111] In other cases, the distal and / or proximal regions of the intermediate radius balloon of the cardiac tissue conforming element have stretchability or semi-stretchability or non-stretchability such that the distal and / or proximal regions themselves seat at a desired anatomical location during treatment, for example, by engaging cardiac vascular tissue such as a cardiac valve leaflet or cardiac valve commissure. In still other cases, the central region of the intermediate radius balloon of the cardiac tissue conforming element has stretchability or semi-stretchability or non-stretchability such that it engages cardiac vascular tissue such as a cardiac valve leaflet or cardiac valve commissure to seat at a desired anatomical location during treatment. For example, in an embodiment where the intermediate radius balloon is hourglass-shaped, the proximal and distal regions of such an intermediate radius balloon have stretchability such that the diameter of such regions of the balloon corresponds to the inflation pressure and / or volume of the fluid injected into the balloon, and the central region of the intermediate radius balloon has non-stretchability.

[0112] In some embodiments, the distal and / or proximal regions of the intermediate radius balloon of the cardiac tissue conforming element include passive features that improve the ability of the cardiac tissue conforming element to identify and maintain a fixed position relative to cardiac vascular tissue. For example, an embodiment includes components such as protrusions or positioning elements configured to maintain the position of the cardiac tissue conforming element and / or catheter assembly relative to a desired anatomical feature (e.g., relative to a cardiac valve leaflet or commissure) during treatment using the system of the present invention. That is, in an embodiment, components such as protrusions or positioning elements are located on the outer surface of the intermediate radius balloon and are configured to engage such an aspect of the cardiac vascular tissue to position and hold the cardiac tissue conforming element in a substantially fixed position relative to the cardiac vascular tissue. In some cases, such components may be configured such that the cardiac tissue conforming element self-aligns. For example, in some cases, an outer balloon located on the intermediate radius balloon may first be inflated to expand prior to inflation of one or more intermediate radius balloons, and upon expansion, is induced by the outer balloon, and the outer balloon seats at a desired feature of the cardiac vascular tissue, such as a valve commissure, to align the cardiac tissue conforming element as desired.

[0113] In other examples, the outer surface of the intermediate radius balloon of the heart tissue conforming element, i.e., the surface that interfaces with the cardiovascular tissue, may be rough or otherwise have features that reduce the smoothness and / or slipperiness of the surface in order to facilitate maintaining a fixed position rather than sliding relative to the cardiovascular tissue at different positions or orientations on the surface of the heart tissue conforming element.

[0114] In an embodiment, the heart tissue conforming element may comprise a series of intermediate radius balloons circumferentially disposed around the catheter, i.e., as described above, one or more of the intermediate radius balloons may include a configuration in which the intermediate radius balloons are circumferentially positioned as such. In such a circumferential positioning configuration of the intermediate radius balloons, the intermediate radius balloons may be fused to each other at respective attachment points, e.g., points on the circumference of each balloon, and also fused to the distal region of the catheter. Such circumferentially positioned intermediate radius balloons may be fused to each other and / or to the catheter using any convenient and physiologically suitable adhesion technique, such as epoxy, cyanoacrylate, plastic cement, solvent bonding techniques, thermoplastic reflow, or combinations thereof, or any other suitable glue or adhesive or adhesion technique.

[0115] In some examples, the intermediate radius balloons, including a series of circumferentially positioned balloons of the heart tissue conforming element, are non-extensible such that when inflated, the diameter of such intermediate radius balloons is fixed, known, and structurally stable. Additionally, in an embodiment, the heart tissue conforming element may be configured such that when such intermediate radius balloons are inflated, such balloons do not occupy the entire volume between the overall outer diameter of the heart tissue conforming element and the catheter. That is, for example, in a cross-section of the heart tissue conforming element, the set of such circumferentially positioned intermediate radius balloons does not completely utilize the cross-sectional area between the outer surface of the heart tissue conforming element and the outer surface of the catheter. Such a configuration of the heart tissue conforming element enables the use of additional perfusion area (i.e., cross-sectional area) for blood to flow across the heart tissue conforming element, e.g., from proximal to distal or vice versa.

[0116] In embodiments where the cardiac tissue conforming element includes a series of intermediate radius balloons positioned circumferentially, such intermediate radius balloons can have a diameter of 1 mm to 20 mm, such as 1 mm or 5 mm or 6 mm or 10 mm or 20 mm. In embodiments where the cardiac tissue conforming element includes a series of circumferentially positioned intermediate radius balloons, there can be 1 to 30 or more balloons, such as 1 balloon or 2 balloons or 3 balloons or 4 balloons or 5 balloons or 6 balloons or 7 balloons or 8 balloons or 9 balloons or 10 balloons or 20 balloons or 30 or more balloons. Such balloons can all have the same diameter or can have different diameters. Further, such balloons can have various diameters over the length of the balloon, such that, for example, the proximal and / or distal regions of the balloon have a diameter that is larger or smaller than the diameter at the intermediate length of the balloon.

[0117] Balloons of the cardiac tissue conforming element In embodiments, as described above, balloons of the cardiac tissue conforming element, such as intermediate radius balloons or configurations of intermediate radius balloons positioned circumferentially, can be made of any convenient biocompatible material, as is well known in the art. For example, such balloons can be made of a stretchable or semi-stretchable or non-stretchable material. For example, in the case of a non-stretchable material, it can be made of polyamide such that the diameter of the balloon is substantially fixed (i.e., remains substantially constant) regardless of the inflation pressure applied to the balloon, or polyimide, or a combination of a thermoplastic or thermosetting resin and a metal braid or fiber braid, etc.

[0118] Any convenient balloon can be used as part of the heart tissue conforming element. Suitable balloons include, but are not limited to, standard angioplasty balloons such as stretchable and non-stretchable angioplasty balloons, or in other cases, composite balloons including two different layers, a non-stretchable layer and a stretchable layer. In one embodiment of the composite angioplasty balloon, the non-stretchable balloon is covered with a stretchable sleeve to achieve "pressurized stretching as indicated by the arrow", as further described, for example, in the co-pending PCT application serial number PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The stretchable layer can be rubber, silicone, polyurethane, or nitinol material, or another material that can be stretched up to 100-500% before breaking, can withstand thousands of cycles before breaking, and minimizes plastic deformation even when plastic deformation occurs during expansion.

[0119] In certain examples, the heart tissue conforming element includes a thin sheath of material disposed on its outer surface, for example, on all or a subset of the balloons constituting the heart tissue conforming element, to define the outer surface of the heart tissue conforming element. Such a thin sheath of material can be made of any convenient biocompatible material, as is well known in the art. For example, such a sheath can be made of a stretchable or non-stretchable polymeric material such as polyamide or polyimide, or a combination of a thermoplastic or thermosetting resin and a metal braid or fiber braid.

[0120] In an embodiment, balloons of the heart tissue conforming element, for example, intermediate radius balloons, are fused to each other and to a thin material sheath as well as not only to the distal region of the catheter such that the overall structure of the heart tissue conforming element has rigidity and can provide a substantial radial force (e.g., a force on the cardiovascular tissue) without collapsing inwardly (e.g., without collapsing axially). In such an embodiment, one or more internal regions between the balloons of the heart tissue conforming element can also function to allow blood to perfuse across the heart tissue conforming element even while such balloons are inflated and expanded. In an exemplary case where the heart tissue conforming element includes a non-stretchable balloon with a diameter of 6 mm circumferentially positioned around the distal region of the catheter with a diameter of 6 mm, the space between such balloons provides a cross-sectional area of about 10 - 70 mm for blood to flow across the heart tissue conforming element, e.g., from proximal to distal. 2 to provide.

[0121] In an embodiment, the surface of the balloon, for example, an intermediate radius balloon, or the thin sheath cover of the heart tissue conforming element may include an active agent. For example, the outer surface may be coated with an active agent such as a drug or other agent or substance that can have a physiological effect, such as an anticoagulant, or may have a hydrophilic or hydrophobic surface.

[0122] Winged balloon In embodiments configured to break and crush calcium or sclerotic deposits on cardiovascular tissue such as heart valves, techniques such as pulsatile endovascular lithotripsy can be used to generate high-intensity stress waves in the calcium structure. To facilitate such treatment, in some embodiments, the heart tissue conforming element further includes one or more winged balloons (or outer balloons) located on the outer surface of one or more intermediate radius balloons or on the outer surface of a configuration located circumferentially of the intermediate radius balloon. For example, an embodiment can comprise three separate winged balloons spaced equidistantly from each other around the circumference of one or more intermediate radius balloons or around the outer perimeter of a configuration located circumferentially of the intermediate radius balloon of the heart tissue conforming element. Such embodiments can be configured such that the winged balloons can be actuated, for example, by using standard pulsatile endovascular lithotripsy techniques while the one or more intermediate radius balloons are expanding. That is, the system can be configured such that such winged balloons can be pressurized separately and independently from the one or more intermediate radius balloons. In an embodiment, the winged balloons can be fixed at the distal and proximal locations of the catheter or other elements of the heart tissue conforming element (e.g., the distal and proximal locations of one or more intermediate radius balloons) and can be fluidly coupled such that fluid can be supplied to the winged balloons by small tubes (i.e., dedicated fluid passages of the catheter) that cross the interior or exterior of the catheter. In an embodiment, the small tubes for supplying the winged balloons can be formed from any physiologically suitable material, can have any convenient diameter, such as, for example, the diameter of such small tubes can be in the range of 0.1 mm to 4 mm, such as 0.1 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 3 mm, or 4 mm.

[0123] In an embodiment, the heart tissue conforming element may be configured such that each of the wing balloons is fixed in a single location along one or more intermediate radius balloons, or is fixed in a configuration circumferentially located on the intermediate radius balloon, or the wing balloons are configured to translate circumferentially around one or more intermediate radius balloons to find a path of least resistance to a desired region of the cardiovascular tissue (e.g., the commissure where the wing balloon is configured to engage the heart valve commissure) while the one or more intermediate radius balloons are inflated and the wing balloons are pulsating. In an embodiment, the wing balloon may be configured and disposed on the heart tissue conforming element such that when pulsating energy is applied to the wing balloon, the wing balloon functions to orient and / or position the heart tissue conforming element relative to the heart valve, e.g., by engaging the heart valve commissure. That is, the wing balloon may be configured to seat on, e.g., the heart valve commissure when pulsating energy is applied to the wing balloon. Orienting the heart tissue conforming element in this way allows different pulsating energy to be applied to the heart valve commissure as opposed to the heart valve leaflets, i.e., the pulsating energy transmitted by the wing balloon is transferred to the heart valve commissure while the pulsating energy transmitted to a configuration circumferentially located on one or more intermediate radius balloons or the intermediate radius balloon is applied to the heart valve leaflets. That is, the heart tissue conforming element may be configured such that different aspects of the cardiovascular tissue can receive different forms of specific, targeted, concentrated pulsating energy.

[0124] In an embodiment, the flapped balloon is configured to pulsate at any convenient rate required by the applicable treatment, and the pulsation of the flapped balloon can vary at a rate of 2 to 50 Hz, such as 2 Hz or 5 Hz or 10 Hz or 20 Hz or 30 Hz or 40 Hz or 50 Hz, etc., so that the pulsation of the flapped balloon causes the cardiac tissue conforming element to periodically load the cardiovascular tissue such as the cardiac valve commissure. Further, in an embodiment, the duty cycle (i.e., on and off periods) of the flapped balloon can be adjusted and can be configured to apply any convenient duty cycle. Further, in an embodiment, the pressure and / or force profile of the flapped balloon is such that the pressure inside the balloon oscillates between, for example, 0 atm on the trough of the cycle to 50 atm on the peak of the cycle, 0 atm on the trough of the cycle to or 3 atm on the peak of the cycle, or 3 atm on the trough side of the cycle to 50 atm on the peak of the cycle, or 3 atm on the trough side of the cycle to a pressure exceeding 3 atm on the peak of the cycle, etc., oscillating between 0 to 10 atm on the trough of the cycle to 3 to 50 atm on the peak of the cycle. In embodiments including two or more flapped balloons, such balloons can be configured to pulsate in a synchronized manner or pulsate independently of each other, i.e., the flapped balloons can be pressurized and depressurized synchronously, i.e., pressurized and depressurized simultaneously, or pressurized and depressurized independently at different times. For example, the flapped balloons can be inflated sequentially so that the intermediate shape of the cardiac tissue conforming element when the flapped balloon is inflated conforms to the desired shape or feature of the cardiovascular tissue, for example, facilitating the alignment of the cardiac tissue conforming element with the cardiovascular tissue. Other embodiments with flapped balloons can be configured such that different energies can be supplied to different regions of the flapped balloon. For example, in some examples, it may be desirable to apply pulsating energy with a larger amplitude or frequency to the tip (e.g., proximal or distal region of the flapped balloon) of one or more flapped balloons than to the central region (e.g., the central region between the proximal and distal ends of the flapped balloon) of the flapped balloon. For example, pressurizing the tip of the flapped balloon can be paused to apply more energy to the stenotic valve than to the left ventricular region or aorta region.In embodiments having both a wing balloon and an intermediate radius balloon, such balloons can be configured such that the intermediate radius balloon and the wing balloon are pulsed in a synchronized manner or pulsed independently of each other, i.e., the intermediate radius balloon and the wing balloon can be pressurized and depressurized synchronously, i.e., pressurized and depressurized simultaneously, or pressurized and depressurized independently and at different times.

[0125] Furthermore, in embodiments, the characteristics of the pulsatile energy applied by the wing balloon can change during the process of applying pulsatile energy to cardiovascular tissue using the wing balloon. Changes to the characteristics of the pulsatile energy applied by the wing balloon can be predefined using a controller, e.g., a controller such as a pre-programmed controller, i.e., can be pre-programmed, for example, or can be changed dynamically, i.e., on-the-fly, based on any convenient parameter such as sensor inputs such as pressure or volume measurements (e.g., the pressure or volume of the balloon), or based on other feedback signals or user inputs, etc. For example, the pulsatile energy applied by the wing balloon can continuously increase or continuously decrease (i.e., the maximum or minimum or average energy applied to the wing balloon can continuously increase or continuously decrease), or can pause (i.e., it is possible to keep constant, including by not applying pulsatile energy, e.g., pressure, to the balloon for a certain period of time, i.e., a relaxation period). Furthermore, in embodiments, the pulsatile energy applied by the wing balloon can decelerate or accelerate (i.e., the pulsatile energy applied by the wing balloon can be applied at a higher or lower frequency, or in other cases, the rate of change of the maximum or minimum or average energy applied by the wing balloon can be increased or decreased).

[0126] In an embodiment, the flanged balloon may have any convenient shape, such a shape may vary, for example, based on a feature of the cardiovascular tissue or a calcium deposit in the cardiovascular tissue. For example, in an embodiment, the flanged balloon may be cylindrical or may have a triangular cross-section, whereby the relatively wide side of the triangle is seated on the balloon at an intermediate of one or more radii. The embodiment may be configured to facilitate dispersing the pulsatile force applied to the flanged balloon over a larger area of the cardiovascular tissue around the one or more intermediate radius balloons. In such an embodiment where the cross-section of the flanged balloon is triangular, the pointed side of the triangular balloon may be oriented towards the valve commissure such that the pulsatile energy of the cardiac tissue conforming element is directed particularly towards such a valve commissure. In an embodiment, the flanged balloon may be made of any convenient biocompatible non-extensible or semi-extensible material, i.e., the same or a similar material as the intermediate radius balloon.

[0127] Any convenient balloon can be used as one or more balloons of intermediate radius or a winged balloon or outer balloon fixed to the outer surface of a configuration located circumferentially of the balloon of intermediate radius. Suitable balloons include, but are not limited to, standard angioplasty balloons such as expandable and non-expandable angioplasty balloons. In one embodiment, the winged balloon is a composite balloon comprising two different layers, which layers include, for example, a non-expandable layer and an expandable layer, as further described in U.S. Application No. 63274832, the disclosure of which is incorporated herein by reference. In one embodiment of a composite angioplasty balloon, the non-expandable balloon is covered with an expandable sleeve to achieve, for example, "pressurized stretching as indicated by the arrow", as further described in co-pending PCT Application Serial No. PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The expandable layer can be rubber, silicone, polyurethane, or nitinol material, or another material that can be stretched up to 100 - 500% before breaking, can withstand thousands of cycles (i.e., expansion / relaxation cycles or application of pulsatile energy) before breaking, and minimizes plastic deformation even when plastic deformation occurs during expansion.

