Systems and methods for treating cardiovascular tissue

Abstract

A system for delivering pulsatile energy to cardiovascular tissue is provided. Aspects of the system include: a console assembly including a potential source; a manifold assembly operably connected to an output of the console assembly, where the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the potential source; and a conduit assembly operably connected to the output end of the manifold assembly. The catheter assembly of the present invention comprises: a connector operably connecting the catheter assembly to a manifold assembly and configured to convert a first pulsed energy generated by the manifold assembly into a second pulsed energy; a catheter including a fluid channel operably connected to the output end of the connector and configured to transmit a second pulse energy; and a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid passage of the catheter to apply the pulsatile energy to the cardiovascular tissue. Also provided are methods for delivering pulsatile energy to cardiovascular tissue, e.g., deploying the system such that the heart tissue compliant element of the system is adjacent to the cardiovascular tissue, and engaging the system in such a manner that the heart tissue compliant element delivers energy to the cardiovascular tissue. In addition, provided are separate catheter assemblies as well as kits comprising components of the systems described herein. These systems, assemblies, methods, and kits can be used for a variety of different applications, including balloon angioplasty applications or other catheter-based therapies or treatments.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority under 35 USC § 119(e) to the filing date of U.S. Provisional Patent Application Serial No. 63 / 346,703, filed on May 27, 2022; the disclosure of which is incorporated herein by reference in its entirety.

[0003] introduction

[0004] Cardiovascular tissue, including heart valve tissue, is susceptible to the formation of atherosclerotic plaques through a mechanism called atherosclerosis, which is the accumulation of fatty and calcified material that causes stenosis, narrowing of the arterial lumen, or failure of the heart valve to function properly. Calcific aortic stenosis is a common cause of aortic valve disease, which leads to syncope (fainting), dyspnea (shortness of breath), heart failure, and ultimately death. The prevalence of aortic stenosis increases dramatically with age. It has been reported that up to one-third of elderly patients have some form of evidence of calcific aortic stenosis, with a prevalence of 25% in those over 65 years of age and almost 50% in those over 85 years of age. Under normal circumstances, the aortic valve is composed of three leaflets, each of which is a thin (e.g., less than 1 mm), smooth, flexible, and mobile structure. In aortic stenosis, these leaflets become thickened, fibrotic, and calcified, leading to reduced leaflet mobility and progressive valve obstruction. Calcium deposits cause increased stress in the leaflets, which leads to more damage to the blood vessels, which in turn causes increased calcium deposits.

[0005] Existing treatment options include catheter-based valvuloplasty. However, the shape of typical catheter balloons tends to obstruct blood flow through the heart when inflated, limiting, for example, the duration of treatment. In addition, overinflation of balloon aortic valvuloplasty can lead to aortic valve ring rupture. The aortic valve area in affected patients can be as small as 0.1 cm 2 and 1.5 cm 2 , and balloon aortic valvuloplasty delivers the average effect of the balloon pressure over such tissue areas. That is, it does not deliver focal pressures, for example, at the commissures of the valve, but relies on the compression of the valve leaflets between the annulus and the balloon.

[0006] Balloon aortic valvuloplasty is currently being offered as a bridge to transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), either as a means of palliation for those who are not suitable for TAVR or SAVR, or as part of TAVR to facilitate the delivery of a transcatheter valve. Isolated balloon aortic valvuloplasty is associated with high morbidity and has a high rate of restenosis. To the best of the inventors' knowledge, existing perfusion catheters used for such procedures lack the stability and radial force required to alter calcified valves and separate valve commissures. Furthermore, to the best of the inventors' knowledge, current treatments do not provide a solution for balloon aortic valvuloplasty that provides a localized or focal stress point for a heart valve feature, such as a commissure or valve leaflet, while also enabling perfusion, and further do not provide a mechanism for locating features of cardiovascular tissue, such as valve commissures, during treatment. Summary of the invention

[0007] Therefore, there remains a need for improved systems and methods for successfully delivering pulsatile energy to cardiovascular tissue (e.g., heart valves, such as the aortic valve), including simultaneously providing perfusion through the cardiovascular tissue. For example, a more consistent balloon aortic valvuloplasty procedure requiring minimal rapid pacing and longer treatment periods can improve preparation for transcatheter aortic valve replacement (TAVR) or potentially more durable treatment of calcific aortic stenosis. Improved systems and methods for successfully delivering pulsatile energy to cardiovascular tissue can also result in more durable valvuloplasty and eliminate or significantly delay the need for TAVR or SAVR.

[0008] As described herein, the present invention relates to systems and methods for delivering pulsatile energy to cardiovascular tissue, including in the context of balloon valvuloplasty treatment. Specifically, the systems and methods of the present invention facilitate providing localized stress points or focal stress points to cardiovascular tissue (such as aspects of cardiovascular tissue, e.g., heart valves, e.g., commissures or valve leaflets) while also providing perfusion to distal vessels, such that, for example, focal forces on commissures and leaflets are maintained while allowing blood to continue to perfuse to distal tissue. Such embodiments allow for longer treatment durations, thereby promoting the occurrence of calcium fatigue rupture in cardiovascular tissue (e.g., valve commissures and leaflets).

[0009] Embodiments of the system of the present invention provide a mechanism for positioning the valve commissures during treatment by, for example, providing an external balloon configured to vibrate prior to inflation of a full valvuloplasty balloon so that the balloon positions the path of least resistance (i.e., the valve commissures). The position and proper alignment of the pulsation 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 pulsation devices (e.g., on the balloon) or other identification marks that can also verify the alignment of the commissures in some cases. Once properly positioned relative to the cardiovascular tissue, further pulsations can be generated within the valve commissures to achieve calcium rupture and separation of the tissue (e.g., heart valve leaflets).

[0010] A system for delivering pulsating energy to cardiovascular tissue is provided. Aspects of the system include a console assembly, the console assembly including an electric potential source; a manifold assembly, the manifold assembly operably connected to the output end of the console assembly, wherein the manifold assembly includes an oscillator, the oscillator is configured to generate pulsed energy from energy transmitted by the electric potential source; and a catheter assembly, the catheter assembly operably connected to the output end of the manifold assembly. The catheter assembly of the present invention includes: a connector, the connector operably connects the catheter assembly to the manifold assembly and is configured to convert a first pulsed energy generated by the manifold assembly into a second pulsed energy; a catheter, the catheter includes a fluid channel operably connected to the output end of the connector and configured to transmit the second pulsed energy; and a cardiac tissue compliant element, the cardiac tissue compliant element is configured to receive the second pulsed energy transmitted through the fluid channel of the catheter to apply the pulsating energy to the cardiovascular tissue. A method for delivering pulsating energy to cardiovascular tissue is also provided, for example, a deployment system is provided so that the cardiac tissue compliant element of the system is adjacent to the cardiovascular tissue, and the system is engaged in a manner in which the cardiac tissue compliant element delivers energy to the cardiovascular tissue. In addition, a separate catheter assembly and a kit including components of the system described herein are provided. These systems, assemblies, methods and kits may be used in a variety of applications, including balloon angioplasty applications or other catheter-based therapies or treatments. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 A schematic diagram of an embodiment of a system for delivering pulsatile energy to cardiovascular tissue according to the present invention is provided.

[0012] Figure 2A and Figure 2B A schematic diagram of a console component of a system according to an embodiment of the present invention is provided.

[0013] Figure 3A and Figure 3B Depicted are views of exemplary embodiments of a console assembly of a system in accordance with embodiments of the present invention.

[0014] Figure 4A and Figure 4B A schematic diagram of a manifold assembly of a system according to an embodiment of the present invention is provided.

[0015] Figure 5 A perspective view of a manifold assembly of a system according to an embodiment of the present invention is provided.

[0016] FIG. 6A to FIG. 6E Depicted are various views of embodiments of a connector for a system configured to deliver low volume, high frequency, and high voltage pulses in accordance with embodiments of the present invention.

[0017] Figure 7 A schematic diagram of an alternative connector configured to deliver high volume, low frequency and low pressure pulses is provided in accordance with an embodiment of the present invention.

[0018] FIG. 8A to FIG. 8C Various views of a cardiac tissue compliant element of a system according to an embodiment of the present invention are depicted.

[0019] Fig. 9 Embodiments of cardiac tissue compliant elements of a system according to embodiments of the present invention are depicted.

[0020] Fig.10 Balloon pressurization measurements and corresponding electrocardiogram (ECG) readings are depicted.

[0021] FIG. 11A to FIG. 11D Various views of embodiments of a cardiac tissue compliant element of a system according to embodiments of the present invention are depicted.

[0022] Fig. 12A and Fig. 12B A cross-sectional view of a heart valve is depicted.

[0023] FIG. 13A to FIG. 13C Depicted are cross-sectional views of certain embodiments of a cardiac tissue compliant element for a bi-leaflet valve, such as a mitral valve.

[0024] Fig.14A and Fig. 14B Embodiments of catheter assemblies configured to enable perfusion through a cardiac tissue compliant element when the catheter assembly is engaged with cardiovascular tissue are depicted.

[0025] Fig.15 Depicted is a schematic diagram of a control loop for a control system according to an embodiment of the present invention.

[0026] Fig.16Depicted is a schematic diagram of a robotic approach for delivering therapy energy from a control room to a diseased valve.

[0027] Fig.17 Depicted are pressure-volume curves of cardiovascular tissue before and after treatment with a system according to an embodiment of the present invention.

[0028] Fig.18A and Fig.18B Examples of measurements of changes in tissue compliance obtained during treatment using a system according to the present invention are provided.

[0029] Fig.19 Shown is a graphical user interface (GUI) with which an operator of the system of the present invention may interact during a treatment procedure involving the delivery of pulsatile energy to a heart valve.

[0030] Fig. 20 Photographs of aspects of catheter assemblies according to embodiments of the present invention are provided.

[0031] Fig.21 Provided Fig. 20 Various photographic views of the connectors of the catheter assemblies.

[0032] Fig. 22 Provided in the attachment to Fig. 20 Two examples of experimentally measured pressure and force output from a single balloon of a catheter assembly. DETAILED DESCRIPTION

[0033] A system for delivering pulsating energy to cardiovascular tissue is provided. Aspects of the system include a console assembly, the console assembly including an electric potential source; a manifold assembly, the manifold assembly operably connected to the output end of the console assembly, wherein the manifold assembly includes an oscillator, the oscillator is configured to generate pulsed energy from energy transmitted by the electric potential source; and a catheter assembly, the catheter assembly operably connected to the output end of the manifold assembly. The catheter assembly of the present invention includes: a connector, the connector operably connects the catheter assembly to the manifold assembly and is configured to convert the first pulsed energy generated by the manifold assembly into a second pulsed energy; a catheter, the catheter includes a fluid channel operably connected to the output end of the connector and configured to transmit the second pulsed energy; and a cardiac tissue compliance element, the cardiac tissue compliance element is configured to receive the second pulsed energy transmitted through the fluid channel of the catheter to apply the pulsating energy to the cardiovascular tissue. A method for delivering pulsating energy to cardiovascular tissue is also provided, for example, a deployment system is provided so that the cardiac tissue compliance element of the system is adjacent to the cardiovascular tissue, and the system is engaged in a manner in which the cardiac tissue compliance element delivers energy to the cardiovascular tissue. In addition, a separate catheter assembly and a kit including components of the system described herein are provided. These systems, assemblies, methods and kits may be used in a variety of applications, including angioplasty applications or other catheter-based therapies or treatments, such as treatment of heart valve calcification.

[0034] Before describing the present invention in more detail, it should be understood that the present invention is not limited to the specific embodiments described, but can certainly be varied. It should also be understood that the terminology used herein is only for the purpose of describing specific embodiments, and is not intended to be limiting, because the scope of the present invention is limited only by the appended claims.

[0035] Where a numerical range is provided, it is understood that unless the context clearly indicates otherwise, each intermediate value to the tenth lower limit unit between the upper and lower limits of the range and any other stated value or intermediate value in the range is encompassed within the present invention. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges and are also encompassed within the present invention, but are subject to any explicitly excluded limitations in the range. Where the range includes one or both of the limitations, the range excluding either or both of those included limitations is also encompassed within the present invention.

[0036] Certain ranges are presented herein with a numerical value preceded by the term "about." The term "about" is used herein to provide literal support for the exact numerical value that follows it, as well as numbers that are close to or approximately the numerical value that follows the term. In determining whether a number is close to or approximately a specifically recited number, a close or approximate unrecited number may be a number that, in the context in which the number is given, provides a substantial equivalence to the specifically recited number.

[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

[0038] All publications and patents cited in this specification are incorporated herein by reference as if each individual publication or patent was specifically and individually indicated to be incorporated by reference and is incorporated herein by reference to disclose and describe the methods and / or materials related to the cited publication. The citation of any publication is due to its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. In addition, the publication dates provided may be different from the actual publication dates, which may need to be independently confirmed.

[0039] It should be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should also be noted that the claims can be drafted to exclude any optional elements. As such, this statement is intended to serve as antecedent basis for use of special terminology, such as "solely," "only," etc., in connection with the recitation of claim elements, or use of a "negative" limitation.

[0040] It will be apparent to those skilled in the art after reading this disclosure that each of the various embodiments described and illustrated herein has discrete components and features that can be easily separated or combined with the features of any of the other several embodiments without departing from the scope or spirit of the invention. Any enumerated method can be performed in the order of the enumerated events or in any other order that is logically possible.

[0041] Although the apparatus and methods have been or will be described using functional interpretations for grammatical fluency, it should be clearly understood that unless expressly stated pursuant to 35 USC §112, the claims should not be interpreted as necessarily being limited in any way to the construction of "device" or "step" limitations, but should be given the full meaning and equivalent meaning of the claims defined under the doctrine of judicial equivalents, and if the claims are expressly stated pursuant to 35 USC §112, they should be given the full legal equivalent meaning pursuant to 35 USC §112.

[0042] In further describing various aspects of the invention, the system and its components are first described in more detail, followed by a review of methods of using the system and kits for practicing the subject methods.

[0043] Systems for treating cardiovascular tissue

[0044] As summarized above, a system for delivering pulsating energy to cardiovascular tissue is provided. The system of an embodiment of the present invention is configured to generate pulsating energy and transmit it to a cardiac tissue compliant element for applying pulsating energy to cardiovascular tissue. In some cases, the cardiac tissue compliant element is used to apply pulsating energy to a heart valve or a feature thereof or a tissue supporting a heart valve. In an embodiment, the cardiac tissue compliant element can be configured to focus the pulsating energy on a specific area or feature or aspect of the cardiovascular tissue. For example, the cardiac tissue compliant element can be configured to deliver concentrated pulsating energy to a heart valve commissure or a heart valve leaflet.

[0045] The catheter assembly and the cardiac tissue compliant element can be configured so that when the cardiac tissue compliant element applies pulsating energy to cardiovascular tissue, fluid can be perfused through the cardiac tissue compliant element. In an embodiment, the catheter assembly comprising the cardiac tissue compliant element is configured so that when deployed to adjacent cardiovascular tissue, blood can be perfused through the cardiac tissue compliant element via an active perfusion mechanism or a passive perfusion mechanism as a part of the catheter assembly and the cardiac tissue compliant element. This type of configuration helps to extend the treatment time, increasing the amount of pulsating energy that can be applied to cardiovascular tissue rather than otherwise available.

[0046] The systems of the present invention can be used for a variety of applications, including angioplasty applications or other catheter-based therapies or treatments, such as treatment of heart valve calcification. In some instances, the systems can be used to disrupt sclerotic materials, such as calcium deposits embedded in cardiovascular tissue, such as heart valve leaflets or heart valve commissures, or other cardiovascular tissue or tissue surrounding the heart, such as pericardial calcification. Specifically, the systems of the present invention can be used to treat cardiovascular tissue, including, for example, (1) utilizing features of a cardiac tissue compliant element to position a cardiac tissue compliant element at a desired location adjacent to cardiovascular tissue (e.g., a heart valve); (2) utilizing features of a cardiac tissue compliant element to apply pulsating energy to the cardiovascular tissue in a focused manner, i.e., wherein the pulsating energy is directed to specific aspects of the cardiovascular tissue (as opposed to, for example, a monolithic balloon that applies substantially equal amounts of pulsating energy to all aspects of the cardiovascular tissue); and (3) utilizing features of a catheter assembly and a cardiac tissue compliant element to achieve perfusion through the cardiac tissue compliant element. The present disclosure describes applications of embodiments related to treating cardiovascular tissue involving, for example, calcification and / or deposits within cardiovascular tissue (such as a heart valve or features thereof or tissue supporting a heart valve or tissue surrounding the heart), such as pericardial calcification. However, the systems and teachings of the present invention are not limited solely to delivering pulsatile energy to cardiovascular tissue associated with cardiovascular tissue calcification, but may be generally applied to other applications as determined by one skilled in the art.

[0047] The system can be used to deliver pulsatile energy to cardiovascular tissue of any number of different subjects. In some instances, the subject is a "mammal" or "mammal," where these terms are broadly used to describe organisms in the class Mammalia, including the order Carnivora (e.g., dogs and cats), the order Rodentia (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In some instances, the subject is a human.

[0048] Aspects of the system include a console assembly, which includes an electric potential source; a manifold assembly, which is operably connected to the output of the console assembly, wherein the manifold assembly includes an oscillator, which is configured to generate pulse energy from the energy transmitted by the electric potential source; and a catheter assembly, which is operably connected to the output of the manifold assembly. The catheter assembly of the present invention includes: a connector, which operably connects the catheter assembly to the manifold assembly and is configured to convert the first pulse energy generated by the manifold assembly into a second pulse energy; a catheter, which includes a fluid channel operably connected to the output of the connector and configured to transmit the second pulse energy; and a cardiac tissue compliance element, which is configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsating energy to cardiovascular tissue. In addition, in certain embodiments, the cardiac tissue compliance element is configured to engage heart valve tissue. In other embodiments, the cardiac tissue compliance element includes a plurality of distal balloons arranged circumferentially around the rigid distal region of the catheter. In some embodiments, the catheter assembly is configured to allow fluid perfusion through the distal region of the catheter. These components and their configuration will be described in more detail further below.

[0049] Console Components :

[0050] 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 required for treating cardiovascular tissue using the system.

[0051] The embodiment of the console assembly of the system according to the present invention includes a potential source. The potential source of the embodiment of the present invention is configured to provide energy, which can be adjusted by a regulator as needed. Any convenient potential source can be used, wherein examples of potential sources include voltage sources, pressure sources, electromagnetic sources, electric field sources, chemical sources, etc. In some embodiments, the potential source is a pressure source, wherein examples of suitable pressure sources include, but are not limited to: compressed gas cylinders, compressors, etc. Where necessary, the potential source can be operably coupled to a regulator, which is used to modulate the energy from the potential source into a suitable form so that it can be further, for example, acted upon by an oscillator of a manifold assembly. For example, in the case where the potential source is a high-pressure gas source, the regulator can be used to adjust the pressure of the gas to a suitable value that can be input to an oscillator. In addition to a positive potential source (e.g., a high-pressure gas), the potential source of interest can also include a negative potential compared to a reference potential or a standard potential, for example, a potential source configured to provide a vacuum potential compared to standard atmospheric conditions.

[0052] In some embodiments, the console assembly includes more than one potential source. In embodiments that include more than one potential source, the potentials provided by each potential source can all be of the same type, or can be a combination of different potential types. For example, each potential source can be a pressure source (at the same or different potential levels), or alternatively, one potential source can be a pressure source and another potential source can be a voltage source.

[0053] In an embodiment, the console assembly may further include one or more regulators (i.e., power regulators), output ports, and controllers. With respect to the power regulator, as described above, in an embodiment, the potential of the potential source may be adjusted from a first input potential to a second potential, for example, a potential suitable for transmission to an oscillator of a manifold assembly and ultimately used to treat cardiovascular tissue. The potential of the potential source may be adjusted to a predetermined value, a user-set value, or may be adjusted according to various feedback inputs that occur during treatment. In some cases, the potential of the potential source may be dynamically adjusted based at least in part on conditions associated with treatment involving the transfer of pulsating energy to cardiovascular tissue, such as changes in tissue compliance during treatment, as described below. In some cases, the potential of the potential source may be adjusted in real time or substantially in real time. In certain embodiments, the potential of the potential source may be adjusted to an optimal value for a treatment. For example, the potential of the potential source may be adjusted to an optimal value for treating a diseased heart valve (such as a heart valve with calcification on or around the valve commissure). In some cases, one or more inputs from one or more of a console component, a manifold component, a catheter component, or from a source external to the system (e.g., other measurements about the subject, such as imaging of the subject) can be used to determine optimal treatment conditions, such as the output potential of a potential source appropriate for the desired treatment, and then adjust to that condition.

[0054] In embodiments including a regulator configured to regulate 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 preset or user-adjustable regulator) or an active regulator (i.e., a regulator controlled, for example, by an electrical pulse or other dynamic signal from, for example, a controller). Regulators of interest may include regulators typically used for fluid regulation, such as directional valves or diaphragm valves, regulators for electrical regulation, such as voltage regulators, regulators for optical power regulation, etc. In embodiments including more than one potential source, the potentials of the various potential sources may be regulated together or individually.

[0055] In an embodiment, the regulated potential and / or unregulated potential (i.e., potential energy) from the potential source is output through an output port that is operably coupled to a manifold assembly of the system. In an embodiment, any convenient output port may be employed, such as a commercially available connector, such as a pneumatic connector, a hydraulic connector, an electrical connector, or an optical connector. In some instances, the unregulated potential energy or the regulated potential energy may be converted to another energy form before or in some cases after the energy is transferred or otherwise transmitted to the manifold assembly.

[0056] In some cases, a console assembly may include more than one physically separate or connected unit, i.e., each console unit, which can be operably interconnected (e.g., electrically, fluidly, using radio frequency (RF) etc.) That is, a console assembly may include a single assembly or two or more distinct, operably connected units.

[0057] In some examples, at least some of the console assembly components are present in a unit that is configured to be held or manipulated (e.g., moved) by hand. While the form factor of such a unit can vary as desired, in some examples, such a unit can be configured substantially as a rectangular box having a height in the range of 10 cm to 100 cm (this is 20 cm to 30 cm), a width of 5 cm to 100 cm (such as 10 cm to 20 cm), and a depth in the range of 10 cm to 100 cm (such as 20 cm to 30 cm), and a mass in the range of 1 kg to 20 kg (such as 5 kg to 8 kg).

[0058] In an embodiment, the console assembly may include a first console component that houses a source of electrical potential and a regulator and actuator, such as a manipulable button, for a pressure source. The console assembly may include an electrical connector for providing electrical connections to various other components of the system as needed. For example, the electrical connector may be used to receive data about the position and / or configuration of the cardiac tissue compliant element, such as the position or orientation relative to a cardiac valve undergoing treatment, or pressure or volume measurements, and to provide power to a sensor configured to collect such data about treatment using the system.

[0059] In some examples, at least some of the console assembly components are present in a mountable unit that is configured to be positioned or secured on an operating table near or proximal to a subject (i.e., a patient) so that an operator (e.g., a physician) does not need to physically interact with the console assembly (e.g., the operator does not need to be physically present in the operating room and can communicate with the system at a distance via remote control) to treat the subject. In such examples, the mountable unit is designed to be easily clamped, secured, or independently stabilized on or proximal to the operating table and can be operated by a remote control unit (as described below in conjunction with Fig.16 In such instances, the mountable unit may include a communicator that provides communication between the console assembly and the remote control unit, which may be implemented by any desired hardware and / or software configuration and may be configured to communicate using a wired or wireless protocol.

[0060] As needed, the console assembly and / or its potential source used in the system of the present invention can be configured to be reusable or single-use. The console assembly used in the system of the present invention can be configured to receive a sterile cannula so that the console assembly can be used without contaminating the sterile area of ​​the operating room. Further details on the console unit, potential source, regulator, etc. that may be used in embodiments of the present invention are provided in patent application publication number 20200046949 published in the United States, pending PCT application serial number PCT / US2020 / 055458, and U.S. application number 63274832; the disclosures of these applications are incorporated herein by reference.

[0061] Controller :

[0062] Embodiments of the console assembly of the system according to the present invention include a control subsystem, also referred to as a controller or control assembly. Embodiments of the system can utilize a controller to control the amount and duration of energy transmitted to tissue (i.e., cardiovascular tissue, such as a heart valve). In some instances, embodiments of the system can utilize a controller to measure the effects of treatment on cardiovascular tissue, such as the extent of destruction of calcified tissue, for example, the compliance of cardiovascular tissue, as described in detail below. In still other instances, embodiments of the system can utilize a controller to measure or control a perfusion mechanism, for example, controlling the perfusion of a fluid (e.g., blood) through a cardiac tissue compliance element present in a subject.

[0063] In an embodiment, the control subsystem can be connected to one or more 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 cardiac tissue compliance element), receive information from it, and / or adjust (i.e., control) aspects thereof. The control subsystem can also be configured to receive information from an external system and / or control an external system, such as an electrocardiogram (ECG), an intravascular or external pressure monitor, a blood volume sensor, a patient vital sign 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 imaging subsystems (e.g., imaging subsystems utilizing light, fluoroscopy, intravascular ultrasound (IVUS), or optical coherence tomography (OCT), or other available imaging techniques) or aspects thereof can be integrated into a catheter assembly, for example, into a catheter of the catheter assembly, and the control subsystem can be configured to receive information from such catheter-integrated imaging systems. In addition, the control subsystem can include a plurality of interconnected control units so that one or more of the units are synchronized and communicated with each other.

[0064] In some cases, the control subsystem (or a control unit including the control subsystem) can be configured to communicate with components of the system so that the energy transmitted via the catheter assembly (including via the cardiac tissue compliant element) is appropriate, i.e., suitable for a particular treatment involving application of pulsatile energy to cardiovascular tissue. In other embodiments, the control subsystem (or a control unit including the control subsystem) can receive information (e.g., a data signal) about the status of a cardiovascular tissue treatment (such as, for example, a heart valve delivery treatment) from a sensor, wherein the sensor provides information about the position (e.g., the position of a replacement heart valve), the percentage of deployment (e.g., the deployment of a replacement heart valve), the amount of valve opening, the nominal characteristics (e.g., the characteristics of a replacement heart valve), the eccentricity of the valve, paravalvular leakage, the ambient pressure on the valve, the proximal and / or distal pressures, the position of the valve in the annulus, etc.

[0065] In an embodiment, the controller is configured to receive a treatment plan, i.e., control instructions related to a specific treatment of a specific treatment for a subject. The treatment plan may include, for example, a specific amount of electrical potential, frequency of an oscillator, or duty cycle. In addition, the treatment plan may include information about the type of cardiac tissue compliant element to be employed, such as size or orientation. Fig.15. Additional details regarding aspects of a controller for implementing a treatment plan are set forth in conjunction with the exemplary control loop depicted in . Further details regarding treatment plans, control systems, and the behavior of updating a catheter-based procedure based on data collected about the procedure are described in U.S. Application Serial No. 63,346,704, entitled “Systems and Methods Related to Catheter-Based Procedures” and filed on the same day as the present application (Attorney Docket No. AVSI-005 PRV); the disclosure of which is incorporated herein by reference. In an embodiment, the cardiac tissue compliant element is configured to expand during the diastolic phase of the cardiovascular tissue. That is, when the cardiovascular tissue (e.g., the cardiovascular tissue of a subject to which the cardiac tissue compliant element is applied) enters the diastolic phase of the cardiac cycle, the cardiac tissue compliant element expands. In other embodiments, the cardiac tissue compliant element is configured to expand during the systolic phase of the cardiovascular tissue. That is, when the cardiovascular tissue (e.g., the cardiovascular tissue of a subject to which the cardiac tissue compliant element is applied) enters the systolic phase of the cardiac cycle, the cardiac tissue compliant element expands. Expansion means that energy is transmitted to the cardiac tissue compliant element. In some cases, expanding the cardiac tissue compliant element includes expanding aspects of the cardiac tissue compliant element, such as, for example, expanding one or more mid-radius balloons of the cardiac tissue compliant element. For example, in some cases, expanding the cardiac tissue compliant element includes applying pressure to the balloon of the cardiac tissue compliant element or injecting fluid into the balloon of the cardiac tissue compliant element, increasing its volume, including, for example, expanding the outer diameter of the cardiac tissue compliant element. Contraction or systole or contraction portion means the portion of the cardiac cycle in which the cardiovascular tissue contracts (e.g., in some cases, when the ventricles contract after refilling with blood). Diastole or diastole or diastolic portion means the portion of the cardiac cycle in which the cardiovascular tissue relaxes (opposite to contraction) (e.g., in some cases, when the ventricles relax and refill with blood after emptying during systole).

[0066] In other embodiments, the cardiac tissue compliant element is further configured to relax during the systolic period of the cardiovascular tissue. That is, when the cardiovascular tissue (e.g., the cardiovascular tissue of the subject on which the cardiac tissue compliant element is applied) enters the systolic period of the cardiac cycle, the cardiac tissue compliant element relaxes. In other embodiments, the cardiac tissue compliant element is further configured to relax during the diastolic period of the cardiovascular tissue. That is, when the cardiovascular tissue of the subject on which the cardiac tissue compliant element is applied enters the diastolic period of the cardiac cycle, the cardiac tissue compliant element relaxes. Relaxation means that energy is not transmitted to the cardiac tissue compliant element. In some cases, relaxing the cardiac tissue compliant element includes collapsing aspects of the cardiac tissue compliant element, such as, for example, relaxing or collapsing one or more mid-radius balloons of the cardiac tissue compliant element. For example, in some cases, relaxing the cardiac tissue compliant element includes decompressing the fluid in the balloon of the cardiac tissue compliant element or removing fluid from the balloon or allowing fluid to be discharged from the balloon, thereby reducing its volume, including reducing the outer diameter of the cardiac tissue compliant element. In some embodiments, upon relaxing or collapsing or contracting the heart tissue compliant element, as described above, the radial force exerted by the balloon on the heart valve can be reduced.

[0067] In an embodiment, the system is configured such that when the cardiac tissue compliant element is expanded, the cardiac tissue compliant element applies pulsating energy to the cardiovascular tissue. That is, in an embodiment, the cardiac tissue compliant element can cycle between an expanded state and a relaxed state, and can be further configured such that in such a cycle, the cardiac tissue compliant element applies pulsating energy to the cardiovascular tissue only when expanded, but not when relaxed or collapsed. In some embodiments, the cardiac tissue compliant element can be expanded and relaxed by periodically applying pressure to one or more mid-radius balloons of the cardiac tissue compliant element, and is further configured such that when the one or more mid-radius balloons are inflated (i.e., expanded), the winged balloon (i.e., the balloon laminated to the outer surface of the one or more mid-radius balloons) applies pulsating energy to the cardiovascular tissue, and when the one or more mid-radius balloons are deflated or decompressed, pulsating energy is not applied to the cardiovascular tissue.

[0068] In embodiments, the cardiac tissue compliant element can be configured to expand and relax (i.e., contract) in a manner synchronized with the diastole and systole of the cardiac cycle. Such expansion and relaxation of the cardiac tissue compliant element can be configured to promote the stable positioning of the cardiac tissue compliant element relative to cardiovascular tissue. That is, the expansion and relaxation of the cardiac tissue compliant element can contribute to positioning the cardiac tissue compliant element in a desired position relative to cardiovascular tissue, and can further contribute to keeping the cardiac tissue compliant element in a relatively fixed (i.e., stable) position and orientation relative to cardiovascular tissue. In some cases, the cardiac tissue compliant element is configured to expand and contract in a manner simulating the behavior of a heart valve.

[0069] In an embodiment, the expansion and / or relaxation of the cardiac tissue compliance element together with the systolic and / or diastolic phase of the cardiovascular tissue can be determined (i.e., controlled) based on a pressure signal, i.e., the result of a pressure sensor, such as, for example, an intravascular pressure monitor or a pressure sensor that measures the pressure across the cardiac tissue compliance element (i.e., the pressure gradient between the proximal position and the distal position relative to the cardiac tissue compliance element), or can be determined based on an electrocardiogram (ECG)-, i.e., the result of an electrocardiogram of the cardiovascular tissue. In other embodiments, the expansion and / or relaxation of the cardiac tissue compliance element in the systolic or diastolic phase of the cardiovascular tissue can be determined (i.e., controlled) based on the result of a blood volume monitor or the result of an imaging system. In an embodiment, the system further includes a controller such as described above, which is configured to expand or contract the cardiac tissue compliance element in the systolic and / or diastolic phase of the cardiovascular tissue. In such embodiments, the controller can be configured to expand or relax the cardiac tissue compliance element based on 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 compliant element based on a predetermined configuration, such as, for example, at a specific frequency (such as a frequency corresponding to an induced cardiac cycle). That is, the controller can be configured to expand or relax the cardiac tissue compliant element according to a predetermined pattern, such as, for example, can be preprogrammed for operating the controller. In some embodiments, the controller can be configured to expand the cardiac tissue compliant element for a period of time between 40 beats per minute and 150 beats per minute.

[0070] In embodiments, the controller may be configured to provide feedback to an operator of the system of the invention in any convenient manner. In some cases, the controller is configured to provide tactile feedback to the operator by, for example, vibration. For example, the controller may be configured to cause a handle or other interface with the operator of the system to vibrate upon a relevant change or determination (such as a measurement of a sensor, e.g., a change in the compliance of cardiovascular tissue). Such tactile feedback may be used in conjunction with indicating to an operator of an embodiment of the system a change in the configuration of the system.

[0071] Manifold Assemblies :

[0072] The system of the present invention includes a manifold assembly. The manifold assembly (also referred to as a manifold unit or a manifold subsystem) is used in embodiments of the system according to the present invention to receive energy transmitted from a potential source of a console assembly and transmit such energy to a catheter assembly. In an embodiment, the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the potential source. In such instances, the oscillator is used to adjust the amplitude and timing of the potential energy from the potential energy source so as to provide the desired energy for applying the pulsating energy to the cardiovascular tissue via the cardiac tissue compliance element.

[0073] 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. In some embodiments in which the console assembly includes one or more console units, as described above, 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 can 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 the energy to one or more oscillators in the manifold assembly. In an embodiment, any convenient input and output connection can be adopted, such as commercially available connectors, such as pneumatic connectors, hydraulic connectors, electrical connectors, or optical connectors.

[0074] In some instances, the manifold assembly may receive potential energy, such as from one or more console units of the console assembly, and distribute the potential energy to one or more oscillators in the manifold assembly. In some cases, there is a one-to-one correspondence between the console units and the oscillators in 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 as, for example, such that the potential energy of one or more console units is combined in a single oscillator.

[0075] In an embodiment, the energy transmitted to the manifold system oscillator includes a regulated fluid or an unregulated fluid under pressure. The oscillator can be actuated to output pulsation and / or static pressure output. In certain embodiments, in the case where the potential energy transmitted by the console assembly is a regulated fluid or an unregulated fluid under pressure, the oscillator can include a solenoid valve. Such solenoid valves can include, for example, two-position, three-way, normally closed solenoid valves. In such instances, the solenoid valve is configured to receive a fluid or an unregulated fluid regulated by high pressure. Such solenoid valves can be configured to have two modes, i.e., an "open" mode and a "closed" mode. Such solenoid valves can be configured to have three ports: a port (i.e., an input port) operably connected to a fluid or an unregulated fluid regulated by high pressure, a port (i.e., a first output port) operably connected to a conduit assembly that is ultimately connected to the conduit assembly, and a discharge port (i.e., a second output port). The solenoid valve can be configured so that when opened (i.e., in "open" mode), the valve allows a fluid or an unregulated fluid regulated by high pressure to be transmitted, i.e., transmitted downstream in the system, such as a conduit assembly transmitted to the system. The valve can be further configured such that when closed (i.e., in an "off" mode), the solenoid changes (i.e., reverses) the connected port so that the distal side of the valve is vented (e.g., to atmosphere or 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.

[0076] In some embodiments, the frequency and / or duty cycle of the oscillator can be adjusted to produce an appropriate output for treatment and for the catheter assembly (including its cardiac tissue compliant element). 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 some instances, an oscillator configured to deliver, for example, pulsatile intravascular lithotripsy to cardiovascular tissue can be configured to oscillate at a frequency between 0 and 50 Hz (such as 1-10 Hz or 10-20 Hz or 21-30 Hz or 31-40 Hz or 41-50 Hz) and a duty cycle between 10% and 90% (such as 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%). In instances where the oscillator is configured to deliver pulsatile pressure pulses using fluid pressure for treatment involving achieving vascular perfusion of cardiovascular tissue, the oscillator may oscillate at a frequency between 0.25 Hz and 5 Hz, such as 1 Hz or 2 Hz or 3 Hz or 4 Hz or 5 Hz, and at a duty cycle between 10% and 90%, such as 10% or 20% or 30% or 40% or 50% or 60% or 70% or 80% or 90%. In instances where the oscillator is configured to deliver pulsed energy comprising an optical source or a high voltage source, the oscillator can oscillate at a frequency of 0.1 Hz to 1 GHz, such as 1 Hz or 2 Hz or 3 Hz or 4 Hz or 5 Hz or higher, and at a duty cycle of between 0.0001% and 90%, such as 0.001% 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%.

[0077] Additional details regarding various aspects of manifold assemblies, oscillators, etc., and components thereof that may be employed in embodiments of the present invention are provided in U.S. published patent application publication number 20200046949 and pending PCT application serial number PCT / US2020 / 055458 and U.S. application number 63274832; the disclosures of these applications are incorporated herein by reference.

[0078] In certain embodiments, the output from an oscillator of a manifold assembly, or in embodiments having more than one oscillator, the output from various oscillators, can be transmitted to one or more locations. In other embodiments including more than one oscillator, the oscillators can be synchronized with each other, for example, so that the pulsating energy transmitted from each oscillator is synchronized as desired, for example, in amplitude, frequency, phase, duty cycle, etc. In other embodiments having one or more oscillators, the oscillators can be synchronized with external factors or systems or sensors, such as, for example, the results of an electrocardiogram (ECG), or can be adjusted based on feedback from a controller or other subsystem (e.g., such as volume or pressure measurements derived from the catheter assembly, such as volume or pressure measurements detected by sensors present on the cardiac tissue compliance element or catheter). In other embodiments, one or more oscillators may be controlled based on signals from a heart valve delivery system (e.g., a transcatheter aortic valve replacement (TAVR) delivery system), such as data regarding position, percentage of valve deployment, amount of valve opening, nominal characteristics, eccentricity of the valve, paravalvular leakage, ambient pressure and / or stress on the valve, proximal and / or distal pressures, position of the valve in the annulus, etc. That is, the controller may be configured to adjust the behavior of the oscillator based at least in part on such data.

[0079] In other embodiments, the manifold assembly can further include multiple inlet sources (e.g., connections to a console unit), a manifold housing (e.g., a casing for the manifold assembly), multiple oscillators, oscillator connection points (e.g., for transmitting energy from the oscillators to the catheter assembly), controller connection points (e.g., for transmitting input from sensors internal and / or external to the system), and a user feedback and / or control area (e.g., for a user to adjust the operation of the system).

[0080] In the various embodiments described, the manifold assembly, like the console assembly, can be configured as disposable or reusable. Where the manifold assembly (or console assembly) is reusable and can contact the patient area, such assembly can be configured to be covered in 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 components of the console assembly and the manifold assembly are retained within a single common housing). In other embodiments, the manifold assembly can be configured in the form of a handle so that an operator of the system can hold the manifold assembly during use or therapy.

[0081] In some embodiments, as described above, components of the control subsystem or controller may be located within the manifold assembly housing and / or within the console assembly housing. In some cases, the manifold assembly and / or the console assembly include a user interface configured to allow an operator of the system to access the manifold assembly or the console assembly to start or stop treatment, adjust treatment intensity, adjust treatment mode, or adjust other relevant aspects or configurations of the system.

[0082] Catheter components :

[0083] The system of the present invention includes a catheter assembly. The catheter assembly (also referred to as a catheter subsystem) is used in an embodiment of the system according to the present invention to receive energy transmitted from the manifold assembly and apply pulsating energy to cardiovascular tissue. An embodiment of the catheter assembly includes a connector that operably connects the catheter assembly to the manifold assembly and is configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy; a catheter that includes a fluid channel that is operably connected to an output end of the connector and is configured to transmit the second pulse of energy; and a cardiac tissue compliance element that is configured to receive the second pulse of energy transmitted through the fluid channel of the catheter to apply pulsating energy to cardiovascular tissue.

[0084] Connectors :

[0085] As described above, in the system according to the present invention, the catheter assembly includes a connector, also referred to as a proximal connector. The embodiment of the connector operably connects the manifold assembly to the catheter assembly and is configured to convert the first pulse energy generated by the manifold assembly into a second pulse energy. In certain embodiments, one or more connectors are used to connect the manifold assembly to the catheter assembly and are configured to receive and transmit the potential energy transmitted by one or more oscillators of the manifold assembly. The embodiment of the connector has a proximal connection point so that in some instances, the connector can be releasably coupled to the manifold assembly or fixed to the manifold assembly. The embodiment of the connector also has a distal transmission point. The connector can be configured so that the distal transmission point delivers the energy transmitted from the oscillator to the fluid channel of the catheter, for example, and finally delivers to the cardiac tissue compliance element for applying such energy to cardiovascular tissue. In an embodiment, the connector is a component of the system located at the proximal end of the assembled system, for example, close to the proximal end, for example, within 1 m or closer to the proximal end.

[0086] In some instances, the energy transmitted via the connector can be in the form of hydraulic pulses, including, for example, hydraulic pulses such as those useful in pulsating intravascular lithotripsy, or hydraulic pulses used to pulsate a cardiac tissue compliant element (i.e., its balloon) to allow perfusion to pass through the cardiac tissue compliant element to a distal vessel. In other instances, the energy transmitted via the connector can be in the form of electrical pulses, so that cavitation bubbles, ultrasound, plasma bubbles, or other high-voltage pulses are generated. In still other instances, the energy transmitted via the connector can be in the form of light pulses or laser pulses, so that cavitation bubbles, ultrasound, plasma bubbles, or other high-voltage pulses are generated. In still other instances, such energy transmitted via the connector can be in the form of thermal energy or energy, for example, for cryotherapy, i.e., applying heat or cold to cardiovascular tissue.

[0087] In embodiments, connector comprises proximal chamber and distal chamber separated by film.The volume of each in proximal chamber and distal chamber can change, in some instances in the range of 0.1 mL to 100 mL (such as 1 mL to 4 mL), wherein in some instances, proximal chamber and / or distal chamber are occupied by liquid.In each case, proximal chamber is finally (that is, via oscillator) operably connected to potential source, such as for example pressure source, and is configured to convert energy (that is, pressure) to distal chamber via film.Although the form of connector in embodiments can change, in some instances, proximal chamber is limited by proximal flange, and distal chamber is limited by distal flange, wherein proximal flange and distal flange are positioned on either side of film, to limit proximal chamber and distal chamber, proximal chamber and distal chamber can be sealed to each other by separation membrane.

[0088] The membrane is configured to move in response to pressure applied to the proximal chamber and, based on such movement, to generate pressure in the distal chamber of the connector. The size of the membrane can vary, with the membrane having a diameter of 100 mm in some examples. 2 Up to 5,000 mm 2 within the range (such as 500 mm 2 Up to 2,000 mm 2 ) area. The membrane can be made of any convenient elastic (e.g., pliable) material, wherein in some instances, the material has a hardness in the range of Shore 10A to Shore 90A (such as Shore 50A), and a thickness between 0.5 mm and 5 mm (such as 1.0 mm to 2.5 mm). Examples of suitable membrane materials include, but are not limited to, silicone, rubber, and the like, and in some cases can be strengthened by adding reinforcing components such as braids. Where necessary, a biasing member such as a spring can be provided to provide a default or baseline membrane position. For example, a spring can be provided on the distal chamber side of the membrane, and when the force is removed from the proximal chamber side of the membrane, the spring pushes the membrane back to the initial position.

[0089] In an embodiment, the proximal chamber of the connector includes a port that operably connects the proximal chamber ultimately (i.e., via an oscillator) to a source of electrical potential, such as a pressure source. Similarly, in an embodiment, the distal chamber of the connector includes a port that operably connects the distal chamber ultimately to a fluid passage of a catheter and ultimately to a cardiac tissue compliant element.

[0090] Where necessary, the connector may include one or more sensors, for example, the sensor is configured to provide data about one or more components of the system. Any convenient type of sensor may be included in the proximal connector, where the sensors of interest include, but are not limited to, pressure sensors, position sensors, displacement sensors, proximity sensors, flow sensors, temperature sensors, and the like. In some instances, the connector includes a pressure sensor operably coupled to the distal chamber. In such instances, the pressure sensor may detect the pressure of a fluid (such as a liquid) in the distal chamber and changes therein. When included, any convenient type of pressure sensor may be present, where examples of pressure sensors that may be present include, but are not limited to, resistive pressure sensors, capacitive pressure sensors, piezoelectric pressure sensors, optical pressure sensors, and MEMS-based pressure sensors, and the like. In some instances, the proximal connector includes a membrane position sensor configured to provide spatial data about the position of the membrane at a given time (e.g., during use of the system). When present, any convenient membrane position sensor may be employed. In some examples, the film position sensor is a Hall sensor, for example, it can be used in combination with one or more magnets (e.g., one or more permanent magnets or electromagnets or a combination thereof) present at one or more fixed positions relative to the film (such as a fixed position of a proximal connector, etc.), so that one or more fixed magnets are positioned to adjust the voltage of the Hall sensor when the film moves. For example, in an embodiment, the magnets can be present on both sides of the Hall sensor, with the magnetic poles facing each other. That is, in some cases, the magnets can be oriented so that their magnetic poles face each other across the Hall sensor. In some cases, one or more magnets are used in the position sensor of the embodiment of the present invention to generate a linear voltage or current output in each case, because such a voltage or current output may be related to the position of the film. In other examples, the film position sensor can be an optical sensor, an electric field potential sensor, a resistance sensor, a magnetic sensor, an angle sensor, or an acceleration sensor. In addition, any combination of these sensors can be used to collect the position data of the film or diaphragm. In the case of a combination of film position sensors, for example, in order to ensure that the sensor provides correct data under various conditions, such as frequency, the sensor data can be combined by "sensor fusion" technology (such as those known in the art). The manufacturing methods of the film sensor may include but are not limited to: adhesives, direct printing, welding, embedding, etc.

[0091] In instances where the connector is configured to deliver hydraulic pulses, including, for example, situations such as those useful in pulsatile intravascular lithotripsy, a connector configured to deliver low volume, high frequency, and high pressure pulses may be used. As described above, an embodiment of the connector includes an inlet port that receives pulsatile energy and / or static energy from a manifold assembly and outputs the pulsatile energy and / or static energy to a distal transmission point of the connector. Additional details regarding embodiments of connectors that may be employed in conjunction 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.

[0092] In the example where the connector is configured to pulse various aspects of the cardiac tissue compliance element, such as to allow perfusion to the distal blood vessels (i.e., to allow perfusion through the cardiac tissue compliance element), a connector that can deliver high-volume, low-frequency and low-pressure pulses can be used. In some embodiments, such connectors can be substantially in the form of a barrel syringe to deliver large volume changes. The barrel syringe connector of interest may include a pneumatic input port, a fluid output port, a plunger, a pneumatic chamber and a fluid chamber. In some instances, the plunger (i.e., the piston) of the barrel syringe can be connected to a bias spring, which will enable the piston to quickly return to its initial state. In this case, some or all of the fluid volume will be removed from the fluidically coupled cardiac tissue compliance 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), which will help to empty the proximal side of the barrel syringe so that the piston of the barrel syringe type connector will return to the initial position, i.e., the equilibrium position. In embodiments of such connectors, a fluidly coupled cardiac tissue compliant element (i.e., one or more balloons of the cardiac tissue compliant element) positioned at the distal region of the catheter can be rapidly inflated or deflated. Embodiments of such connectors can have various sensors that monitor the state of the cardiac tissue compliant element, such as pressure sensors, volume sensors, etc.

[0093] In other examples, the connector does not include a pneumatic connection or a fluid connection. Embodiments of connectors that do not include a pneumatic connection or a fluid connection can be configured to deliver pulsating energy using any convenient technology, including, for example, pulsating energy such as useful in intravascular lithotripsy, as such technologies are known to those skilled in the art, including, for example, by generating cavitation bubbles. In some cases, such embodiments of the connector are configured to deliver pulsating energy using cavitation-based technology, plasma-based technology, voltage-based technology, light-based technology, laser-based technology, ultrasound-based technology, or other sound-based technology, including pulsating energy associated with performing intravascular lithotripsy. Such embodiments of the connector may include one or more power cables or optical cables that exist transversely over the length of the system and are configured to enable cavitation, ultrasound-based therapy, or laser-based therapy to treat cardiovascular tissue (such as, for example, a heart valve). Embodiments of the connector can transmit light or high pressure or acoustic energy from an oscillator in a manifold subsystem to a distal transmission point of the connector via a proximal connection port of the connector. In such instances, the distal transmission point of the connector may include a series of electrodes or one or more laser targets configured to generate cavitation bubbles or plasma bubbles.

[0094] In an example, an embodiment of the connector can receive power from an oscillator mechanism to heat or cool a fluid in a distal chamber of the connector or at a distal connection of the connector such that the temperature change has a therapeutic effect on the cardiovascular tissue, or, for example, dissolves an active agent present on the system, such as an active agent coating a cardiac tissue compliant element, such as a drug, etc.

[0095] In other examples, the connector can be configured to collect information from the catheter and / or cardiac tissue compliant element and / or transmit information to the manifold subsystem. Such information can include, for example, pressure, temperature, volume, preload data (e.g., characteristics of cardiovascular tissue before application of pulsatile energy), state of the cardiac tissue compliant element, balloon state, lesion compliance, lesion opening, intravascular imaging data, drug delivery volume, blood volume delivered during perfusion, etc.

[0096] Input signal relative to output signal in a mechanical system :

[0097] The described embodiments are dynamic physical systems in which the output of the system (e.g., actual frequency, duty cycle, and amplitude) is controlled by system inputs (e.g., desired frequency, duty cycle, and amplitude) and system characteristics (e.g., catheter length, friction, and flow channel lumen diameter). Embodiments of the system are configured to generate controlled mechanical pulses, such as lithotripsy pulses, in a cardiac tissue compliant element (e.g., via one or more balloons thereof) such that the system output tracks the commanded input signal or the desired input signal with minimal attenuation in some instances. Signal attenuation is a decrease in the amplitude of the system output relative to the input due to the characteristics of the physical system. Minimal attenuation is required for successful treatment because when the input pulsatile energy propagates from the system input (e.g., potential source, oscillator, and / or connector) to the system output (e.g., cardiac tissue compliant element or one or more balloons thereof), the output pulsatile energy remains substantially similar to the input pulsatile energy in terms of, for example, frequency, duty cycle, and / or amplitude. Thus, in some instances, any change in frequency between the system input and the cardiac tissue compliant element (or one or more balloons thereof), if any, will be 30% or less, such as 20% or less or 10% or less or 5% or less. In some instances, any change in amplitude of the pulsating energy between the system input and the cardiac tissue compliant element (or one or more balloons thereof), if any, will be 30% or less, such as 20% or less or 10% or less or 5% or less. In some instances, any change in duty cycle of the pulsating energy between the proximal connector and the distal balloon, if any, will be 30% or less, such as 20% or less or 10% or less or 5% or less.

[0098] Prior art in the art (e.g., as described in WO 2017 / 168145A1; US ​​2019 / 0000491A1; US6348048 B1; WO 2001 / 010491A2 and US 8574248 B2) has described methods of generating pressure pulses in angioplasty balloons. However, due to system characteristics, the prior art needs to be performed at low frequencies to achieve full pressure pulses, or the prior art suffers from severe attenuation of the signal. In the case of low-frequency pressure pulses, the balloon does not generate enough pulses in the vessel to achieve any improved treatment results. In the case of high-frequency pressure pulses, the system output (i.e., balloon pulses) does not track the system input and / or the system output is severely attenuated by the system characteristics so that the treatment is ineffective. In other cases, the system is designed so that the system input pressure itself is generated with such high friction losses (e.g., piston pump systems) that the high-frequency input pressure pulses are attenuated before being transmitted to the distal region of the system.

[0099] Connector to Conduit Transition Hub :

[0100] In an embodiment (including, for example, an embodiment comprising a plurality of connectors), various connectors converge to one or more connectors to a catheter hub region, wherein the connector output is coupled to transition to a flexible elongated 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), and the output of the connector may be connected to these tubes and transmit energy. In an embodiment, the connector may be connected to such a tube or fluid channel that energy is transmitted to the catheter via the inflatable lumen. In an embodiment, such a tube or fluid channel may traverse the entire transverse length of the catheter assembly, or may only traverse a portion of the length of the catheter assembly.

[0101] The connector-to-conduit hub may be made of any convenient material such as polyvinyl chloride (PVC) or polycarbonate (PC), etc., and may include strain relief elements such as, for example, flexible tubing to provide flexibility in positioning the hub relative to the conduit and relative to one or more connectors.

[0102] In an embodiment, a guidewire channel can be integrated into the connector to catheter transition hub to enable a standard over-the-wire approach for translating a catheter assembly or its cardiac tissue compliant element to a position proximal to a desired region of cardiovascular tissue. Embodiments of the system can be configured with respect to the guidewire and the guidewire channel so that it is an over-the-wire catheter system, a rapid exchange catheter system, a monorail catheter system, etc.

[0103] catheter :

[0104] As described above, in the system according to the present invention, the catheter assembly includes a catheter, also referred to as an elongated catheter. The embodiment of the catheter includes a fluid channel operably connected to the output end of the connector and is configured to transmit pulse energy to the cardiac tissue compliance element (i.e., the second pulse energy).

[0105] In embodiments, the catheter assembly may include a semi-rigid, flexible, elongated catheter that is intended to be traversed from a position away from cardiovascular tissue (e.g., from the position of the femoral artery or radial artery) to a treatment site (e.g., other positions of the aortic valve or proximal cardiovascular tissue). Although the size of the catheter may vary, in some instances, as required, the catheter of the present invention may be configured so that their size is set to be suitable for passing through a 4 to 26 Fr introducer sheath, such as a 4 Fr introducer sheath, a 10 Fr introducer sheath, a 15 Fr introducer sheath, a 20 Fr introducer sheath, or a 25 Fr introducer sheath or larger introducer sheath, depending on, for example, the size of the subject's associated artery, the size of the cardiac tissue compliant element, or other factors. In embodiments, 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 that the outer diameter falls within the range of 6 Fr to 12 Fr. In some cases, the desired outer diameter is 20 Fr or less, such as 20 Fr, 19 Fr, 18 Fr, 17 Fr, 16 Fr, 15 Fr, 14 Fr, 13 Fr, 12 Fr, 11 Fr, 10 Fr, 9 Fr, 8 Fr, 7 Fr, 6 Fr, 5 Fr, 4 Fr, 3 Fr, 2 Fr or 1 Fr or less. In other cases, the desired outer diameter falls within the range of 2 mm to 4 mm. In an embodiment, the outer diameter of the catheter can be varied as needed, which depends in particular on the characteristics of cardiovascular tissue, including the diameter of proximal luminal tissue such as arteries or veins or other vessels. In other examples, the outer diameter of the catheter can vary according to the characteristics of cardiovascular tissue (such as the size of a heart valve such as a heart valve leaflet or a heart valve commissure, or the degree or scope of calcification).

[0106] The outer diameter of the catheter can vary in different areas of the catheter. In some instances, the catheter can be tapered. In such instances, the catheter can include a taper in the range of 0.01º to 5º, such as 1º or 2º or 3º or 4º, over a certain area of ​​the catheter. In some instances, different areas of the catheter can include different amounts of tapering, including no tapering in some instances. The amount of tapering can vary, in particular, depending on different applications of the system, including the shape or other characteristics of the cardiac tissue compliant element, and different characteristics of the cardiovascular tissue to which the system is to be applied.

[0107] In embodiments, the length of the conduit can vary. For example, the conduit can have a length between 50 and 300 cm, such as a length of 50 cm or 100 cm or 145 cm or 200 cm or 250 cm or 300 cm.