[0128] In certain examples, the fenestrated balloon may comprise cutting or scoring elements on the outer surface of the fenestrated balloon such that expansion and pulsation of the balloon enables cutting, scoring, or otherwise applying further stress to calcified or stenotic tissue. In embodiments, as described above, the distal region of the catheter where the fenestrated balloon and one or more intermediate radius balloons are located may be configured to provide structural support for delivering substantial radial force, i.e., the force applied to cardiovascular tissue, such that the calcified cardiovascular tissue may be stressed by compression, bending, tension, or other means to disrupt calcium inside and / or outside the cardiovascular tissue. In some examples, the pulsatile stress delivered to the calcified cardiovascular tissue may cause low stress fatigue fracture of calcium within the cardiovascular tissue. In embodiments, in some cases, hundreds or thousands or more pulsation cycles may be required before low stress fracture of calcium occurs to cause fatigue fracture. In such cases, for example, a perfusion mechanism for perfusing blood into the distal vessel as described herein may be used to extend the treatment time before hypotension occurs or other adverse effects due to lack of perfusion beyond the cardiac tissue conforming element occur.

[0129] In other embodiments, the cardiac tissue conforming element may include a pulsatile balloon, such as a fenestrated balloon, comprising elements configured to generate cavitation or plasma bubbles or other forms of pulsatile or vibrational energy that cause disruption of calcium in cardiovascular tissue. In embodiments, such elements may include, for example, one or more wires (e.g., one wire coupled to two electrodes) or one or more optical fibers coupled to electrodes.

[0130] In other embodiments, the heart tissue conforming element may include a pulsatile balloon, such as a winged balloon configured to deliver an active agent, such as a drug, to the treatment site, i.e., the cardiovascular tissue or tissue proximal thereto, to, for example, prevent re-fusion of valvular commissures. In certain examples, the active agent may be coated on the outside of the winged balloon of the heart tissue conforming element or on other outer surfaces of the heart tissue conforming element, and may be delivered through cracks or pockets in the winged balloon of the heart tissue conforming element or other outer surfaces of the heart tissue conforming element, such as the balloon wall (e.g., the outer surface of the winged balloon or intermediate radius balloon, or the outer surface of a sheath covering a plurality of intermediate radius balloons). In some cases, the heart tissue conforming element is configured such that the active agent slowly moves into the cardiovascular tissue over the course of treatment, or in other cases, the heart tissue conforming element is configured such that the active agent is dissolved after reaching a certain number of pulses during treatment.

[0131] In some embodiments, the winged balloon and / or one or more intermediate radius balloons may be configured to deliver pulsatile lithotripsy to the cardiovascular tissue or re-seat a previously placed replacement heart valve to ensure optimal seating of the heart valve, such as a replacement heart valve. In certain embodiments, the winged balloon may be configured to be reduced in size after successful treatment of the cardiovascular tissue, such as a heart valve, such that one or more intermediate radius balloons can be further inflated to effect final dilation of the cardiovascular tissue, i.e., dilation via inflation of the one or more intermediate radius balloons.

[0132] Pulsatile energy applied to the heart tissue conforming element In embodiments where the cardiac tissue conforming element includes one or more balloons, such as intermediate radius balloons, winged balloons, etc., such balloons can be inflated and deflated in connection with applying pulsatile energy to the cardiovascular tissue. In such embodiments, the balloons of the cardiac tissue conforming element can be inflated or deflated at any convenient rate, and such rate can vary. Generally, the inflation of the balloon is repeated over time, i.e., inflated once after being deflated once. The configuration of the inflation and deflation cycles can be selected, for example, to promote blood flow from a distal region of the cardiovascular tissue, such as the distal region of a heart valve, to a proximal region of the cardiovascular tissue, such as the proximal region of a heart valve. In such embodiments, the one or more balloons of the cardiac tissue conforming element can be inflated and deflated at any desired frequency or rate, and such frequency and rate can vary. In an embodiment, the rate of inflation and deflation can correspond to the cardiac cycle of the cardiovascular tissue to which the cardiac tissue conforming element is applied. For example, the rate of inflation and deflation of the one or more balloons of the cardiac tissue conforming element can be once per heartbeat, or the rate can be synchronized with the heart rate adjusted by the clinician, such as during rapid ventricular pacing. In some examples, the catheter assembly of the system includes at least one port of the perfusion inflow or outflow zone as described above (i.e., configured to facilitate perfusion across the cardiac tissue conforming element), and such port can be pulsed in synchronization with the cardiac cycle of the cardiovascular tissue such that the flow through the port is blocked during a first segment of the cardiac cycle and opened during another segment of the cardiac cycle. For example, when an embodiment of the present system is used in connection with the treatment of cardiovascular tissue including the aortic valve, at least one port of the perfusion inflow or outflow zone can be blocked during the P-S wave measured by an electrocardiogram (ECG) that enables atrial contraction, isovolumetric contraction of the ventricle, and prevention of backflow from the aorta, and can be opened during the ST segment measured by an electrocardiogram (ECG) that enables ventricular dilation.

[0133] In some embodiments, a more complex inflation process is applied. In such embodiments, one or more balloons of the heart tissue conforming element are inflated and pulsed simultaneously during diastole and then crushed during systole. That is, during diastole, a first set of one or more balloons of the heart tissue conforming element is inflated, and simultaneously, a second set of one or more balloons of the heart tissue conforming element is inflated and pulsed, followed by both the first set and the second set of balloons of the heart tissue conforming element being crushed during systole. For example, one or more intermediate radius balloons can be inflated during diastole, and simultaneously, one or more winged balloons attached to the one or more intermediate radius balloons can also be inflated and pulsed during diastole, and then the one or more intermediate radius balloons as well as the one or more winged balloons can be crushed during systole. Some embodiments that utilize such an inflation process include two or more potential sources, i.e., two or more console assemblies, with at least one console assembly being associated with the inflation and deflation of one or more intermediate radius balloons and at least one other console assembly being associated with the inflation of one or more winged balloons, the application of pulsatile energy to those winged balloons, and the deflation of those winged balloons.

[0134] Heart tissue conforming element having a radial member In an embodiment, the heart tissue conforming element includes a plurality of radial members attached to a catheter. Such radial members can be configured and arranged on the catheter such that they can engage the cardiovascular tissue by bending or flexing or folding or pulling the cardiovascular tissue to split calcifications. For example, such radial members can be arranged on the catheter such that they can engage a single heart valve leaflet between the radial members to bend the leaflet tip between the radial members.

[0135] Such radial members may be arranged offset from one another along the distal region of the catheter and may include an eccentric plate, a triangular plate, or a rectangular plate and / or may include a balloon. In an embodiment, the radial member is configured to extend radially, i.e., away from the longitudinal axis of the catheter, so as to protrude radially outward. In an embodiment, the radial member may have any convenient length, width, and depth configured to sufficiently engage cardiovascular tissue such as a heart valve. The radial member may extend radially with a length greater than its cross-sectional width, which, in profile, means that the radial member has a substantially rectangular shape. For example, embodiments of the radial member may have a length in the range of about 2 mm to 150 mm, such as 20 mm to 60 mm or 2 mm or 10 mm or 20 mm or 30 mm or 40 mm or 50 mm or 60 mm or 70 mm or 80 mm or 90 mm or 100 mm or 110 mm or 120 mm or 130 mm or 140 mm or 150 mm, a width in the range of 2 mm to 20 mm, such as 2 mm or 5 mm or 10 mm or 15 mm or 20 mm, and a radius in the range of 2 mm to 50 mm, such as 25 mm to 35 mm or 2 mm or 10 mm or 20 mm or 30 mm or 40 mm or 50 mm. In an embodiment, the radial member may have a rotational angle of 0° to 360°, such as a rotational angle of 0° to 90° including 30° to 45°, about any desired rotational angle about the longitudinal axis of the catheter to which it is attached. The "rotational angle" means the angle between two radii of the sector occupied by the radial member as seen in cross-section along the longitudinal axis of the catheter. In an embodiment where the radial member has a rotational angle of 360°, such a radial member is equivalent to a lobe or hemisphere of a yo-yo configuration of a heart tissue conforming element as described herein.

[0136] In an embodiment, the radial member includes a radial balloon. In such an embodiment, the shape of the radial balloon can be substantially cylindrical and can be adapted to the final shape during inflation, for example, by applying a restraint element such as a braid made of nitinol to the balloon. In some cases, the shape of the radial balloon can be configured such that the balloon assumes an appropriate desired shape during the balloon forming process, i.e., is formed into the final shape. The radial balloon of interest can be made of any suitable physiologically compatible material, such as a non-stretchable material or a combination of a non-stretchable material and a stretchable material, whereby during inflation, the radial balloon extends only towards a particular cardiovascular tissue, for example, towards a calcified valve leaflet, and applies a force, such as a bending force, to such a particular cardiovascular tissue, for example, a calcified valve leaflet, to fragment or otherwise split the embedded calcium. Any convenient balloon can be used as the balloon of the radial member. Suitable balloons include, but are not limited to, standard angioplasty balloons such as stretchable and non-stretchable angioplasty balloons. In one embodiment, the balloon of the radial member is a composite balloon including two different layers, the layers including, for example, a non-stretchable layer and a stretchable layer, as further described in U.S. Application No. 63274832, the disclosure of which is incorporated herein by reference. In one embodiment of a balloon of a radial member comprising a composite angioplasty balloon, the non-stretchable balloon is covered with a stretchable sleeve to achieve, for example, the "pressurized stretching indicated by the arrow", as further described in co-pending PCT Application Serial No. PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The stretchable layer can be rubber, silicone, polyurethane, or a nitinol material, or another material that can be stretched up to 100 - 500% before breaking, can withstand thousands of cycles (i.e., expansion / relaxation cycles or application of pulsatile energy) before breaking, and minimizes plastic deformation even when plastic deformation occurs during expansion.

[0137] In an embodiment, the balloon of the radial member of the heart tissue conforming element can be inflated with fluid via a fluid connection between the interior of the balloon and the fluid passage of the catheter. Such a fluid connection between the interior of the balloon and the fluid passage of the catheter can comprise one or more port holes configured such that the interior of the balloon is in fluid communication with the fluid passage. Any convenient number, size, and configuration of port holes can be applied to operably connect the fluid passage of the catheter to the balloon of the radial member. In an embodiment, the port hole can be, for example, a radial hole connecting the inner wall of the fluid passage of the catheter (i.e., the surface closest to the longitudinal axis of the fluid passage) and the outer wall of the fluid passage (i.e., the surface farthest from the longitudinal axis, e.g., the surface to which the radial member is attached). The port hole can be configured to allow passage of fluid between the fluid passage and the balloon of the radial member. In an embodiment, the balloon of the radial member can be inflated using fluid transferred from the fluid passage of the catheter into the interior of the balloon via the port hole of the fluid passage. That is, in some embodiments, the pressure applied at the proximal end of the fluid passage that propagates along the fluid passage of the catheter can further propagate to the balloon of the radial member via the port hole.

[0138] The number of port holes can vary in embodiments of the present invention. The port holes can be of any convenient diameter, and those diameters can vary. The arrangement of the port holes on the fluid passage can assume any convenient pattern. The number of port holes, their diameters, and their arrangement on the catheter's fluid passage can be selected to ensure that the catheter retains its desired structural properties despite the presence of the port holes. In some embodiments, specifically, the number of port holes, their diameters, and their arrangement on the catheter are selected to ensure that the catheter maintains sufficient radial rigidity to accommodate the action of the radial member, including expansion of the balloon of the radial member and application of pulsatile energy to cardiovascular tissue through the radial member. For example, some embodiments of a catheter according to the present invention can include 1 to 5000 port holes (such as 100 or 300 or 1,000 or 3,000), with diameters of 0.1 mm to 0.5 mm (such as 0.1 mm or 0.25 mm or 0.4 mm) and spaced apart from each other by at least 0.1 mm to 5 mm (such as 0.5 mm or 1 mm or 5 mm).

[0139] In some cases, the radial member is arranged to form a three-point bending configuration. The radial member can include a balloon configured such that when the balloon is pressurized, the balloon expands such that the radial member bends or flexes or folds the cardiovascular tissue. In some cases, the radial member includes a balloon configured to expand and contract along a direction that is (substantially) proximal or distal (with respect to the radial direction) such that cardiovascular tissue, such as a heart valve leaflet, present between the radial members is bent or flexed or folded during balloon expansion. Embodiments can have one or more radial members configured to compress, bend, or pull on internal calcifications of the cardiovascular tissue such that when pulsatile energy is received by such a radial member, or when such a member is expanded, for example, via fluid inflation, the member wraps around an aspect of the cardiovascular tissue, such as a leaflet, and the calcifications are disrupted. In an example where the cardiac tissue conforming element includes a radial member, the catheter assembly can be configured to translate the first radial member laterally with respect to the second radial member, i.e., such that the radial member engages the cardiovascular tissue better and enables the cardiovascular tissue engaged by the radial member to be bent, curved, folded, or otherwise pulled between the radial members. In an embodiment, the cardiac tissue conforming element including the radial member can be configured to engage a single leaflet at a time. In one example, the catheter assembly can be configured to enable the cardiac tissue conforming element to pivot and / or reorient itself with respect to the cardiovascular tissue such that the radial member can treat each leaflet of, for example, a heart valve, sequentially.

[0140] In an embodiment, the radial member comprises a surface of the radial member configured to engage or contact or apply a force (i.e., compress) to cardiovascular tissue, such as a heart valve leaflet. Such a surface of the radial member that joins with the cardiovascular tissue may include the material of the radial balloon itself, or a nitinol cut or scoring element, a protruding feature (such as a diamond or hemispherical shape, an object on the surface for enhancing stress concentration), or any number of one or more elements attached to the radial balloon to facilitate splitting of calcium deposits within the cardiovascular tissue, such as a serrated scoring pattern.

[0141] Sensor In certain embodiments, for example, a catheter assembly including a heart tissue conforming element and / or a catheter may comprise one or more sensors (such as pressure, temperature, volume sensors, etc.) configured to obtain data from one or more locations throughout the catheter assembly, i.e., as described above in relation to the controller. Some embodiments may include one or more sensors at one or more locations throughout the system. For example, an embodiment may include one or more sensors at a connector of the catheter assembly, the catheter, or a heart tissue conforming element, such as one or more balloons of the heart tissue conforming element. In some cases, the sensors are present proximal and / or distal to the heart tissue conforming element and are configured to measure, for example, a pressure generated by the heart (i.e., contraction of the cardiovascular tissue) or at a location distal to the heart or a pressure gradient across the heart tissue conforming element.

[0142] In such embodiments, the sensor is configured to send information to and / or receive information from a controller, such as a controller of the console assembly, as described above. In such examples, data collected from the sensor can be fused to evaluate the behavior of the system or cardiovascular tissue that occurs at different frequencies or amplitudes of pressure applied to aspects of the heart tissue conforming element. The controller can be configured to read data from the sensor and adjust a treatment applied to the cardiovascular tissue in the form of a feedback and / or feedforward loop. The controller can also be configured to determine a more optimal treatment profile or treatment plan (i.e., system configuration such as pressure, frequency, and / or duty cycle configuration for implementation by the system to address calcifications present in the cardiovascular tissue). The controller can also be configured to adjust the treatment profile so that the treatment is executed according to a previously determined optimal treatment profile. Further details regarding the configuration and adjustment of the treatment plan are described in U.S. Application No. 63346704, entitled "Systems and Methods Related to Catheter-Based Procedures," filed on the event date with this specification (Attorney Docket No. AVSI-005PRV), the disclosure of which is incorporated herein by reference. Any convenient commercially available sensor (e.g., pressure, temperature, volume sensor, etc.) can be utilized and integrated into aspects of the system as needed based on the sensor, e.g., a pressure and / or volume sensor can be integrated into an embodiment of the connector of the catheter assembly.

[0143] Robotic aspects of the system Another aspect of the embodiments of the system relates to robotic treatment of cardiovascular tissue having a disease. In one configuration, an embodiment of the system according to the present invention, including a console assembly, a manifold assembly, and a catheter assembly, is located at a treatment site, i.e., a location such as a treatment room or an operating room where the system is used to treat a subject. The treatment site is connected to a control room that includes system control and / or system results, such as data collected by sensors of the system. The control room can be operably connected to components of the system present at the treatment site via any convenient connection, such as a wired or wireless data connection. The control room may include various displays for displaying information related to the procedure using an embodiment of the system of the present invention, such as an imaging sensor or a device sensor. In addition, the control room may include a treatment controller so that an operator can control various aspects of the treatment, such as the start of the treatment and the positioning of the device, i.e., the position of the catheter assembly including a heart tissue conforming element with respect to the cardiovascular tissue of the subject, i.e., the cardiovascular tissue of the subject present in the treatment room. Another aspect may include a connection to a database configured to generate, store, and / or transmit information about the subject, as well as treatment database, i.e., treatment plan information related to the control of the aspects of the system when applying the system to the cardiovascular tissue of the subject. As described above, the treatment profile or treatment plan may include system configurations such as pressure, frequency, and / or duty cycle configurations for implementation by the system to address calcifications present in the cardiovascular tissue.

[0144] In some cases, the control room can be located several feet away from the operating table, such as behind a lead curtain or other form of shielding, or at a different geographical location, such as a different building or a different city or country. One or more operators may be able to interact in the control room and communicate information with the subject or other operators at the treatment site.