[0108] The catheter can be made of any convenient and appropriate physiologically acceptable material, including but not limited to rubber, silicone, polyurethane, polyimide (such as polyimide braid) or polyimide-type materials, etc. The embodiment of the catheter may further include a thermoplastic sheath, such as polyimide. In some instances, the catheter may include an external coating selected based on the application of the system. For example, in some cases, the embodiment of the catheter may further include a lubricating external coating. Any convenient coating that reduces the friction associated with the interaction of the catheter and the internal luminal tissue through which the catheter passes can be used. In some cases, such an external coating may include polytetrafluoroethylene (i.e., PTFE). In an embodiment, the catheter or its aspects (e.g., the distal region of the catheter) can utilize stainless steel or nitinol or a hypotube such as a laser-cut hypotube (e.g., composed in whole or in part of it).

[0109] As described above, embodiments of the catheter can have one or more channels, such as fluid channels or passages, with various functions as desired. For example, embodiments of the catheter can include one or more channels that are used, among other things, to: (1) pass at least one guidewire for navigating the catheter assembly and / or the cardiac tissue compliant element to a treatment site, i.e., a designated proximal end of cardiovascular tissue; (2) inflate various aspects of the cardiac tissue compliant element (e.g., one or more balloons of the cardiac tissue compliant element) by, for example, propagating pressure along the fluid channel; (3) deliver intravascular lithotripsy pulses; (3) allow blood perfusion (e.g., from the left ventricle to the aorta); and / or (4) perform various measurements, such as pressure measurements, such as aortic or ventricular pressure, pressure of the cardiac tissue compliant element, such as pressure of a balloon of the cardiac tissue compliant element, expansion of the cardiac tissue compliant element, such as expansion of a balloon of the cardiac tissue compliant element, presence or extent of calcium cracking (i.e., disruption of calcification), valve tissue impedance, valve compliance, commissure opening, replacement heart valve opening, etc.

[0110] In embodiments, it is configured to propagate energy (that is, the second pulse energy), such as the fluid channel of the conduit of fluid pressure longitudinally extends along the conduit, for example, extends from the proximal region of the conduit to the distal region of the conduit. In some embodiments, the fluid channel of the conduit is configured to receive the energy converted from one or more connectors. For example, the fluid channel of the conduit can be configured to receive energy from each of the proximal connectors of the barrel syringe connector and the proximal chamber and the distal chamber separated by the film, as described above, and 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 work synchronously, to fill the fluid channel and produce pulse energy. In such embodiments, the barrel syringe can be used for filling the system, that is, the baseline pressure is applied to the fluid present in the fluid channel, and the proximal connector is used to provide pulsating energy to the fluid present in the fluid channel at the baseline pressure subsequently. In embodiments, the fluid channel can be connected to one or more connectors, such as one, two, three, four, five, six, seven, eight, nine, ten, 20, 50 or 100 or more connectors. Such connectors that are connected to a single fluid channel can be of the same type and / or configuration, or can be different in any relevant aspect. A plurality of connectors attached to a single fluid channel can be synchronous, or otherwise configured to convert energy to fluid channel in any convenient manner. In other cases, the output of a single connector can be operably connected to a plurality of fluid channels. For example, in an embodiment, the output of a single barrel syringe can be operably connected to a plurality of fluid channels so that the barrel syringe can be used to fill the fluid present in each fluid channel in a plurality of fluid channels. In other words, the barrel syringe can be configured to apply a baseline pressure to the fluid present in each fluid channel in a plurality of fluid channels, and because a barrel syringe is operably connected to a plurality of fluid channels, each fluid channel in the fluid channel is filled simultaneously. In an embodiment, a connector can be operably connected to a single conduit or a plurality of fluid channels more than one conduit.

[0111] The cross-sectional flow area of ​​the internal passage (ie, fluid passage) of the catheter can vary. In some examples, the cross-sectional flow area of ​​the fluid passage of the catheter is between 0.1 mm 2 Up to 50 mm 2 In the range of 1 mm 2 Up to 5 mm 2. In an embodiment, the cross-sectional flow area can take any convenient geometric shape, such as, for example, substantially circular or substantially elliptical or substantially triangular or substantially rectangular or substantially polygonal or a combination thereof. In some instances, the fluid channel of the catheter extends from the proximal region of the catheter to the cardiac tissue compliant element (e.g., the balloon of the cardiac tissue compliant element). In such instances, the fluid channel is configured to propagate energy (e.g., pressure) from the proximal region of the catheter (i.e., from the connector or the output end of the connector to the catheter hub) to the distal region of the catheter along the fluid channel, such as propagating to the cardiac tissue compliant element operably connected to the fluid channel. In an example, the fluid channel can be configured to include a fluid. In such instances, applying pressure to the fluid enables the pressure to propagate along the fluid channel. Any convenient fluid can be used, for example, a saline solution containing a contrast agent fluid or not containing a contrast agent fluid.

[0112] At a distal region of the catheter assembly, one or more channels (e.g., fluid channels) of the catheter extending the length of the catheter can be separated or manifolded or otherwise separated so that the one or more channels are directed (i.e., routed to) their respective destinations, e.g., a balloon, an electrode, a target, a sensor, a port, etc.

[0113] In certain embodiments, the catheter is configured to pass through the guide wire so that the catheter assembly and its cardiac tissue compliant element can be guided to the correct anatomical position. The guide wire of interest can include any convenient, commercially available guide wire as needed, such as standard 0.014 "or 0.035" or other size of the guide wire. The embodiment can include a guide wire lumen in the catheter, which is configured to receive such a guide wire. The catheter assembly can be configured so that the guide wire lumen can be located axially of the catheter or can be located on one side of the catheter. In an embodiment, the guide wire lumen is configured so that the guide wire present in the guide wire lumen of the catheter can be longitudinally traversed relative to the catheter, thereby guiding the catheter and the cardiac tissue compliant element to the treatment site. In some cases, the guide wire is configured to extend beyond the distal end of the catheter, that is, the catheter can be configured to include both a guide wire inlet port and an outlet port.

[0114] In embodiments, the catheter assembly, including the catheter of the catheter assembly in some cases, includes an integrated imaging subsystem. In some embodiments, the imaging subsystem is an imaging subsystem based on light, an imaging subsystem based on fluoroscopy, an imaging subsystem based on ultrasound, or an imaging subsystem based on OCT or an imaging subsystem based on other available imaging techniques. The imaging subsystem of interest can utilize one or more such imaging modalities. Such integrated imaging subsystems can be used to confirm that the embodiments of the system of the present invention are applied to the desired anatomical region or feature of the subject. Such integrated imaging subsystems can be configured to produce images of the internal luminal tissue of the subject, for example. Such integrated imaging subsystems can realize the visualization of the positions of various aspects of the system (such as cardiac tissue compliance elements) relative to various aspects of the anatomical structure of the subject. In embodiments, as described above, the integrated imaging subsystem can be further integrated with the control subsystem of the device. For example, the control subsystem of the device can receive imaging data from the imaging subsystem, and / or the control subsystem can control various aspects of the imaging subsystem, such as indicating the imaging subsystem to start imaging or switching the imaging subsystem between different imaging modalities, for example ultrasound relative to OCT, or guiding the imaging subsystem towards different fields of view. In an embodiment, the imaging subsystem may include one or more ultrasound probes, transducers and receivers, and associated electronics. In an embodiment, the imaging subsystem may include radiopaque labels present at specified locations on a catheter assembly (e.g., a catheter or a cardiac tissue compliant element). In an embodiment, the imaging subsystem may include an illumination element and a light detector or camera and associated electronics.

[0115] Perfusion mechanism :

[0116] In some embodiments, catheter assembly can be configured to use active mechanism and / or passive perfusion mechanism to allow fluid (for example, blood) to perfuse through catheter assembly, i.e., through cardiac tissue compliant element.That is to say, catheter assembly can be configured to make when catheter assembly (comprising catheter and cardiac tissue compliant element) is positioned at cardiovascular tissue proximal end, for example, when being applied to cardiovascular tissue (such as, the cardiovascular tissue in the artery of experimenter), catheter assembly is configured to allow blood to perfuse through catheter assembly, especially comprises the cardiac tissue compliant element through catheter assembly, i.e., otherwise may block or impedance blood flow to distal blood vessel.For example, catheter assembly can be configured to allow blood to perfuse in the proximal aorta of experimenter from left ventricle when cardiac tissue compliant element is present near aortic valve.

[0117] The region of the conduit through which the perfusion mechanism enables blood to flow is referred to as the distal conduit perfusion section. The remainder of the conduit that is not the distal conduit perfusion section (that is, the part of the conduit that does not include the perfusion mechanism) is referred to as the proximal conduit section. In an embodiment, the distal conduit perfusion section can have any convenient length, such as, for example, between 5 mm and 150 mm, such as a length of 5 mm or 10 mm or 40 mm or 100 mm or 150 mm. The length of the distal conduit perfusion section can vary according to, for example, the length or other features of the heart tissue compliant element. In an embodiment, the distal conduit perfusion section and the proximal conduit section can include two separate parts, which are attached together to form a conduit assembly. Such configuration can easily change the heart tissue compliant element attached to the distal conduit perfusion section from one application to another. In an embodiment, the conduit assembly can be configured so that the distal conduit perfusion section is connected to the proximal conduit section by a traumatic tapering section or step.

[0118] Active perfusion refers to an active mechanism for pulling or pushing or otherwise displacing a fluid (e.g., blood) from one region to another, i.e., through a distal catheter perfusion segment and through a cardiac tissue compliance element. Passive perfusion refers to a mechanism configured to achieve fluid (e.g., blood) perfusion based on, for example, a pressure gradient, such as an existing pressure gradient generated by, for example, pressure exerted by cardiac contraction on different tissue regions (e.g., inside and outside 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 allowing 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 in cardiovascular tissue (such as a pressure gradient generated by the left ventricle entering the aorta). Active-passive perfusion refers to a combination of an active mechanism and a passive mechanism, such that a portion of the energy that drives perfusion (i.e., the flow of fluid through the cardiac tissue compliance element) is generated by the active mechanism and a portion is generated by the passive pressure gradient.

[0119] In an embodiment, a distal region of the catheter at or near the distal end of the catheter (i.e., a distal catheter perfusion section) is configured such that a portion of its internal cross-sectional area is dedicated to allowing blood to be perfused from a relatively distal location of the catheter assembly to a relatively proximal location of the catheter assembly, such as from the left ventricle to the aorta, through the cardiac tissue compliance element. In such embodiments, in some cases, the cross-sectional area of ​​the distal catheter configured to enable blood to flow (i.e., the distal catheter perfusion section) can be within 1 mm 2 and 50 mm 2 between, such as 1 mm 2 or 5 mm 2or 12 mm 2 or 15 mm 2 or 20mm 2 or 30 mm 2 or 40 mm 2 or 50 mm 2 .

[0120] In some cases, the distal region of the catheter can include a tip attached to the distal region of the catheter that is configured to provide an opening for blood to enter the distal catheter perfusion segment (i.e., a distal catheter perfusion inlet port) and is also shaped or otherwise configured to reduce any trauma to surrounding tissue as the catheter tip including the distal catheter perfusion inlet port and the catheter and cardiac tissue compliant element traverses through, for example, a blood vessel and across, for example, a heart valve to a location proximal to the cardiovascular tissue of a subject being treated.

[0121] In an embodiment, the catheter assembly may include one or more ports (i.e., port holes) configured to allow blood to enter and leave, i.e., to be perfused to, for example, the aorta from the distal region of the catheter assembly. For example, such ports may be present in one or both of the catheter and the cardiac tissue compliant element. Such ports may be arranged in the perfusion inlet area and the perfusion outlet area. The ports in the perfusion inlet area and the perfusion outlet area may be uniformly configured on the region of the catheter assembly, or may be gathered near important branches, which are intended to be anatomical branches at the proximal end of the catheter assembly when the catheter assembly is positioned to apply treatment to cardiovascular tissue (such as, for example, the coronary artery ostium). Embodiments may include any convenient number of ports in each of the perfusion inlet area and the perfusion outlet area, and these ports may vary. For example, embodiments can include between 1 and 5,000 or more ports in each of the perfusion inlet area and the perfusion outlet area, such as one, two, three, four, five, six, seven, eight, nine, ten, 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 embodiments, the quantity and configuration of the ports constituting the perfusion inlet area and the perfusion outlet area can be different. In embodiments, the perfusion inlet area and the perfusion outlet area can include the configuration of multiple ports and / or ports so that the ports will not introduce structural weaknesses in the catheter assembly. Depending on the circumstances, the ports can be configured to have any convenient diameter, cross-sectional shape and arrangement on the catheter or heart tissue compliant element, and these can vary. For example, embodiments may 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 that the port have a diameter of 1 mm or greater, so as to allow sufficient fluid perfusion through the perfusion inlet area and / or the perfusion outlet area. In embodiments, the ports of the perfusion inlet area and the perfusion outlet area may be configured to reduce or minimize the amount of internal resistance encountered by the fluid perfused from the perfusion inlet area to the perfusion outlet area. In some cases, one or more ports of the perfusion outlet area are configured so that the total flow area (i.e., the cross-sectional area available for fluid perfusion) matches or exceeds the flow area of ​​the perfusion inlet area. The arrangement of the ports on the catheter and / or the cardiac tissue compliant element may adopt any convenient mode. The number of ports, their diameters, and their arrangement on the catheter assembly may be selected to ensure that the catheter maintains its desired structural characteristics despite the presence of ports.In some embodiments, specifically, the number of ports, their diameters, and their arrangement on the catheter assembly can be selected to ensure that the catheter maintains sufficient rigidity for applying pulsatile energy to cardiovascular tissue (i.e., via the cardiac tissue compliant element), and to enable sufficient blood to be perfused through the cardiac tissue compliant element to fully perfuse the distal blood vessels. In an embodiment, any convenient technique capable of forming a port with desired characteristics can be used to form the port. For example, in some cases, a laser can be used to form the port, i.e., the embodiment can be a laser port. In other cases, the port can be scraped, i.e., by using a scraping technique in an embodiment to produce a desired port. In still other cases, the port can be formed using a braided configuration, i.e., the embodiment can be formed in part using a braiding technique that forms a desired port.

[0122] As mentioned above, in embodiments, conduit assembly is configured so that a part of conduit assembly is configured to retrieve blood (for example, retrieve blood from the relative distal region of conduit), and another part of conduit can be configured to deliver blood (for example, deliver to the relative proximal region of conduit).In embodiments, the continuous reciprocating motion of tubular syringe connector can be configured to evacuate (or otherwise produce low pressure region) on inlet (that is, blood is retrieved) port, and fluid (that is, blood perfusion) is pushed to the port in conduit assembly, to keep blood flowing, that is, although there is conduit assembly, still keep blood perfusion to distal blood vessel.For example, in embodiments, two one-way valves can be configured to ensure that a complete stroke of the reciprocating motion of connector (for example, tubular syringe connector) extracts blood from a region of for example blood vessel, and is pushed to another region.In some instances, active perfusion can be performed repeatedly to simulate the pumping motion of the heart, or in other instances, active perfusion can be performed to start pressure gradient, for example, the pressure gradient across the heart valve.

[0123] In some cases, the perfusion mechanism, in particular the cross-sectional area of ​​the perfusion mechanism as described above, includes a valve configured so that fluid (e.g., blood) cannot flow back from the proximal position (e.g., the perfusion inlet area) to the distal position (e.g., the perfusion outlet area). Any convenient valve can be applied, and can be located in any convenient area of ​​the perfusion mechanism (such as the perfusion inlet area or the perfusion outlet area), or in the fluid channel connecting the perfusion inlet area and the perfusion outlet area. In some instances, such valves can be passive one-way valves. Such one-way valves can be configured to open when the pressure on the distal side of the valve (i.e., in the relative distal area of ​​the catheter assembly) becomes higher than the pressure on the proximal side of the valve (i.e., in the relative proximal area of ​​the catheter assembly), and close when the pressure difference is reversed (i.e., when the blood flow is reversed). In other configurations, the oscillating balloon can be configured in the fluid channel or blood flow path of the perfusion mechanism of the catheter assembly (i.e., in the perfusion cross-sectional area of ​​the perfusion mechanism), and can be used to open and close one or more ports to allow and / or prevent blood from flowing through such one or more ports.

[0124] In some configurations, the surface of the inner lumen of the perfusion cross-sectional area of ​​the catheter assembly (that is, the inner surface of the perfusion mechanism) can be coated so that it is smooth or prevents the coagulation of blood passing through such areas. In embodiments, the inner surface of the catheter can be coated with a hydrophilic coating or a hydrophobic coating. In other examples, the inner surface of the catheter can be coated with an activating agent, such as a heparinized coating.

[0125] In other configurations, the interior lumen of the perfused 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, for example, contrast media, saline, or an active agent such as a drug into the bloodstream.

[0126] Distal region of the catheter :

[0127] In an example, the distal region of the catheter is configured to form a rigid structural tube that provides radial support for the heart tissue compliant element or its components (e.g., a balloon or other object attached to and / or surrounding such a distal region of the catheter). As described above, the catheter can be made of 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, etc. For example, in some cases, the heart tissue compliant element may include one or more balloons, such as four or more balloons (referred to as mid-radius balloons, including mid-radius balloons in a circumferentially positioned configuration), which surround such a distal region of the catheter. When such a mid-radius balloon is inflated, the outer diameter of the catheter shaft is configured to support and maintain contact with the opposite face of the inflated mid-radius balloon around it without significantly deforming the outer diameter or shape of the catheter. When such a mid-radius balloon is inflated to a high pressure, and for example, if they are non-compliant balloons, these mid-radius balloons can provide high radial forces at a diameter larger than the diameter of the distal region of the catheter itself. Such a configuration forms a stacked structure (i.e., where the mid-radius balloons are layered or "stacked" around the outer circumference of the catheter) as well as a collapsible structure (i.e., when the mid-radius balloon is deflated, the mid-radius balloon collapses to a diameter substantially similar to the outer diameter of the catheter) that can pass through narrow lumens (e.g., arteries). In addition, such a multi-layer structure (i.e., wherein the mid-radius balloon is layered around the outer circumference of the catheter) produces a rigid mid-radius structure (i.e., a rigid structure surrounding the outermost diameter of the structure formed by the inflated mid-radius balloon) that provides substantial radial support for elements such as other components of the cardiac tissue compliant element (e.g., balloons, positioning nubs, or other objects, such as, for example, a heart valve), including other elements configured for performing intravascular lithotripsy as known in the art, which are present on or around such mid-radius balloons. In an embodiment, the rigid mid-radius structure including the distal region of the catheter and one or more mid-radius balloons is configured to provide sufficient structural stability and support for such elements (e.g., additional balloons, such as winged balloons as described herein) to apply pulsating energy, such as applying pulsating force, to cardiovascular tissue (such as heart valve leaflets or heart valve commissures).

[0128] In some embodiments, in order to ensure both rigidity and flexibility of such distal region of the catheter, the cross-sectional shape of such distal region of the catheter is configured to take the form of a specific geometric shape. The catheter can be configured so that its cross section has any convenient geometric shape, and this can be changed according to the characteristics of the cardiac tissue compliant element and the structural requirements of the catheter, for example. For example, the catheter can be configured so that its cross section takes the form of a circle, a lobed-circle, an ellipse, a triangle, a star, etc.

[0129] Cardiac tissue compliant element :

[0130] As described above, in the system according to the present invention, the catheter assembly includes a cardiac tissue compliant element. Embodiments of the cardiac tissue compliant element are configured to receive pulse energy (ie, second pulse energy) transmitted through the fluid channel of the catheter to apply pulsatile energy to cardiovascular tissue.

[0131] In embodiments, the cardiac tissue compliant element can be configured to conform to any aspect of the cardiovascular tissue related to the treatment involving application of pulsating energy thereto. In some embodiments, the cardiac tissue compliant element is configured to engage cardiac valve tissue, including tissue of, for example, mitral valve, tricuspid valve, bicuspid valve, aortic valve or pulmonary valve. In certain embodiments, the cardiac tissue compliant element is configured to engage cardiac valve leaflets or cardiac valve commissures or cardiac valve leaflet tubercles or cardiac valve rings. In embodiments, the cardiac tissue compliant element includes a shape that engages cardiac valve leaflets or cardiac valve commissures or cardiac valve leaflet tubercles or cardiac valve rings. In embodiments, the cardiac tissue compliant element includes a shape that engages cardiac valve leaflets or cardiac valve commissures or cardiac valve leaflet tubercles or cardiac valve rings when one or more balloon elements of the cardiac tissue compliant element are inflated or pressurized. In some cases, the cardiac tissue compliant element is configured to engage tissue that supports a cardiac valve. In particular, in some embodiments, the cardiac tissue compliant element is configured to engage the aortic valve, including, for example, the aortic valve leaflets or the aortic valve commissures or the aortic valve ring. In other embodiments, the cardiac tissue compliant element is configured to engage the aortic valve or the ventricular septum. In other embodiments, the cardiac tissue compliant element is configured to engage the mitral valve and the bicuspid aortic valve. In an embodiment, the cardiac tissue compliant element includes a shape of tissue that engages to support the heart valve or the aortic valve, including, for example, the aortic valve leaflets or the aortic valve commissures or the aortic valve ring or the atrial septum or the ventricular septum or the mitral valve or the bicuspid aortic valve. In an embodiment, the cardiac tissue compliant element includes a shape of tissue that engages to support the heart valve or the aortic valve when one or more balloon elements of the cardiac tissue compliant element are inflated or pressurized, including, for example, the aortic valve leaflets or the aortic valve commissures or the aortic valve ring or the atrial septum or the ventricular septum or the mitral valve or the bicuspid aortic valve.

[0132] In an embodiment, the cardiac tissue compliant element is located in a distal region of the catheter, such as, for example, within 20 cm or less of the distal end of the catheter, such as within 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 of the distal end of the catheter. The cardiac tissue compliant element or aspects thereof may be bonded or otherwise secured to the catheter using any convenient and physiologically appropriate technique, such as using epoxy, cyanoacrylate, plastic cement, solvent bonding technique, thermoplastic reflow or a combination thereof, or any other suitable glue or adhesive or bonding technique.

[0133] Medium Radius Balloon :

[0134] In some embodiments, the cardiac tissue compliant element includes one or more distal balloons present on the rigid distal region of the catheter. Such balloons can be referred to as mid-radius balloons and can be configured to directly or indirectly contact the cardiovascular tissue and apply pulsating energy to the cardiovascular tissue via an additional element fixed to the mid-radius balloon (i.e., its outer surface), such as an additional balloon, such as a winged balloon or a small block as described below, or a combination thereof; that is, the mid-radius balloon can directly contact the cardiovascular tissue and apply pulsating energy to the cardiovascular tissue, and can also indirectly apply pulsating energy to the cardiovascular tissue via, for example, a winged balloon attached to its rigid surface. Such balloons are referred to as "mid-radius" in part because the balloon expands to a radius that radially extends beyond the outer circumference of the catheter, but does not extend to the extent that it fully engages the cardiovascular tissue, as described below; that is, it occupies an intermediate radius position. In some embodiments, one or more mid-radius balloons are primarily configured to maintain radial forces so that an external element (i.e., an element attached to the outer circumference of one or more mid-radius balloons), such as, for example, a winged balloon, can deliver pulses, i.e., pulsating energy, at a distance from the longitudinal axis of the catheter. That is, in such embodiments, one or more mid-radius balloons can be configured to include a substrate upon which an additional element, such as, for example, a winged balloon, can deliver pulsatile energy to cardiovascular tissue. Such methods enable additional elements, such as winged balloons, to apply pulsatile energy at specific targeted locations around the outer surface of one or more mid-radius balloons (i.e., such that the pulsatile energy is not applied to every aspect of the cardiovascular tissue to the same degree), such as, for example, targeting heart valve commissures or leaflets.

[0135] Embodiments may include one to ten or more mid-radius balloons, such as one mid-radius balloon, two mid-radius balloons, three mid-radius balloons, four mid-radius balloons, five mid-radius balloons, six mid-radius balloons, seven mid-radius balloons, eight mid-radius balloons, nine mid-radius balloons, or ten or more mid-radius balloons. In some cases, the cardiac tissue compliant element includes one or more mid-radius balloons that are secured to the catheter both proximally and distally (relative to the balloon) and configured to surround or substantially surround the outer circumference of the catheter at a distal region of the catheter (including, in some cases, the distal end of the catheter). In some cases, a single mid-radius balloon surrounds the distal region of the catheter, for example, such that the mid-radius balloon and the catheter share a longitudinal axis.

[0136] Embodiments of the present invention may be configured to enable a cardiac tissue compliant element or one or more mid-radius balloons thereof to translate into and out of a lumen of a catheter assembly, such as a central lumen of a catheter, such as one present in a distal region of the catheter. That is, the cardiac tissue compliant element or one or more mid-radius balloons thereof, including any accessories thereof, such as a winged balloon as described below, or other features attached to or present on one or more mid-radius balloons, such as the surface of such balloons, may be moved into and out of, for example, a central lumen of a catheter, such as by control of an operator using any convenient technique. Embodiments of the present invention may be configured to enable a cardiac tissue compliant element or one or more mid-radius balloons thereof to translate into and out of a lumen of a catheter assembly using any convenient technique, such as any convenient mechanical connection between a cardiac tissue compliant element and a proximal device for controlling translation of the cardiac tissue compliant element, and the like. One or more mid-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 mid-radius balloons may be moved out of such catheter lumen prior to inflation of the one or more mid-radius balloons (i.e., prior to utilizing the cardiac tissue compliant element by inflating the one or more mid-radius balloons or other features thereof) to, for example, engage with anatomical tissue (such as a heart valve) or disrupt calcium deposits on anatomical tissue (such as a heart valve). Embodiments configured to enable translation of the one or more mid-radius balloons into and out of the lumen of the catheter assembly may provide certain advantages, including, for example: easier rewrapping of the one or more mid-radius balloons and any of their attachments, easier folding of the one or more mid-radius balloons and any of their attachments, easier tracking of the cardiac tissue compliant element or its one or more mid-radius balloons, such as tracking its location, or using a narrower introducer to guide the cardiac tissue compliant element to the desired anatomical location.

[0137] During the use of the embodiment of the cardiac tissue compliant element, initially, the mid-radius balloon of the cardiac tissue compliant element can be tightly wrapped and / or folded around the outer surface of the catheter to allow the catheter assembly or its distal region to pass through, for example, an introducer sheath and enter an appropriate, desired anatomical position, such as near cardiovascular tissue. After being delivered to the proximal end of the desired anatomical position and positioned at (i.e., close to) the proximal end of the desired anatomical position, the mid-radius balloon of the cardiac tissue compliant element can be filled with fluid via the fluid coupling between the inside of the balloon and the fluid channel of the catheter. Such fluid coupling between the inside of the balloon and the fluid channel of the catheter can include one or more port holes, which are configured so that the inside of the balloon is in fluid communication with the fluid channel. Any convenient number, size, and configuration of port holes can be applied to operably connect the fluid channel of the catheter to the mid-radius balloon. The port hole in the embodiment can be a radial hole connecting the inner wall of the fluid channel of the catheter (i.e., the surface closest to the longitudinal axis of the fluid channel) with the outer wall of the fluid channel (i.e., the surface farthest from the longitudinal axis, for example, the surface to which the mid-radius balloon is attached). The port hole can be configured to allow fluid to pass between the fluid channel and the medium radius balloon. In an embodiment, the medium radius balloon can be inflated using fluid that is transferred from the fluid channel of the catheter to the interior of the balloon via the port hole of the fluid channel. That is, in some embodiments, the pressure applied to the proximal end of the fluid channel and propagated along the fluid channel of the catheter can be further propagated to the medium radius balloon via the port hole.

[0138] In embodiments of the present invention, the number of port holes can vary. The port holes can be any convenient diameter, and their diameters can vary. The arrangement of the port holes on the fluid channel can adopt any convenient mode. The number of port holes, their diameters, and their arrangement on the fluid channel of the catheter can be selected to ensure that the catheter maintains its desired structural characteristics despite the presence of 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 for supporting the expansion of the mid-radius balloon and applying pulsating energy to cardiovascular tissue via an element attached to the mid-radius balloon (such as, for example, a winged balloon). For example, some embodiments of the catheter according to the present invention can include between 1 and 5,000 port holes (such as 100 or 300 or 1,000 or 3,000), wherein the diameter is between 0.1 mm and 0.5 mm (such as 0.1 mm or 0.25 mm or 0.4 mm), spaced at least 0.1 mm to 5 mm (such as 0.5 mm or 1 mm or 5 mm) from each other.