[0145] Visualization Embodiments of the system may further include marker bands present in the form of a catheter assembly. In an embodiment, the marker bands may be fixed to different components of the system, such as, for example, various positions on the catheter, the heart tissue conforming element, one or more balloons of the heart tissue conforming element, the inlet or outflow zone of the perfusion mechanism, or a guide wire passing through the catheter. The marker bands may be used to visualize the position of the system or component when the system, or a component of the system such as the heart tissue conforming element, is applied to a subject. The marker bands may further be used to confirm the proper location and alignment (e.g., cross-link alignment) of aspects of the system, such as the heart tissue conforming element, in relation to the delivery of treatment.

[0146] The marker bands used in the embodiments are any convenient, readily available marker bands that can be attached to the components of the system, such as, for example, crimped, or pressure-bonded, or thermally bonded, or welded, or coupled. The marker band of interest may be a polymer band loaded with gold or platinum or tungsten, or another material that facilitates visualization, such as visualization by fluoroscopy. The marker bands may be visualized via visualization techniques of fluoroscopy or radioscopy.

[0147] Various aspects of the system of the present invention have been outlined above, and the elements of the system of the present invention will be considered further in the context of specific embodiments.

[0148] Specific Embodiments Aspects of the claimed invention are described in relation to such embodiments without limiting the invention to the embodiments depicted in FIGS. 1 through 16, which are for purposes of facilitating illustration only.

[0149] A system according to an embodiment of the present invention for imparting pulsatile energy to cardiovascular tissue is schematically illustrated in FIG. 1. In some examples, the system can include a console assembly having a potential energy source, such as a high voltage or pressure source, for example, a regulator for adjusting the output of the pressure source, and a controller for controlling, for example, aspects of the system. The system can also include a manifold assembly operably connected to the output of the console assembly, the manifold assembly comprising an oscillator for converting the output of the potential energy source into pulsed energy. The system can also include a catheter assembly operably connected to the output of the manifold assembly for converting the output of the manifold assembly (i.e., the first pulsatile energy) into, for example, hydraulic vibrations or other forms of vibrational potential energy (i.e., the second pulsatile energy) and transmitting the second pulsed energy to a heart tissue conforming element via a catheter (i.e., the fluid passage of the catheter). The heart tissue conforming element can be configured to receive the vibrational potential energy and apply pulsatile energy to the cardiovascular tissue. In an embodiment, the vibrational potential energy acts to drive aspects of the heart tissue conforming element, such as balloon angioplasty vibrations or the movement of a radial member, to bend or flex the cardiovascular tissue, for example. The controller can control the frequency, duty cycle, and / or amplitude of the energy output from the potential energy source of the console assembly and the oscillator of the manifold assembly. The connector of the catheter assembly can convert the energy output by the manifold assembly into, for example, hydraulic vibrations, thereby generating vibrations in the aspects of the heart tissue conforming element. Variations of this system are provided in each of the following embodiments. The following embodiments are not intended to be an exhaustive list, but rather are intended to provide examples of various configurations of the overall system.

[0150] FIG. 1 depicts a schematic view of an exemplary embodiment of a system 100 for imparting pulsatile energy to cardiovascular tissue according to the present invention. In some embodiments, as schematically illustrated in FIG. 1, system 100 may include a console assembly (i.e., console subsystem) 110 that may include one or more console units 120, a manifold assembly (i.e., manifold subsystem) 140 that may include one or more sub-units including an oscillator 141, and a catheter assembly (i.e., catheter and balloon subsystem) 150 that may include one or more connectors 151, as well as a catheter 154 having a fluid passageway (not shown) and a heart tissue conforming element 165. Each connector 151 of catheter assembly 150 is connected to an oscillator 141 of manifold assembly 140 and one or more connector catheter transition hubs 153 for transmitting pulsatile energy (i.e., second pulse energy) to heart tissue conforming element 165 via catheter 154.

[0151] The console assembly 110 may include one or more console units 120. When the console assembly includes a plurality of console units, such console units may be combined in a single physical component (i.e., housing) or separated into a plurality of housings, e.g., one housing per console unit. In each case, the console units are configured to operate independently of each other, i.e., they can be controlled independently regardless of whether the console units are present within a single housing or within a plurality of housings. The console unit 120 includes a potential source 121 for generating energy that is transmitted to the manifold assembly 140, a potential regulator (not shown), and a controller 130. The output from the potential source 121 may include regulated potential energy 122 or unregulated potential energy, such as from a high-pressure fluid or voltage. The potential regulator may be used to modify the potential energy output from the potential source 121 into a form that can be transmitted and further manipulated by the manifold assembly 140, i.e., the oscillator 141 can generate pulsed energy from the energy transmitted from the potential source 121. A plurality of console units 120 (i.e., console units numbered from 1 to n) may be included in the console assembly 110 and can operate substantially in parallel (i.e., independently) to generate a plurality of potential outputs 122 that are transmitted to the plurality of oscillators 141. In some examples, the plurality of console units 120 may be configured to generate a plurality of potential outputs 122 when the treatment of cardiovascular tissue includes applying pulsatile energy of different configurations to the cardiovascular tissue, e.g., the heart tissue conforming element includes a plurality of balloons configured to potentially expand independently at different frequencies, duty cycles, and / or amplitudes.In such examples, different potential outputs 122 can be applied separately to the cardiovascular tissue, for example, via different balloons or other aspects of the heart tissue conforming element, or over different times (i.e., one potential output is operably connected to the balloon at a first time, and then another potential output is operably connected to the balloon at a second time). In other examples, potential outputs 122 from multiple console units 120 can be combined. In still other examples, when the treatment of the cardiovascular tissue requires the application of different forms of energy, multiple console units 120 can be configured to generate multiple potential outputs 122 that include different forms of potential energy (e.g., high pressure or voltage).

[0152] The console assembly 110 further includes a controller 130 configured to receive an input from at least one of the console assembly 110, the manifold assembly 140, and the catheter assembly 150. In FIG. 1, the controller 130 is shown receiving an input from the catheter assembly 150, i.e., from the sensor 152 of the catheter assembly 150. The sensor 152 can comprise any sensor configured to sense any relevant characteristic of the detectable catheter assembly 150. For example, the sensor 152 can comprise a pressure transducer configured to measure the pressure within the catheter assembly 150, such as, for example, the pressure in a fluid channel of the catheter 154 or the pressure of an aspect of a heart tissue conforming element 165 such as an angioplasty balloon. Alternatively, the sensor 152 can include a volume sensor configured to measure, for example, the volume of fluid present in the balloon. In one example, the controller 130 can be configured to receive inputs from a plurality of sensors including sensors (such as pressure sensors, temperature sensors, volume sensors, etc.) configured to measure any relevant aspect of the system 100 or the environment to which the system 100 is applied, and can be configured to capture data from any location throughout the system 100, including, for example, one or more locations of the system 100, such as the heart tissue conforming element 165, the catheter 154, the connector catheter-to-catheter transition hub 153, the connector 151, the oscillator 141, or a location on the console unit 120. Generally, in embodiments, sensors can be configured at any desired location of the system to collect any desired information regarding the use of the system, for example, in relation to a treatment procedure. In other examples, the controller 130 can be configured to receive inputs from user inputs such as buttons or switches for specifying treatment options (such as system pressure, frequency, duty cycle, etc.).In FIG. 1, the controller 130 receives an input from the pressure transducer 152 of the catheter assembly 150 and generates a control signal for controlling an aspect of the console assembly 110, such as, for example, the magnitude of the potential output 122, based at least in part on such input, i.e., generates via an active regulator (not shown) that is used to adjust the magnitude of the potential output 122 (e.g., the output pressure).

[0153] In the embodiment schematically illustrated in FIG. 1, the output of the console assembly 110 is operably connected to the manifold assembly 140, and the energy transmitted from the potential source 121 of the console unit 120 (i.e., the regulated potential output 122) is transmitted to the oscillator 141 of the manifold assembly 140. The oscillator 141 is configured to generate pulsating energy or static energy from the energy transmitted from the potential source 121 (i.e., the regulated potential output 122). In one example, the oscillator 141 may include a solenoid valve (not shown) configured to enable or interrupt the transmission of energy to the catheter assembly 150. In other examples, the oscillator 141 may include any applicable electrical, e.g., an electrical solenoid, optical, or mechanical switch, as is well known in the art. As further described below, the behavior of the oscillator 141 may be controlled by the controller 130 based on any desired feedback, such as, for example, feedback from the system 100, or an external signal, such as, for example, an input from an operator.

[0154] In FIG. 1, a controller 130 connected to the manifold assembly 140 is shown. In one example, the oscillator 141 may be configured such that the oscillation frequency and / or duty cycle may be controlled by the controller 130, such as, for example, the controller 130 controls the position or other aspect of the solenoid behavior of the oscillator 141.

[0155] In the embodiment schematically illustrated in FIG. 1, the output of oscillator 141 of manifold assembly 140 is operably connected to catheter assembly 150. In particular, the output of oscillator 141 is connected to the input of connector 151. Connector 151 is configured to convert potential energy, such as pneumatic pressure (i.e., first pulse energy) generated by oscillator 141, into a second potential energy, such as hydraulic pressure (i.e., second pulse energy). The system 100 shown in FIG. 1 includes a plurality of connectors 151 (connectors 1 to n), where one connector 151 corresponds to each oscillator 141. The output of connector 151 is operably connected to a connector catheter transition hub 153 configured to allow the potential energy output of connector 151 (i.e., second pulse energy) to be input into catheter 154, such as one or more fluid channels (not shown) of catheter 154. In some cases, catheter assembly 150 includes two or more catheters 154, or catheter 154 includes two or more fluid channels inside or outside catheter 154, i.e., different aspects of heart tissue conforming element 159 can be operated independently (e.g., different angioplasty balloons or radial members constituting heart tissue conforming element 159 can be pressurized or inflated and deflated independently).

[0156] In the catheter assembly 150 of the system 100, the catheter 154 includes a guide wire - dedicated channel such that the catheter 154 and the heart tissue - conforming element 159 can be navigated to a cardiovascular tissue treatment site via a standard over - the - wire guide wire technique. The connector catheter - to - transition hub 153 is configured to include a guide wire exit port 161 for the proximal region of the guide wire that is screwed through the guide wire channel of the catheter 154. The guide wire exit port 161 faces a guide wire entry port 157 that is present in a relatively distal region of the heart tissue - conforming element 165. For purposes of illustration only, and to emphasize the location of the guide wire exit port 161 relative to other components of the system 100, the guide wire exit port 161 is depicted as being oriented away from the longitudinal axis of the catheter 154. In an embodiment, the guide wire exit port 161 is oriented in a manner parallel to the longitudinal axis of the catheter 154 (and thus parallel to the longitudinal axis of the guide wire channel within the catheter 154) to avoid unnecessary bending of the guide wire present in the system 100. As described above, the system 100 can be configured with respect to the guide wire such that the system 100 is an over - the - wire, rapid - exchange, monorail, etc. system.

[0157] In the embodiment schematically illustrated in FIG. 1, the heart tissue conforming element 165 is present in the distal region of the catheter 154. In the system 100, the heart tissue conforming element 165 spans the leaflets of the aortic heart valve such that the distal region of the heart tissue conforming element 165 where the heart tissue conforming element 165 is present on the ventricular side of the aortic valve and the proximal region present on the aortic side of the aortic valve, and is configured to conform to cardiovascular tissue including the aortic heart valve. The heart tissue conforming element 165 includes a plurality of angioplasty balloons and other features (e.g., positioning elements or protrusions, etc.) configured to engage the aspect of the aortic heart valve. The angioplasty balloons of the heart tissue conforming element 165 include one or more outer cross-linking balloons (e.g., wing balloons) 158 and one or more inner valve-forming balloons (e.g., intermediate radius balloons) 159. The angioplasty balloons 158, 159 of the heart tissue conforming element 165 can be operable independently (i.e., pressurization and depressurization are possible regardless of whether other balloons are pressurized or depressurized).

[0158] The outer cross-linking balloon 158 is present at a relatively outer radial distance from the longitudinal axis of the heart tissue conforming element 165 such that the outer cross-linking balloon 158 can engage the aortic valve commissure (i.e., apply pulsatile energy to the aortic valve commissure), for example, to split the calcium layer within the aortic valve commissure that inhibits proper valve function. The outer cross-linking balloon 158 can include a non-extensible / extensible composite material as described above. The heart tissue conforming element 165 can include a plurality of outer cross-linking balloons 158 configured such that the outer cross-linking balloon 158 engages each commissure of the aortic valve, for example, three outer cross-linking balloons 158 for engaging each aortic valve commissure.

[0159] The outer cross-linked balloon (e.g., the winged balloon) 158 is operable independently of the second outer cross-linked balloon and the inner valve-forming balloon 159, i.e., can be configured to be pressurized and depressurized independently, by being pressurized, for example, by hydraulic pressure transmitted through a separate fluid chamber of the catheter 134. Alternatively, the outer cross-linked balloon 158 can be configured to be pressurized and simultaneously depressurized by hydraulic pressure transmitted through a single fluid channel of the catheter 134 that supplies hydraulic pressure to, for example, a plurality of outer cross-linked balloons 158.

[0160] The inner valve-forming balloon (e.g., the intermediate radius balloon) 159 is present at a relatively inner radial distance from the longitudinal axis of the heart tissue conforming element 165 sufficient to allow the inner valve-forming balloon 159 to engage (i.e., apply pulsatile energy) the aortic valve leaflets, for example, to split a calcium layer of the aortic valve leaflets that inhibits proper valve function. The heart tissue conforming element 165 can comprise a plurality of inner valve-forming balloons 159 configured such that the inner valve-forming balloon 159 engages each leaflet of the aortic valve. For example, the heart tissue conforming element 165 can comprise three inner valve-forming balloons 159 for engaging each aortic valve leaflet or a single inner valve-forming balloon 159 configured such that different surfaces of the single balloon engage each aortic valve leaflet.

[0161] The inner valve-forming balloon 159 is operable independently of the second inner valve-forming balloon and the outer cross-linked balloon 158, i.e., can be configured to be pressurized and depressurized independently, by being pressurized, for example, by hydraulic pressure transmitted through a separate fluid chamber of the catheter 134. Alternatively, the inner valve-forming balloon 158 can be configured to be pressurized and simultaneously depressurized by hydraulic pressure transmitted through a single fluid channel of the catheter 134 configured to supply hydraulic pressure to a plurality of balloons such that all are pressurized and depressurized simultaneously.

[0162] In the embodiment schematically illustrated in FIG. 1, the catheter 154 and the heart tissue conforming element 165 are configured to allow fluid, such as blood, to perfuse across the heart tissue conforming element 165 even while pulsatile energy is being applied to the cardiovascular tissue at the treatment site. For example, in the system 100, the catheter 154 and the heart tissue conforming element 165 allow blood to be moved from the perfusion inflow zone 156 to the perfusion outflow zone 155 via one or more passageways (not shown), i.e., to be perfused, for example, by fluidly connecting the perfusion inflow zone 156 to the perfusion outflow zone 155 and enabling blood received from the distal region (i.e., the ventricular region) to flow out from the proximal region of the heart tissue conforming element 165 (i.e., the aortic region). The perfusion inflow zone 156 and the perfusion outflow zone 155 include perforations or ports (not shown) in the catheter 154 or the heart tissue conforming element 165 through which blood can flow. Such a configuration allows blood flow through the heart tissue conforming element 165 and allows for an extended treatment time. Such a perfusion mechanism may further include a structure (e.g., a valve or a vibrating balloon mechanism) within the catheter 154 or the heart tissue conforming element 165 that allows fluid to flow in only one direction. The catheter 154 includes a proximal catheter section 163 and a distal catheter perfusion section 162. The distal catheter perfusion section 162 includes the perfusion inflow zone 156, the perfusion outflow zone 155, and, for example, one or more passageways (not shown) that fluidly connect the perfusion inflow zone 156 to the perfusion outflow zone 155. The proximal catheter section 163 and the distal catheter perfusion section 162 may be connected by a connector (not shown).

[0163] Any convenient perfusion mechanism can be used in the catheter 154 and the heart tissue conforming element 165 to direct the flow of fluid, such as blood, through the perfusion zone, i.e., from the perfusion inflow zone 156, across the heart tissue conforming element 165, to the perfusion outflow zone 155, i.e., the flow of blood is such that when the fluid, such as blood, is present, for example, within a blood vessel, the heart tissue conforming element 165 does not completely block the flow of blood and is moved from the distal region to the proximal region of the heart tissue conforming element 165. As described above, a passive perfusion mechanism can be used to direct the flow of fluid from the perfusion inflow zone 156 to the perfusion outflow zone 155 based on an existing pressure gradient, i.e., an existing pressure difference caused, for example, by ventricular contraction, or an active perfusion mechanism comprising a syringe, such as a barrel syringe, configured to move fluid through a perfusion zone from the perfusion inflow zone 156 across the heart tissue conforming element 165 to the perfusion outflow zone 155.

[0164] In one example, aspects of the system 100, such as, for example, the console assembly 110 (e.g., the controller 130), the manifold assembly 140 (e.g., the oscillator 141), and aspects of the catheter assembly 150 (e.g., the connector 151 and the interconnector transition hub 153), can be configured to be reusable. In one example, aspects of the system 100, such as, for example, the catheter 154 or the heart tissue conforming element 159, can be configured to be single-use (e.g., disposable). The terms "reusable" and "disposable" as used herein and elsewhere in the description are used for convenience in describing embodiments of the invention illustrated in FIG. 1. However, the invention is not so limited. Thus, any part of the system can be configured, as desired, for single-use or for multiple uses.

[0165] Figures 2A and 2B provide a schematic diagram of a console assembly 200 according to an embodiment of the present invention that can be used in a system such as system 100 schematically illustrated in FIG. 1, for example. The console assembly 200 is configured to deliver a regulated high-pressure gas and is controlled by several inputs. FIG. 2A provides a schematic diagram of a console assembly 200 configured to provide a treatment including, for example, pulsatile intravascular lithotripsy, and FIG. 2B provides a schematic diagram of a console assembly 200 configured to provide a treatment including, for example, a one-way valve operation synchronized with an electrocardiogram (ECG). The console assembly 200 includes a potential source that is a high-pressure gas source 121. The potential energy output of the high-pressure gas source 121 is supplied to a regulator 123. The regulator 123 is configured to modify the potential energy output 121a (dotted line) (i.e., a constant high pressure) of the high-pressure gas source 121 to a regulated pressure output 122.

[0166] In FIG. 2A, a characteristic treatment profile for a lithotripsy procedure according to an embodiment of the present invention is depicted by showing the regulated output pressure 122 over time. As a function of time on the X-axis, the regulated pressure 122 initially slopes slowly and is held constant for a period of time. When a change in the destruction or balloon volume is detected, the pressure drops and then slowly increases again, i.e., slowly re-slopes, for the final treatment segment.

[0167] In FIG. 2B, a treatment profile is shown in which an adjusted output pressure 122 for applying a pressure pulse to the intermediate radius balloon layer is timed in accordance with the results of an electrocardiogram (ECG). Such a treatment profile enables the system 200 to synchronize the adjusted output pressure 122 that circulates with the features of the cardiac cycle. In some embodiments, such a configuration requires the application of a vacuum (i.e., the adjusted output pressure 122 is depicted to periodically measure negative pressure on the plot of the adjusted output pressure 122 over time) to facilitate the rapid evacuation of the balloon of the cardiac tissue conforming element. Such a vacuum can be applied in any convenient manner well known in the art, including, for example, a switch or solenoid as part of the regulator 123. Such a vacuum pressure facilitates deflating and evacuating the balloon, i.e., rapidly deflating and evacuating the balloon and enabling fluid, such as blood, to perfuse beyond the deflated balloon. In some embodiments, a stretchable / non-stretchable composite balloon material is used to ensure sufficiently rapid balloon evacuation. (In another embodiment of the treatment profile in which a pressure pulse is applied to the intermediate radius balloon layer in a manner timed in accordance with the results of an electrocardiogram (ECG), the adjusted output pressure 122 is held constant and, instead of the regulator 123, an oscillator of the manifold assembly is used to circulate the balloon pressure based on the results of the ECG. In such an embodiment, the adjusted output pressure 122 (i.e., the input pressure to the balloon) can inflate the balloon and the outlet of the oscillator can be attached to a vacuum or the atmosphere to facilitate rapid decompression and evacuation of the balloon.))

[0168] In FIGS. 2A and 2B, two console units 200, each having a high-pressure gas source 121, are depicted in connection with the two different treatment profiles described above. In other embodiments, a single console unit 200 having one or more high-pressure gas sources 121 may be connected to a plurality of manifold assemblies, and each oscillator of the manifold assemblies is configured to generate different treatment profiles such as the two treatment profiles described above in connection with FIGS. 2A and 2B.

[0169] The high-pressure gas potential energy output 121a is supplied to a regulator 123. The output of the regulator 123, i.e., the regulated pressure output 122, is transmitted via an output port 126 to the input of a manifold assembly (not shown), whereby the regulated output pressure 122 is transmitted to an oscillator, which turns on and off and transmits pulsating energy (the maximum pulse pressure is below the regulated output pressure 122). The regulator 123 is an active regulator configured to be controlled by a signal generated by a controller 130. The control of the regulator 123 by the controller 130 includes manipulating the output pressure level of the regulator output 122, e.g., increasing or decreasing the regulated pressure at a specified time.

[0170] The controller 130 is an electronic component configured to receive an input 124 that includes data input from one or more of a catheter assembly, user input, electrocardiogram input, imaging input, electrocardiogram input, and other inputs, such as an input from a manifold assembly. The input 124 that includes data received from the catheter assembly can include a measurement of the pressure applied to the heart tissue conforming element, or a volume measurement of, for example, the aspect of a balloon that constitutes the heart tissue conforming element. The input 124 that includes imaging data can include any relevant data that can be imaged, such as, for example, fluoroscopic data related to the position of the heart tissue conforming element relative to the cardiovascular tissue, or the function of a heart valve, or the degree of calcification of the cardiovascular tissue. Such fluoroscopic data that includes the controller input 124 can be obtained, for example, using a radiopaque marker.

[0171] Based on the input 124 as described above, and a treatment plan or treatment mode, for example, a pulsatile intravascular lithotripsy treatment mode or a one-way valve operation synchronized with an electrocardiogram (ECG) mode, the controller 130 generates a signal that includes a controller output 125. The controller output 125 includes, for example, a regulator control signal, display data for controlling a user display to provide the user with information regarding the ongoing treatment, such as a pressure measurement in various aspects of the system, and other outputs.

[0172] Figures 3A and 3B depict two exemplary embodiments of a console assembly 300 configured to generate the power and control necessary for the treatment of cardiovascular tissue using the system of an embodiment of the present invention. FIG. 3A provides a first perspective view of the console assembly 300, and FIG. 3B provides a second perspective view of the console assembly 300. The console assembly 300 includes a console input 310 for input to a controller (not shown) for adjusting the behavior of the system. The input 310 includes buttons for selecting treatment intensity and mode, as well as an emergency shut-off button. The console assembly 300 includes a console input / output port 340, which in some cases may include an HDMI (registered trademark) port or a USB port for transmitting data between the console assembly 300. The console assembly 300 includes an on-off switch 350 for activating and deactivating the console assembly 300. The console assembly 300 also includes an output port 320 for transmitting potential energy, including a connector for connecting to a manifold assembly, such as a pneumatic connector or a hydraulic connector or an electrical connector or an optical connector. For example, an external potential source, such as a connection to high-pressure gas, may be connected to the console assembly via the connector 330. The console assembly 300 also includes a console enclosure 390 configured to form a housing, for example, configured to protect the console assembly components, for example, during accidental drops or during packaging. The console enclosure 390, if present, may be manufactured from a suitable rigid material, such as a polymeric material, and may be transparent or opaque as desired.

[0173] Figures 4A and 4B provide schematic views of a manifold assembly 400 according to an embodiment of the present invention that can be used in a system such as system 100 schematically illustrated in FIG. 1. The manifold assembly 400 uses an oscillator 441 to convert the regulated potential energy 422 received from a potential source of a console assembly (not shown) into treatment energy 442 for use by a catheter assembly (not shown). In FIG. 4A, an application of the manifold assembly 400 related to the provision of pulsatile intravascular lithotripsy, as seen in the potential output 442, is depicted, with pressure changes over time corresponding to pulsatile intravascular lithotripsy treatment. The sawtooth shape of the potential output 442 represents the oscillator output and pulsatile potential applied to cardiovascular tissue, for example, via a balloon of a heart tissue conforming element. The maximum potential output 442 of the oscillator corresponds to the solid line seen above the potential output 442 (e.g., the regulated output pressure 122 of FIGS. 2A and 2B). The high-pressure gas potential energy output 421a is plotted on the graph for reference. In FIG. 4B, an application of the manifold assembly 400 related to the provision of a one-way valve operation synchronized with the results of an electrocardiogram (ECG), as seen in the potential output 442, is depicted, with pressure changes over time corresponding to the ECG results. The manifold assembly 400 includes receiving energy transmitted from a potential source (not shown) via the potential source output 422. For example, the oscillator 441 is exposed to such energy to adjust the frequency, duration, and / or duty cycle of the oscillator 441, including turning the oscillator 441 off, and the oscillator 443 is controlled via a vibration control signal 443. FIG. 4A depicts a vibration control signal 443 configured to turn the oscillator on and off, while FIG. 4B depicts a vibration control signal 443 configured to always remain on, i.e., open, such that a regulator changes the potential source output 422 (i.e., the regulated output pressure) based on the results of the ECG, exemplifying the difference between applying the manifold assembly 400 in relation to pulsatile intravascular lithotripsy and providing a one-way valve operation synchronized with the results of the ECG.In another embodiment of the manifold assembly 400 for providing a one-way valve operation synchronized with the results of an electrocardiogram (ECG), the potential source output 422 (i.e., the regulated output pressure) is a constant pressure, and the oscillator 441 is circulated to vary the potential output 442 in a manner synchronized with the results of the ECG. In some cases, synchronizing the potential output with the results of the ECG controls the potential applied to one or more balloons or other aspects of the heart tissue conforming element to collapse (i.e., collapse one or more balloons of the heart tissue conforming element) immediately before or after the QRS spike of the ECG, and then pressure is applied to inflate one or more balloons or other aspects of the heart tissue conforming element during diastole, including starting the collapse of one or more balloons or other aspects of the heart tissue conforming element before the P wave.

[0174] In any case, the pulse energy 442 resulting from the operation of the oscillator 441 of the manifold assembly 400 is transmitted via the oscillator output connector 444 to a catheter assembly (not shown). The vibration control signal 443 is generated by a controller 430 configured to receive the input 424 and generate an output 425 including the vibration control signal 443, at least in part based on the input 424. In FIG. 4A, the controller 430 is configured to receive an input signal 424 corresponding to at least the pressure and / or volume of a connector of the catheter assembly (not shown) and / or a heart tissue conforming element of the catheter assembly (not shown), i.e., an input signal internal to the system. In FIG. 4B, the controller 430 is configured to receive an input signal 424 corresponding to the pressure and / or volume of a connector of the catheter assembly (not shown) and / or a heart tissue conforming element of the catheter assembly (not shown), i.e., an input signal internal to the system, as well as an input signal corresponding to the results of an electrocardiogram (ECG), i.e., an input signal external to the system. The controller 430 may be included as part of a console assembly (not shown) (i.e., the controller 130 of FIG. 1 or FIGS. 2A and 2B), or in some cases, may be included as part of the manifold assembly 400.

[0175] FIG. 5 provides a perspective view of a manifold assembly 500 of a system according to an embodiment of the present invention, such as the manifold assembly 400 of FIGS. 4A and 4B. The manifold assembly 500 includes a plurality of inlet sources 545 including cables such as, for example, optical cables or electrical cables (optical cables or electrical cables configured to transmit power or signals such as data or control signals), or tubes such as, for example, pneumatic or hydraulic tubes for receiving a potential input to the manifold assembly 500, and a potential output 542 for transmitting energy from the manifold assembly 500. The manifold assembly 500 includes, for each pair of inlet source 545 and potential output 542, one of a plurality of oscillators (not shown) configured to convert the energy transmitted from the potential source into pulsed energy.

[0176] The manifold assembly 500 also includes a manifold encasement 590 configured to form a housing, for example, configured to protect the manifold assembly components, for example, during accidental drops or during packaging. The manifold encasement 590 can be manufactured from a suitable rigid material, such as, for example, a polymeric material, and can be transparent or opaque, as desired. In some cases, the manifold assembly can include a controller connection point and a user feedback and / or control area (not shown).

[0177] Figures 6A - 6E depict multiple figures of an exemplary embodiment of a connector 600 configured to deliver small amounts, high frequencies, and high - voltage pulses, according to an embodiment of the present invention. Figure 6A provides a cut - away side view of the connector 600. The connector 600 includes a proximal flange 610 and a distal flange 650 separated by a membrane 630. The proximal flange 610 defines a proximal chamber 615 accessed by a proximal port 620. The distal flange 650 defines a distal chamber 655 accessed by a distal port 660. A pressure transducer 625 is operatively coupled to the distal port 660 and the distal chamber 655. The proximal and distal flanges 610, 650 are held together by screws, as illustrated by screws 670. Alternatively, the flanges can be fixed via any other suitable assembly method such as adhesives, welding, or other means. In other examples, the flanges can be manufactured as a single component via multi - shot injection molding or over - molding processes around a flexible membrane and electronic devices. A hall sensor 635, a permanent magnet 648, an electrical connector 690, and a flexible printed circuit board 697 are also shown. A threaded portion 698 at the distal end of the distal port functions as an interface between the proximal flexible tube and the distal flange.

[0178] Figure 6B provides an end view of the proximal flange 610 of the connector 600. As seen in Figure 6B, the screws 670 are circumferentially positioned around the flange to provide connection to a distal flange (not shown). Also shown are the proximal port 620 and the electrical connector 690 that provide an operable electrical connection to a console assembly (not shown), i.e., to a controller. Figure 6C shows an outside side view of the connector 600, showing the proximal and distal flanges 610, 650 connected together by the screws 670. Also shown is a memory 695, which is electrically coupled to a flexible printed circuit board 697 that is electrically coupled to the electrical connector 690. Similarly, a pressure sensor 625 is electrically coupled to the flexible printed circuit board 697. Figure 6D shows a perspective view of the connector 600.

[0179] Figure 6E provides a view of a connector 600 with an overmold 680 made of a rigid opaque material that functions to protect various components of the connector, such as circuits, sensors, etc. The connector can be connected to a common manifold assembly while the diameter and width can vary to accommodate different types of heart tissue conforming elements. For example, in the case of a peripheral heart tissue conforming element or a coronary heart tissue conforming element, the connector can have dimensions corresponding to a volume change of 1 to 20 mL. In the case of a larger heart tissue conforming element, such as one that includes a valve forming balloon, the connector can be enlarged to accommodate a volume change of up to 50 mL to 100 mL.

[0180] Figure 7 provides a schematic view of an alternative connector 700 configured to deliver large volume, low frequency, and low pressure pulses as described above. Connector 700 includes a barrel syringe 710 having a plunger (i.e., piston) 720 that separates a pneumatic chamber 730 from a fluid chamber 740. The pneumatic chamber 730 includes a pneumatic input port 770 configured to receive energy (i.e., a first pulse energy) in the form of pneumatic pressure from, for example, a manifold assembly (not shown) and transfer such energy to the pneumatic chamber 730. The plunger 720 is configured to translate in response to the pressure applied to the pneumatic chamber 730 and then transfer energy to the fluid chamber 740. The fluid chamber 740 includes a fluid output port 750 operably connected to a catheter (not shown) and configured to transfer energy to the catheter (i.e., its fluid chamber) in response to the movement of the plunger 720 that compresses the fluid chamber 740. Connector 700 further includes a biasing spring 760 configured to urge the plunger 720 back to its starting position when the plunger 720 is moved as described above.

[0181] When the connector contains internal fluid, the connector can be configured to receive fluid through a fluid coupling priming port (not shown). For example, such a fluid port can be connected to the fluid chamber 740 within the connector 700 of FIG. 7. Through such a port, fluids such as radiopaque contrast agents, saline, CO2, etc. can be injected to prime the fluid chamber. Additionally, a vacuum can be applied to such a port so that the connector and the entire system can be evacuated of gas, for example, prior to treatment. The priming port can be closed and sealed so that fluid does not exit the port during treatment.

[0182] Figures 8A - 8C depict a plurality of illustrations of an exemplary embodiment of a heart tissue conforming element 800 according to an embodiment of the present invention that can be used in a system such as system 100 schematically illustrated in FIG. 1. FIG. 8A shows a front view of the heart tissue conforming element 800 (i.e., a view along the longitudinal axis of catheter 899 from the distal region). FIG. 8B shows a side view of the heart tissue conforming element 800 (i.e., a view perpendicular to the longitudinal axis of catheter 899). FIG. 8C shows an isometric view of the heart tissue conforming element 800. In FIGS. 8A - 8C, the heart tissue conforming element 800 includes a single intermediate radius balloon 810 and is attached to the distal catheter perfusion section of catheter 899, i.e., the region near the distal end. The heart tissue conforming element 800 further comprises wing - like balloons 820a, 820b, and 820c configured as cylinders evenly spaced around the circumference of the intermediate radius balloon 810. The wing - like balloons 820a, 820b, and 820c are fluidly coupled to small tubes 830a, 830b, and 830c that extend externally along catheter 899, and pulsatile energy is transmitted from the tubes and applied to the wing - like balloons 820a, 820b, and 820c via the fluid injected into the wing - like balloons 820a, 820b, and 820c. Separate tubes 830a, 830b, and 830c enable the independent inflation of the wing - like balloons 820a, 820b, and 820c, as well as the intermediate radius balloon 810, i.e., to different sizes and at different frequencies and duty cycles. Tubes such as separate tubes 830a, 830b, and 830c included in embodiments of a system such as system 100 can be configured to hold and transmit any type of fluid, such as saline or contrast agent solution. Further, in an embodiment, tubes such as separate tubes 830a, 830b, and 830c can include an optical cable or an electrical cable configured to apply energy to the cardiovascular tissue, such as for generating cavitation bubbles, etc.