[0139] In an embodiment, the system can be configured to inflate and deflate one or more mid-radius balloons of the cardiac tissue compliant element periodically. In some cases, the system is configured to inflate and deflate one or more mid-radius balloons so that they simulate 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, and periodically inflate and deflate one or more mid-radius balloons. In an embodiment, various aspects of the cardiac cycle can be determined by measuring the pressure gradient across the cardiac tissue compliant element (i.e., the gradient across the proximal and distal positions of the cardiac tissue compliant element) using a sensor. As further described below, in an embodiment, during the time when one or more mid-radius balloons are inflated (i.e., expanded so that they form a rigid substrate for additional elements (such as, for example, winged balloons) to apply pulsating energy to cardiovascular tissue), additional elements (such as, for example, outer radius balloons or winged balloons) are pulsed multiple times, such as, for example, up to 15 to 20 times, i.e., at a higher frequency than the frequency of one or more mid-radius balloons, such as, for example, at a frequency of 15 to 20 Hz. That is, in such embodiments, therapy (i.e., pulsatile energy) is applied when the one or more mid-radius balloons are inflated, rather than when the one or more mid-radius balloons are relaxed or collapsed. Such a configuration can help prevent the onset of ischemia (because, for example, in embodiments, periodic deflation or relaxation of the one or more mid-radius balloons promotes blood perfusion through the cardiac tissue compliant element), and further helps ensure that appropriate therapeutic energy is delivered to cardiovascular tissue (such as, for example, a heart valve). In embodiments including more than one mid-radius balloon, the mid-radius balloons can be pressurized and depressurized synchronously, i.e., simultaneously, or can be pressurized and depressurized independently and at different times; for example, the mid-radius balloons can be inflated in a sequential manner such that when the mid-radius balloons are inflated, the intermediate shape of the cardiac tissue compliant element conforms to a desired shape or feature of the cardiovascular tissue, which, for example, promotes alignment of the cardiac tissue compliant element with the cardiovascular tissue.

[0140] In addition, in embodiments, the characteristics of the pulsating energy applied by the one or more mid-radius balloons can be changed during use of the mid-radius balloon in conjunction with applying pulsating energy to cardiovascular tissue. The change in the characteristics of the pulsating energy applied by the mid-radius balloon can be predefined, i.e., preprogrammed using, for example, a controller (such as a preprogrammed controller, etc.), or can be dynamically changed, i.e., changed on the fly, based on any convenient parameter (such as, for example, sensor input, such as pressure or volume measurement (e.g., pressure or volume of the balloon)) or based on other feedback signals or user input, etc. For example, the pulsating energy applied to the one or more mid-radius balloons can be continuously increased or continuously decreased (i.e., the maximum energy or minimum energy or average energy applied to the one or more mid-radius balloons can be continuously increased or continuously decreased) or paused (i.e., the maximum energy or minimum energy applied to the one or more mid-radius balloons can be kept constant, including, for example, by not applying pulsating energy, such as pressure, to the balloon for a period of time (i.e., a relaxation period). Additionally, in embodiments, the pulsating energy applied to the mid-radius balloon can be slowed down or accelerated (i.e., the pulsating energy applied to the mid-radius balloon can be applied at a higher or lower frequency, or in other cases, the rate of change of the maximum energy or minimum energy or average energy applied to the mid-radius balloon can be increased or decreased).

[0141] In the inflated state, the mid-radius balloon of the cardiac tissue compliant element can be configured to present any desired shape, and thus can vary according to, for example, the intended treatment or anatomical features of the cardiovascular tissue or the structural requirements of the catheter assembly. For example, the mid-radius balloon of the cardiac tissue compliant element can present various shapes, including, for example, a sphere, a yo-yo, an ellipse, a cylinder, a peace-sign, etc. In some embodiments, the cross-sectional shape of the cardiac tissue compliant element or one or more of its mid-radius balloons is substantially an elliptical shape. Such an elliptical shape may be meaningful for the use of a bicuspid valve. In some cases, such an elliptical shape may be useful for solving mitral valve calcification. In other cases, such an elliptical shape may be meaningful for the use of both the mitral valve and the bicuspid aortic valve. In an embodiment in which the cardiac tissue compliant element includes more than one mid-radius balloon, each mid-radius balloon may present the same shape or a different shape. The yo-yo shape means that one or more mid-radius balloons, when inflated, form a bulge or hemisphere, equivalent to two hemispherical sections of a yo-yo, e.g., two pieces of a yo-yo connected by the axis of the yo-yo, such that they abut each other in a manner that allows cardiovascular tissue to reside between the two bulges or hemispheres. Such a yo-yo configuration can be employed to apply pulsating energy to cardiovascular tissue that resides between the two hemispheres of the mid-radius balloon that forms the yo-yo configuration. That is, the yo-yo configuration can be configured to allow cardiovascular tissue, such as, for example, a heart valve leaflet, to be sandwiched between the two hemispheres of the yo-yo configuration of the mid-radius balloon, such that applying pulsating energy to the cardiovascular tissue includes squeezing the sandwich together in a cyclical manner, compressing the cardiovascular tissue.

[0142] In an embodiment, a mid-radius balloon of a cardiac tissue compliant element may be configured such that increasing the pressure applied to such balloon (e.g., via increasing the pressure applied to the fluid present in the balloon) increases the force applied by such balloon to the cardiovascular tissue, i.e., increases the force applied to the heart valve or heart valve leaflets or heart valve commissures. That is, applying greater pressure to a mid-radius balloon of a cardiac tissue compliant element may cause such balloon to apply greater force to nearby cardiovascular tissue. In an embodiment, a mid-radius balloon of a cardiac tissue compliant element may be configured such that increasing the pressure applied to such balloon (e.g., via increasing the pressure applied to the fluid present in the balloon) expands the volume of the balloon, including in some cases expanding the diameter of the mid-radius balloon. For example, increasing the pressure applied to a mid-radius balloon may cause such balloon to protrude a greater radial distance from the longitudinal axis of the catheter.

[0143] In some instances, the diameter of the above-mentioned mid-radius balloon of the cardiac tissue compliant element can correspond to the amount of pressure and / or volume of the fluid injected into the balloon, i.e., such balloon can be compliant or semi-compliant. In other instances, the diameter of the mid-radius balloon of the cardiac tissue compliant element can remain substantially fixed (i.e., constant) regardless of the amount of internal pressure and / or volume of the fluid injected into the balloon, e.g., an additional pressure exceeding a threshold amount.

[0144] Any convenient balloon may be used as the mid-radius balloon. Suitable balloons include, but are not limited to, standard angioplasty balloons, such as compliant angioplasty balloons and non-compliant angioplasty balloons. In one embodiment, the mid-radius balloon is a composite balloon comprising two different layers, the layers comprising a non-compliant layer and a compliant layer, for example as further described in U.S. Application No. 63274832, the disclosure of which is incorporated herein by reference. In one embodiment of the mid-radius balloon comprising a composite angioplasty balloon, the non-compliant balloon is covered by a compliant sleeve to achieve "arrowed" pressure stretching, for example, as further described in pending PCT Application Serial No. PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The compliant layer can be a rubber, silicone, polyurethane or nitinol material or another material that can stretch up to 100%-500% before failure, can withstand thousands of cycles (i.e., expansion / relaxation cycles or application of pulsating energy) before failure, and encounters minimal plastic deformation (if any) during expansion.

[0145] In embodiments, the mid-radius balloon of the cardiac tissue compliant element or each of the mid-radius balloons of the plurality of mid-radius balloons can have any convenient length and inflated diameter, and this can vary as desired, for example, depending on the intended treatment or anatomical features of the cardiovascular tissue or the structural requirements of the catheter. In some embodiments, the mid-radius balloon of the cardiac tissue compliant element can have a length between about 1.5 cm and 4 cm or any variation thereof, such as 1.5 cm or 2 cm or 3 cm or 4 cm, and a diameter (i.e., unconstrained diameter) when inflated in a range between about 1.5 cm and 4 cm or any variation thereof, such as, for example, a diameter of 1.5 cm or 2 cm or 3 cm or 4 cm, for the above, including, for example, a balloon having one or more tips of 1.5 cm diameter and a distal tip of a smaller diameter (e.g., 1.5 cm or less), the one or more tips being configured to be able to pass (e.g., through cardiovascular tissue, such as luminal tissue), the distal tip being configured to reduce the risk of left ventricular outflow tract dilatation or dissection. In such embodiments, such balloons can extend radially from the outer surface of the catheter to varying sizes, and the balloons can be fixed in place prior to energy application (e.g., applying pulsatile energy). Typically, in embodiments, the length of the balloon is between 3 cm and 6 cm, such as, for example, 3 cm or 4 cm or 5 cm or 6 cm in length.

[0146] In an embodiment, the distal region and / or proximal region of the mid-radius balloon of the cardiac tissue compliant element can be configured to expand to a greater or lesser extent than the middle region of the balloon. That is, embodiments of such balloons can take a substantially hourglass shape or an elliptical shape, or can be configured such that multiple mid-radius balloons take such shapes together. Typically, in an embodiment, the mid-radius balloon can be asymmetric, e.g., symmetric via all planes passing through its longitudinal axis or a plane perpendicular to its longitudinal axis.

[0147] In other cases, the distal region and / or proximal region of the mid-radius balloon of the cardiac tissue compliant element is compliant or semi-compliant or non-compliant so that it engages with cardiovascular tissue (e.g., heart valve leaflets or heart valve commissures) to position itself in a desired anatomical position during treatment. In still other cases, the middle region of the mid-radius balloon of the cardiac tissue compliant element is compliant or semi-compliant or non-compliant so that it engages with cardiovascular tissue (e.g., heart valve leaflets or heart valve commissures) to position itself in a desired anatomical position during treatment. For example, in an embodiment in which the mid-radius balloon is hourglass-shaped, the proximal and distal regions of such mid-radius balloon will be compliant so that the diameter of such regions of the balloon corresponds to the inflation pressure and / or the volume of fluid injected into the balloon, and the middle region of the mid-radius balloon will be non-compliant.

[0148] In some embodiments, the distal region and / or proximal region of the mid-radius balloon of the cardiac tissue compliant element includes a passive feature that improves the ability of the cardiac tissue compliant element to be positioned and maintained in a fixed position relative to cardiovascular tissue. For example, embodiments include components such as small pieces or positioning elements that are configured to maintain the position of the cardiac tissue compliant element and / or catheter assembly relative to desired anatomical features (such as relative to a heart valve leaflet or commissure) during treatment using the system of the present invention. That is, in embodiments, components such as small pieces or positioning elements can be located on the outer surface of the mid-radius balloon and configured to conform to the relevant cardiovascular tissue so as to engage with various aspects of such cardiovascular tissue and substantially position the cardiac tissue compliant element and maintain it in a fixed position relative to the cardiovascular tissue. In some cases, such components can be configured to make the cardiac tissue compliant element self-centering. For example, in some cases, outer balloons located over the mid-radius balloon can be inflated first so that they expand prior to inflation of one or more mid-radius balloons and, as they expand, are guided by the outer balloons, which position themselves within desired features of the cardiovascular tissue (e.g., valve commissures) to align cardiac tissue compliant elements as desired.

[0149] In other examples, the outer surface of the mid-radius balloon of the cardiac tissue compliant element (i.e., the surface that interfaces with the cardiovascular tissue) can be roughened or otherwise include features that reduce the smoothness and / or slipperiness of the surface so as to facilitate maintaining the surface of the cardiac tissue compliant element in a fixed position rather than sliding to different positions or orientations relative to the cardiovascular tissue.

[0150] In an embodiment, the cardiac tissue compliant element may include a series of medium-radius balloons positioned circumferentially around the catheter, i.e., as described above, one or more medium-radius balloons may include such a circumferentially positioned configuration of medium-radius balloons. In such a circumferentially positioned configuration of medium-radius balloons, the medium-radius balloons may be fused to each other and to the distal region of the catheter at their respective attachment points (e.g., at a certain point on the circumference of each balloon). Such circumferentially positioned medium-radius balloons may be fused to each other and / or to the catheter using any convenient and physiologically appropriate bonding technique, such as using epoxy resin, cyanoacrylate, plastic cement, solvent bonding technique, thermoplastic reflow or a combination thereof, or any other suitable glue or adhesive or bonding technique.

[0151] In some instances, a mid-radius balloon of a series of circumferentially positioned balloons comprising a cardiac tissue compliant element is non-compliant such that when inflated, the diameter of such mid-radius balloon is fixed, known, and structurally stable. In addition, in embodiments, when such mid-radius balloons are inflated, the cardiac tissue compliant element can be configured so that such balloons do not occupy the entire volume between the total outer diameter of the cardiac tissue compliant element and the catheter. That is, for example, in a cross-section of the cardiac tissue compliant element, such a collection of circumferentially positioned mid-radius balloons does not completely consume the cross-sectional area between the outer surface of the cardiac tissue compliant element and the outer surface of the catheter. Such a configuration of the cardiac tissue compliant element allows additional perfusion area (i.e., cross-sectional area) for blood to flow through the cardiac tissue compliant element, such as from the proximal end to the distal end or vice versa.

[0152] In the embodiment where the cardiac tissue compliant element includes a series of circumferentially positioned mid-radius balloons, such mid-radius balloons can have a diameter between 1 mm and 20 mm, such as 1 mm or 5 mm or 6 mm or 10 mm or 20 mm. In the embodiment where the cardiac tissue compliant element includes a series of circumferentially positioned mid-radius balloons, there can be between one and 30 or more balloons, such as one balloon or two balloons or three balloons or four balloons or five balloons or six balloons or seven balloons or eight balloons or nine balloons or ten balloons or 20 balloons or 30 balloons or more. Such balloons can all have the same diameter, or can have different diameters. In addition, such balloons can have different diameters across their length, for example, so that the proximal region and / or distal region of the balloon have a larger or smaller diameter than the mid-length of the balloon.

[0153] Balloon of cardiac tissue compliant element :

[0154] In an embodiment, the balloon of the cardiac tissue compliant element, such as a medium radius balloon or a circumferentially positioned configuration of medium radius balloons as described above, can be made of any convenient biocompatible material as known in the art. For example, such balloons can be made of a compliant material or a semi-compliant material or a non-compliant material, such as a polyamide in the case of a non-compliant material so that the diameter of the balloon is substantially fixed (i.e., remains substantially constant) regardless of the inflation pressure applied to the balloon, or a polyimide or a combination of a thermoplastic or thermoset with a metal or a fiber braid.

[0155] Any convenient balloon may be employed as part of the cardiac tissue compliant element. Suitable balloons include, but are not limited to, standard angioplasty balloons, such as compliant angioplasty balloons and non-compliant angioplasty balloons, or in other cases, composite balloons comprising two different layers, the layers comprising a non-compliant layer and a compliant layer. In one embodiment of the composite angioplasty balloon, the non-compliant balloon is covered by a compliant sleeve to achieve "arrowed" pressure stretching, for example, as further described in pending PCT application serial number PCT / US2020 / 055458; the disclosure of which is incorporated herein by reference. The compliant layer may be a rubber, silicone, polyurethane, or nitinol material or another material that can be stretched up to 100%-500% before failure, can withstand thousands of inflation cycles before failure, and encounters minimal plastic deformation (if any) during expansion.

[0156] In some instances, the cardiac tissue compliant element includes a thin sheath placed on its outer surface, such as a thin sheath placed on all balloons or a subset of balloons including the cardiac tissue compliant element, so as to define the outer surface of the cardiac tissue compliant element. Such thin sheaths can be made of any convenient biocompatible material as known in the art. For example, such sheaths can be made of a compliant or non-compliant polymer material, such as a combination of a polyamide or polyimide or a thermoplastic or thermosetting plastic and a metal or fiber braid.

[0157] In an embodiment, the balloons (e.g., mid-radius balloons) of the cardiac tissue compliant element can be configured such that they are each fused to each other, to the distal region of the catheter, and to the thin material sheath so that the overall structure of the cardiac tissue compliant element is rigid and can provide substantial radial forces (e.g., provide substantial radial forces to cardiovascular tissue) without collapsing inwardly (e.g., axially collapsing). In such embodiments, one or more interior regions between the balloons of the cardiac tissue compliant element can also be used to allow blood perfusion through the cardiac tissue compliant element even when such balloons are inflated and expanded. In the exemplary case in which the cardiac tissue compliant element includes six 6 mm diameter non-compliant balloons (these balloons are circumferentially positioned around the 6 mm diameter distal region of the catheter), the spaces between such balloons provide approximately 10-70 mm of blood. 2 A cross-sectional area is defined to flow through the cardiac tissue compliant element, for example from the proximal end to the distal end.

[0158] In an embodiment, the surface of a balloon (e.g., a mid-radius balloon) or a thin sheath covering of a cardiac tissue compliant element can include an active agent, for example, the outer surface can be coated with an active agent, such as, for example, a drug or other agent or substance that can have a physiological effect, such as an anticoagulant, etc., or can include a hydrophilic surface or a hydrophobic surface.

[0159] Winged balloon :

[0160] In embodiments configured to rupture and fragment calcium or sclerotic deposits on cardiovascular tissue (such as heart valves), techniques such as, for example, pulsating intravascular lithotripsy can be used to generate high-intensity stress waves in calcium structures. To facilitate such treatments, in some embodiments, the cardiac tissue compliant element further includes one or more winged balloons (or outer balloons) located on the outer surface of one or more medium-radius balloons or the outer surface of a circumferentially positioned configuration of a medium-radius balloon. For example, an embodiment may include three separate winged balloons that are equally spaced from each other around the circumference of one or more medium-radius balloons or the outer circumference of a circumferentially positioned configuration of a medium-radius balloon of a cardiac tissue compliant element. Such embodiments may be configured so that during the expansion of one or more medium-radius balloons, the winged balloons may be activated, for example, by using standard pulsating intravascular lithotripsy techniques. That is, the system may be configured so that such winged balloons may be pressurized separately and independently from one or more medium-radius balloons. In an embodiment, the winged balloon can be fixed to a distal position and a proximal position on the catheter (e.g., the distal and proximal ends of one or more medium radius balloons), or other elements of the cardiac tissue compliant element, and can be fluidically coupled so that fluid can be fed to them through a small tube traversing inside or outside the catheter (i.e., a dedicated fluid channel of the catheter). In an embodiment, the small tube used to feed the winged balloon can be formed of any physiologically suitable material and can have any convenient diameter, and this can vary, for example, the diameter of such a small tube can range between 0.1 mm and 4 mm, such as 0.1 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 3 mm, or 4 mm.

[0161] In an embodiment, the cardiac tissue compliant element can be configured such that each of the winged balloons is fixed in a single position along one or more mid-radius balloons or a configuration of circumferential positioning of the mid-radius balloons, or is configured such that the winged balloon is allowed to translate, for example, circumferentially around one or more mid-radius balloons, to find a path of least resistance to a desired region of cardiovascular tissue (e.g., to a desired region of a valve commissure, where the winged balloon is configured to engage with the heart valve commissure) during expansion of the one or more mid-radius balloons and pulsation of the winged balloons. In an embodiment, the winged balloon can be configured and arranged on the cardiac tissue compliant element such that when pulsating energy is applied to the winged balloon, the winged balloon is used to orient and / or position the cardiac tissue compliant element relative to, for example, a heart valve by engaging, for example, the heart valve commissure. That is, when pulsating energy is applied to the winged balloon, the winged balloon can be configured to position itself, for example, on the heart valve commissure. When the cardiac tissue compliant element is so oriented, different pulsatile energies can be applied to the cardiac valve commissures as compared to the cardiac valve leaflets, i.e., the pulsatile energy transmitted by the winged balloon is delivered to the cardiac valve commissures, while the pulsatile energy transmitted to one or more medium-radius balloons or a circumferentially positioned configuration of medium-radius balloons is applied to the cardiac valve leaflets. That is, the cardiac tissue compliant element can be configured so that different aspects of the cardiovascular tissue can receive different forms of specific, targeted, and focused pulsatile energy.

[0162] In embodiments, the winged balloon is configured to pulsate at any convenient rate required for the applicable treatment, and this can be varied, for example, at a rate between 2-50 Hz (such as 2 Hz or 5 Hz or 10 Hz or 20 Hz or 30 Hz or 40 Hz or 50 Hz), such that the pulsation of the winged balloon causes the cardiac tissue compliant element to apply a cyclic load to the cardiovascular tissue (such as the heart valve commissures). In addition, in embodiments, the system can be configured so that the duty cycle (i.e., the on and off cycle) of the winged balloon can be adjusted, and any convenient duty cycle can be applied. In addition, in embodiments, the pressure and / or force profile of the winged balloon can be adjusted so that the pressure in the balloon oscillates between, for example, 0 to 10 atm at the trough of the cycle and 3 to 50 atm at the peak of the cycle, such as between 0 atm at the trough of the cycle and 50 atm at the peak of the cycle, or between 0 atm at the trough of the cycle and 3 atm at the peak of the cycle, or between 3 atm on either side of the trough of the cycle and 50 atm at the peak of the cycle, or between 3 atm at the trough of the cycle and just over 3 atm at the peak of the cycle. In embodiments including more than one winged balloon, such balloons can be configured so that all winged balloons are pulsed in a synchronized manner or independently of one another, i.e., the winged balloons can be pressurized and decompressed synchronously, i.e., simultaneously, or can be pressurized and decompressed independently and at different times; for example, the winged balloons can be inflated in a sequential manner so that when the winged balloons are inflated, the intermediate shape of the cardiac tissue compliant element conforms to the desired shape or feature of the cardiovascular tissue, for example, which promotes alignment of the cardiac tissue compliant element with the cardiovascular tissue. Other embodiments with winged balloons can be configured so that different energies can be supplied to different regions of the winged balloon. For example, in some instances, it may be desirable to apply pulsating energy of greater amplitude or frequency in the central region of one or more winged balloons (e.g., the central region between the proximal and distal ends of the winged balloon) relative to the tip of the winged balloon (e.g., the proximal region or the distal region of the winged balloon); for example, pressurization of the tip of the winged balloon may be paused to allow more energy to be applied to a stenotic valve compared to the left ventricular region or the aortic region. In embodiments having both winged balloons and mid-radius balloons, such balloons may be configured such that the mid-radius balloon and the winged balloon are pulsed in a synchronized manner or independently of one another, i.e., the mid-radius balloon and the winged balloon may be pressurized and depressurized synchronously, i.e., simultaneously, or may be pressurized and depressurized independently and at different times.

[0163] In addition, in an embodiment, the characteristics of the pulsating energy applied by the winged balloon can be changed during the application of pulsating energy to cardiovascular tissue using the winged balloon. The change in the characteristics of the pulsating energy applied by the winged balloon can be predefined, i.e., preprogrammed using, for example, a controller (such as a preprogrammed controller, etc.), or can be dynamically changed, i.e., changed on the fly, based on any convenient parameter (such as, for example, sensor input, such as pressure or volume measurement (e.g., pressure or volume of the balloon)) or based on other feedback signals or user inputs, etc. For example, the pulsating energy applied by the winged balloon can be continuously increased or continuously decreased (i.e., the maximum energy or minimum energy or average energy applied to the winged balloon can be continuously increased or continuously decreased) or paused (i.e., the maximum energy or minimum energy applied to the balloon can be kept constant, including, for example, by not applying pulsating energy, such as pressure, to the balloon for a period of time (i.e., a relaxation period). In addition, in embodiments, the pulsating energy applied by the winged balloon can be slowed down or accelerated (i.e., the pulsating energy applied by the winged balloon can be applied at a higher or lower frequency, or in other cases, the rate of change of the maximum energy or minimum energy or average energy applied by the winged balloon can be increased or decreased).

[0164] In embodiments, the winged balloon may have any convenient shape, and this may vary based on, for example, the characteristics of the cardiovascular tissue or the calcium deposits of the cardiovascular tissue. For example, in embodiments, the shape of the winged balloon may be cylindrical, or the cross-section may be triangular, such that the relatively wide sides of the triangle abut against one or more mid-radius balloons. Embodiments may be configured to facilitate dispersing the pulsating forces applied to the winged balloon to a larger area of ​​the cardiovascular tissue surrounding the one or more mid-radius balloons. In such embodiments where the cross-section of the winged balloon is triangular, the pointed sides of the triangular balloon may be oriented toward the valve commissures so that the pulsating energy of the cardiac tissue compliant element is specifically directed to such valve commissures. In embodiments, the winged balloon may be made of any convenient biocompatible non-compliant material or semi-compliant material (i.e., the same or similar material as the mid-radius balloon).

[0165] Any convenient balloon may be employed as a winged balloon or outer balloon fixed to the outer surface of one or more medium radius balloons or a circumferentially positioned configuration of a medium radius balloon. Suitable balloons include, but are not limited to, standard angioplasty balloons, such as compliant angioplasty balloons and non-compliant angioplasty balloons. In one embodiment, the winged balloon is a composite balloon comprising two different layers, the layers comprising a non-compliant layer and a compliant layer, for example, as further described in U.S. Application No. 63274832, the disclosure of which is incorporated herein by reference. In one embodiment of a winged balloon comprising a composite angioplasty balloon, the non-compliant balloon is covered by a compliant sleeve to achieve "arrowed" pressure stretching, for example, as further described in pending PCT Application Serial No. PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The compliant layer can be a rubber, silicone, polyurethane or nitinol material or another material that can stretch up to 100%-500% before failure, can withstand thousands of cycles (i.e., expansion / relaxation cycles or application of pulsating energy) before failure, and encounters minimal plastic deformation (if any) during expansion.

[0166] In some instances, the winged balloon may include a cutting element or a scoring element on its outer surface so that the expansion and pulsation of the balloon can cut through or score or otherwise further stress the calcified tissue or stenotic tissue. In embodiments, as described above, the distal region of the catheter where the winged balloon and one or more mid-radius balloons are located can be configured to provide structural support to the winged balloon to deliver a considerable radial force (i.e., a force applied to the cardiovascular tissue) so that the calcified cardiovascular tissue can be compressed, bent, tensioned or otherwise stressed so as to rupture the internal and / or external calcium of the cardiovascular tissue. In some instances, the pulsating stress delivered to the calcified cardiovascular tissue may produce low-stress fatigue rupture of calcium in the cardiovascular tissue. In embodiments, in order to produce fatigue rupture, in some cases, hundreds or thousands or more pulsation cycles may be required before the low-stress rupture of calcium occurs. In such cases, a perfusion mechanism may be used, such as a perfusion mechanism for perfusing blood to a distal vessel as described herein, to extend the treatment time before hypotension occurs or other side effects are caused by lack of perfusion through the cardiac tissue compliance element.

[0167] In other embodiments, the cardiac tissue compliant element may include a pulsating balloon, such as a winged balloon, that includes an element configured to generate cavitation or plasma bubbles or other forms of pulsating or vibrating energy that cause calcium rupture in cardiovascular tissue. In embodiments, such an element may include, for example, one or more wires coupled to electrodes (e.g., one wire coupled to two electrodes) or one or more optical fibers.

[0168] In other embodiments, the cardiac tissue compliant element may include a pulsating balloon, such as a winged balloon, which is configured to deliver an active agent (such as, for example, a drug) to the treatment site, i.e., cardiovascular tissue or tissue proximal thereto, to, for example, prevent re-fusion of the valvular commissures. In some instances, the active agent may be coated on the outside of the winged balloon of the cardiac tissue compliant element or other outer surfaces of the cardiac tissue compliant element, or may be delivered through cracks or pockets in the winged balloon of the cardiac tissue compliant element or other outer surfaces of the cardiac tissue compliant element, such as, for example, the balloon wall (e.g., the balloon wall of a winged balloon or a mid-radius balloon or a sheath covering multiple mid-radius balloons). In some cases, the cardiac tissue compliant element is configured so that the active agent will migrate into the cardiovascular tissue in a slow manner during treatment, or in other cases, the cardiac tissue compliant element is configured so that the active agent dissolves after a certain number of pulses are reached during treatment.

[0169] In some embodiments, the winged balloon and / or one or more mid-radius balloons can be configured to deliver pulse lithotripsy to cardiovascular tissue to ensure optimal fit of a heart valve (such as a replacement heart valve), or to reposition an already placed replacement heart valve. In certain embodiments, the winged balloons can be configured so that they can be deflated after successful treatment of cardiovascular tissue (such as a heart valve), so that one or more mid-radius balloons can be further inflated to perform final expansion (i.e., via expansion of the one or more mid-radius balloons) of the cardiovascular tissue (such as a heart valve and / or surrounding annulus).

[0170] Pulsatile energy applied to cardiac tissue compliance element :

[0171] In the embodiment where the cardiac tissue compliant element includes one or more balloons (e.g., medium radius balloons, winged balloons, etc.), such balloons can be inflated and deflated in combination with applying pulsating energy to cardiovascular tissue. In such embodiments, the balloon of the cardiac tissue compliant element can be inflated or deflated at any convenient rate, and the rate can vary. Usually, the inflation of the balloon is repeated in time, i.e., inflation once after a deflation. The configuration of the inflation and deflation cycle can be selected to promote blood flow, such as, for example, from the distal region of cardiovascular tissue (e.g., the distal region of a heart valve) to the proximal region of cardiovascular tissue (e.g., the proximal region of a heart valve). In such embodiments, one or more balloons of the cardiac tissue compliant element can be inflated and deflated at any desired frequency or rate, and these 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 compliant element is applied. For example, the rate of inflation and deflation of one or more balloons of the cardiac tissue compliant 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 instances, the catheter assembly of the system includes at least one port of the perfusion inlet area or the perfusion outlet area, as described above (i.e., configured to facilitate perfusion through the cardiac tissue compliant element), and such port can be pulsed synchronously with the cardiac cycle of the cardiovascular tissue, so that 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 system is used in conjunction with treating cardiovascular tissue including the aortic valve, at least one port of the perfusion inlet area or the perfusion outlet area can be blocked during the PS wave measured by an electrocardiogram (ECG), which allows atrial contraction, isovolumetric contraction of the ventricles and prevention of reverse flow from the aorta, and opened during the ST segment measured by the electrocardiogram (ECG), which allows ventricular relaxation.

[0172] In some embodiments, a more complex inflation process is applied. In such embodiments, one or more balloons of a cardiac tissue compliant element are inflated and pulsated simultaneously during diastole, and then collapsed during systole. That is, during diastole, a first group of one or more balloons of a cardiac tissue compliant element are inflated, and at the same time, a second group of one or more balloons of a cardiac tissue compliant element are inflated and pulsated, and then, during systole, both the first group of balloons and the second group of balloons of a cardiac tissue compliant element collapse. For example, one or more mid-radius balloons can be inflated during diastole, and at the same time, one or more winged balloons attached to the one or more mid-radius balloons can also be inflated and pulsated during diastole, and then the one or more mid-radius balloons and the one or more winged balloons can collapse during systole. Some embodiments utilizing such an inflation process include more than one potential source, i.e., more than one console assembly, at least one associated with inflating and deflating one or more mid-radius balloons, and at least more than one associated with inflating, applying pulsating energy, and deflating one or more winged balloons.

[0173] Cardiac tissue compliant element having radial members :

[0174] In an embodiment, the cardiac tissue compliant element comprises a plurality of radial members attached to a catheter. Such radial members can be configured and arranged on the catheter so that they can engage cardiovascular tissue by bending or flexing or folding or tensioning the cardiovascular tissue to disrupt calcification. For example, such radial members can be arranged on the catheter so that they can engage a single heart valve leaflet between the radial members so as to flex the leaflet between the radial members.

[0175] In some embodiments, the radial members are arranged to extend radially, i.e., away from the longitudinal axis of the conduit, so that the radial members protrude radially outward. In some embodiments, the radial members can have any convenient length, width and depth, which are configured to fully engage with cardiovascular tissue (such as heart valve). The radial members can extend radially with a length greater than its cross-sectional width, which means that when viewed from the profile, they present a substantially rectangular shape. For example, embodiments of radial members can have a length in the range of about 2 mm to 150 mm, such as, for example, 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, for example, 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, for example, 25 mm to 35 mm or 2 mm or 10 mm or 20 mm or 30 mm or 40 mm or 50 mm. In embodiments, radial members can have any desired rotation angle around the longitudinal axis of the catheter to which they are attached, i.e., between 0° and 360°, such as a rotation angle between 0° and 90°, including between 30° and 45°. "Rotation angle" means the angle between two radii of the sector occupied by a radial member when viewed in cross-section along the longitudinal axis of the catheter. In embodiments where the radial members have a 360° rotation angle, such radial members are equivalent to the protrusions or hemispheres of a yo-yo configuration of a cardiac tissue compliant element, as described herein.

[0176] In an embodiment, the radial member includes a radial balloon. In such embodiments, the shape of the radial balloon can be substantially cylindrical and can conform to the final shape during inflation by applying a constraint element (such as a braid made of, for example, nitinol) to the balloon. In some cases, during balloon molding, the shape of the radial balloon can be configured, i.e., formed into a final shape, so that during inflation, the balloon presents an appropriate desired shape. The radial balloon of interest can be made of any suitable physiologically compatible material (such as a non-compliant material or a combination of a non-compliant material and a compliant material) so that during inflation, the radial balloon only extends toward specific cardiovascular tissue, such as toward a calcified leaflet, causing a force such as a bending force to be applied to such designated cardiovascular tissue (e.g., a calcified leaflet) to break or otherwise destroy 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 compliant angioplasty balloons and non-compliant angioplasty balloons. In one embodiment, the balloon of the radial member is a composite balloon comprising two different layers, including a non-compliant layer and a compliant layer, for example, as further described in U.S. Application No. 63274832, the disclosure of which is incorporated herein by reference. In one embodiment of the balloon of the radial member comprising a composite angioplasty balloon, the non-compliant balloon is covered by a compliant sleeve to achieve "arrowed" pressure stretching, for example, as further described in pending PCT application serial number PCT / US2020 / 055458, the disclosure of which is incorporated herein by reference. The compliant layer can be a rubber, silicone, polyurethane or nitinol material or another material that can stretch up to 100%-500% before failure, can withstand thousands of cycles (i.e., expansion / relaxation cycles or application of pulsating energy) before failure, and encounters minimal plastic deformation (if any) during expansion.

[0177] In an embodiment, the balloon of the radial member of the cardiac tissue compliant element can be filled with fluid via the fluid coupling between the inside of the balloon and the fluid channel of the catheter. Such fluid coupling between the inside of the balloon and the fluid channel of the catheter can include one or more port holes, which are configured so that the inside of the balloon is in fluid communication with the fluid channel. Any convenient number, size and configuration of port holes can be applied to operably connect the fluid channel of the catheter to the balloon of the radial member. The port hole in the embodiment can be a radial hole connecting the inner wall of the fluid channel of the catheter (that is, the surface closest to the longitudinal axis of the fluid channel) and the outer wall of the fluid channel (that is, the surface farthest from the longitudinal axis, for example, the surface to which the radial member is attached). The port hole can be configured to allow fluid to pass between the fluid channel and the balloon of the radial member. In an embodiment, the fluid that is transferred to the inside of the balloon from the fluid channel of the catheter via the port hole of the fluid channel can be used to inflate the balloon of the radial member. That is, in some embodiments, the pressure applied to the proximal end of the fluid channel propagated along the fluid channel of the catheter can be further propagated to the balloon of the radial member via the port hole.

[0178] In embodiments of the present invention, the number of port holes can vary. The port holes can be any convenient diameter, and their diameters can vary. The arrangement of the port holes on the fluid passage can adopt any convenient mode. The number of port holes, their diameters, and their arrangement on the fluid passage of the catheter can be selected to ensure that the catheter maintains its desired structural characteristics despite the presence of 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 rigidity for supporting the action of the radial member, including the expansion of the balloon of the radial member, and applying pulsating energy to cardiovascular tissue via the radial member. For example, some embodiments of the catheter according to the present invention can include between 1 and 5,000 port holes (such as 100 or 300 or 1,000 or 3,000), wherein the diameter is between 0.1 mm and 0.5 mm (such as 0.1 mm or 0.25 mm or 0.4 mm), and is spaced at least 0.1 mm to 5 mm (such as 0.5 mm or 1 mm or 5 mm) from each other.

[0179] In some cases, the radial members are arranged to form a three-point flex configuration. The radial members may include a balloon configured so that when the balloon is pressurized, the balloon expands, causing the radial members to bend or flex or fold the cardiovascular tissue. In some cases, the radial members include a balloon configured to expand and contract substantially along a proximal direction or a distal direction (i.e., opposite to the radial direction) so that the cardiovascular tissue (such as the heart valve leaflets) present between the radial members bends or flexes or folds when the balloon is expanded. An embodiment may have one or more radial members configured so that when pulsatile energy is received by these radial members, or when such members expand, for example, via inflation of a fluid, such members engulf aspects of the cardiovascular tissue, such as the valve leaflets, to compress, bend or tension the internal calcification of the cardiovascular tissue, causing the calcification to rupture. In the example that wherein cardiac tissue compliant element comprises radial member, catheter assembly can be configured to force first radial member to translate laterally relative to second radial member, that is, radial member can be better engaged with cardiovascular tissue, and cardiovascular tissue engaged by radial member is flexed, bent and folded or otherwise tensioned between radial members.In embodiments, cardiac tissue compliant element comprising radial member can be configured to once engage single valve leaflet.In example, catheter assembly can be configured to enable cardiac tissue compliant element to rotate and / or redirect itself relative to cardiovascular tissue, so that radial member can sequentially treat each leaflet of for example heart valve.

[0180] In embodiments, the radial members include a surface of the radial member that is configured to engage or contact cardiovascular tissue (e.g., heart valve leaflets), or to apply force to (i.e., crush) cardiovascular tissue. Such a surface of the radial member that interfaces with the cardiovascular tissue may include the material of the radial balloon itself, or may be configured to have any number of one or more elements attached thereto to aid in the destruction of calcium deposits in the cardiovascular tissue, such as nitinol cutting or scoring elements, protruding features (such as objects such as diamonds or hemispheres on the surface to enhance stress concentration), or a sawtooth scoring pattern.

[0181] sensor :

[0182] In certain embodiments, the catheter assembly including, for example, a cardiac tissue compliant element and / or a catheter may include one or more sensors (e.g., pressure sensors, temperature sensors, volume sensors, etc.), which are configured to obtain data from one or more locations throughout the catheter assembly, i.e., as described above in conjunction with 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 in a connector of the catheter assembly, in a catheter, or in a cardiac tissue compliant element (e.g., one or more balloons of a cardiac tissue compliant element). In some cases, the sensor is present at the proximal and / or distal end of the cardiac tissue compliant element and is configured to measure, for example, the pressure generated by the heart (i.e., the contraction of cardiovascular tissue) or the pressure generated at the distal end of the heart or the pressure gradient across the cardiac tissue compliant element.

[0183] In such embodiments, the sensor is configured to transmit information to and / or receive information from a controller (as described above, such as a controller of a console assembly). In such instances, data collected from the sensor can be fused to assess the behavior of the system or cardiovascular tissue that occurs at different frequencies or amplitudes of pressure applied to various aspects of the cardiac tissue compliant element. The controller can be configured to read data from the sensor and adjust the 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., a system configuration, such as a pressure, frequency, and / or duty cycle configuration, for implementation by the system to address calcification present on the cardiovascular tissue). The controller can also be configured to adjust the treatment profile so that treatment is performed according to a previously determined optimal treatment profile. Additional details regarding configuring and adjusting treatment plans are described in U.S. Application Serial No. 63,346,704, entitled “Systems and Methods Related to Catheter-Based Procedures” and filed on the same day as the present application (Attorney Docket No. AVSI-005 PRV); the disclosure of which is incorporated herein by reference. Any convenient commercially available sensor (e.g., pressure sensor, temperature sensor, volume sensor, etc.) may be utilized and integrated into various aspects of the system based on the sensor as desired, for example, a pressure sensor and / or a volume sensor may be integrated into an embodiment of a connector of a catheter assembly.

[0184] The robotics aspect of the system :

[0185] Another aspect of an embodiment of the system relates to robotic treatment of diseased cardiovascular tissue. 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 location, i.e., a location where the system is used to treat a subject, such as a procedure room or an operating room. Connected to the treatment location is a control room, which includes system controls and / or system results, such as data collected by sensors of the system. The control room can be operably connected to the components of the system present at the treatment location via any convenient connection, such as a wired or wireless data connection. The control room can include various displays for displaying information related to surgery using an embodiment of the system of the present invention, such as for imaging or device sensors. In addition, the control room can include a treatment controller that enables an operator to control various aspects of the treatment, such as treatment start and device positioning, i.e., the position of the catheter assembly, including cardiac tissue compliance elements relative to cardiovascular tissue (i.e., cardiovascular tissue of the subject present in the treatment room). Other aspects can include information about the subject and a connection to a program database, i.e., configured to generate, store and / or transmit treatment plan information related to control aspects of the system when the system is applied to the subject's cardiovascular tissue. As described above, a 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 calcification present on cardiovascular tissue.

[0186] In some cases, the control room may be several feet away from the operating table, such as behind a lead curtain or other form of shielding, or may be located in a different geographic location, such as in another building or another city or country. One or more operators can interact in the control room and can communicate with the subject or other operators at the treatment location.

[0187] Visualization :

[0188] The embodiment of system can further include the marker band present in each aspect of catheter assembly.In an embodiment, the marker band can be fixed to the different parts of system, such as for example catheter, cardiac tissue compliant element, one or more balloons of cardiac tissue compliant element, inlet area or outlet area of ​​perfusion mechanism or different positions on the guide wire that thread passes through catheter.When being applied to experimenter, the marker band can be used for the position of visualization system or its parts such as cardiac tissue compliant element.The marker band can further be used to confirm the proper position and alignment (for example, suturing alignment) of each aspect of system (such as for example cardiac tissue compliant element relevant to providing treatment).

[0189] The marker band used in the embodiments can be any convenient, easily available, ready-made marker band that can be fixed to, for example, forged or crimped or thermally bonded or welded or bonded to a component of the system. The marker band of interest can be a polymer band loaded with gold or platinum or tungsten or another material that contributes to visualization (such as visualization via fluoroscopy). The marker band can be visualized via fluoroscopic or radioscopic visualization techniques.

[0190] Having generally described various aspects of the system of the present invention above, elements of the system of the present invention will now be further reviewed in the context of specific embodiments. Specific implementation plan

[0191] For ease of explanation only, Figures 1 to 16 The embodiments of the system described in describe aspects of the invention without limiting the invention to such embodiments.

[0192] exist Figure 1 Schematically illustrates a system for delivering pulsating energy to cardiovascular tissue according to an embodiment of the present invention. In some examples, the system may include a console assembly having a potential energy source, such as a high pressure source or a pressure source; a regulator, such as for regulating the output of the pressure source, etc.; and a controller, such as for controlling various aspects of the system. The system may also include a manifold assembly operably connected to the output end of the console assembly, the manifold assembly including an oscillator for converting the output of the potential source into pulsed energy. The system may also include a catheter assembly operably connected to the output end of the manifold assembly for converting the output of the manifold assembly (i.e., the first pulsating energy) into, for example, hydraulic oscillation or other forms of oscillating potential energy (i.e., the second pulsating energy), and transmitting the second pulsed energy to the cardiac tissue compliance element via the catheter (i.e., the fluid channel of the catheter). The cardiac tissue compliance element may be configured to receive the oscillating potential energy and apply the pulsating energy to the cardiovascular tissue. In an embodiment, the oscillating potential energy is used to drive various aspects of the cardiac tissue compliance element, such as, for example, balloon angioplasty oscillation or the movement of the radial member to bend or flex the cardiovascular tissue. The controller can control the frequency, duty cycle and / or amplitude of the output energy of the potential source from 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 oscillations, thereby generating oscillations in various aspects of the cardiac tissue compliant element. Variations of the system are provided in each of the embodiments below. The following embodiments are not meant to be an exhaustive list, but rather to provide examples of various configurations of the entire system.

[0193] Figure 1A schematic diagram of an exemplary embodiment of a system 100 for delivering pulsatile energy to cardiovascular tissue according to the present invention is depicted. Figure 1 In some embodiments schematically shown in , the system 100 includes three components: a console assembly (i.e., console subsystem) 110, which may include one or more console units 120; a manifold assembly (i.e., manifold subsystem) 140, which may include one or more subunits, the one or more subunits including an oscillator 141; and a catheter assembly (i.e., catheter and balloon subsystem) 150, which may include one or more connectors 151, and a catheter 154 having a fluid channel (not shown) and a cardiac tissue compliant element 165. Each connector 151 of the catheter assembly 150 is connected to the oscillator 141 and one or more connector-to-catheter transition hubs 153 of the manifold assembly 140 for transmitting the pulsating energy (i.e., the second pulse of energy) to the cardiac tissue compliant element 165 via the catheter 154.

[0194] The console assembly 110 may include one or more console units 120. When the console assembly includes multiple console units, such console units may be combined into a single physical component (i.e., a housing) or divided into multiple housings, such as one housing for each console unit. In each case, the console units are configured to operate independently of each other, i.e., to be independently controlled, whether the console units are present in a single housing or in multiple housings. The console unit 120 includes a potential source 121, a potential regulator (not shown), and a controller 130 for generating energy for transmission to the manifold assembly 140. The output from the potential source 121 may include regulated potential energy 122 or unregulated potential energy, such as potential energy from a high-pressure fluid or voltage. The potential regulator may be used to change 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., to enable the oscillator 141 to generate pulse energy from the energy transmitted by the potential source 121. A plurality of console units 120 (i.e., console units numbered 1 to n) may be included in the console assembly 110 and may be operated substantially in parallel (i.e., independently) to generate a plurality of potential outputs 122 for transmission to a plurality of oscillators 141. In some instances, the plurality of console units 120 may be configured to generate a plurality of potential outputs 122 in the case where treatment of cardiovascular tissue includes applying different configurations of pulsatile energy to the cardiovascular tissue, for example, in the case where the cardiac tissue compliant element includes a plurality of balloons configured to be independently inflated at potentially different frequencies, duty cycles, and / or amplitudes. In such instances, the different potential outputs 122 may be applied to the cardiovascular tissue separately, for example, via different balloons or other aspects of the cardiac tissue compliant element or via different times (i.e., where one of the potential outputs 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 instances, the potential outputs 122 from the plurality of console units 120 may be combined. In still other examples, multiple console units 120 may be configured to generate multiple potential outputs 122 including different forms of potential energy (eg, high voltage or voltage) where treatment of cardiovascular tissue requires application of different forms of energy.

[0195] The console assembly 110 further includes a controller 130 configured to receive input from at least one of the console assembly 110, the manifold assembly 140, and the catheter assembly 150. Figure 1, controller 130 is shown as receiving input from catheter assembly 150, namely sensor 152 of catheter assembly 150. Sensor 152 may include any sensor configured to sense any relevant characteristic of catheter assembly 150 that can be detected. For example, sensor 152 may include a pressure transducer configured to measure the pressure within catheter assembly 150, such as, for example, the pressure of the fluid channel of catheter 154 or the pressure of an aspect of cardiac tissue compliance element 165, such as an angioplasty balloon; alternatively, sensor 152 may include a volume sensor configured to measure, for example, the volume of fluid present in the balloon. In an example, controller 130 can be configured to receive input from a plurality of sensors, including sensors configured to measure any relevant aspect of system 100 or the environment in which system 100 is applied (e.g., pressure sensors, temperature sensors, volume sensors, etc.), and can be configured to capture data from any location throughout system 100, including, for example, one or more locations of system 100, such as cardiac tissue compliance element 165, catheter 154, connector-to-catheter transition hub 153, connector 151, oscillator 141, or a location on 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, such as information related to a treatment procedure. In other examples, controller 130 can be configured to receive input from a user input, such as a button or switch for specifying a treatment option (e.g., system pressure, frequency, duty cycle, etc.). In Figure 1 , the controller 130 receives input from the pressure sensor 152 of the catheter assembly 150 and, based at least in part on such input, generates control signals for controlling various aspects of the console assembly 110, such as, for example, the amplitude of the potential output 122, i.e., via an active regulator (not shown) for adjusting the amplitude of the potential output 122 (e.g., the output pressure).

[0196] In such Figure 1In the embodiment schematically shown in FIG. 1 , the output end of the console assembly 110 is operably connected to the manifold assembly 140 so that 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 pulsed energy or static energy from the energy transmitted by the potential source 121 (i.e., the regulated potential output 122). In an example, the oscillator 141 may include a solenoid valve (not shown) configured to allow or interrupt the transmission of energy to the catheter assembly 150. In other examples, the oscillator 141 may include any applicable electrical switch as known in the art, such as a solenoid valve, an optical switch, or a mechanical switch. As further described below, the behavior of the oscillator 141 can 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, input from an operator.

[0197] exist Figure 1 , the controller 130 is shown connected to the manifold assembly 140. In an example, the oscillator 141 can be configured so that the oscillation frequency and / or duty cycle can be controlled by the controller 130, for example, so that the controller 130 controls the position of the solenoid of the oscillator 141 or other aspects of the behavior.

[0198] In such Figure 1 In the embodiment schematically shown in FIG. 1 , the output end of the oscillator 141 of the manifold assembly 140 is operably connected to the conduit assembly 150. In particular, the output end of the oscillator 141 is connected to the input end of the connector 151. The connector 151 is configured to convert the potential energy generated by the oscillator 141, such as, for example, pneumatic pressure (i.e., the first pulse energy), into a second potential energy, such as, for example, hydraulic pressure (i.e., the second pulse energy). Figure 1 The system 100 shown in includes a plurality of connectors 151 (connectors 1 to n), one connector 151 corresponding to each oscillator 141. The output end of the connector 151 is operably connected to a connector-to-catheter transition hub 153, which is configured to enable the potential energy output of the connector 151 (i.e., the second pulse energy) to be input into a catheter 154, such as one or more fluid channels (not shown) of the catheter 154. In some cases, the catheter assembly 150 includes more than one catheter 154, or the catheter 154 includes more than one fluid channel inside or outside the catheter 154, i.e., to enable different aspects of the cardiac tissue compliant element 159 to be independently operated (e.g., to enable different angioplasty balloons or radial members including the cardiac tissue compliant element 159 to be independently pressurized or inflated and deflated).

[0199] In the catheter assembly 150 of the system 100, the catheter 154 includes a channel dedicated to the guidewire so that the catheter 154 and the cardiac tissue compliant element 159 can be navigated to the cardiovascular tissue treatment site via a standard over-the-wire guidewire method. The connector to the catheter transition hub 153 is configured to include a guidewire outlet port 161 at the proximal region of the guidewire for threading through the guidewire channel of the catheter 154. The guidewire outlet port 161 is opposite to the guidewire inlet port 157 present in the relatively distal region of the cardiac tissue compliant element 165. For illustrative purposes only, in order to highlight the position of the guidewire outlet port 161 relative to the other components of the system 100, the guidewire outlet port 161 is depicted as being oriented away from the longitudinal axis of the catheter 154. In an embodiment, the guidewire outlet port 161 is oriented in a manner parallel to the longitudinal axis of the catheter 154 (and therefore parallel to the longitudinal axis of the guidewire channel in the catheter 154) so ​​as to avoid any unnecessary bending of the guidewire present in the system 100. As described above, the system 100 can be configured relative to a guidewire such that the system 100 is an over-the-wire system, a rapid exchange system, a monorail system, or the like.

[0200] In such Figure 1 In the embodiment schematically shown in , the cardiac tissue compliant element 165 is present at the distal region of the catheter 154. In the system 100, the cardiac tissue compliant element 165 is configured to adapt to cardiovascular tissue including the aortic heart valve, so that the cardiac tissue compliant element 165 spans the leaflets of the aortic valve, wherein the distal region of the cardiac tissue compliant element 165 is present on the ventricular side of the aortic valve and the proximal region is present on the aortic side of the aortic valve. The cardiac tissue compliant element 165 includes a plurality of angioplasty balloons and other features (e.g., positioning elements or nubs, etc.) configured to engage various aspects of the aortic heart valve. The angioplasty balloons of the cardiac tissue compliant element 165 include one or more outer commissure balloons (e.g., winged balloons) 158 and one or more inner valvuloplasty balloons (e.g., mid-radius balloons) 159. The angioplasty balloons 158, 159 of the cardiac tissue compliant element 165 may be independently operable (ie, capable of being pressurized and depressurized independent of whether the other balloon is pressurized or depressurized).

[0201] The outer commissure balloon 158 is present at a sufficient relative outer radial distance from the longitudinal axis of the cardiac tissue compliant element 165 so that the outer commissure balloon 158 can engage the aortic valve commissures (i.e., apply pulsatile energy to the aortic valve commissures), for example, to disrupt calcium formation in the aortic valve commissures that inhibits normal valve function. As described above, the outer commissure balloon 158 may include a non-compliant material / compliant material. The cardiac tissue compliant element 165 may include a plurality of outer commissure balloons 158 configured such that the outer commissure balloon 158 engages each valve commissure of the aortic valve, for example, including three outer commissure balloons 158 to engage each aortic valve commissure.

[0202] The outer commissure balloons (e.g., winged balloons) 158 can be configured to be independently operable, i.e., independently pressurized and depressurized from a second outer commissure balloon and from the inner valvuloplasty balloon 159, by pressurization, e.g., by hydraulic pressure transmitted via separate fluid chambers of the catheter 134. Alternatively, the outer commissure balloons 158 can be configured so that they are simultaneously pressurized and depressurized, e.g., by hydraulic pressure transmitted via a single fluid channel of the catheter 134 that feeds multiple outer commissure balloons 158.

[0203] The endovalvuloplasty balloon (e.g., a mid-radius balloon) 159 is present at a sufficient relative inner radial distance from the longitudinal axis of the cardiac tissue compliant element 165 so that the endovalvuloplasty balloon 159 can engage the aortic valve leaflets (i.e., apply pulsatile energy to the aortic valve leaflets), for example, to disrupt calcium formation in the aortic valve leaflets that inhibits normal valve function. The cardiac tissue compliant element 165 may include a plurality of endovalvuloplasty balloons 159 configured such that the endovalvuloplasty balloon 159 engages each valve leaflet of the aortic valve. For example, the cardiac tissue compliant element 165 may include three endovalvuloplasty balloons 159 to engage each aortic valve leaflet, or include a single endovalvuloplasty balloon 159 configured such that a different surface of the single balloon engages each aortic valve leaflet.

[0204] The inner valvuloplasty balloons 159 may be configured to be independently operable, i.e., independently pressurized and depressurized from the second inner valvuloplasty balloon and from the outer commissure balloon 158, e.g., by pressurization by hydraulic pressure transmitted via separate fluid channels of the catheter 134. Alternatively, the inner valvuloplasty balloons 158 may be configured so that they are pressurized and depressurized together simultaneously, e.g., by pressurization by hydraulic pressure transmitted via a single fluid channel of the catheter 134 configured to feed multiple balloons.

[0205] In such Figure 1In the embodiment schematically shown in FIG. 1 , the catheter 154 and the cardiac tissue compliant element 165 are configured to allow fluid (e.g., blood) to perfuse through the cardiac tissue compliant element 165, even when pulsatile energy is applied to the cardiovascular tissue at the treatment site. For example, in the system 100, the catheter 154 and the cardiac tissue compliant element 165 are configured to enable blood to be displaced (i.e., perfused) from the perfusion inlet region 156 to the perfusion outlet region 155 via one or more channels (not shown), for example, the perfusion inlet region 156 is fluidly connected to the perfusion outlet region 155, allowing blood received from the distal region (i.e., the ventricular region) to exit at the proximal region (i.e., the aortic region) of the cardiac tissue compliant element 165. The perfusion inlet region 156 and the perfusion outlet region 155 include perforations or ports (not shown) in the catheter 154 or the cardiac tissue compliant element 165 through which blood can flow. Such a configuration enables blood to flow through the cardiac tissue compliance element 165, enabling extended treatment time. Such a perfusion mechanism may further include a structure (e.g., a valve or an oscillating balloon mechanism) in the catheter 154 or the cardiac tissue compliance element 165 that allows fluid to flow in only one direction. The catheter 154 includes a proximal catheter segment 163 and a distal catheter perfusion segment 162. The distal catheter perfusion segment 162 includes a perfusion inlet area 156, a perfusion outlet area 155, and one or more channels (not shown), such as fluidly connecting the perfusion inlet area 156 to the perfusion outlet area 155. The proximal catheter segment 163 and the distal catheter perfusion segment 162 may be connected by a connector (not shown).