[0183] The cardiac tissue conforming element 800 is present on the distal catheter perfusion section 870 of a catheter 899 that includes a perfusion inflow zone 850 and a perfusion outflow zone 860. The perfusion inflow zone 850 and the perfusion outflow zone 860 are configured to enable blood to perfuse beyond the cardiac tissue conforming element 800. The perfusion inflow zone 850 and the perfusion outflow zone 860 include a plurality of ports configured such that blood flows in and out through a fluid passageway (not shown) connecting the perfusion inflow zone 850 to the perfusion outflow zone 860. That is, the cardiac tissue conforming element 800 and / or the catheter 899 includes one or more internal fluid paths (not shown) that fluidly connect the perfusion inflow zone 850, through which blood flows during treatment using the cardiac tissue conforming element 800, to the perfusion outflow zone 860.

[0184] The cardiac tissue conforming element 800 further includes a guidewire inlet port 870 configured to enable a standard guidewire to be screwed into a guidewire exit port (not shown) in a more proximal region of the catheter through a guidewire channel (not shown). The guidewire inlet port 870, along with the guidewire channel and the exit port, facilitate guiding the cardiac tissue conforming element 800 through associated anatomical structures via a standard over-the-wire technique.

[0185] The cardiac tissue conforming element 800 may further include one or more markers (not shown), such as radiopaque markers, present at any convenient location on the cardiac tissue conforming element 800, and the markers are configured to be used, for example, to confirm a desired location and / or orientation or alignment of the cardiac tissue conforming element 800 with respect to cardiovascular tissue, such as diseased cardiovascular tissue. In some cases, such markers may be configured to verify alignment of commissures and alignment with other aspects of cardiac valves.

[0186] In some cases, the configurations of the intermediate radius balloon 810 and the wing balloons 820a, 820b, and 820c can be configured to facilitate a cardiac tissue conforming element 800 that self-aligns, i.e., self-centers, with cardiovascular tissue such as a heart valve. For example, in some cases, an expandable balloon is used for the wing balloons 820a, 820b and 820c, an expandable balloon is used for the intermediate radius balloon 810, and in other cases, an expandable balloon can be used for only one of the wing balloons 820a, 820b and 820c and the intermediate radius balloon 810, or may not be used for either. In such embodiments, the wing balloons 820a, 820b, and 820c can first be inflated, and subsequently, the intermediate radius balloon 810 is inflated, and as the intermediate radius balloon 810 inflates, it automatically centers the wing balloons 820a, 820b, and 820c at the heart valve commissures. In other cases, the order of balloon inflation and / or the use of expandable or non-expandable materials in such balloons can be varied according to the needs or characteristics of the cardiovascular tissue having a disease. In still other cases, the balloons of the cardiac tissue conforming element 800 can be inflated, pulsed, and deflated / nested as follows. First, the intermediate radius balloon 810 can be inflated during diastole. At the same time, the wing balloons 820a, 820b and 820c are also inflated and pulsed during diastole. Thereafter, the intermediate radius balloon 810, as well as the wing balloons 820a, 820b, and 820c, are deflated or nested during systole. Embodiments that utilize such inflation, pulsation, and deflation patterns, i.e., embodiments where different balloons are inflated and / or pulsed and / or deflated at different times, can include a plurality of potential sources, i.e., a plurality of console assemblies, to facilitate such inflation patterns.

[0187] FIG. 9 depicts an exemplary embodiment of a heart tissue conforming element 900 that can be used in a system, such as system 100 schematically illustrated in FIG. 1, according to an embodiment of the present invention. FIG. 9 is a cross-sectional view of a heart tissue conforming element 900 that is similar to heart tissue conforming element 800 but has a different balloon configuration (i.e., a view along the longitudinal axis of heart tissue conforming element 900 as seen from the distal region of catheter 999). In FIG. 9, heart tissue conforming element 900 comprises a plurality of intermediate radius balloons 910a, 910b, 910c, 910d, 910e, and 910f that are circumferentially attached and surround catheter 999. That is, each of intermediate radius balloons 910a, 910b, 910c, 910d, 910e, and 910f is attached, i.e., coupled, to an adjacent intermediate radius balloon and to catheter 999.

[0188] The heart tissue conforming element 900 further includes wing-shaped balloons 920a, 920b, and 920c that are present on the outer surface. The wing-shaped balloons 920a, 920b, and 920c are configured such that their cross-sections are triangular in shape and are evenly spaced around the circumference of the heart tissue conforming element 900, that is, the wing-shaped balloons 920a, 920b, and 920c are configured to engage with a heart valve commissure such as the aortic valve commissure, while the regions of the intermediate radius balloons 910a, 910b, 910c, 910d, 910e, and 910f are configured to engage with a heart valve leaflet such as an aortic valve leaflet. The long sides of the triangular cross-sections of the wing-shaped balloons 920a, 920b, and 920c are each attached to the heart tissue conforming element 900. The heart tissue conforming element 900 further includes an outer sheath (i.e., an outer restraint band) 930 that surrounds and covers the intermediate radius balloons 910a, 910b, 910c, 910d, 910e, and 910f and is configured to maintain a substantially constant configuration of the heart tissue conforming element 900. The wing-shaped balloons 920a, 920b, and 920c are configured such that they are attached to the outer surface of the outer sheath 930. The heart tissue conforming element 900 includes a distal catheter perfusion zone and only the perfusion inflow zone including a plurality of input ports such as its perfusion zone inlet port 950 is depicted in FIG. 9. The perfusion inflow zone including input ports such as the input port 950 is configured such that blood can flow into the heart tissue conforming element 900 and ultimately flow out through a perfusion outflow zone (not shown) on a relatively proximal region of the catheter assembly, that is, the distal blood vessel can be perfused.

[0189] Figure 10 depicts an exemplary balloon pressurization (i.e., inflation / deflation) sequence of a cardiac tissue conforming element based on measured electrocardiogram (ECG) values from a subject being treated using the device of the present invention, i.e., an exemplary balloon pressurization sequence of a cardiac tissue conforming element adjusted using the measured ECG values. Plot 1000 includes an ECG signal 1010 measured from a subject being treated using the device of the present invention. Plot 1000 also includes pressure measurements 1020, 1030 representative of the pressure applied to the balloon of the cardiac tissue conforming element of an exemplary device of the present invention, indicating how pressure was applied at different times and with different amplitudes with respect to the ECG signal 1010. In the example depicted in Figure 10, as shown in Figure 10, for performing a desired treatment using the device of the present invention, the pressures 1020, 1030 are controlled based on the measured values of the ECG signal 1010.

[0190] Pressure signal 1020 indicates the pressure applied to one or more intermediate radius balloons of a cardiac tissue conforming element, such as intermediate radius balloon 810 of cardiac tissue conforming element 800 depicted in Figure 8, or intermediate radius balloons 910a, 910b, 910c, 910d, 910e, and 910f of cardiac tissue conforming element 900 depicted in Figure 9.

[0191] Pressure signal 1030 indicates the pressure applied to one or more wing balloons of a cardiac tissue conforming element, such as wing balloons 820a, 820b, and 820c of cardiac tissue conforming element 800 depicted in Figure 8, or wing balloons 920a, 920b, and 920c of cardiac tissue conforming element 900 depicted in Figure 9.

[0192] The pressure signal 1030 is depicted as a wavy line and a dotted line. The wavy line is used to depict relatively small oscillations over time (i.e., oscillations of relatively high frequency), i.e., relatively small oscillations within relatively long oscillations (i.e., oscillations of relatively low frequency) in which the pressure 1030 cycles between zero and the maximum pressure. The shorter-period oscillations (i.e., oscillations of relatively high frequency) seen in the wavy line of pressure 1030 do not depict large changes in pressure, but in embodiments, any convenient pressure change may be applied. For example, a relatively high-frequency pressure change (i.e., the pressure change represented by a wavy line section of pressure 1030) may cycle between zero and the maximum pressure according to a relatively long oscillation of pressure 1030 (i.e., an oscillation of relatively low frequency), or any range between zero and such maximum pressure.

[0193] With respect to the ECG signal 1010 and the pressure signals 1020, 1030, in each case, the x-axis represents time. With respect to the ECG signal 1010, the y-axis represents the change in potential. With respect to the pressure signals 1020, 1030, the y-axis represents the change in pressure.

[0194] As described above, FIG. 10 shows two phases of the pressure cycles 1020, 1030. As explained above, the pressure 1020 corresponds to the major inflation of one or more intermediate-radius balloons and rises and falls during diastole (starting when the heart is relaxed and then the one or more intermediate-radius balloons deflate before the heart contracts again). As explained above, the pressure 1030 has a jagged edge (i.e., a wavy line) representing a faster ongoing oscillatory wave generated by a secondary structure (e.g., a wing-shaped balloon) attached to one or more intermediate-radius balloons. Applying the pressures 1020, 1030 substantially as shown in FIG. 10 has the effect of better engaging the space between the heart valve leaflets with the heart tissue conforming element and, in some cases, affects the treatment time.

[0195] FIG. 10 shows pressures 1020, 1030 applied during a particular time associated with a particular aspect or feature of an ECG signal 1010, although any convenient adjustment between the pressures 1020, 1030, and the ECG signal 1010 may be applied, and such adjustments may vary, for example, according to the desired treatment applied to the subject or the characteristics of the subject, or any other relevant considerations.

[0196] FIG. 10 shows that the pressures 1020, 1030 are phase-shifted relative to each other for the purpose of better illustrating two pressure curves 1020, 1030. However, any convenient phase (i.e., the time distance between the maxima of the pressure curves 1020, 1030) may be applied. For example, in some cases, the pressures 1020 and 1030 may each reach their maximum pressure simultaneously. In other cases, pressure 1020 may reach its maximum pressure at the same time that pressure 1030 is at its minimum pressure, e.g., zero pressure. In still other cases, pressure 1030 may reach its maximum pressure at the same time that pressure 1020 is at its minimum pressure, e.g., zero pressure. Similarly, the pressures 1020, 1030 may exhibit the same frequency (i.e., with respect to the lower frequency of pressure 1030 shown in FIG. 10) or different frequencies, as desired, and may be controlled separately and independently using the same or different potential sources and / or oscillators, as desired, to achieve the desired relative characteristics of the pressures 1020, 1030.

[0197] Figures 11A - 11D depict multiple views of an alternative radially - member - based embodiment of the heart tissue conforming element 1100. Figure 11A shows an isometric view of the heart tissue conforming element 1100. Figure 11B shows a top view of the heart tissue conforming element 1100 (i.e., a view along the longitudinal axis of the catheter 1199 from the proximal region). Figure 11C shows a bottom view of the heart tissue conforming element 1100 (i.e., a view along the longitudinal axis of the catheter 1199 from the distal region). Figure 11D shows a side view of the heart tissue conforming element 1100. In Figures 11A - 11D, the heart tissue conforming element includes radial members 1110a, 1110b, and 1110c, and the heart tissue conforming element 1100 is attached in the distal region near the distal end of the catheter 1199. In Figures 11A - 11D, the heart tissue conforming element 1100 is shown engaging a heart valve leaflet 1150 having heart vascular tissue, i.e., calcification, i.e., calcium deposits 1155.

[0198] The heart tissue conforming element 1100 depicted in Figures 11A - 11D comprises radial members 1110a and 1110b which are eccentric balloons located at a relatively proximal location on the catheter 1199, i.e., at substantially the same distance from the distal end of the catheter 1199. The heart tissue conforming element 1100 shown in Figures 11A - 11D includes two such radial members 1110a and 1110b, although other embodiments may comprise one or more than three such radial members. When the balloons comprising the radial members 1110a and 1110b are inflated, the distal ends of the radial members 1110a and 1110b extend to the side of the leaflet 1150, i.e., the aortic side of the leaflet 1150. The radial members 1110a and 1110b comprising the balloons are configured to be inflated so as to exert a significant resistance force on the upper (i.e., proximal side) of the valve leaflet 1150.

[0199] The heart tissue conforming element 1100 depicted in FIGS. 11A-11D further comprises a radial member 1110c which is an eccentric balloon attached at a relatively distal location of the catheter 1199. The heart tissue conforming element 1100 shown in FIGS. 11A-11D includes one such radial member 1110c, although other embodiments may comprise one or more such radial members. The proximal end of the radial member 1110c with the balloon, when inflated, engages, for example, the left ventricular side of the heart valve leaflet 1150. FIGS. 11B and 11C depict how the radial member 1110c is positioned at a location that substantially bisects the angle formed between the radial member 1110a and the radial member 1110b. The port hole 1190a includes a fluid connection between the fluid passage of the catheter 1199 and the balloons of the radial members 1110a and 1110b, such that fluid can be moved to the balloons of the radial members 1110a and 1110b, including expanding the radial members 1110a and 1110b and applying pulsatile energy to the cardiovascular tissue. The port hole 1190b includes a fluid connection between the fluid passage of the catheter 1199 and the balloon of the radial member 1110c, thereby enabling fluid to be moved to the balloon of the radial member 1110c, including causing expansion of the radial member 1110c for applying pulsatile energy to the cardiovascular tissue.

[0200] When the balloons of the radial members 1110a, 1110b, and 1110c are inflated, such balloons act to create a three-point bending state in which the heart valve leaflet 1150 and the embedded calcium 1155 are bent, compressed, or pulled. That is, the leaflet 1150 is pushed proximally by the inflation of the radial member 1110c and simultaneously pushed distally by the inflation of the radial members 1110a and 1110b. Sustained pressure and / or pulsatile pressure can be applied to the balloons of the radial members 1110a, 1110b, and 1110c to controllably disrupt the internal calcium 1155 of the leaflet 1150.

[0201] In a particular example, the radial member 1110c with a distal eccentric balloon can be attached to the inner shaft 1160 of a catheter 1199 configured to translate axially (i.e., translate along the long access of the catheter 1199). When the radial member 1110c is translated in the proximal direction, the distal eccentric balloon of the radial member 1110c can further wrap around or surround or engage the valve tip 1150 (i.e., the distal side of the valve tip 1150) so that a secure connection can be made between the proximal eccentric balloon and the distal eccentric balloon, i.e., between the radial members 1110a, 1110b and the radial member 1110c.

[0202] In some examples, for instance, a portion of a radial member comprising a balloon, such as radial members 1110a, 1110b, or 1110c that contact a heart valve, such as heart valve leaflet 1150 of a cardiovascular tissue, may be stretchable or semi-stretchable to cause the balloon to expand against the leaflet, for example, by applying an increased pressure to the balloon. This additional expansion, for example, increases the force applied to the heart valve leaflet in a bent configuration, and this force increases the ability to break internal calcifications, such as calcification 1155 of a heart valve, such as heart valve leaflet 1150 of a cardiovascular tissue. In other examples, for instance, a portion of a radial member comprising a balloon, such as radial members 1110a, 1110b, or 1110c that contact a heart valve, such as heart valve leaflet 1150 of a cardiovascular tissue, may be configured to have raised or cut or scored elements such that when contacting the cardiovascular tissue, such as heart valve leaflet 1150, the ends of these features cause stress concentration in the calcium of the cardiovascular tissue, such as heart valve leaflet 1150. Such stress concentration may function to reduce the pressure that needs to be applied to the balloon of the radial member while causing an increase in calcium destruction. Similarly, a portion of the balloon of a radial member that contacts a cardiovascular tissue, such as the proximal or distal side of radial members 1110a, 1110b, and 1110c that contact heart valve leaflet 1150, may be configured to elute an active agent, such as a drug, such that when contacting the cardiovascular tissue, the active agent is eluted onto the heart valve leaflet to minimize restenosis and extend the lifespan of valve treatment.

[0203] In other embodiments, various numbers of radial members may be positioned around the axis of a catheter, such as catheter 1199, such that the heart tissue conforming element is configured to treat one or more heart valve leaflets simultaneously. In the former example, i.e., when the heart valve conforming element is configured to treat one heart valve leaflet at a time, blood can still perfuse through the heart valve via the other side of the catheter, e.g., the side of the catheter opposite the radial members, thereby potentially extending the treatment time. In the latter example, i.e., when the heart valve conforming element is configured to treat two or more heart valve leaflets at a time, such a configuration may restrict blood to a greater extent than when the heart valve conforming element is configured to treat one heart valve leaflet at a time.

[0204] In some embodiments, a catheter, such as catheter 1199, may include a port (not shown) configured to apply a vacuum to an area near the cardiovascular tissue to engage the cardiovascular tissue and hold it in place at the leaflet during treatment.