[0206] Any convenient perfusion mechanism may be employed in the catheter 154 and the cardiac tissue compliant element 165 to induce a fluid (e.g., blood) to flow through the perfusion region, i.e., from the perfusion inlet region 156 to the perfusion outlet region 155, past the cardiac tissue compliant element 165, i.e., displaced from a distal region to a proximal region of the cardiac tissue compliant element 165, such that the cardiac tissue compliant element 165 does not completely obstruct the flow of the fluid (e.g., blood) when present, for example, in a blood vessel. As described above, a passive perfusion mechanism may be employed to induce a fluid to flow from the perfusion inlet region 156 to the perfusion outlet region 155 based on an existing pressure gradient (i.e., an existing pressure difference caused, for example, by ventricular contraction), or an active perfusion mechanism may be employed, including, for example, a syringe (such as a cartridge syringe), which is configured to displace a fluid from the perfusion inlet region 156 to the perfusion outlet region 155 and past the cardiac tissue compliant element 165 through the perfusion region.

[0207] In an example, aspects of system 100, such as, for example, console assembly 110 (e.g., controller 130), manifold assembly 140 (e.g., oscillator 141), and aspects of catheter assembly 150 (e.g., connector 151 and connector-to-catheter transition hub 153) can be configured to be reusable. In an example, aspects of system 100, such as, for example, catheter 154 or cardiac tissue compliant element 159 can be configured to be used a single time (e.g., such that it is disposable). The terms "reusable" and "disposable" as used herein and elsewhere throughout the description are for convenience in describing Figure 1 The present invention is used in the embodiment of the present invention shown in . However, the present invention is not limited thereto. Therefore, any part of the system can be configured for single use or for multiple use as required.

[0208] Figure 2A and Figure 2B A schematic diagram of a console assembly 200 according to an embodiment of the present invention is provided, which console assembly may be used, for example, in a computer system such as a computer system. Figure 1 The system 100 is schematically shown in FIG. The console assembly 200 is configured to deliver regulated high pressure gas and is controlled by a plurality of inputs. Figure 2A A schematic diagram of a console assembly 200 is provided, the console assembly being configured to provide treatment including, for example, pulsatile intravascular lithotripsy, and Figure 2B A schematic diagram of a console assembly 200 is provided, which is configured to provide therapy including, for example, one-way valve operation synchronized with an electrocardiogram (ECG). The console assembly 200 includes an electrical potential source, namely a high pressure gas source 121. The potential output of the high pressure gas source 121 is supplied to a regulator 123. The regulator 123 is configured to modify the potential output 121a (dashed line) (i.e., a constant high pressure) of the high pressure gas source 121 to a regulated pressure output 122.

[0209] exist Figure 2A , a characteristic treatment profile of a lithotripsy procedure according to an embodiment of the present invention is depicted by showing the regulated output pressure 122 as a function of time. As a function of time on the x-axis, the regulated pressure 122 initially ramps up slowly and then remains constant for a period of time. When a rupture or balloon volume change is detected, the pressure is reduced before slowly increasing again for the final treatment portion, i.e., slowly ramping back up.

[0210] exist Figure 2B, a treatment profile in which the regulated output pressure 122 for applying pressure pulses to the mid-radius balloon layer is synchronized with the results of an electrocardiogram (ECG). Such a treatment profile enables the system 200 to synchronize the cyclically regulated output pressure 122 with the characteristics of the cardiac cycle. In some embodiments, such a configuration requires the application of a vacuum (i.e., the regulated output pressure 122 is depicted as periodically taking a negative pressure on the curve of the regulated output pressure 122 over time) to promote rapid emptying of the balloon of the cardiac tissue compliant element. Such a vacuum can be applied in any convenient manner as known in the art, including, for example, including a switch or solenoid as part of the regulator 123, etc. Such vacuum pressure promotes deflation and emptying of the balloon, i.e., deflation and emptying of the balloon in a rapid manner, allowing fluid (e.g., blood) to perfuse the deflated balloon. In some embodiments, a composite compliant balloon material / non-compliant balloon material is used to ensure sufficiently rapid balloon emptying. (In another embodiment of the treatment profile, in which pressure pulses are applied to the mid-radius balloon layer in synchronization with electrocardiogram (ECG) results, the regulated output pressure 122 is maintained constant, and in place of regulator 123, an oscillator of the manifold assembly is used to cycle the balloon pressure based on the results of the ECG. In such an embodiment, the regulated output pressure 122 (i.e., the input pressure to the balloon) will cause the balloon to inflate, and the outlet of the oscillator can be attached to a vacuum or atmosphere to facilitate rapid decompression and emptying of the balloon).

[0211] exist Figure 2A and Figure 2B In the embodiment, two console units 200, each with a high pressure gas source 121, are depicted in conjunction with the two different treatment profiles described above. In other embodiments, a single console unit 200 with one or more high pressure gas sources 121 can be connected to multiple manifold assemblies, wherein each oscillator of the manifold assembly is configured to produce a different treatment profile, such as the above combined with Figure 2A and Figure 2B Two treatment profiles are described.

[0212] The high pressure gas potential energy output 121a is supplied to the regulator 123. The output of the regulator 123 (i.e., the regulated pressure output 122) is transmitted to the input end of the manifold assembly (not shown) via the output port 126, so that the regulated output pressure 122 is transmitted to the oscillator, which opens and closes to transmit pulsating energy (with a maximum pulse pressure equal to or less than the regulated output pressure 122). The regulator 123 is an active regulator that is configured to be controlled by a signal generated by the controller 130. Control of the regulator 123 by the controller 130 includes manipulating the output pressure level of the regulator output 122, such as increasing or decreasing the regulated pressure at a specified time.

[0213] Controller 130 is an electronic component configured to receive input 124, which includes one or more data inputs, user inputs, electrocardiogram inputs, imaging inputs, electrocardiogram inputs and other inputs from the catheter assembly, such as inputs from the manifold assembly. Input 124 including data received from the catheter assembly may include a measured value of the pressure applied to the cardiac tissue compliant element or, for example, a volume measurement of various aspects of the balloon including the cardiac tissue compliant element. Input 124 including imaging data may include any relevant data that can be imaged, such as, for example, fluoroscopic data related to the position of the cardiac tissue compliant element relative to the cardiovascular tissue or the function of the heart valve or the calcification degree of the cardiovascular tissue. Such fluoroscopic data including controller input 124 may be obtained using, for example, radiopaque markers.

[0214] Based on the inputs 124 as described above and a treatment plan or treatment mode, such as a pulsatile intravascular lithotripsy treatment mode or one-way valve operation synchronized with an electrocardiogram (ECG) mode, the controller 130 generates signals including controller outputs 125. The controller outputs 125 include regulator control signals as well as display data, for example, to control a user display for providing information to the user regarding the treatment being performed, such as pressure measurements at various aspects of the system, and other outputs.

[0215] Figure 3A and Figure 3B Depicted are two views of an exemplary embodiment of a console assembly 300 configured to generate the desired power and control for treating cardiovascular tissue using a system according to an embodiment of the present invention. Figure 3A A first perspective view of the console assembly 300 is provided, and Figure 3BA second perspective view of the console assembly 300 is provided. The console assembly 300 includes a console input 310 for inputting into a controller (not shown) for adjusting the behavior of the system. The input 310 includes buttons for selecting treatment intensity and mode and an emergency shut-off button. The console assembly 300 includes a console input / output port 340, which in some cases may include an HDMI port or a USB port for transmitting data to and from the console assembly 300. The console assembly 300 includes an on-off switch 350 for enabling and disabling the console assembly 300. The console assembly 300 also includes an output port 320 for transmitting potential energy, which includes 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. An external potential source, such as a connection to a high-pressure gas, can be connected to the console assembly via a connector 330. The console assembly 300 also includes a console housing 390 configured to form a housing, such as configured to protect the console assembly components, such as during an accidental drop or during packaging. The console housing 390 , when present, may be made of a suitably rigid material (eg, a polymeric material), and may be transparent or opaque as desired.

[0216] Figure 4A and Figure 4B A schematic diagram of a manifold assembly 400 according to an embodiment of the present invention is provided, which manifold assembly may be used, for example, in a Figure 1 The system 100 is schematically shown in FIG. The manifold assembly 400 employs an oscillator 441 to convert regulated potential energy 422 received from a potential source of a console assembly (not shown) into therapeutic energy 442 for use by a catheter assembly (not shown). Figure 4A 4 illustrates an application of manifold assembly 400 in conjunction with providing pulsatile intravascular lithotripsy, as can be seen in potential output 442, where changes in pressure over time correspond to pulsatile intravascular lithotripsy treatment. The sawtooth shape of potential output 442 represents the oscillator output and the pulsatile potential applied to cardiovascular tissue, for example, via a balloon of a cardiac tissue compliant element. The maximum potential output 442 of the oscillator corresponds to a maximum potential output 442 (e.g., Figure 2A and Figure 2B The solid line is seen above the regulated output pressure 122). The high pressure gas potential energy output 421a is depicted in the figure for reference. Figure 4B4 depicts an application of a manifold assembly 400 in conjunction with providing one-way valve operation synchronized with the results of an electrocardiogram (ECG), which is visible in a potential output 442, where changes in pressure over time correspond to the ECG results. The manifold assembly 400 includes receiving energy transmitted from a potential source (not shown) via a potential source output 422. Such energy is exposed to an oscillator 441, which is controlled via an oscillation control signal 443, i.e., for adjusting the frequency, duration and / or duty cycle of the oscillator 441, including, for example, shutting down the oscillator 441. Figure 4A An oscillation control signal 443 is depicted, which is configured to turn the oscillator on and off, while Figure 4B An oscillating control signal 443 is depicted, which is configured to remain constantly on, i.e., turned on, so that the regulator varies the potential source output 422 (i.e., the regulated output pressure) based on the results of the ECG, illustrating the difference in applying the manifold assembly 400 in conjunction with pulsatile intravascular lithotripsy relative to providing one-way valve operation synchronized with the results of the ECG. (In another embodiment of the manifold assembly 400 for providing one-way valve operation synchronized with the results of the ECG, the potential source output 422 (i.e., the regulated output pressure) is a constant pressure, and the oscillator 441 is cycled 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 includes controlling the potential applied to one or more balloons or other aspects of the cardiac tissue compliant element to collapse immediately before or after the QRS spike of the ECG (i.e., collapsing the one or more balloons of the cardiac tissue compliant element), and then applying pressure to inflate the one or more balloons or other aspects of the cardiac tissue compliant element during the diastole phase, wherein the collapse of the one or more balloons or other aspects of the cardiac tissue compliant element begins before the P wave.

[0217] In any case, the resulting pulse energy 442 generated by the oscillator 441 of the manifold assembly 400 is transmitted to the catheter assembly (not shown) via the oscillator output connector 444. The oscillation control signal 443 is generated by the controller 430, which is configured to receive the input 424 and generate an output 425 including the oscillation control signal 443 based at least in part on the input 424. Figure 4A In the embodiment, the controller 430 is configured to receive an input signal 424 corresponding to a pressure and / or volume of at least a connector (not shown) of the catheter assembly and / or a cardiac tissue compliance element (not shown) of the catheter assembly, i.e., an input signal internal to the system. Figure 4BIn the embodiment, the controller 430 is configured to receive an input signal 424 corresponding to the pressure and / or volume of the connector (not shown) of the catheter assembly and / or the cardiac tissue compliance element (not shown) of the catheter assembly, i.e., an input signal inside the system, and an input signal corresponding to the result of an electrocardiogram (ECG), i.e., an input signal outside the system. The controller 430 can be used as a console component (not shown) (i.e., Figure 1 or Figure 2A and Figure 2B 130 ), or in some cases, is included as part of the manifold assembly 400 .

[0218] Figure 5 A manifold assembly 500 (such as Figure 4A and Figure 4B 4 ). The manifold assembly 500 includes a plurality of inlet sources 545, which include cables, such as, for example, optical cables or power cables (configured to transmit power or signals, such as data or control signals), or tubes, such as, for example, pneumatic tubes or hydraulic tubes, for receiving potential inputs into the manifold assembly 500 and potential outputs 542 for transmitting energy out of the manifold assembly 500. The manifold assembly 500 includes a plurality of oscillators (not shown), one oscillator for each pair of inlet source 545 and potential output 542, for converting energy transmitted from the potential source into pulsed energy.

[0219] The manifold assembly 500 also includes a manifold housing 590 configured to form a housing, such as configured to protect the manifold assembly components, such as during an accidental drop or during packaging. The manifold housing 590, if present, can be made of a suitable rigid material (e.g., a polymer 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).

[0220] FIG. 6A to FIG. 6E Depicted are various views of an exemplary embodiment of a connector 600 configured to deliver low volume, high frequency, and high voltage pulses in accordance with an embodiment of the present invention. Fig. 6AA cross-sectional side illustration of connector 600 is provided. Connector 600 includes a proximal flange 610 and a distal flange 650 separated by a membrane 630. Proximal flange 610 defines a proximal chamber 615 into which a proximal port 620 enters. Distal flange 650 defines a distal chamber 655 into which a distal port 660 enters. A pressure transducer 625 is operably coupled to distal port 660 and distal chamber 655. Proximal flange 610 and distal flange 650 are held together by screws, as shown by screw 670. Alternatively, the flange can be fixed via any other suitable assembly method such as adhesive, welding or other means. In other examples, the flange can be manufactured as a single component via a multi-stage injection molding or overmolding process around a flexible membrane and electronic devices. Hall sensor 635, permanent magnet 648, electrical connector 690 and flexible printed circuit board 697 are also shown. The threaded portion 698 at the distal end of the distal port serves as an interface between the proximal flexible tube and the distal flange.

[0221] Figure 6B An end view of the proximal flange 610 of the connector 600 is provided. Figure 6B As seen in FIG. 6 , screws 670 are positioned circumferentially around the flange to provide connection to a distal flange (not shown). Also shown are a proximal port 620 and an electrical connector 690 that provide an operable electrical connection to a console assembly (not shown) (ie, to a controller).

[0222] Figure 6C An outside view of connector 600 is shown showing proximal flange 610 and distal flange 650 connected together by screws 670. Also shown is memory 695, which is electrically coupled to flexible printed circuit board 697, which is electrically coupled to electrical connector 690. Similarly, pressure sensor 625 is electrically coupled to flexible printed circuit board 697. Fig.6D A perspective view of connector 600 is shown.

[0223] Fig. 6E A view of a connector 600 is provided having an overmold 680 made of a rigid, opaque material for protecting various components of the connector, such as circuits, sensors, etc. The connector can have diameter and width variations to accommodate different types of cardiac tissue compliant elements while still being able to connect to a common manifold assembly. For example, for peripheral or coronary cardiac tissue compliant elements, the connector can have dimensions that accommodate volume variations between 1-20 mL. For larger cardiac tissue compliant elements, such as those that include valvuloplasty balloons, the connector can be enlarged to accommodate volume variations of up to 50 mL-100 mL.

[0224] Figure 7A schematic diagram of an alternative connector 700 configured to deliver high volume, low frequency and low pressure pulses as described above is provided. The connector 700 includes a barrel syringe 710 with 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 that is configured to receive energy (i.e., a first pulse of energy) from a manifold assembly (not shown), for example, in the form of pneumatic pressure, and transmit such energy to the pneumatic chamber 730. The plunger 720 is configured to translate in response to pressure applied to the pneumatic chamber 730, thereby transmitting energy to the fluid chamber 740. The fluid chamber 740 includes a fluid output port 750 that is operably connected to a conduit (not shown) and is configured to transmit energy to the conduit (i.e., its fluid chamber) in response to the movement of the plunger 720 compressing the fluid chamber 740. The connector 700 further includes a biasing spring 760 configured to urge the plunger 720 back to the starting position when the plunger 720 is displaced as described above.

[0225] In instances where the connector includes an internal fluid, the connector can be configured to receive the fluid through a fluidically coupled filling port (not shown). For example, such a fluid port can be connected to Figure 7 The fluid chamber 740 in the connector 700 of the embodiment of the present invention can be connected to the patient's own fluid chamber 740. Through such a port, fluids such as radiopaque contrast agents, saline, CO2, etc. can be injected to fill the fluid chamber. In addition, a vacuum can be applied to such a port so that the connector and the entire system can be degassed, for example, before treatment. The filling port can be closed and sealed so that no fluid can leave the port during treatment.

[0226] FIG. 8A to FIG. 8C Depicting various views of an exemplary embodiment of a cardiac tissue compliant element 800 according to an embodiment of the present invention, the cardiac tissue compliant element may be used, for example, in Figure 1 A system 100 is schematically shown in FIG. Fig. 8A A front view (ie, a view along the longitudinal axis of catheter 899 from the distal region) of cardiac tissue compliant element 800 is shown. Figure 8B A side view (ie, a view perpendicular to the longitudinal axis of catheter 899) of cardiac tissue compliant element 800 is shown. Figure 8C An isometric view of a cardiac tissue compliant element 800 is shown. Figure 8A-8C, the cardiac tissue compliant element 800 includes a single mid-radius balloon 810, and the cardiac tissue compliant element 800 is attached to the distal catheter perfusion section of the catheter 899, i.e., the area near the distal end. The cardiac tissue compliant element 800 further includes winged balloons 820a, 820b, and 820c, which are configured as cylinders evenly spaced around the circumference of the mid-radius balloon 810. The winged balloons 820a, 820b, and 820c are fluidly coupled to small tubes 830a, 830b, and 830c extending outwardly along the catheter 899, and pulsating energy is transmitted from these small tubes and applied to the winged balloons 820a, 820b, and 820c via the fluid injected into the winged balloons 820a, 820b, and 820c. The separate tubes 830a, 830b, and 830c enable the winged balloons 820a, 820b, and 820c and the medium radius balloon 810 to be inflated independently, i.e., to different amplitudes and at different frequencies and duty cycles. The tubes (such as the separate tubes 830a, 830b, and 830c) included in embodiments of systems (such as system 100) can be configured to hold and transport any type of fluid, such as, for example, saline solution or contrast medium solution, etc. In addition, in embodiments, the tubes (such as the separate tubes 830a, 830b, and 830c) can include optical cables or power cables configured to apply energy to cardiovascular tissue, such as, for example, to generate cavitation bubbles.

[0227] The cardiac tissue compliant element 800 is present on the distal catheter perfusion section 870 of the catheter 899, including a perfusion inlet area 850 and a perfusion outlet area 860. The perfusion inlet area 850 and the perfusion outlet area 860 are configured to allow blood to be perfused through the cardiac tissue compliant element 800. The perfusion inlet area 850 and the perfusion outlet area 860 include a plurality of ports configured for blood to flow in and out via a fluid channel (not shown) connecting the perfusion inlet area 850 to the perfusion outlet area 860. That is, the cardiac tissue compliant element 800 and / or the catheter 899 include one or more internal fluid passages (not shown) that fluidly connect the perfusion inlet area 850 and the perfusion outlet area 860, through which blood flows during treatment using the cardiac tissue compliant element 800.

[0228] The cardiac tissue compliant element 800 further includes a guidewire entry port 870, which is configured to allow a standard guidewire to be threaded into the cardiac tissue compliant element 800 through a guidewire channel (not shown) to reach a guidewire exit port (not shown) at a more proximal region of the catheter. The guidewire entry port 870 and the guidewire channel and exit port facilitate guiding the cardiac tissue compliant element 800 through the relevant anatomical structure via a standard trans-guidewire approach.

[0229] The cardiac tissue compliant element 800 may further include one or more markings (not shown), such as radiopaque markings, present at any convenient location on the cardiac tissue compliant element 800, which is configured to confirm the desired position and / or orientation or alignment of the cardiac tissue compliant element 800 relative to, for example, cardiovascular tissue (e.g., diseased cardiovascular tissue). In some cases, such markings may be configured to verify suture alignment or alignment with other aspects of the heart valve.

[0230] In some cases, aspects of the mid-radius balloon 810 and the winged balloons 820a, 820b, and 820c can be configured to facilitate self-alignment, i.e., self-centering, of the cardiac tissue compliant element 800 relative to cardiovascular tissue, such as a heart valve. For example, in some cases, a compliant balloon is used with the winged balloons 820a, 820b, and 820c, and a compliant balloon is used with the mid-radius balloon 810; and in other cases, a compliant balloon can be used with only one of the winged balloons 820a, 820b, and 820c and the mid-radius balloon 810, or neither. In such embodiments, the winged balloons 820a, 820b, and 820c can be inflated first, followed by the mid-radius balloon 810, and as it inflates, the winged balloons 820a, 820b, and 820c automatically center into the heart valve commissures. In other cases, the order of balloon inflation and / or the use of compliant or non-compliant materials in such balloons may be changed depending on the needs or properties of the diseased cardiovascular tissue. In still other cases, the balloons of the cardiac tissue compliant element 800 can be inflated, pulsated, and deflated / collapsed as follows. First, the medium radius balloon 810 can be inflated during diastole. At the same time, the winged balloons 820a, 820b, and 820c are also inflated and pulsated during diastole. Thereafter, the medium radius balloon 810 and the winged balloons 820a, 820b, and 820c are deflated or collapsed during systole. Embodiments utilizing such inflation, pulsation, and deflation patterns, i.e., embodiments in which different balloons are inflated and / or pulsated and / or contracted at different times, can include more than one potential source, i.e., more than one console assembly, to facilitate such inflation patterns.

[0231] Fig. 9 An exemplary embodiment of a cardiac tissue compliant element 900 according to an embodiment of the present invention is depicted, which can be used, for example, in Figure 1 A system 100 is schematically shown in FIG. Fig. 9 A cross-sectional view of cardiac tissue compliant element 900 (i.e., a view along the longitudinal axis of cardiac tissue compliant element 900 viewed from the distal region of catheter 999) is shown that is similar to cardiac tissue compliant element 800, but has a different balloon configuration. Fig. 9, the cardiac tissue compliant element 900 includes a plurality of mid-radius balloons 910a, 910b, 910c, 910d, 910e, and 910f that are circumferentially attached to and surround a catheter 999. That is, each of the mid-radius balloons 910a, 910b, 910c, 910d, 910e, and 910f is attached (i.e., bonded) to its neighbors as well as the catheter 999.

[0232] The cardiac tissue compliant element 900 further includes winged balloons 920a, 920b, and 920c present on the outer surface. The winged balloons 920a, 920b, and 920c are configured so that their cross-sections are triangular in shape and are evenly spaced around the circumference of the cardiac tissue compliant element 900, i.e., so that the winged balloons 920a, 920b, and 920c are configured to engage the heart valve commissures (such as the aortic valve commissures), while the areas of the mid-radius balloons 910a, 910b, 910c, 910d, 910e, and 910f are configured to engage the heart valve leaflets (such as the aortic valve leaflets). The long sides of the triangular cross-sections of the winged balloons 920a, 920b, and 920c are each attached to the cardiac tissue compliant element 900. The cardiac tissue compliant element 900 further includes an outer sheath (i.e., outer restraining band) 930 that is configured to surround and enclose the mid-radius balloons 910a, 910b, 910c, 910d, 910e, and 910f and maintain a substantially constant configuration of the cardiac tissue compliant element 900. The winged balloons 920a, 920b, and 920c are configured such that they are attached to the outer surface of the outer sheath 930. The cardiac tissue compliant element 900 includes a distal catheter perfusion region, Fig. 9 Only a perfusion inlet region of the distal catheter perfusion region is depicted, which includes a plurality of input ports, such as perfusion region inlet port 950. The perfusion inlet region, including input ports (such as input port 950), is configured so that blood can enter and traverse through the cardiac tissue compliant element 900, ultimately exiting through a perfusion outlet region (not shown) on a relatively proximal region of the catheter assembly, i.e., to perfuse the distal blood vessels.

[0233] Fig.10 Depicted is an exemplary cardiac tissue compliant element balloon pressurization (i.e., inflation / deflation) sequence that is based on (i.e., coordinated with) electrocardiogram (ECG) readings from a subject being treated using a device according to the present invention. Graph 1000 includes an ECG signal 1010 measured from a subject being treated using a device according to the present invention. Graph 1000 also includes pressure readings 1020, 1030 that represent the pressure applied to the balloon of the cardiac tissue compliant element of the exemplary device according to the present invention, illustrating how the pressure is applied at different times and at different amplitudes relative to the ECG signal 1010. Fig.10In the example depicted in FIG. 1 , in order to perform a desired treatment using the device of the present invention, pressures 1020, 1030 are controlled based on the reading of the ECG signal 1010, such as Fig.10 shown.

[0234] Pressure signal 1020 illustrates the pressure applied to one or more mid-radius balloons of a cardiac tissue compliant element, such as mid-radius balloon 810 of cardiac tissue compliant element 800 depicted in FIG. 8 or Fig. 9 1 and 2. Mid-radius balloons 910a, 910b, 910c, 910d, 910e and 910f of the cardiac tissue compliant element 900 are depicted in FIG.

[0235] Pressure signal 1030 illustrates the pressure applied to one or more winged balloons of a cardiac tissue compliant element, such as winged balloons 820a, 820b, and 820c of cardiac tissue compliant element 800 depicted in FIG. 8 or 820c of a cardiac tissue compliant element. Fig. 9 Winged balloons 920a, 920b and 920c of the cardiac tissue compliant element 900 are depicted in FIG.

[0236] Pressure signal 1030 is depicted as a wavy line and a dotted line. The wavy line is used to depict relatively small oscillations (i.e., relatively high frequency oscillations) over time, i.e., relatively small oscillations in relatively long oscillations (i.e., relatively low frequency oscillations) of pressure 1030 that cycle between zero and maximum pressure. Although the oscillations of shorter time periods (i.e., relatively high frequency oscillations) seen in the wavy line of pressure 1030 do not depict large changes in pressure, any convenient pressure changes may be applied in embodiments. For example, relatively high frequency pressure changes (i.e., represented by wavy line segments of pressure 1030) may cycle between zero and maximum pressure (where such maximum pressure increases and decreases according to relatively long oscillations (i.e., relatively low frequency oscillations) of pressure 1030), or cycle within any range between zero and such maximum pressure.

[0237] With respect to the ECG signal 1010 and the pressure signals 1020, 1030, the x-axis represents time in each case. With respect to the ECG signal 1010, the y-axis represents the change in electric potential. With respect to the pressure signals 1020, 1030, the y-axis represents the change in pressure.

[0238] As mentioned above, Fig.10Two phases of the pressure cycle 1020, 1030 are shown. As described above, pressure 1020 corresponds to the primary inflation of the one or more mid-radius balloons and fluctuates up and down during diastole (beginning when the heart relaxes and then the one or more mid-radius balloons collapse before the heart contracts again). As described above, pressure 1030 has jagged edges (i.e., wavy lines) that represent faster ongoing oscillatory waves generated by secondary structures (e.g., winged balloons) attached to the one or more mid-radius balloons. Essentially as Fig.10 The application of pressure 1020, 1030 as shown will have the effect of causing the heart tissue compliant element to better engage the space between the heart valve leaflets and, in some cases, will affect treatment time.

[0239] Although Fig.10 The pressures 1020, 1030 are shown applied during particular times associated with particular aspects or features of the ECG signal 1010, but any convenient coordination between the pressures 1020, 1030 and the ECG signal 1010 may be applied and this may vary, for example, depending on the desired treatment to be applied to the subject or the characteristics of the subject or any other relevant considerations.

[0240] Fig.10 The pressures 1020, 1030 are shown out of phase with respect to one another for the purpose of better illustrating the two pressure curves 1020, 1030. However, any convenient phase (i.e., time distance between relative maxima of the pressure curves 1020, 1030) may be applied. For example, in some cases, the pressures 1020 and 1030 may each reach a relative maximum pressure at the same time. In other cases, the pressure 1020 may reach a relative maximum pressure while the pressure 1030 is at a minimum pressure (e.g., zero pressure). In still other cases, the pressure 1030 may reach a relative maximum pressure while the pressure 1020 is at a minimum pressure (e.g., zero pressure). Similarly, the pressures 1020, 1030 may exhibit the same frequency (i.e., relative to the pressure) as desired. Fig.10 1030) or different frequencies and can be individually and independently controlled using the same or different potential sources and / or oscillators as needed to achieve the desired relative characteristics of pressures 1020, 1030.

[0241] FIG. 11A to FIG. 11D Various views of an alternative radial-member-based embodiment of a cardiac tissue compliant element 1100 are depicted. Fig.11A An isometric view of cardiac tissue compliant element 1100 is shown. Fig. 11B A top view of the cardiac tissue compliant element 1100 is shown (ie, a view along the longitudinal axis of the catheter 1199 from the proximal region). Fig. 11CA bottom view (ie, a view along the longitudinal axis of the catheter 1199 from the distal region) of the cardiac tissue compliant element 1100 is shown. Fig.11D A side view of the cardiac tissue compliant element 1100 is shown. Figures 11A-11D In the embodiment of the present invention, the cardiac tissue compliant element includes radial members 1110a, 1110b and 1110c, and the cardiac tissue compliant element 1100 is attached to the distal region near the distal end of the catheter 1199. Figures 11A-11D , cardiac tissue compliant element 1100 is shown engaged with cardiovascular tissue (ie, a heart valve leaflet 1150 having calcifications or calcium deposits 1155).

[0242] Figures 11A-11D The cardiac tissue compliant element 1100 depicted in FIG. 1 includes radial members 1110a and 1110b, which are eccentric balloons located at relatively proximal locations on the catheter 1199 (ie, substantially the same distance from the distal end of the catheter 1199). Figures 11A-11D The cardiac tissue compliant element 1100 shown in 100 includes two such radial members 1110a and 1110b, but other embodiments may include one or more than two such radial members. When the balloon including the radial members 1110a and 1110b is inflated, the distal ends of the radial members 1110a and 1110b span one side of the valve leaflet 1150, i.e., the aortic side of the valve leaflet 1150. The radial members 1110a and 1110b including the balloon are configured to be inflated so that they provide significant resistance to the top (i.e., the proximal side) of the valve leaflet 1150.

[0243] Figures 11A-11D The cardiac tissue compliant element 1100 depicted in FIG. 1 further includes a radial member 1110c, which is an eccentric balloon attached to a relatively distal position of the catheter 1199. Figures 11A-11D The cardiac tissue compliant element 1100 shown in includes one such radial member 1110c, but other embodiments may include one or more such radial members.When inflated, the proximal end of the radial member 1110c including the balloon will engage the left ventricular side of the heart valve leaflet 1150, for example. Fig. 11B and Fig. 11CDepicted is how radial member 1110c is located at a position that substantially bisects the angle formed between radial members 1110a and 1110b. Port aperture 1190a includes a fluid connection between a fluid channel of catheter 1199 and the balloons of radial members 1110a and 1110b, such that fluid can be displaced into the balloons of radial members 1110a and 1110b, causing radial members 1110a and 1110b to expand, including applying pulsatile energy to cardiovascular tissue. Port aperture 1190b includes a fluid connection between a fluid channel of catheter 1199 and the balloon of radial member 1110c, such that fluid can be displaced into the balloon of radial member 1110c, causing radial member 1110c to expand, including applying pulsatile energy to cardiovascular tissue.

[0244] When the balloons of radial members 1110a, 1110b, and 1110c are inflated, such balloons are used to create a three-point flexed state in which the heart valve leaflets 1150 and embedded calcium 1155 are flexed, compressed, or tensioned. That is, the leaflets 1150 are pushed in the proximal direction by the expansion of radial members 1110c, and are simultaneously pushed in the distal direction by the expansion of radial members 1110a and 1110b. Sustained pressure and / or pulsatile pressure can be applied to the balloons of radial members 1110a, 1110b, and 1110c to controllably rupture the internal calcium 1155 of the leaflets 1150.

[0245] In some examples, radial members 1110c including a distal eccentric balloon can be attached to an inner shaft 1160 of a catheter 1199 that is configured to translate axially (i.e., along the long passage of the catheter 1199). As radial members 1110c translate in the proximal direction, the distal eccentric balloon of radial members 1110c can further engulf or surround or engage with valve leaflets 1150 (i.e., the distal side of leaflets 1150), such that a secure connection can be made between the proximal and distal eccentric balloons (i.e., between radial members 1110a, 1110b, and radial member 1110c).

[0246] In some examples, a portion of a radial member (such as radial member 1110a, 1110b, or 1110c) comprising a balloon (e.g., that contacts cardiovascular tissue, such as a heart valve, such as heart valve leaflet 1150) can be compliant or semi-compliant, such that application of increased pressure to the balloon causes the balloon to expand into the valve leaflet. This additional expansion increases the force applied to the heart valve leaflet, which, for example, increases the ability to rupture internal calcifications (such as calcifications 1155) of cardiovascular tissue (e.g., a heart valve, such as heart valve leaflet 1150) in a bent configuration. In other examples, a portion of a radial member (such as radial member 1110a, 1110b, or 1110c) comprising a balloon (e.g., which contacts cardiovascular tissue, such as a heart valve, such as heart valve leaflets 1150) can be configured with ridges or cutting or scoring elements such that the edges of these features create stress concentrations in the calcium of the cardiovascular tissue, such as heart valve leaflets 1150, when in contact with cardiovascular tissue, such as heart valve leaflets 1150. Such stress concentrations can act to create increased calcium rupture while reducing the required pressure that needs to be applied to the balloon of the radial member. Similarly, the portion of the balloon of the radial member that contacts cardiovascular tissue, such as the proximal side or distal side of the radial members 1110a, 1110b, and 1110c that contact heart valve leaflets 1150, can be configured to elute an active agent, such as a drug, such that the active agent is eluted onto the heart valve leaflets when in contact with cardiovascular tissue to minimize restenosis and increase the longevity of the valve treatment.

[0247] In other embodiments, various numbers of radial members can be located around the axis of a catheter (e.g., catheter 1199) such that the heart tissue compliant element is configured to treat one or more heart valve leaflets simultaneously. It will be appreciated that in the former instance, i.e., when the heart valve compliant element is configured to treat one heart valve leaflet at a time, blood can still be perfused through the heart valve via the other side of the catheter (e.g., the side of the catheter opposite the radial members), thereby extending the treatment time. In the latter instance, i.e., when the heart valve compliant element is configured to treat more than one heart valve leaflet at a time, such a configuration can result in blood being restricted to a greater extent than when the heart valve compliant element is configured to treat one heart valve leaflet at a time.

[0248] In some embodiments, a catheter (eg, catheter 1199) can include a port (not shown) configured to apply a vacuum to an area adjacent to the cardiovascular tissue such that the port engages the cardiovascular tissue and holds the leaflet in a fixed position during treatment.

[0249] In some examples, the face of the radial member or its balloon that contacts cardiovascular tissue (such as a heart valve leaflet) is shaped according to, for example, the contour of the heart valve leaflet. For example, the face of the radial member or its balloon that contacts cardiovascular tissue can be shaped so that they are convex on the aortic side and concave on the ventricular side. For example, the distal faces of radial members 1110a and 1110b (i.e., the surface in contact with leaflet 1150) can have a substantially concave shape, while the distal face of radial member 1110c (i.e., the surface in contact with leaflet 1150) can have a substantially convex shape.

[0250] Fig. 12A and Fig. 12B Depicted is a cross-sectional view of a heart valve, such as one that may be treated using embodiments of the present invention. Figure 12A-12B A tri-leaflet valve 1210 and a bi-leaflet valve or a bi-leaflet valve 1220 are depicted. The mitral valve is an example of a bi-leaflet valve or a bi-leaflet valve. As described herein, some embodiments of cardiac tissue compliant elements according to the present invention can be customized for treating tri-leaflet valves (such as tri-leaflet valve 1210), while other embodiments of cardiac tissue compliant elements according to the present invention can be customized for treating bi-leaflet valves (such as bi-leaflet valve 1210). For example, in some cases, better results are obtained with a bi-leaflet valve or a bi-leaflet valve if such valves are treated with a cardiac tissue compliant element (or one or more mid-radius balloons thereof) that is wider in one dimension than the circular cross-section of the cardiac tissue compliant element, that is, a cardiac tissue compliant element with a rectangular cross-section or a cardiac tissue compliant element with an elliptical cross-section.

[0251] Figure 13A-13C Embodiments of a cardiac tissue compliant element having a cross-sectional shape that is wider in one dimension compared to the circular cross-sectional shape of the cardiac tissue compliant element are depicted. Fig.13A The cardiac tissue compliant element 1300a is shown in cross-section. The cardiac tissue compliant element 1300a includes a mid-radius balloon 1310 that is substantially rectangular or elliptical in shape, with a winged balloon 1320 attached to opposite ends of the mid-radius balloon 1310. The mid-radius balloon 1310 has an outward expansion and can be inflated and deflated at a certain frequency, i.e., pulsating (i.e., the mid-radius balloon 1310 can have a certain frequency of pulsation), and the winged balloon 1320 on the side of the cardiac tissue compliant element can be inflated and deflated at a different or the same frequency, i.e., pulsating. The cardiac tissue compliant element 1300a includes a cross-sectional shape such that it will preferentially expand along a valve (i.e., a bicuspid or double-leaflet valve, such as a valve) compared to embodiments of the cardiac tissue compliant element (or its balloon) that expand equally in all directions. Fig. 12BThe heart tissue compliant element 1300a includes a guide wire channel 1350 in its center, for example, for use with a guide wire.

[0252] Fig. 13B Another embodiment of a cardiac tissue compliant element 1300b is presented, which has a structure configured for use with a bi-leaflet or double-leaflet valve (such as Fig. 12B The cross-sectional shape of the heart tissue compliant element 1300b is used in conjunction with the bi-leaflet valve 1210 depicted in Figure 1. The aspects of the heart tissue compliant element 1300b that are the same as the heart tissue compliant element 1300a are not repeated herein. The heart tissue compliant element 1300b includes an additional winged balloon 1330 present on the rectangular or relatively elongated side of the heart tissue compliant element 1300b. The additional winged balloon 1330 can pulsate at the same or different frequency than the medium radius balloon 1310 and the winged balloon 1320.

[0253] Fig. 13C Another embodiment of a cardiac tissue compliant element 1300c is presented, which has a structure configured to be attached to a bi-leaflet or double-leaflet valve (such as Fig. 12B 1300a and 1300b). Aspects of the cardiac tissue compliant element 1300c that are the same as the cardiac tissue compliant elements 1300a and 1300b are not repeated herein. The cardiac tissue compliant element 1300c includes a perfusion zone 1340 (or perfusion path or central channel) that is part of the perfusion mechanism of the cardiac tissue compliant element 1300c and has a wire cage that maintains the shape of the perfusion zone 1340 (i.e., keeps the perfusion zone 1340 open) during treatment, even if the mid-radius balloon 1310 is pressurized and inflated. The perfusion zone 1340 is used to allow fluid (i.e., blood) to be perfused through the cardiac tissue compliant element 1300c during treatment, and the cage of the perfusion zone 1340 maintains the structural stability of the opening during treatment, preventing the perfusion zone 1340 from collapsing, even when the mid-radius balloon 1310 is pressurized. The perfusion zone 1340 is Fig. 13C is shown in cross section so that the inlet and outlet paths are not depicted in the figure, but they are routed via Fig. 13C The cross-sectional paths shown in FIG. 1 are fluidly interconnected.

[0254] Fig.14AThe figure shows a passive perfusion mechanism 1400 through a cardiac tissue compliant element 1450, wherein perfusion can be achieved by a ventricular region (Phigh) with a dominant relatively high pressure and an aortic region (Plow) with a dominant relatively low pressure. The relatively high pressure ventricular region forces blood to enter a perfusion inlet region 1410 including a plurality of ports via a fluid channel (not shown) through the cardiac tissue compliant element 1450, and flow out of a perfusion outlet region 1420 including a plurality of ports.

[0255] Fig. 14B An active perfusion mechanism 1405 is shown through a cardiac tissue compliant element 1450, wherein perfusion is facilitated by a perfusion pump 1430 configured to draw blood from a perfusion inlet region 1410 including a plurality of ports and push the blood to a perfusion outlet region 1420 including a plurality of ports. The perfusion pump 1430 draws fluid (i.e., blood) from the perfusion inlet region 1410 and pushes the fluid out of the perfusion outlet 1420 using continuous reciprocating motion of a barrel-shaped syringe connector.

[0256] Fig.15 A schematic diagram of a control loop for controlling an operation using an embodiment of the present invention to treat diseased cardiovascular tissue (such as a diseased valve) is depicted. In this embodiment, the controller includes a treatment plan that is supplied as an input to a controller subsystem. The controller subsystem sends a signal such as a voltage or data form 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 a signal to the oscillator, such as a frequency (f), i.e., an oscillation frequency, and a duty cycle (t open and t closed) to control the circulating energy transmitted by the oscillator. A feedforward model of a separate subsystem (e.g., a console assembly, a manifold assembly, a catheter assembly) or the system as a whole can be injected into the controller signal (i.e., the controller signal can be enhanced with such data about the feedforward model) to improve the convergence of the controller (i.e., the control algorithm) to the correctly supplied energy.

[0257] Therapeutic energy (i.e., potential energy) is transmitted to the oscillator, but the sensor can be used to track the amplitude of the potential energy transmitted to the oscillator. The sensor signals can be fed back into the controller so that they can be used to converge the output of the system (i.e., the pulsating energy applied to the cardiovascular tissue) to the desired output. The oscillator is turned on and off at an appropriate frequency and duty cycle so that the energy is transmitted to the distal position (i.e., transmitted to the cardiac tissue compliance element and ultimately transmitted to the cardiovascular tissue) in an appropriate manner, solving any attenuation, heat transfer, bubble formation, tissue relaxation, etc. The sensor measures system properties and characteristics of the cardiovascular tissue (such as pressure, volume, temperature, flow, etc.). The sensor data from the catheter assembly is fed back into the controller so that such measurements can be used to converge the output of the system (i.e., the pulsating energy applied to the cardiovascular tissue) to the desired output. The catheter assembly sensors can be located at any convenient position of the catheter assembly, where they 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 sensors may be sensors located in the catheter or cardiac tissue compliant element (e.g., in a balloon of the cardiac tissue compliant element) and connected to a guide wire configured to pass through the catheter. In other cases, such sensors may include an X-ray image of the cardiac tissue compliant element that is used to determine the position or inflation of one or more balloons of the cardiac tissue compliant element.

[0258] The catheter assembly may include one or more sensors configured to measure information at one location as a means for determining conditions at other locations. For example, a pressure transducer and a flow transducer may be configured to measure pressure and flow at a connector, but, for example, in conjunction with a fluid model of the system and X-ray or CT imaging, the sensor data may be used to measure pressure and / or volume of a balloon of a cardiac tissue compliance element. In addition, the sensor data may be provided to a clinician feedback transfer function, wherein such sensor feedback may be combined with feedback generated from a potential transfer device or imaging data for processing to a feedback mechanism device for providing feedback to a provider (i.e., an operator of the system) regarding the behavior of the system.

[0259] In other examples, pressure sensors and flow rate sensors can be used to measure the compliance or compliance change of the balloon of the cardiac tissue compliance element. Assuming that the diseased tissue provides resistance to balloon expansion, the amount of volume forced into the balloon at a certain pressure is an indirect indication of the compliance of the surrounding tissue. In this way, the measurement of compliance or compliance change can be used as a treatment metric or target.

[0260] Fig.16A schematic diagram of a system configuration 1600 for a robotic method of delivering therapy energy from a control room to a diseased valve is depicted. As described above, embodiments of the system can be separated into physically separate control rooms 1610 and treatment locations 1620, which can be separate, such as in the next room or in a different city or state or country.

[0261] 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 program database. The console display may be used to provide important information about the system status associated with the ongoing treatment (such as, for example, pressure measurements or volume measurements) or other information about the cardiac tissue compliance element (such as the type of cardiac tissue compliance element used). The information provided on the console display may be updated periodically during treatment, such as substantially in real time. The imaging display may be used to provide imaging information, such as fluoroscopic imaging results, such as showing the position of the cardiac tissue compliance element relative to cardiovascular tissue (e.g., heart valves). The fluoroscopic imaging results may also provide information about the status of various aspects of the cardiac tissue compliance element, such as, for example, whether the balloon is inflated and to what extent. The treatment controller may be used to adjust aspects of how the system is applied to provide treatment, such as applying pulsatile energy to cardiovascular tissue, such as, for example, adjusting pressure or frequency or duty cycle settings. The device position controller may be used to adjust the position of the device relative to the cardiovascular tissue being treated, such as adjusting the catheter position to move the cardiac tissue compliance to a more proximal or distal end. The patient information may include a display of any important patient data relevant to the treatment, such as, for example, information regarding the treatment site, patient age, disease state, vital sign measurements (such as blood pressure or pulse oximeter readings). The program database includes relevant information regarding past treatment plans (i.e., information regarding system configurations used to treat cardiovascular tissue, such as oscillation frequency, duty cycle, and / or amplitude and corresponding details regarding the underlying cardiovascular tissue, such as the extent of calcification), which may be accessed to identify potential treatment plans relevant to a new treatment.

[0262] Treatment location 1620 may include a system according to the present invention, i.e., an embodiment of a system including a console assembly having a source of electrical potential, a manifold assembly, and a catheter assembly having a connector, a connector-to-catheter transition hub, a catheter, and a cardiac tissue compliant element. Treatment room 1620 may be, for example, an operating room or an operating room. Any convenient operable connection capable of transmitting data and control signals between treatment room 1620 and control room 1610 may be employed, such as a wired or wireless connection.

[0263] Compliance Measurement :

[0264] As described in detail below, tissue (e.g., cardiovascular tissue or blood vessel) compliance is a measurable property of a blood vessel or cardiovascular tissue (such as cardiovascular tissue including a heart valve) that is calculated based on the ratio of tissue volume change for a given pressure change. Vascular compliance is an important property to observe because improving vascular compliance is a prerequisite for the definitive treatment of certain underlying disease conditions (such as atherosclerosis or the presence of calcification in cardiovascular tissue). Fig.17 The changes in vascular compliance are seen in the different pressure-volume curves depicted in . Fig.17 In FIG, volume is plotted on the x-axis and pressure is plotted on the y-axis. Pressure-volume (i.e., vascular compliance) is a property of an unconstrained balloon (i.e., a balloon that is not present in the cardiovascular tissue or whose volume expansion is constrained when the balloon pressure is increased) relative to untreated (i.e., before treatment) cardiovascular tissue (i.e., untreated vessel) relative to treated (i.e., after treatment) cardiovascular tissue (i.e., treated vessel).

[0265] like Fig.17 As shown, during treatment, such as applying pulsatile energy to cardiovascular tissue using an embodiment of the system of the present invention, the pressure-volume curve shifts to the right, closer to the curve of an unconstrained balloon. That is, during treatment, the same change in tissue volume corresponds to a reduced tissue pressure; that is, less pressure is applied to the tissue to expand the tissue volume by a similar amount.

[0266] Systems according to the present invention may be configured to assess tissue (eg, blood vessel) compliance by obtaining in vivo measurements of volume changes at different pressures (or different changes in pressure) applied to cardiovascular tissue (such as a blood vessel). Fig.18A and Fig.18B An example of measurements of changes in tissue compliance obtained during treatment using a system according to the present invention, ie during pulsating lithotripsy within a heart valve, is provided. Fig.18A The use of dynamic changes in pressure to obtain a measure of tissue compliance, ie, the corresponding changes in pressure and volume applied to the tissue over time, is demonstrated. Fig.18A It is shown that the peak volume change trends upward while the peak applied pressure remains constant. That is, as treatment progresses, when the same pressure change is applied, the tissue volume increases to a greater extent, which is a sign of increased tissue compliance.

[0267] Fig.18B It is demonstrated that dynamic changes in pressure as well as static pressure (i.e., at the third pressure oscillation, the pressure applied to the tissue is maintained for approximately half a cycle) are used to obtain a measure of tissue compliance, i.e., the corresponding changes in pressure and volume applied to the tissue over time. Fig.18BIt is shown that the peak volume change trends upward while the peak applied pressure remains constant. That is, as treatment progresses, when the same pressure change is applied, the tissue volume increases to a greater extent, which is a sign of increased tissue compliance.

[0268] Embodiments of the present invention are capable of measuring in real time the relative compliance changes of cardiovascular tissue (e.g., blood vessels) during application of 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 the compliance changes of the cardiovascular tissue. For example, after calcium cracking (i.e., calcified plaque tissue fragmentation), the cardiovascular tissue and cardiac tissue compliance element or its balloon can expand significantly, which contributes to a larger gain in compliance, as measured by the system. However, after the blood vessel is fully expanded, the compliance change as measured by the system may be weakened. Identification of such conditions (i.e., changes in compliance to varying degrees) can indicate that treatment can be stopped because no further significant gain occurs.

[0269] The system can be configured to measure pressure in any convenient manner. In some instances, embodiments of the system according to the present invention may include a pressure gauge as described herein for measuring pressure in a catheter of a balloon or catheter assembly, such as a fluid channel and / or a cardiac tissue compliant element. In some instances, the pressure gauge may be installed so that it is configured to measure the pressure of a distal chamber of a proximal connector, such as in Fig. 6A As seen in the pressure transducer 625 in FIG.

[0270] The system can be configured to measure changes in the volume of cardiovascular tissue (e.g., blood vessels) in any convenient manner. In some examples, embodiments of the system according to the present invention can be configured so that separate connectors (such as Fig. 6A The membrane of the proximal chamber and the distal chamber of the connector 600 (such as Fig. 6AA change in position of a membrane 630 in the heart tissue compliance element (e.g., a balloon) reflects a change in volume of an aspect of the heart tissue compliance element (e.g., a balloon). The change in volume of the balloon reflects a change in the cross-sectional area of ​​cardiovascular tissue (such as a blood vessel), and therefore reflects a change in volume of the cardiovascular tissue. Such embodiments may further include a Hall sensor and a permanent magnet for measuring the change in position of such a membrane. 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. As desired, the permanent magnet may be composed of any convenient magnetic material or electromagnet, so that a change in the relative position of the Hall sensor relative to the permanent magnet can be detected by the Hall sensor. Sensors such as the above-described Hall sensors and permanent magnets can be used to measure changes in volume of a heart tissue compliance element or one or more of its balloons, as well as the rate at which aspects of the heart tissue compliance element (e.g., one or more of its balloons) are inflated, i.e., the rate of change in volume of the cardiovascular tissue and the corresponding change in compliance.

[0271] method

[0272] A method of delivering pulsatile energy to cardiovascular tissue is also provided, and similarly benefits are found in the above applications. The method according to the present invention includes deploying a system so that the cardiac tissue compliance element of the system is adjacent to the cardiovascular tissue. Such a system includes: a console assembly, the console assembly includes an electric potential source; a manifold assembly, the manifold assembly is operably connected to the output end of the console assembly, wherein the manifold assembly includes an oscillator, the oscillator is configured to generate pulse energy from the energy transmitted by the electric potential source; and a catheter assembly, the catheter assembly is operably connected to the output end of the manifold assembly, wherein the catheter assembly includes: a connector, the connector operably connects the catheter assembly to the manifold assembly and is configured to convert the first pulse energy generated by the manifold assembly into a second pulse energy; (ii) a catheter, the catheter includes a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse energy; and a cardiac tissue compliance element, the cardiac tissue compliance element is configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply the pulsatile energy to the cardiovascular tissue. Such components of the system are described in detail above. The method according to the present invention further includes engaging the system in a manner that the cardiac tissue compliant element transfers energy to the cardiovascular tissue. "Transferring energy to the cardiovascular tissue" means that the cardiac tissue compliant element applies pulsating energy to the cardiovascular tissue, that is, sufficient to destroy the formation of calcium. For example, the cardiac tissue compliant element can be configured to engage the desired features of the cardiovascular tissue, and various aspects of the cardiac tissue compliant element (e.g., a balloon including the cardiac tissue compliant element) are repeatedly inflated and deflated as described in detail above in conjunction with the embodiments of the system of the present invention. The system can be configured so that different types and degrees of energy are applied to different aspects of the cardiovascular tissue, for example, such as between the heart valve leaflets and the heart valve commissures. Any suitable inflation and deflation frequency can be used, and the frequency can vary. In the embodiment in which the cardiac tissue compliant element includes multiple balloons (or other mobile members for transferring pulsating energy to the cardiovascular tissue), the frequency of inflation and deflation and the amplitude and duty cycle can be different between such balloons or other mobile members.

[0273] In embodiments, the system is engaged in a manner that the heart tissue compliant element transfers energy to cardiovascular tissue, including transferring energy to heart valve tissue, such as, for example, heart valve leaflets, heart valve commissures, heart valve leaflet tubercles, or heart valve rings. For example, in embodiments, the system is engaged in a manner that the heart tissue compliant element transfers energy to cardiovascular tissue, including transferring energy to the aortic valve, such as, for example, aortic valve leaflets, aortic valve commissures, or aortic valve rings. In other embodiments, the system is engaged in a manner that the heart tissue compliant element transfers energy to cardiovascular tissue, including transferring energy to cardiovascular tissue including tissue supporting the heart valve. In still other embodiments, the system is engaged in a manner that the heart tissue compliant element transfers energy to cardiovascular tissue, including transferring energy to the atrial septum or the ventricular septum. In such embodiments, the heart tissue compliant element can be configured so that when the heart tissue compliant element receives a second pulse of energy transmitted through the fluid channel of the catheter, the characteristics of the heart tissue compliant element apply the pulsating energy primarily to a specific area of ​​the cardiovascular tissue. For example, embodiments of the cardiac tissue compliant element may be configured such that the balloon engages the heart valve commissures such that energy applied to the cardiac tissue compliant element is transmitted to the heart valve commissures.

[0274] The system can be configured so that the cardiac tissue compliant element applies different forms or degrees or types of energy to different aspects of the cardiovascular tissue. For example, the cardiac tissue compliant element can be configured so that the valve commissure receives pulsating energy at a first frequency, amplitude, duty cycle, and / or duration, and the valve leaflets receive pulsating energy at a second frequency, amplitude, duty cycle, and / or duration. That is, applying the system of the present invention to treat cardiovascular tissue can include treating different aspects of the cardiovascular tissue differently.

[0275] In embodiments, engaging the system in a manner that allows the cardiac tissue compliant element to transfer energy to the cardiovascular tissue includes engaging the system in a manner that allows fluid to flow through a distal region of the system. "Fluid flows through a distal region of the system" means that the fluid can be displaced from a relatively distal region of the system (e.g., the distal end of the cardiac tissue compliant element) to a relatively proximal region of the system (e.g., the proximal end of the cardiac tissue compliant element). In such embodiments, engaging the system causes the cardiac tissue compliant element to transfer energy to the cardiovascular tissue while allowing fluid (e.g., blood) to perfuse through the cardiac tissue compliant element.

[0276] In some embodiments, engaging the system in a manner that the cardiac tissue compliant element transfers energy to the cardiovascular tissue includes engaging the system in a manner that simulates the function of a heart valve. That is, in embodiments, engaging the system can cause an area of ​​the cardiovascular tissue to be substantially sealed or closed or blocked in the same manner that a functional heart valve would cause the area of ​​the cardiovascular tissue to be substantially sealed or closed or blocked relative to the flow of a fluid (e.g., blood). In some embodiments, engaging the system so that the cardiac tissue compliant element substantially behaves as, for example, a heart valve, while the system is used to apply energy to cardiovascular tissue (such as a heart valve). In some cases, engaging the system in a manner that the cardiac tissue compliant element transfers 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 cases, the cardiac tissue compliant element is configured to substantially behave as a heart valve by sealing or closing or blocking an area of ​​the cardiovascular tissue at a rate determined by the results of the electrocardiogram.

[0277] In other embodiments, engaging the system in a manner that the cardiac tissue compliance element delivers energy to the cardiovascular tissue includes adjusting the configuration of the system based on program-based feedback. Any desired program-based feedback can be applied, such as the results of sensors deployed on the system, including, for example, a pressure sensor or volume sensor for measuring the fluid pressure applied to the balloon or the fluid volume change 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 or frequency or duty cycle of the energy applied to the cardiovascular tissue, i.e., the frequency or duty cycle of the oscillator. In an embodiment, the method of delivering pulsating energy to the cardiovascular tissue is a method for treating cardiovascular tissue (such as a diseased valve) that relies on feedback received during the treatment procedure. Such methods can rely on capturing data from internal pressure sensors and volume sensors during treatment so that the compliance of the valve can be measured before, during, and after treatment. In addition to internal sensors, external sensors such as pressure sensors, imaging sensors, temperature sensors, etc. can also be utilized. In addition, sensors can be provided so that they can be integrated together to operate and provide information at different frequencies. In addition to feedback sensors, feedforward information, such as a physical model of an embodiment of the system of the present invention, can be supplied to the feedforward system. Such a feedforward system allows for further control of the system through enhanced modeling of the system in conjunction with the feedback sensors.