[0205] In some examples, the surface of a radial member or its balloon that contacts cardiovascular tissue, such as a heart valve leaflet, is shaped, for example, according to the profile of the heart valve leaflet. For example, the surface of a radial member or its balloon that contacts cardiovascular tissue may be shaped such that they are convex on the aortic side and concave on the ventricular side. For example, the distal surfaces (i.e., the surfaces that contact leaflet 1150) of radial members 1110a and 1110b may be substantially concave, while the distal surface (i.e., the surface that contacts leaflet 1150) of radial member 1110c may be substantially convex.

[0206] Figures 12A and 12B depict cross-sectional views of heart valves, such as heart valves that can be treated using embodiments of the present invention. Figures 12A and 12B depict the tricuspid valve 1210, as well as the mitral valve or bicuspid valve 1220. The mitral valve is an example of a mitral valve or bicuspid valve. As described herein, some embodiments of the heart tissue conforming element according to the present invention can be adjusted for the treatment of a tricuspid valve, such as the tricuspid valve 1210, while other embodiments of the heart tissue conforming element according to the present invention can be adjusted for the treatment of a bicuspid valve, such as the bicuspid valve 1210. For example, in some cases, when the mitral valve or bicuspid valve is treated with a heart tissue conforming element that is wider in one dimension compared to the circular cross-section of the heart tissue conforming element, i.e., a heart tissue conforming element having an elliptical cross-section or a circular cross-section of a heart tissue conforming element having an oval cross-section (or one or more intermediate radius balloons of the heart tissue conforming element), better results are achieved using such a valve.

[0207] Figures 13A - 13C depict embodiments of a heart tissue conforming element having a cross-sectional shape that is wider in one dimension compared to the circular cross-sectional shape of the heart tissue conforming element. The heart tissue conforming element 1300a of Figure 13A is shown in cross-section. The heart tissue conforming element 1300a comprises a substantially elliptical or oval intermediate radius balloon 1310 formed using wing-shaped balloons 1320 attached to both ends of the intermediate radius balloon 1310. The intermediate radius balloon 1310 has an outward expansion and can be inflated and deflated, i.e., pulsed, at a specific frequency (i.e., the intermediate radius balloon 1310 can have pulsatility at a specific frequency), and the wing-shaped balloons 1320 on the side surface of the heart tissue conforming element can be inflated and deflated, i.e., pulsed, at a different or the same frequency. The heart tissue conforming element 1300a preferentially expands along the natural commissure of the valve (i.e., a mitral valve or bicuspid valve such as the bicuspid valve 1210 depicted in Figure 12B) and has a cross-sectional shape that expands along the natural healing line compared to embodiments of a heart tissue conforming element (or its balloon) that expands equally in all directions. The center of the heart tissue conforming element 1300a comprises, for example, a wire channel 1350 for use with a guide wire.

[0208] Figure 13B presents another embodiment of a heart tissue conforming element 1300b having a cross-sectional shape configured for use with a mitral or bicuspid valve such as the bicuspid valve 1210 depicted in Figure 12B. Aspects of the heart tissue conforming element 1300b that are the same as those of the heart tissue conforming element 1300a are not repeated here. The heart tissue conforming element 1300b includes an additional wing-shaped balloon 1330 present on an oval or relatively elongated side of the heart tissue conforming element 1300b. The additional wing-shaped balloon 1330 can be pulsated at the same or a different frequency than the intermediate radius balloon 1310 and the wing-shaped balloon 1320.

[0209] Figure 13C presents another embodiment of a heart tissue conforming element 1300c having a cross-sectional shape configured for use with a mitral or bicuspid valve such as the bicuspid valve 1210 depicted in Figure 12B. Aspects of the heart tissue conforming element 1300c that are the same as those of the heart tissue conforming elements 1300a and 1300b are not repeated here. The heart tissue conforming element 1300c includes a perfusion zone 1340 (or perfusion path or central channel) that is part of the perfusion mechanism of the heart tissue conforming element 1300c, and includes a wire cage that maintains the shape of the perfusion zone 1340 (i.e., keeps the perfusion zone 1340 open) even when the intermediate radius balloon 1310 is pressurized and expanded during treatment. The perfusion zone 1340 is used to enable fluid, i.e., blood, to perfuse across the heart tissue conforming element 1300c during treatment, and the cage of the perfusion zone 1340 maintains the structural stability of the opening and prevents the perfusion zone 1340 from collapsing even when the intermediate radius balloon 1310 is pressurized. The perfusion zone 1340 is shown in the cross-sectional view of Figure 13C such that the inflow and outflow paths are not depicted in the figure, but those paths are fluidly interconnected via the cross-sectional path shown in Figure 13C.

[0210] Figure 14A illustrates a passive perfusion mechanism 1400 across a heart tissue conforming element 1450, and perfusion occurs from a predominantly relatively high-pressure ventricular region (P 高 ) and a predominantly relatively low-pressure aortic region (P 低)enabled by. The relatively high-pressure ventricular region pumps blood into the perfusion inflow zone 1410 with a plurality of ports, and through the cardiac tissue conforming element 1450, out through the outer perfusion outflow zone 1420 with a plurality of ports via a fluid channel (not shown).

[0211] FIG. 14B illustrates an active perfusion mechanism 1405 across the cardiac tissue conforming element 1450, and perfusion is facilitated by a perfusion pump 1430 configured to draw blood from the perfusion inflow zone 1410 with a plurality of ports and push it into the perfusion outflow zone 1420 with a plurality of ports. The perfusion pump 1430 utilizes the continuous reciprocating motion of a barrel-shaped syringe connector to draw fluid, i.e., blood, from the perfusion inflow zone 1410 and push it out from the perfusion outlet port 1420.

[0212] FIG. 15 depicts a control loop schematic for controlling a procedure for treating diseased cardiovascular tissue, such as a valve having a disease, using an embodiment of the present invention. In this embodiment, the controller includes a treatment plan supplied to the controller subsystem as an input. The controller subsystem sends a signal, such as in the form of a voltage or data, to a potential source (regulated or unregulated) to control the amount of potential output by the potential source to an oscillator. The controller subsystem also sends signals such as the frequency (f), i.e., the oscillation frequency, and the duty cycle (t オン and t オフ ) to the oscillator to control the periodic energy transmitted by the oscillator. A feed-forward model of an individual subsystem (e.g., the console assembly, the manifold assembly, the catheter assembly) or the entire system can be injected into the controller signal (i.e., the controller signal can be enhanced with such data regarding the feed-forward model) to improve the convergence of the controller (i.e., the control algorithm) to the correctly supplied energy.

[0213] Therapeutic energy (i.e., potential energy) is transmitted to the oscillator, and a sensor can be used to track the magnitude of the potential energy transmitted to the oscillator. The sensor signal can be fed back to the controller such that it can be used to converge the output of the system (i.e., the pulsatile energy applied to the cardiovascular tissue) to a desired output. The oscillator is turned on and off at an appropriate frequency and duty cycle such that energy is transmitted to the distal location (i.e., the cardiac tissue conforming element and ultimately the cardiovascular tissue) in an appropriate manner, taking into account any attenuation, heat conduction, bubble formation, tissue relaxation, etc. The sensor measures system attributes as well as characteristics of the cardiovascular tissue such as pressure, volume, temperature, flow rate, etc. Sensor data from the catheter assembly is fed back to the controller such that such measurements can be used to converge the output of the system (i.e., the pulsatile energy applied to the cardiovascular tissue) to a desired output. The catheter assembly sensor can be located at any convenient location of the catheter assembly that can be configured to generate appropriate measurements that can be used to control the system. For example, the sensor can be a pressure sensor or a volume sensor located on the connector. In other examples, such a sensor can be a sensor located within the catheter or the cardiac tissue conforming element (e.g., within the balloon of the cardiac tissue conforming element) and is connected to a wire configured to pass through the catheter. In other cases, such a sensor can include an X-ray image of the cardiac tissue conforming element, which is used to determine the position or expansion of one or more balloons of the cardiac tissue conforming element.

[0214] A catheter assembly may comprise one or more sensors configured to measure information at one location, as means for determining a state at another location. For example, pressure and flow transducers may be configured to measure pressure and flow at a connector, but sensor data may be used, for example, in combination with a fluid model of the system and X-ray or CT imaging, to measure the pressure and / or volume of a balloon of a heart tissue conforming element. Additionally, sensor data may be provided to a clinician feedback transfer function, and such sensor feedback may be combined with feedback generated from potential conduction mapping or imaging data and provided to a feedback mechanism plant for providing feedback regarding system behavior to a provider, i.e., an operator of the system, for processing.

[0215] In other examples, pressure and flow sensors may be used to measure the distensibility or change in distensibility of a balloon of a heart tissue conforming element. Considering that diseased tissue resists balloon expansion, the amount of volume forced into the balloon at a particular pressure is an indirect indicator of the distensibility of the surrounding tissue. In this way, a measure of distensibility or change in distensibility may be used as a treatment metric or goal.

[0216] FIG. 16 depicts a schematic diagram of a system configuration 1600 of a robotic method for delivering treatment energy from a control room to a diseased valve. As described above, embodiments of the system may be divided into a physically separated control room 1610 and a treatment location 1620, and the treatment location 1620 may be separated, for example, into an adjacent room or a different city or state or country.

[0217] The control room 1610 may include a console display, an imaging display, a treatment controller, a device position controller, patient information, and a connection to a treatment database. The console display may be used to provide important information regarding the state of the system related to an ongoing treatment, such as pressure or volume measurements, or other information regarding heart tissue conforming elements, such as the type of heart tissue conforming elements being used. The information provided on the console display may be updated periodically, for example, substantially in real-time during the treatment. The imaging display may be used to provide imaging information, such as fluoroscopy imaging results, indicating the position of the heart tissue conforming elements with respect to heart tissue, such as a heart valve. The fluoroscopy imaging results may also provide information regarding the state of the aspect of the heart tissue conforming elements, such as whether a balloon is inflated and to what extent. The treatment controller may be used to adjust the manner in which the system is applied, for example, to apply pulsatile energy to cardiovascular tissue, such as by adjusting pressure or frequency or duty cycle settings. The device position controller may be used to adjust the position of the device with respect to the cardiovascular tissue being treated, for example, to adjust the catheter position to move the heart tissue conforming element more proximally or distally. The patient information may include a display of any important patient data related to the treatment, such as information regarding the treatment site, the patient's age, disease state, vital measurements such as blood pressure or pulse oximeter measurements. The treatment database may include information regarding past treatment plans (i.e., information related to the system configuration for treating cardiovascular tissue, such as oscillation frequency, duty cycle, and / or amplitude, and corresponding details regarding the underlying cardiovascular tissue, such as the degree of calcification), and this information may be accessed to identify potential treatment plans related to a new treatment.

[0218] The treatment location 1620 may comprise an embodiment of a system according to the present invention, namely a console assembly having a potential source, a manifold assembly, and a catheter assembly, the catheter assembly including a connector, a connector-to-catheter transition hub, a catheter, and a heart tissue conforming element. The treatment room 1620 can be, for example, a treatment room or an operating room. Any convenient operative connection capable of transmitting data and control signals between the treatment room 1620 and the control room 1610 can be used, such as a wired connection or a wireless connection.

[0219] Measurement value of extensibility As will be described in detail below, tissue extensibility, for example, cardiovascular tissue or blood vessels, is a measurable property of blood vessels or cardiovascular tissue, such as cardiovascular tissue including heart valves, and is calculated based on the ratio of the change in tissue volume to a given pressure change. Improving vascular extensibility is a prerequisite for definitive treatment of certain underlying disease states, such as atherosclerosis, the presence of calcifications in cardiovascular tissue, and thus vascular extensibility is an important feature to be observed. Changes in vascular extensibility are seen in the different pressure-volume curves depicted in FIG. 17. In FIG. 17, volume is plotted on the x-axis and pressure is plotted on the y-axis. A comparison is shown between pressure-volume, i.e., an uninhibited balloon (i.e., a balloon that does not exist within the cardiovascular tissue or, otherwise, is inhibited from expanding its volume with an increase in balloon pressure), and untreated (i.e., pre-treatment) cardiovascular tissue, i.e., untreated blood vessels, and treated (i.e., post-treatment) cardiovascular tissue, i.e., treated blood vessels.

[0220] As shown in FIG. 17, when treating using an embodiment of the system of the present invention, for example, applying pulsatile energy to cardiovascular tissue, the pressure-volume curve shifts to the right, i.e., shifts closer to the curve of the uninhibited balloon. That is, during treatment, the same change in tissue volume corresponds to a reduced tissue pressure, i.e., less pressure needs to be applied to the tissue to expand the tissue volume by a similar amount.

[0221] The system according to the present invention can be configured to evaluate the distensibility of blood vessels by obtaining in vivo measurements of volume changes at different pressures (or different changes in pressure) applied to cardiovascular tissues such as blood vessels. FIGS. 18A and 18B provide examples of measurements of changes in tissue distensibility obtained during treatment using the system according to the present invention, i.e., during pulsatile lithotripsy within a heart valve. FIG. 18A demonstrates obtaining measurements of tissue distensibility, i.e., the pressure applied to the tissue and the corresponding changes in volume over time, using dynamic changes in pressure. FIG. 18A shows that the trend of peak volume change is upward while the peak applied pressure remains constant. That is, as the treatment progresses, while the same change in pressure is applied, the tissue volume increases to a greater extent, and an indicator of improved tissue distensibility is obtained.

[0222] FIG. 18B shows obtaining measurements of tissue distensibility, i.e., the pressure applied to the tissue and the corresponding changes in volume over time, using both dynamic changes in pressure and static pressure (i.e., in the third pressure oscillation, the pressure applied to the tissue remains for approximately half of the period). FIG. 18B shows that the trend of peak volume change is upward while the peak applied pressure remains constant. That is, as the treatment progresses, while the same change in pressure is applied, the tissue volume increases to a greater extent, and an indicator of improved tissue distensibility is obtained.

[0223] Embodiments of the present invention enable measurement of relative extensibility changes of cardiovascular tissue (i.e., blood vessels) in real time while applying the system of the present invention to provide pulsatile energy to the cardiovascular tissue. The system of the present invention can be configured to measure and update treatment parameters based on changes in the extensibility of the blood vessels. For example, after calcium cracking (i.e., fragmentation of calcified plaque tissue), as measured by the system, the cardiovascular tissue and the heart tissue conforming element or its balloon expand significantly, contributing to a large gain in extensibility. However, after the blood vessels are fully expanded, the change in extensibility measured by the system may subside. Identification of such a state (i.e., the extensibility changes to a different degree) may indicate that treatment can be stopped as no further gain is occurring.

[0224] The system can be configured to measure pressure in any convenient manner. In some examples, embodiments of the system according to the present invention can include a pressure gauge as described herein for measuring, for example, the pressure within the fluid passageway and / or balloon of the heart tissue conforming element or catheter assembly. In some examples, the pressure gauge can be positioned to measure the pressure in the distal chamber of the proximal connector, as seen, for example, in pressure transducer 625 of FIG. 6A.

[0225] The system can be configured to measure changes in cardiovascular tissue, such as the volume of a blood vessel, in any convenient manner. In some examples, embodiments of the system according to the present invention are configured such that a change in the position of a membrane (such as membrane 630 in FIG. 6A) separating the proximal and distal chambers of a connector (such as connector 600 in FIG. 6A) reflects a change in the aspect of the heart tissue conforming element, such as a change in the volume of a balloon. The change in the volume of the balloon reflects a change in the cross-sectional area of the cardiovascular tissue, such as a blood vessel, and thus reflects a change in the volume of the cardiovascular tissue. Such embodiments may further include a Hall sensor for measuring such a change in the position of such a membrane and one or more permanent magnets. A Hall sensor refers to a sensor configured to sense the presence or change of a magnetic field, i.e., by using the Hall effect. The permanent magnet can be composed of any convenient magnetic material or an electromagnet, as desired, such that a relative change in the position of the Hall sensor with respect to the permanent magnet is detected by the Hall sensor. Sensors such as the above-described Hall sensor and permanent magnets can be used to measure changes in the volume of the heart tissue conforming element, or one or more of its balloons, and aspects of the heart tissue conforming element, such as the rate at which one or more of its balloons expand, i.e., the rate of change of the cardiovascular tissue volume, and the corresponding change in extensibility.

[0226] Method A method of imparting pulsatile energy to cardiovascular tissue is also provided, which similarly provides advantages in the applications described above. The method according to the present invention includes deploying the system such that the heart tissue conforming element of the system is adjacent to the cardiovascular tissue. Such a system includes a console assembly having a potential source, and a manifold assembly operably connected to the output of the console assembly, the manifold assembly comprising an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, a catheter assembly operably connected to the output of the manifold assembly, the catheter assembly comprising a connector configured to operably connect the catheter assembly to the manifold assembly and convert the first pulsed energy generated by the manifold assembly into a second pulsed energy, a catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy, and a heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to the cardiovascular tissue. Such components of the system have been described in detail above. The method according to the present invention further includes engaging the system in such a manner that the heart tissue conforming element imparts energy to the cardiovascular tissue. "Imparting energy to the cardiovascular tissue" means that the heart tissue conforming element applies pulsatile energy, i.e., energy sufficient to split the calcium layer, to the cardiovascular tissue. For example, the heart tissue conforming element may be configured to engage a desired feature of the cardiovascular tissue, and aspects of the heart tissue conforming element, such as the balloon constituting the heart tissue conforming element, are repeatedly inflated and deflated as described in detail above in connection with embodiments of the system of the present invention. The system may be configured such that different types and degrees of energy are applied between different aspects of the cardiovascular tissue, such as between the heart valve leaflet and the heart valve commissure. Any suitable frequency of inflation and deflation may be used and may vary.In embodiments where the heart tissue conforming element comprises a plurality of balloons (or other movable members for imparting pulsatile energy to cardiovascular tissue), the frequency of inflation and deflation, as well as the amplitude and duty cycle, may vary between such balloons or other movable members.

[0227] In embodiments, engaging the system in a manner such that the heart tissue conforming element imparts energy to cardiovascular tissue includes, for example, imparting energy to heart valve tissue such as heart valve leaflets, commissures of heart valves, nodules of heart valve leaflets, or annuli of heart valves. For example, in embodiments, engaging the system in a manner such that the heart tissue conforming element imparts energy to cardiovascular tissue includes, for example, imparting energy to the aortic valve such as aortic valve leaflets, commissures of the aortic valve, or annulus of the aortic valve. In other embodiments, engaging the system in a manner such that the heart tissue conforming element imparts energy to cardiovascular tissue includes imparting energy to cardiovascular tissue including tissue that supports the heart valve. In still other embodiments, engaging the system in a manner such that the heart tissue conforming element imparts energy to cardiovascular tissue includes imparting energy to the atrial septum or ventricular septum. In such embodiments, the heart tissue conforming element may be configured such that when the heart tissue conforming element receives the second pulsed energy transmitted through the fluid passage of the catheter, the feature of the heart tissue conforming element mainly applies pulsatile energy to a specific region of the cardiovascular tissue. For example, an embodiment of the heart tissue conforming element may be configured such that the balloon engages the commissure of the heart valve, and the energy applied to the heart tissue conforming element may be configured to be transmitted to the commissure of the heart valve.

[0228] The system can be configured such that the heart tissue conforming element applies different forms or degrees or types of energy to different aspects of the cardiovascular tissue. For example, the heart tissue conforming element can be configured such that the valve commissure receives pulsatile energy at a first frequency, magnitude, duty cycle, and / or duration, and the valve leaflet receives pulsatile energy at a second frequency, magnitude, duty cycle, and / or duration. That is, applying the system of the present invention to treat the cardiovascular tissue can include treating different aspects of the cardiovascular tissue differently.

[0229] In an embodiment, engaging the system in a manner such that the heart tissue conforming element imparts energy to the cardiovascular tissue includes engaging the system in a manner that allows fluid to pass beyond the distal region of the system. "Fluid flowing beyond the distal region of the system" means that the fluid can be moved from a relatively distal region of the system, for example, distal to the heart tissue conforming element, to a relatively proximal region of the system, for example, proximal to the heart tissue conforming element. In such an embodiment, engaging the system allows the heart tissue conforming element to impart energy to the cardiovascular tissue while at the same time allowing fluid, such as blood, to perfuse beyond the heart tissue conforming element.

[0230] In some embodiments, engaging the system in a manner that the cardiac tissue conforming element imparts energy to the cardiovascular tissue includes engaging the system in a manner that mimics cardiac valve function. That is, in an embodiment, engaging the system can cause the region of the cardiovascular tissue to be substantially sealed, closed, or blocked in the same way that a functioning cardiac valve substantially seals, closes, or blocks that region of the cardiovascular tissue against the flow of a fluid, e.g., blood. In some embodiments, engaging the system causes the cardiac tissue conforming element to operate substantially as a cardiac valve, e.g., while the system is being used to apply energy to the cardiovascular tissue such as a cardiac valve. In some cases, engaging the system in a manner that the cardiac tissue conforming element imparts energy to the cardiovascular tissue includes engaging the system in a manner that is synchronized with the results of an electrocardiogram. For example, in such a case, the cardiac tissue conforming element is configured to behave substantially as a cardiac valve by sealing or closing or blocking the region of the cardiovascular tissue at a rate determined by the results of the electrocardiogram.

[0231] In other embodiments, engaging the system in a manner such that the heart tissue conforming element imparts energy to the cardiovascular tissue includes adjusting the configuration of the system based on treatment-based feedback. For example, any desired treatment-based feedback can be applied, such as the results of sensors deployed on the system, including pressure sensors or volume sensors that measure the fluid pressure applied to the balloon or the change in fluid volume of the fluid used to inflate the balloon. In some embodiments, "adjusting the configuration of the system" means adjusting one or more of the fluid pressure or volume, the frequency or duty cycle of the energy applied to the cardiovascular tissue, i.e., the frequency or duty cycle of the oscillator. In one embodiment, a method of imparting pulsatile energy to cardiovascular tissue is a method for treating cardiovascular tissue, such as a valve having a disease, that depends on the feedback received during a therapeutic treatment. Such a method may depend on capturing data from internal pressure and volume sensors during treatment such that valve extensibility can be measured before, during, and after treatment. In addition to internal sensors, external sensors such as pressure transducers, imaging, temperature sensors, etc. may be utilized. Further, the sensors can be provided such that they are integrated together to operate at various frequencies and provide information. In addition to feedback sensors, feedforward information, such as a model of the physical characteristics of embodiments of the system of the present invention, can be supplied to a feedforward system. Such a feedforward system enables further control of the system through enhanced modeling of the system in combination with feedback sensors.

[0232] During treatment by the method of the present invention, information from various internal and / or external sensors of the system can be read, stored, and / or analyzed by the system, or such data can be transmitted outside the system for analysis at another location, such as a cloud cluster. In other examples, the system can be configured to transmit such data, e.g., sensor data, via a learning algorithm to compare with other examples that have encountered similar and / or equivalent treatment scenarios.

[0233] In embodiments, deploying the system such that the heart tissue conforming element of the system is adjacent to the cardiovascular tissue includes aligning the heart tissue conforming element with a feature of the cardiovascular tissue. In some cases, the heart tissue conforming element is configured to align with a particular feature of the cardiovascular tissue, i.e., to align with, engage with, or hold a fixed position relative to the feature of the cardiovascular tissue, by including passive or active elements configured to do so. In some cases, the order in which the balloons of the heart tissue conforming element are inflated facilitates aligning the heart tissue conforming element as desired, e.g., such that an outer balloon aligns with a commissure of a heart valve. For example, one or more outer balloons, such as winged balloons, can be inflated prior to inflating an intermediate radius balloon to align the heart tissue conforming element as desired, e.g., relative to a valve commissure. In some cases, the heart tissue conforming element includes lobes for engaging a feature of the cardiovascular tissue, and deploying the system includes aligning the lobes with the feature of the cardiovascular tissue. In other embodiments, deploying the system such that the heart tissue conforming element is adjacent to the cardiovascular tissue includes aligning the heart tissue conforming element with a heart valve commissure or a heart valve leaflet. Utilizing an active alignment feature includes pulsating a balloon in a manner that promotes seating of a winged balloon, for example, on the outer surface of a heart tissue conforming element, on a commissure, thereby aligning the heart tissue conforming element relative to the heart valve.

[0234] In some cases, the method according to the present invention is a method of preparing cardiovascular tissue for a heart valve replacement procedure or the implantation of an artificial heart valve. That is, preparing tissue for a replacement heart valve can include disrupting calcium deposits within the cardiovascular tissue or affecting tissue extensibility prior to implanting the heart valve. In other cases, the method is a method of delivering an active agent to the cardiovascular tissue or surrounding tissue. For example, the active agent can be present on the outer surface of the heart tissue conforming element such that pulsating the balloon of the heart tissue conforming element causes the active agent to dissolve and flow into the cardiovascular tissue.

[0235] In some examples, a method of imparting pulsatile energy to cardiovascular tissue further includes aligning a catheter assembly, such as a heart tissue conforming element, with the cardiovascular tissue, such as a heart valve or cardiovascular tissue having a disease, or another treatment site, using imaging technology. Any convenient imaging technology that can visualize the configuration of a catheter present in a lumen, such as the system according to the present invention, can be applied. The imaging technology can include, for example, ultrasonic imaging such as intravascular ultrasound technology, light-based imaging technology, angioplasty-based imaging technology, or optical coherence tomography technology. In some cases, X-ray radiography can be applied.

[0236] As described above, the method of imparting pulsatile energy to cardiovascular tissue of the present invention can include a method for treating cardiovascular diseases. In some cases, the method is a method for treating atherosclerosis, which means thickening and hardening of the arterial wall. In some cases, the method of imparting pulsatile energy to cardiovascular tissue of the present invention includes a method of imparting pulsatile energy to a subject's cardiovascular tissue. The system can be used to impart pulsatile energy to any number of different subject's cardiovascular tissues. In many embodiments, the subject is a "mammal" or "mammalian", and these terms are used to broadly describe organisms within mammals, including carnivores (e.g., dogs and cats), rodents (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In some examples, the subject is a human. For example, in some cases, the method of the present invention is a method for treating atherosclerosis in a human subject.

[0237] Figure 19 shows a graphical user interface (GUI) with which an operator of the system of the present invention can interact during a treatment procedure that includes imparting pulsatile energy to a heart valve in accordance with an embodiment of the method of the present invention. In this embodiment, the GUI may have several information zones, such as a fluoroscopy zone, a balloon information zone, a treatment information zone, and a stretchability zone. The fluoroscopy zone presents imaging results of the heart tissue conforming element and the associated cardiovascular tissue of the heart, i.e., the heart valve. Such imaging shows the interaction between the heart tissue conforming element and the heart valve, i.e., the engagement, e.g., whether the heart tissue conforming element is aligned with the heart valve as desired, and whether the balloon of the heart tissue conforming element is inflated and to what extent, and how the corresponding cardiovascular tissue is responding. The balloon information zone shows information regarding the heart tissue conforming element attached to the catheter or one or more of its balloons. Such information includes, for example, the type and size of the device referring to the heart tissue conforming element or its components. Additional information that may be displayed includes other characteristics such as the diameter, length, nominal pressure, rated pressure of the heart tissue conforming element (or its balloon), and other aspects of the balloon coated with a drug or covered with a stent or the heart tissue conforming element. In addition, heart tissue conforming element catheter connection information (i.e., whether the heart tissue conforming element is connected) may be included in this section. The treatment characteristics zone shows important treatment characteristics that the operator uses during the procedure. Such characteristics include the diameter and area of the heart valve and the valve pressure gradient, i.e., the pressure difference across the heart valve. Other characteristics may be related to measurements indicating the extent of blood that can be perfused into the distal blood vessel beyond the heart tissue conforming element. Some or all of this information may be updated or changed by the system and / or by the user as appropriate. In the stretchability zone, various treatment plots may be displayed, including a stretchability plot and a treatment plot. The stretchability plot may include a nominal pressure - volume curve that may be provided with the heart tissue conforming element (or its balloon). Further, a pressure - volume curve measured in situ during the procedure can be plotted and updated throughout the procedure.The operator can use this plot to determine the treatment effect as a measure of extensibility or effectiveness. The pressure plot may include a display of pressure versus time. Other information that may be included in the GUI (not shown) includes treatment status and intensity, on / off switch, indicator LED, and the like.

[0238] Kit Also provided is a kit, for example, that includes the system, or one or more components thereof, as described above. Thus, the kit may, in some instances, include one or more of a catheter assembly, a manifold assembly, a console assembly, regardless of the presence or absence of a potential energy source, e.g., a pressure source, or its components. The kit components may be present within a package, which may be sterilized as desired. The components of the kit may be disposable or reusable as desired. In some cases, the kit may include multiple components of the same component in different versions, such as multiple catheters of varying diameters, or different sized heart tissue conforming elements configured for different aspects of cardiovascular tissue, such as heart valves.

[0239] The kit may also include instructions for using the kit components. The instructions may be recorded on a suitable recording medium. For example, the instructions may be printed on a substrate such as paper or plastic. Thus, the instructions may be present within the kit as a package insert, or on the labeling of the kit or the container of its components (i.e., associated with the package or sub-package). In other embodiments, the instructions are present as an electronic memory data file on a suitable computer-readable storage medium, such as a portable flash drive, DVD, or CD-ROM. The instructions can take any form, including a complete set of instructions on how to use the device, or a website address that provides access to instructions posted on the World Wide Web.

[0240] The following examples are provided by way of illustration and not by way of limitation.

Example

[0241] FIG. 20 provides a view of an aspect of a catheter assembly of a system according to an embodiment of the present invention. FIG. 21 shows an assembly process for a connector of the catheter assembly shown in FIG. 20. The first step of the assembly process is to secure an electronic flexible printed circuit board assembly to a diaphragm and a pressure sensor. For example, epoxy and solder can be used, respectively. The pressure sensor and the diaphragm can be secured to the distal flange. Using appropriate fastening techniques (e.g., fasteners, welding, etc.), the proximal flange can be secured to the distal flange. The electronic connector can be secured to the front surface of the proximal flange using epoxy, for example, to provide a reliable connection to a handheld actuator. FIG. 22 represents a test performed on a single balloon of the described embodiment and physical assembly. It is shown that as the pressure increases, the force in the balloon also increases. The forces generated during vibration are consistent with the forces generated during static inflation and exhibit minimal attenuation by the system during pulsation.

[0242] Notwithstanding the appended claims, the present disclosure is also defined by the following appendices. 1. A system for imparting pulsatile energy to cardiovascular tissue, the system comprising (a) a console assembly comprising a potential source, and (b) a manifold assembly operably connected to the output of the console assembly, the manifold assembly comprising an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, (c) a catheter assembly operably connected to the output of the manifold assembly, wherein the catheter assembly (i) An apparatus configured to operably connect a catheter assembly to a manifold assembly and convert first pulse energy generated by the manifold assembly into second pulse energy; (ii) A catheter having a fluid passageway operably connected to the output of the connector and configured to transmit the second pulse energy; (iii) A heart tissue conforming element configured to receive the second pulse energy transmitted through the fluid passageway of the catheter and apply pulsatile energy to cardiovascular tissue. A system comprising the above. 2. The system of claim 1, wherein the heart tissue conforming element is configured to engage heart valve tissue. 3. The system of claim 2, wherein the heart tissue conforming element is configured to engage a heart valve leaflet. 4. The system of claim 2, wherein the heart tissue conforming element is configured to engage a heart valve commissure. 5. The system of claim 2, wherein the heart tissue conforming element is configured to engage a heart valve leaflet nodule.

[0243] 6. The system of claim 2, wherein the heart tissue conforming element is configured to engage a heart valve annulus. 7. The system of claim 1, wherein the heart tissue conforming element is configured to engage cardiovascular tissue including tissue that supports a heart valve. 8. The system of claim 2, wherein the heart tissue conforming element is configured to engage an aortic valve. 9. The system of claim 8, wherein the heart tissue conforming element is configured to engage an aortic valve leaflet. 10. The system of claim 8, wherein the heart tissue conforming element is configured to engage an aortic valve commissure.

[0244] 11. The system of claim 8, wherein the heart tissue conforming element is configured to engage an aortic valve annulus. 12. The system of claim 2, wherein the heart tissue conforming element is configured to engage a mitral valve. 13. The system according to appendix 2, wherein the heart tissue conforming element is configured to engage the mitral valve. 14. The system according to appendix 1, wherein the heart tissue conforming element is configured to engage the atrial septum. 15. The system according to appendix 1, wherein the heart tissue conforming element is configured to engage the ventricular septum.

[0245] 16. The system according to any one of appendices 1 to 15, wherein the heart tissue conforming element is located in the distal region of the catheter. 17. The system according to any one of appendices 1 to 16, wherein the heart tissue conforming element comprises a plurality of distal balloons circumferentially arranged around the rigid distal region of the catheter. 18. The system according to appendix 17, wherein the distal balloon is configured to independently receive the pulse energy generated by the manifold assembly. 19. The fluid passage of the catheter is the first fluid passage, The catheter assembly comprises a plurality of fluid passages, and each fluid passage is operably connected to a corresponding distal balloon. The system according to appendix 18. 20. The system according to appendix 19, wherein the plurality of fluid passages comprise fluid passages inside and outside the catheter.

[0246] 21. The connector is the first connector, The catheter assembly includes a plurality of connectors, and each connector is operably connected to a corresponding fluid passage of the catheter. The system according to appendix 19 or 20. 22. The system according to appendix 21, wherein the output of the connector is connected to the catheter by a transition hub. 23. The system according to appendix 22, wherein the transition hub couples the output of the connector to the fluid passage of the catheter. 24. The system according to appendix 22, wherein the transition hub couples the output of the connector to the corresponding fluid passage. 25. The system according to any one of appended claims 17 to 24, wherein in the inflated state, the distal balloon is configured to provide structural rigidity.

[0247] 26. The system according to claim 25, wherein in the inflated state, the distal balloon is configured to assume a geometric shape. 27. The system according to any one of appended claims 17 to 26, wherein in the inflated state, the distal balloon has substantially the same shape. 28. The system according to any one of appended claims 17 to 26, wherein in the inflated state, the distal balloon has different shapes. 29. The system according to any one of appended claims 17 to 26, wherein in the inflated state, the distal balloon has substantially the same diameter. 30. The system according to any one of appended claims 17 to 26, wherein in the inflated state, the distal balloon has different diameters.

[0248] 31. The system according to any one of appended claims 17 to 26, wherein in the inflated state, the diameter of the distal balloon varies between the proximal region, the distal region, or the central region of the distal balloon. 32. The system according to any one of appended claims 17 to 31, wherein the distal balloon is coated with an active agent. 33. The system according to any one of appended claims 17 to 32, wherein in the inflated state, the distal balloon is arranged to leave a space for fluid to pass between the distal balloon and the catheter. 34. The system according to any one of appended claims 17 to 33, further comprising a membrane present in the rigid distal region of the catheter configured to cover the distal balloon. 35. The system according to claim 34, wherein the membrane is coated with an active agent.

[0249] 36. The system according to any one of appended claims 17 to 35, further comprising a plurality of lobes present on the distal balloon and extending radially beyond the distal balloon. 37. The system according to claim 36, wherein the lobes are configured to engage with the characteristic parts of the cardiovascular tissue. 38. The system according to appendix 37, wherein the lobe is configured to engage a characteristic portion of the heart valve tissue. 39. The system according to appendix 37, wherein the lobe is configured to hold the position of the distal balloon with respect to the cardiovascular tissue. 40. The system according to any one of appendices 36 to 39, wherein the cross-section of the lobe is a geometric shape.

[0250] 41. The system according to appendix 40, wherein the cross-section of the lobe is triangular or circular. 42. The system according to any one of appendices 36 to 41, wherein the lobes are arranged substantially equidistantly around the distal balloon. 43. The system according to any one of appendices 17 to 42, wherein the cross-section of the rigid distal region of the catheter is configured to provide structural rigidity. 44. The system according to appendix 43, wherein the cross-section of the rigid distal region of the catheter has a geometric shape. 45. The system according to any one of appendices 1 to 44, wherein the catheter comprises a guide wire channel.

[0251] 46. The system according to any one of appendices 1 to 45, wherein the catheter comprises a pressure sensor. 47. The system according to appendix 46, wherein the pressure sensor is located in the distal region of the catheter. 48. The system according to appendix 1, wherein the heart tissue conforming element comprises a plurality of radially extending members that extend radially with a length longer than the cross-sectional width, and the radially extending members are offset from each other. 49. The system according to appendix 48, wherein the radially extending members are arranged to form a three-point bending configuration. 50. The system according to appendix 49, wherein the three-point bending configuration is configured to engage the heart valve leaflet.

[0252] 51. The system according to appendix 50, wherein the catheter assembly is configured to translate the first radially extending member laterally with respect to the second radially extending member. 52. The system according to any one of appendices 1 to 51, wherein the catheter assembly is configured to allow fluid perfusion through the distal region of the catheter. 53. The system according to appendix 52, wherein the catheter assembly comprises a valve configured to allow fluid to perfuse in only one direction beyond the distal region of the catheter. 54. The system according to appendix 52, wherein the catheter assembly comprises a vibrating balloon configured to allow fluid to perfuse in only one direction beyond the distal region of the catheter. 55. The system according to any one of appendices 52 to 54, wherein the catheter assembly is configured to allow fluid to perfuse beyond the heart tissue conforming element.

[0253] 56. The system according to appendix 55, wherein the catheter assembly further comprises a perfusion zone fluidly connected proximally and distally to the heart tissue conforming element. 57. The perfusion zone comprises an inflow perfusion zone positioned distally to the heart tissue conforming element and an outflow perfusion zone positioned proximally to the heart tissue conforming element, the system according to appendix 56. 58. The system according to appendix 56 or 57, wherein the perfusion zone comprises a perforation in the catheter assembly. 59. The system according to any one of appendices 56 to 58, wherein the perfusion zone is fluidly connected via a perfusion fluid passage of the catheter. 60. The system according to appendix 59, wherein the perfusion fluid passage of the catheter is coated with an activator that promotes fluid flow.

[0254] 61. The system according to appendix 60, wherein the activator is an anticoagulant. 62. The system according to any one of appendices 52 to 61, wherein the catheter assembly comprises a passive perfusion mechanism. 63. The system according to appendix 62, wherein the passive perfusion mechanism comprises a pressure gradient around the distal region of the catheter. 64. A catheter assembly, a system according to any one of appendices 52 to 63. 65. The system according to appendix 64, wherein the active perfusion mechanism is configured to pull or push fluid beyond the distal region of the catheter.

[0255] 66. The system according to appendix 65, wherein the active perfusion mechanism comprises a perfusion connector having an inlet port with a one-way valve and a barrel syringe operably connected to an outlet port with a one-way valve. 67. The system according to any one of appendices 1 to 66, wherein the connector is a proximal connector comprising a proximal chamber and a distal chamber separated by a membrane. 68. The system according to any one of appendices 1 to 66, wherein the connector is a syringe. 69. The syringe is a barrel syringe, and the barrel syringe has an input port fluidly connected to a first chamber, an output port fluidly connected to a second chamber, and a plunger existing between the first chamber and the second chamber. The system according to appendix 68. 70. The system according to appendix 69, wherein the first chamber is a pneumatic chamber, and the second chamber is a fluid chamber.

[0256] 71. The system according to appendix 69 or 70, wherein the barrel syringe is configured to bias the vacuum in the first chamber of the barrel syringe. 72. The system according to appendix 71, wherein the barrel syringe further comprises a biasing spring connected to the plunger. 73. The system according to appendix 72, wherein the biasing spring is configured to apply a force to the plunger to exhaust the first chamber of the barrel syringe. 74. The system according to any one of appendices 69 to 73, wherein the first chamber of the barrel syringe is selectively connected to a low-pressure source to exhaust the first chamber of the barrel syringe. 75. The system according to appendix 74, wherein the low-pressure source is a vacuum.

[0257] 76. The system according to any one of appendices 1 to 75, wherein the connector comprises a pressure sensor. 77. The system according to any one of appendices 1 to 76, wherein the connector comprises a volume sensor. 78. The system according to any one of appendices 1 to 77, wherein the connector is configured to releasably engage with the output of the manifold assembly. 79. The system according to any one of appendices 1 to 78, wherein the connector is configured to heat or cool the fluid transmitted to the heart tissue conforming element. 80. The system according to any one of appendices 1 to 79, wherein the connector is configured to transmit one of electrical impulse energy or light energy.

[0258] 81. The system according to appendix 80, wherein the catheter assembly comprises an electrode configured to receive electrical impulse energy or light energy at the target site. 82. The system according to any one of appendices 1 to 81, wherein the oscillator is further configured to output a static pressure output. 83. The system according to any one of appendices 1 to 82, wherein the oscillator is a solenoid. 84. The system according to any one of appendices 1 to 83, wherein the oscillator is a first oscillator and the manifold assembly comprises a plurality of oscillators. 85. The system according to appendix 84, wherein the oscillation frequencies of the plurality of oscillators are synchronized.

[0259] 86. The system according to any one of appendices 1 to 85, wherein the oscillator is configured such that the oscillation frequency of the oscillator is synchronized with the result of an electrocardiogram. 87. The system according to any one of appendices 1 to 86, wherein the potential source of the console assembly is a voltage potential or an electromagnetic potential or a pressure potential. 88. The system according to appended claim 87, wherein the console assembly comprises a regulator configured to adjust a first energy from a potential source to a second energy. 89. The system according to appended claim 88, wherein the regulator is an active regulator configured to be controlled by an electrical signal. 90. The system according to appended claim 88, wherein the regulator is a passive regulator configured to be preset to a specific output.

[0260] 91. The console assembly further comprises a controller, and the controller receives an input from at least one of the console assembly, the manifold assembly, and the catheter assembly, and is configured to adjust the configuration of at least one of the console assembly, the manifold assembly, and the catheter assembly based at least in part on the received input, the system according to any one of appended claims 1 to 90. 92. The system according to appended claim 91, wherein the controller is further configured to receive an input from a source external to the system. 93. The system according to appended claim 92, wherein the controller is configured to receive an input from at least one of an electrocardiogram, an intravascular pressure monitor, a blood volume monitor, or a result of an imaging system. 94. The console assembly is a first console assembly, and the system comprises a plurality of operably connected console assemblies, the system according to any one of appended claims 1 to 93. 95. The system according to appended claim 94, wherein the manifold assembly is operably connected to a plurality of console assemblies.

[0261] 96. The system according to any one of appended claims 1 to 95, wherein the heart tissue conforming element is configured to expand during diastole of the cardiovascular tissue. 97. The system according to appended claim 96, wherein the heart tissue conforming element is further configured to relax during systole of the cardiovascular tissue. 98. The system according to any one of appendices 1 to 95, wherein the heart tissue conforming element is configured to relax during the diastolic phase of the cardiovascular tissue. 99. The system according to appendix 98, wherein the heart tissue conforming element is further configured to expand during the systolic phase of the cardiovascular tissue. 100. The system according to any one of appendices 96 to 99, wherein the system is configured to apply pulsating energy to the cardiovascular tissue when the heart tissue conforming element expands.

[0262] 101. The system according to any one of appendices 96 to 100, further comprising a controller configured to expand and relax the heart tissue conforming element based on an input from at least one of the results of an electrocardiogram, an intravascular pressure monitor, a blood volume monitor, or an imaging system. 102. The system according to any one of appendices 96 to 100, further comprising a controller configured to expand and relax the heart tissue conforming element based on a predetermined configuration. 103. The system according to appendix 101 or 102, wherein the controller is further configured to cause the heart tissue conforming element to expand and apply pulsating energy to the cardiovascular tissue. 104. The system according to appendix 103, wherein the controller is further configured to cause the heart tissue conforming element to relax and not apply pulsating energy to the cardiovascular tissue.

[0263] 105. A system for transmitting pulsating energy through a fluid passage of a catheter, the system comprising (a) a plurality of pulsating energy generating assemblies, each pulsating energy generating assembly comprising (i) a console assembly comprising a potential source, and (ii) a manifold assembly operably connected to the output of the console assembly, the manifold assembly comprising an oscillator configured to generate pulsed energy from the energy transmitted from the potential source. (iii) A pulsating energy generation assembly comprising a connector operably connected to the output of the manifold assembly and configured to convert the first pulse energy generated by the manifold assembly into a second pulse energy. (b) A catheter comprising fluid passages operably connected to the outputs of the connectors of the plurality of pulsating energy generation assemblies. (c) A controller configured to control the plurality of pulsating energy generation assemblies. A system in which the controller and the plurality of pulsating energy generation assemblies are configured such that the controller independently controls the potential output of each console assembly and the oscillator of each manifold assembly.

[0264] 106. A system for transmitting pulsating energy through a plurality of fluid paths, the system comprising: (a) A pulsating energy generation assembly comprising: (i) A console assembly comprising a potential source; (ii) A manifold assembly operably connected to the output of the console assembly and comprising an oscillator configured to generate pulse energy from the energy transmitted from the potential source; (iii) A pulsating energy generation assembly comprising a connector operably connected to the output of the manifold assembly and configured to convert the first pulse energy generated by the manifold assembly into a second pulse energy. (b) A plurality of fluid passages, each fluid passage being operably connected to the output of the connector of the pulsating energy generation assembly. (c) A controller configured to control the pulsating energy generation assembly. A system in which the controller and the pulsating energy generation assembly are configured such that the controller controls the potential output of the console assembly and the oscillator of the manifold assembly.

[0265] 107. A system for applying pulsatile energy to cardiovascular tissue, the system comprising: (a) A console assembly comprising a potential source; and (b) A manifold assembly operably connected to the output of the console assembly, the manifold assembly comprising an oscillator configured to generate pulsed energy from the energy transmitted from the potential source; and (c) A catheter assembly operably connected to the output of the manifold assembly, the catheter assembly comprising: (i) A connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy; (ii) A catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy; and (iii) A heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to the cardiovascular tissue, the system being configured to expand and contract the heart tissue conforming element at least partially based on the systolic and diastolic phases of the cardiovascular tissue.

[0266] 108. A catheter assembly comprising: (i) A connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy; (ii) A catheter having a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy; and (iii) A heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to the cardiovascular tissue A catheter assembly comprising 109. The assembly according to appended claim 108, wherein the heart tissue conforming element is configured to engage the heart valve tissue. 110. The assembly according to appended claim 109, wherein the heart tissue conforming element is configured to engage th...

Claims

1. A system for applying pulsatile energy to cardiovascular tissue, (a) a console assembly comprising a potential source, and (b) a manifold assembly operably connected to the output of the console assembly, the manifold assembly comprising an oscillator configured to generate pulsed energy from the energy transmitted from the potential source, (c) a catheter assembly operably connected to the output of the manifold assembly and comprising: wherein the catheter assembly (i) a connector configured to operably connect the catheter assembly to the manifold assembly and convert a first pulsed energy generated by the manifold assembly into a second pulsed energy, (ii) a catheter comprising a fluid passage operably connected to the output of the connector and configured to transmit the second pulsed energy, and (iii) a heart tissue conforming element configured to receive the second pulsed energy transmitted through the fluid passage of the catheter and apply pulsatile energy to cardiovascular tissue. A system.

2. The system of claim 1, wherein the heart tissue conforming element is configured to engage heart valve tissue.

3. The system according to any one of the preceding claims, wherein the heart tissue conforming element is located in the distal region of the catheter.

4. The system according to any one of the preceding claims, wherein the heart tissue conforming element comprises a plurality of distal balloons circumferentially arranged around the rigid distal region of the catheter.

5. The system of claim 4, wherein the distal balloon is configured to independently receive the pulse energy generated by the manifold assembly. **Claim 6** The fluid passage of the catheter is a first fluid passage, The system of claim 5, wherein the catheter assembly comprises a plurality of fluid passages, each fluid passage being operably connected to a corresponding distal balloon. **Claim 7** The system according to any one of claims 4 to 6, wherein in the inflated state, the distal balloon is arranged so as to leave a space for fluid to pass between the distal balloon and the catheter. **Claim 8** The system according to any one of claims 4 to 7, further comprising a plurality of lobes present on the distal balloon and extending radially beyond the distal balloon. **Claim 9** The system of claim 8, wherein the lobe is configured to engage a feature of the cardiovascular tissue. **Claim 10** The system of claim 1, wherein the catheter assembly is configured to allow fluid to perfuse beyond the heart tissue conforming element. **Claim 11** The system of claim 10, wherein the catheter assembly further comprises a perfusion zone fluidly connected proximally and distally to the heart tissue conforming element. **Claim 12** The perfusion zone is an inlet perfusion zone positioned distally of the heart tissue conforming element, and an outlet perfusion zone positioned proximally of the heart tissue conforming element The system of claim 11, comprising. **Claim 13** The system of claim 11 or 12, wherein the perfusion zone comprises a perforation in the catheter assembly. **Claim 14** A catheter assembly comprising: (i) a connector configured to operably connect the catheter assembly to a manifold assembly and convert first pulse energy generated by the manifold assembly into second pulse energy; (ii) a catheter operably connected to an output of the connector and having a fluid passage configured to transmit the second pulse energy; (iii) a heart tissue conforming element configured to receive the second pulse energy transmitted through the fluid passage of the catheter and apply pulsatile energy to cardiovascular tissue A catheter assembly comprising:

15. A method of imparting pulsatile energy to cardiovascular tissue, the method comprising: deploying the system such that a heart tissue conforming element of the system is adjacent to cardiovascular tissue, the system comprising: (a) a console assembly comprising a potential source; (b) a manifold assembly operably connected to an output of the console assembly and comprising an oscillator configured to generate pulse energy from energy transmitted from the potential source; (c) a catheter assembly operably connected to an output of the manifold assembly, the catheter assembly comprising: (i) a connector configured to operably connect the catheter assembly to the manifold assembly and convert first pulse energy generated by the manifold assembly into second pulse energy; (ii) a catheter operably connected to an output of the connector and having a fluid passage configured to transmit the second pulse energy; (iii) receiving the second pulse energy transmitted through the fluid passage of the catheter and comprising the heart tissue conforming element configured to apply pulsatile energy to the cardiovascular tissue, deploying; engaging the system in a manner such that the heart tissue conforming element imparts energy to the cardiovascular tissue A method comprising.

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