[0278] During treatment according to the methods of the present invention, information from various sensors internal and / or external to the system may be read, stored and / or analyzed by the system, or such data may be transmitted external to the system for analysis at another location (such as a cloud cluster). In other instances, the system may be configured to transmit such data (e.g., sensor data) through a learning algorithm to compare it with other instances encountering similar and / or equivalent treatment scenarios.

[0279] In embodiments, the deployment system makes the cardiac tissue compliant element of the system adjacent to the cardiovascular tissue including aligning the cardiac tissue compliant element with the feature of the cardiovascular tissue. In some cases, the cardiac tissue compliant element is configured to align with the specific feature of the cardiovascular tissue, that is, by including a passive element or a dynamic element, the passive element or the dynamic element is configured to align or engage with the feature of the cardiovascular tissue or maintain a fixed position relative to the feature of the cardiovascular tissue. In some cases, the order of balloon inflation of the cardiac tissue compliant element helps to align the cardiac tissue compliant element as needed, for example, so that the outer balloon is aligned with the commissure of the heart valve. For example, one or more outer balloons (e.g., winged balloons) can be inflated before the inflation of the centering radius balloon, so as to align the cardiac tissue compliant element as needed, for example, relative to the valve commissure. In some cases, the cardiac tissue compliant element includes a protrusion for engaging the feature of the cardiovascular tissue, and the deployment system includes aligning the protrusion with the feature of the cardiovascular tissue. In other embodiments, the deployment system makes the cardiac tissue compliant element adjacent to the cardiovascular tissue including aligning the cardiac tissue compliant element with the heart valve commissure or the heart valve leaflet. Utilizing the active alignment feature may include pulsating a balloon (eg, a winged balloon) over an outer surface of the cardiac tissue compliant element in a manner that causes the winged balloon to seat itself in the valve commissures, thereby aligning the cardiac tissue compliant element relative to the heart valve.

[0280] In some cases, the method according to the present invention is a method of preparing cardiovascular tissue for placement of a heart valve replacement surgery or an artificial heart valve. That is, preparing tissue for a replacement heart valve may include destroying calcium deposits in the cardiovascular tissue or affecting tissue compliance before implanting the heart valve. In other cases, the method is a method of delivering an active agent to cardiovascular tissue or surrounding tissue. For example, an active agent may be present on the outer surface of a cardiac tissue compliant element such that a pulsating balloon of the cardiac tissue compliant element causes the active agent to dissolve into the cardiovascular tissue.

[0281] In some instances, the method of delivering pulsatile energy to cardiovascular tissue further includes aligning the catheter assembly (e.g., cardiac tissue compliant element) with cardiovascular tissue (e.g., heart valve or diseased cardiovascular tissue or another treatment site) using imaging techniques. Any convenient imaging techniques that can visualize various aspects of the catheter present in the lumen can be applied, such as systems according to the present invention. Imaging techniques can include, for example, ultrasound imaging, such as intravascular ultrasound techniques, light-based imaging techniques, angioplasty-based imaging techniques, or optical coherence tomography-based techniques, etc. In some cases, diagnostic X-ray imaging can be applied.

[0282] As described above, the method for transmitting pulsating energy to the cardiovascular tissue of the present invention may include a method for treating cardiovascular disease. In some cases, the method is a method for treating arteriosclerosis (which means thickening and hardening of the arterial wall). In some cases, the method of transmitting pulsating energy to cardiovascular tissue of the present invention includes a method for transmitting pulsating energy to the cardiovascular tissue of the subject. The method can be used to transmit pulsating energy to the cardiovascular tissue of any number of different subjects. In some instances, the subject is a "mammal" or "mammal", wherein these terms are widely used to describe organisms in 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 instances, the subject is a human. For example, in some cases, the method of the present invention is a method for treating arteriosclerosis of a subject as a human.

[0283] Fig.19A graphical user interface (GUI) is shown, with which an operator of the system of the present invention can interact during a treatment procedure including delivering pulsating energy to a heart valve when performing an embodiment of a method according to the present invention. In this embodiment, the GUI can have several information areas, such as a fluoroscopic area, a balloon information area, a treatment information area, and a compliance area. The fluoroscopic area presents imaging results of a cardiac tissue compliant element and associated cardiovascular tissue (i.e., a heart valve). Such imaging shows the interaction between the cardiac tissue compliant element and the heart valve, i.e., engagement, for example, whether the cardiac tissue compliant element is aligned with the heart valve as desired, and whether and to what extent the balloon of the cardiac tissue compliant element is inflated, and how the corresponding cardiovascular tissue responds. The balloon information area indicates information about the cardiac tissue compliant element or one or more balloons thereof attached to the catheter. Such information includes, for example, the type and size of the device related to the cardiac tissue compliant element or its components. Additional information that may be displayed includes the diameter, length, nominal pressure, rated pressure, and other characteristics of the cardiac tissue compliance element (or its balloon), such as drug-coated or stent-covered balloons or other aspects of the cardiac tissue compliance element. In addition, cardiac tissue compliance element catheter connectivity information (i.e., whether the cardiac tissue compliance element is connected) may be included in this section. The treatment information area indicates important surgical characteristics that the operator adopts during the operation. Such characteristics include heart valve diameter and area and valve pressure gradient (i.e., the pressure difference on both sides of the heart valve). Other characteristics may be related to measurements indicating the extent to which blood can be perfused through the cardiac tissue compliance element to the distal blood vessels. Some or all of this information may be updated or changed by the system and / or by the user, as appropriate. In the compliance area, various program graphs may be displayed, including compliance graphs and treatment graphs. The compliance graph may include a nominal pressure-volume curve, which may be provided by the cardiac tissue compliance element (or its balloon). In addition, throughout the procedure, a pressure-volume curve measured in situ during the procedure can be plotted and updated. The operator can use this graph to determine the effectiveness of the treatment as a measure of compliance or efficacy. The pressure graph can include a display of pressure versus time. Other information (not shown) that can be included on the GUI includes treatment status and intensity, on / off switch, indicator LEDs, etc.

[0284] Reagent test kit

[0285] Also provided is a test kit including, for example, a system as described above, or one or more of its components. Thus, in some instances, the test kit may include one or more of a catheter assembly, a manifold assembly, a console assembly (with or without a potential energy source, such as a pressure source), or its components. The components of the test kit may be present in a package that may be sterile as required. The components of the test kit may be disposable or reusable as required. In some cases, the test kit may include multiple components, including multiple versions of the same component of different sizes, such as, for example, multiple catheters of different diameters or cardiac tissue compliant elements configured for different aspects of cardiovascular tissue (e.g., for heart valves).

[0286] In the test kit, there can also be instructions for using the parts of the test kit. The instructions can be recorded on a suitable recording medium. For example, the instructions can be printed on a substrate (such as paper or plastic, etc.). Therefore, the instructions can be present in the test kit as a package insert, in the label of the container of the test kit or its parts (that is, associated with packaging or sub-packaging), etc. In other embodiments, the instructions exist as an electronic storage data file present in a suitable computer-readable storage medium (for example, a portable flash drive, a DVD-ROM or a CD-ROM, etc.). The instructions can take any form, including the complete instructions for how to use the device, or as a website address, through which the instructions posted on the World Wide Web can be accessed.

[0287] The following examples are offered by way of illustration and not by way of limitation.

[0288] Example

[0289] Fig. 20 Figures are provided of various aspects of a catheter assembly of a system according to embodiments of the present invention. Fig.21 Shows Fig. 20 The assembly process of the connector of the catheter assembly shown in . The first step of the assembly process is to fix the electronic flexible printed circuit board assembly to the diaphragm and the pressure sensor. For example, epoxy resin and solder can be used respectively. The pressure sensor and the diaphragm can be fixed to the distal flange. The proximal flange can be fixed to the distal flange using appropriate fixing techniques (e.g., fasteners, welding, etc.). The electronic connector can be fixed to the front of the proximal flange with, for example, epoxy resin to provide a reliable connection to the handheld actuator. Fig. 22 Represents a test performed on a single balloon of the described embodiment and physical assembly. The pressure is shown to increase, and the force on the balloon also increases. The force generated during the oscillation matches the force generated during static inflation, indicating that the system has minimal attenuation during pulsation.

[0290] Notwithstanding the appended claims, the present disclosure is also defined by the following clauses:

[0291] 1. A system for delivering pulsatile energy to cardiovascular tissue, the system comprising:

[0292] (a) a console assembly, the console assembly comprising a source of electric potential;

[0293] (b) a manifold assembly operably connected to an output of the console assembly, wherein the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the source of electrical potential; and

[0294] (c) a conduit assembly operably connected to an output end of the manifold assembly, wherein the conduit assembly comprises:

[0295] (i) a connector operatively connecting the catheter assembly to the manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy;

[0296] (ii) a catheter comprising a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse of energy; and

[0297] (iii) a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsatile energy to cardiovascular tissue.

[0298] 2. The system of clause 1, wherein the cardiac tissue compliant element is configured to engage cardiac valve tissue.

[0299] 3. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage a heart valve leaflet.

[0300] 4. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage a heart valve commissure.

[0301] 5. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage a heart valve leaflet tubercle.

[0302] 6. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage a heart valve annulus.

[0303] 7. The system of clause 1, wherein the cardiac tissue compliant element is configured to engage cardiovascular tissue including tissue supporting a heart valve.

[0304] 8. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage an aortic valve.

[0305] 9. The system of clause 8, wherein the cardiac tissue compliant element is configured to engage an aortic valve leaflet.

[0306] 10. The system of clause 8, wherein the cardiac tissue compliant element is configured to engage aortic valve commissures.

[0307] 11. The system of clause 8, wherein the cardiac tissue compliant element is configured to engage the aortic valve annulus.

[0308] 12. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage a bileaflet valve.

[0309] 13. The system of clause 2, wherein the cardiac tissue compliant element is configured to engage a mitral valve.

[0310] 14. The system of clause 1, wherein the cardiac tissue compliant element is configured to engage the atrial septum.

[0311] 15. The system of clause 1, wherein the cardiac tissue compliant element is configured to engage the ventricular septum.

[0312] 16. The system according to any of the preceding clauses, wherein the cardiac tissue compliant element is located at a distal region of the catheter.

[0313] 17. The system according to any of the preceding clauses, wherein the cardiac tissue compliant element comprises a plurality of distal balloons arranged circumferentially around a rigid distal region of the catheter.

[0314] 18. The system of clause 17, wherein the distal balloon is configured to independently receive pulsed energy generated by the manifold assembly.

[0315] 19. A system according to clause 18, wherein

[0316] The fluid channel of the conduit is a first fluid channel, and

[0317] The catheter assembly includes a plurality of fluid channels, wherein each fluid channel is operably connected to a corresponding distal balloon.

[0318] 20. The system of clause 19, wherein the plurality of fluid channels comprises fluid channels inside and outside of the catheter.

[0319] 21. A system according to any one of clauses 19 to 20, wherein

[0320] The connector is a first connector, and

[0321] The catheter assembly includes a plurality of connectors, wherein each connector is operably connected to a corresponding fluid channel of the catheter.

[0322] 22. The system of clause 21, wherein the output of the connector is connected to the conduit via a transition hub.

[0323] 23. The system of clause 22, wherein the transition hub couples the output of the connector to the fluid channel of the conduit.

[0324] 24. The system of clause 22, wherein the transition hub couples the output of the connector to a corresponding fluid channel.

[0325] 25. A system according to any one of clauses 17 to 24, wherein in the inflated state, the distal balloon is configured to provide structural rigidity.

[0326] 26. The system of clause 25, wherein in the inflated state, the distal balloon is configured to assume a geometric shape.

[0327] 27. A system according to any one of clauses 17 to 26, wherein in the inflated state, the distal balloon comprises substantially the same shape.

[0328] 28. A system according to any of clauses 17 to 26, wherein in the inflated state, the distal balloon comprises a different shape.

[0329] 29. A system according to any one of clauses 17 to 26, wherein in an inflated state, the distal balloons comprise substantially the same diameter.

[0330] 30. A system according to any of clauses 17 to 26, wherein in the inflated state, the distal balloon comprises different diameters.

[0331] 31. A system according to any one of clauses 17 to 26, wherein in the inflated state, the diameter of the distal balloon varies between a proximal region, a distal region or a middle region of the distal balloon.

[0332] 32. A system according to any one of clauses 17 to 31, wherein the distal balloon is coated with an active agent.

[0333] 33. A system according to any of clauses 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.

[0334] 34. A system according to any one of clauses 17 to 33, further comprising a membrane present at the rigid distal region of the catheter, the membrane being configured to cover the distal balloon.

[0335] 35. The system of clause 34, wherein the membrane is coated with an active agent.

[0336] 36. A system according to any one of clauses 17 to 35, further comprising a plurality of protrusions present on the distal balloon and extending radially beyond the distal balloon.

[0337] 37. The system of clause 36, wherein the protrusion is configured to engage a feature of the cardiovascular tissue.

[0338] 38. The system of clause 37, wherein the protrusion is configured to engage a feature of heart valve tissue.

[0339] 39. The system of clause 37, wherein the protrusion is configured to maintain a position of the distal balloon relative to the cardiovascular tissue.

[0340] 40. A system according to any of clauses 36 to 39, wherein the cross-section of the protrusion is a geometric shape.

[0341] 41. A system according to clause 40, wherein the cross-section of the protrusion is triangular or circular.

[0342] 42. A system according to any of clauses 36 to 41, wherein the protrusions are arranged substantially equidistantly around the distal balloon.

[0343] 43. A system according to any of clauses 17 to 42, wherein the cross-section of the rigid distal region of the catheter is configured to provide structural rigidity.

[0344] 44. The system of clause 43, wherein a cross-section of the rigid distal region of the catheter comprises a geometric shape.

[0345] 45. A system according to any of the preceding clauses, wherein the catheter comprises a guidewire channel.

[0346] 46. ​​A system according to any of the preceding clauses, wherein the catheter comprises a pressure sensor.

[0347] 47. The system of clause 46, wherein the pressure sensor is located at a distal region of the catheter.

[0348] 48. The system of clause 1, wherein the cardiac tissue compliant element comprises a plurality of radial members extending radially with a length greater than a cross-sectional width, wherein the radial members are staggered relative to one another.

[0349] 49. A system according to clause 48, wherein the radial members are arranged to form a three-point flexion configuration.

[0350] 50. The system of clause 49, wherein the three-point flex configuration is configured to engage a heart valve leaflet.

[0351] 51. The system of clause 50, wherein the catheter assembly is configured to force the first radial member to translate laterally relative to the second radial member.

[0352] 52. The system of any of the preceding clauses, wherein the catheter assembly is configured to allow perfusion of fluid through a distal region of the catheter.

[0353] 53. The system of clause 52, wherein the catheter assembly includes a valve configured to allow fluid to flow through the distal region of the catheter in only one direction.

[0354] 54. The system of clause 52, wherein the catheter assembly includes an oscillating balloon configured to allow fluid to be perfused through the distal region of the catheter in only one direction.

[0355] 55. The system of any of clauses 52 to 54, wherein the catheter assembly is configured to allow perfusion of fluid through the cardiac tissue compliant element.

[0356] 56. The system of clause 55, wherein the catheter assembly further comprises fluidly connected perfusion regions at the proximal and distal ends of the cardiac tissue compliant element.

[0357] 57. The system of clause 56, wherein the perfusion zone comprises:

[0358] an inlet perfusion region positioned distal to the cardiac tissue compliant element; and

[0359] An outlet perfusion zone is positioned proximal to the cardiac tissue compliant element.

[0360] 58. A system according to any one of clauses 56 to 57, wherein the irrigation region comprises a perforation in the catheter assembly.

[0361] 59. A system according to any of clauses 56 to 58, wherein the perfusion zone is fluidly connected via a perfusion fluid channel of the catheter.

[0362] 60. The system of clause 59, wherein the perfusion fluid channel of the catheter is coated with an active agent that promotes fluid flow.

[0363] 61. The system of clause 60, wherein the active agent is an anticoagulant.

[0364] 62. A system according to any of clauses 52 to 61, wherein the catheter assembly comprises a passive irrigation mechanism.

[0365] 63. The system of clause 62, wherein the passive perfusion mechanism comprises a pressure gradient surrounding the distal region of the catheter.

[0366] 64. A system according to any of clauses 52 to 63, wherein the catheter assembly comprises an active irrigation mechanism.

[0367] 65. The system of clause 64, wherein the active perfusion mechanism is configured to pull or push fluid through the distal region of the catheter.

[0368] 66. The system of clause 65, wherein the active priming mechanism comprises a priming connector comprising a barrel-type syringe operably connected to an inlet port having a one-way valve and an outlet port having a one-way valve.

[0369] 67. A system according to any of the preceding clauses, wherein the connector is a proximal connector comprising a proximal chamber and a distal chamber separated by a membrane.

[0370] 68. A system according to any one of clauses 1 to 66, wherein the connector is a syringe.

[0371] 69. The system of clause 68, wherein the syringe is a barrel-type syringe, the barrel-type syringe comprising:

[0372] fluidly connected to the input port of the first chamber;

[0373] an output port fluidly connected to the second chamber; and

[0374] A plunger is present between the first chamber and the second chamber.

[0375] 70. A system according to clause 69, wherein

[0376] The first chamber is a pneumatic chamber, and

[0377] The second chamber is a fluid chamber.

[0378] 71. The system of any of clauses 69 to 70, wherein the barrel syringe is configured to bias evacuation of the first chamber of the barrel syringe.

[0379] 72. The system of clause 71, wherein the cartridge syringe further comprises a biasing spring connected to the plunger.

[0380] 73. The system of clause 72, wherein the bias spring is configured to apply a force to the plunger to empty the first chamber of the barrel syringe.

[0381] 74. The system of any of clauses 69 to 73, wherein the first chamber of the barrel syringe is selectively connected to a low pressure source to evacuate the first chamber of the barrel syringe.

[0382] 75. The system of clause 74, wherein the low pressure source is a vacuum.

[0383] 76. A system according to any of the preceding clauses, wherein the connector comprises a pressure sensor.

[0384] 77. A system according to any of the preceding clauses, wherein the connector comprises a volume sensor.

[0385] 78. The system of any preceding clause, wherein the connector is configured to releasably engage the output end of the manifold assembly.

[0386] 79. The system of any of the preceding clauses, wherein the connector is configured to heat or cool a fluid delivered to the cardiac tissue compliant element.

[0387] 80. A system according to any of the preceding clauses, wherein the connector is configured to transmit one of electrical pulse energy or optical energy.

[0388] 81. The system of clause 80, wherein the catheter assembly comprises an electrode configured to receive electrical pulse energy or optical energy at a target site.

[0389] 82. A system according to any of the preceding clauses, wherein the oscillator is further configured to output a static pressure output.

[0390] 83. A system according to any of the preceding clauses, wherein the oscillator is a solenoid.

[0391] 84. The system of any preceding clause, wherein the oscillator is a first oscillator and the manifold assembly comprises a plurality of oscillators.

[0392] 85. The system of clause 84, wherein the oscillation frequencies of the plurality of oscillators are synchronized.

[0393] 86. A system according to any of the preceding clauses, wherein the oscillator is configured such that the oscillation frequency of the oscillator is synchronized with the results of the electrocardiogram.

[0394] 87. A system according to any of the preceding clauses, wherein the source of electrical potential of the console component is a voltage potential or an electromagnetic potential or a pressure potential.

[0395] 88. The system of clause 87, wherein the console assembly comprises a regulator configured to regulate the first energy from the source of electrical potential into a second energy.

[0396] 89. The system of clause 88, wherein the regulator is an active regulator configured to be controlled by an electrical signal.

[0397] 90. The system of clause 88, wherein the regulator is a passive regulator configured to be preset to a specific output.

[0398] 91. A system according to any of the preceding clauses, wherein the console assembly further comprises a controller, the controller being configured to:

[0399] receiving input from at least one of the console assembly, the manifold assembly, and the catheter assembly, and

[0400] The configuration of at least one of the console assembly, the manifold assembly, and the catheter assembly is adjusted based at least in part on the received input.

[0401] 92. The system of clause 91, wherein the controller is further configured to receive input from a source external to the system.

[0402] 93. The system of clause 92, wherein the controller is configured to receive input from at least one of an electrocardiogram, an intravascular pressure monitor, a blood volume monitor, or results from an imaging system.

[0403] 94. A system according to any of the preceding clauses, wherein the console assembly is a first console assembly and the system comprises a plurality of operably connected console assemblies.

[0404] 95. The system of clause 94, wherein the manifold assembly is operably connected to the plurality of console assemblies.

[0405] 96. A system according to any of the preceding clauses, wherein the cardiac tissue compliant element is configured to expand during diastole of the cardiovascular tissue.

[0406] 97. The system of clause 96, wherein the cardiac tissue compliant element is further configured to relax during systole of the cardiovascular tissue.

[0407] 98. A system according to any of clauses 1 to 95, wherein the cardiac tissue compliant element is configured to relax during diastole of the cardiovascular tissue.

[0408] 99. The system of clause 98, wherein the cardiac tissue compliant element is further configured to expand during contraction of the cardiovascular tissue.

[0409] 100. A system according to any of clauses 96 to 99, wherein the system is configured to apply pulsatile energy to cardiovascular tissue when the cardiac tissue compliant element expands.

[0410] 101. The system of any one of clauses 96 to 100, wherein the system further comprises a controller configured to expand and relax the cardiac tissue compliant element based on input from at least one of an electrocardiogram, an intravascular pressure monitor, a blood volume monitor, or results from an imaging system.

[0411] 102. The system of any of clauses 96 to 100, wherein the system further comprises a controller configured to expand and relax the cardiac tissue compliant element based on a predetermined configuration.

[0412] 103. The system of any of clauses 101 to 102, wherein the controller is further configured to cause the cardiac tissue compliant element to apply pulsatile energy to the cardiovascular tissue when the cardiac tissue compliant element is in an expanded state.

[0413] 104. The system of clause 103, wherein the controller is further configured to cause the cardiac tissue compliant element to not apply pulsatile energy to cardiovascular tissue when the cardiac tissue compliant element is in a relaxed state.

[0414] 105. A system for transmitting pulsatile energy through a fluid channel of a catheter, the system comprising:

[0415] (a) a plurality of pulsating energy generating components, each pulsating energy generating component comprising:

[0416] (i) a console assembly, the console assembly comprising a source of electrical potential;

[0417] (ii) a manifold assembly operably connected to an output of the console assembly, wherein the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the source of electrical potential; and

[0418] (iii) a connector operably connected to an output end of the manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy;

[0419] (b) a conduit comprising a fluid passage, wherein the fluid passage is operably connected to the output end of each connector of the plurality of pulsating energy generating assemblies; and

[0420] (c) a controller configured to control the plurality of pulsating energy generating components,

[0421] Wherein the controller and the plurality of pulsating energy generating assemblies are configured such that the controller independently controls each potential output of each console assembly and each oscillator of each manifold assembly.

[0422] 106. A system for transmitting pulsatile energy through a plurality of fluid channels, the system comprising:

[0423] (a) A pulsating energy generating component, the pulsating energy generating component comprising:

[0424] (i) a console assembly, the console assembly comprising a source of electrical potential;

[0425] (ii) a manifold assembly operably connected to an output of the console assembly, wherein the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the source of electrical potential; and

[0426] (iii) a connector operably connected to an output end of the manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy;

[0427] (b) a plurality of fluid channels, wherein each fluid channel is operably connected to the output end of the connector of the pulsating energy generating assembly; and

[0428] (c) a controller configured to control the pulsating energy generating component,

[0429] Wherein the controller and the pulsating energy generating assembly are configured such that the controller controls the potential output of the oscillator of the console assembly and the manifold assembly.

[0430] 107. A system for delivering pulsatile energy to cardiovascular tissue, the system comprising:

[0431] (a) a console assembly, the console assembly comprising a source of electric potential;

[0432] (b) a manifold assembly operably connected to an output of the console assembly, wherein the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the source of electrical potential; and

[0433] (c) a conduit assembly operably connected to an output end of the manifold assembly, wherein the conduit assembly comprises:

[0434] (i) a connector operatively connecting the catheter assembly to the manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy;

[0435] (ii) a catheter comprising a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse of energy; and

[0436] (iii) a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsatile energy to cardiovascular tissue,

[0437] Therein, the system is configured to expand and contract the cardiac tissue compliant element based at least in part on systole and diastole of the cardiovascular tissue.

[0438] 108. A catheter assembly comprising:

[0439] (i) a connector operatively connecting the catheter assembly to a manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy;

[0440] (ii) a catheter comprising a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse of energy; and

[0441] (iii) a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsatile energy to cardiovascular tissue.

[0442] 109. The assembly of clause 108, wherein the cardiac tissue compliant element is configured to engage cardiac valve tissue.

[0443] 110. The assembly of clause 109, wherein the cardiac tissue compliant element is configured to engage a heart valve leaflet.

[0444] 111. The assembly of clause 109, wherein the cardiac tissue compliant element is configured to engage a heart valve commissure.

[0445] 112. The assembly of clause 109, wherein the cardiac tissue compliant element is configured to engage a heart valve leaflet tubercle.

[0446] 113. The assembly of clause 109, wherein the cardiac tissue compliant element is configured to engage a heart valve annulus.

[0447] 114. The assembly of clause 108, wherein the cardiac tissue compliant element is configured to engage cardiovascular tissue including tissue supporting a heart valve. [...

Claims

1. A system for delivering pulsatile energy to cardiovascular tissue, the system comprising: (a) a console assembly, the console assembly comprising a source of electric potential; (b) a manifold assembly operably connected to an output of the console assembly, wherein the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the source of electrical potential; and (c) a conduit assembly operably connected to an output end of the manifold assembly, wherein the conduit assembly comprises: (i) a connector operatively connecting the catheter assembly to the manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy; (ii) a catheter comprising a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse of energy; and (iii) a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsatile energy to cardiovascular tissue.

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

3. A system according to any of the preceding claims, wherein the cardiac tissue compliant element is located in a distal region of the catheter.

4. A system according to any of the preceding claims, wherein the cardiac tissue compliant element includes a plurality of distal balloons arranged circumferentially around the rigid distal region of the catheter.

5. The system of claim 4, wherein the distal balloon is configured to independently receive pulsed energy generated by the manifold assembly.

6. The system according to claim 5, wherein The fluid channel of the conduit is a first fluid channel, and The catheter assembly includes a plurality of fluid channels, wherein each fluid channel is operably connected to a corresponding distal balloon.

7. A system according to any one of claims 4 to 6, wherein in an inflated state, the distal balloon is arranged to leave a space for fluid to pass between the distal balloon and the catheter.

8. The system of any one of claims 4 to 7, further comprising a plurality of protrusions present on the distal balloon and extending radially beyond the distal balloon.

9. The system of claim 8, wherein the protrusion is configured to engage a feature of the cardiovascular tissue.

10. The system of claim 1, wherein the catheter assembly is configured to allow perfusion of fluid through the cardiac tissue compliant element.

11. The system of claim 10, wherein the catheter assembly further comprises fluidly connected perfusion regions at the proximal and distal ends of the cardiac tissue compliant element.

12. The system of claim 11, wherein the perfusion zone comprises: an inlet perfusion region positioned distal to the cardiac tissue compliant element; and An outlet perfusion zone is positioned proximal to the cardiac tissue compliant element.

13. The system of any one of claims 11 to 12, wherein the irrigation region comprises a perforation in the catheter assembly.

14. A catheter assembly comprising: (i) a connector operatively connecting the catheter assembly to a manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy; (ii) a catheter comprising a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse of energy; and (iii) a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsatile energy to cardiovascular tissue.

15. A method for delivering pulsatile energy to cardiovascular tissue, the method comprising: Deploying a system such that a cardiac tissue compliant element of the system is adjacent to cardiovascular tissue, the system comprising: (a) a console assembly, the console assembly comprising a source of electric potential; (b) a manifold assembly operably connected to an output of the console assembly, wherein the manifold assembly includes an oscillator configured to generate pulsed energy from energy transmitted by the source of electrical potential; and (c) a conduit assembly operably connected to an output end of the manifold assembly, wherein the conduit assembly comprises: (i) a connector operatively connecting the catheter assembly to the manifold assembly and configured to convert a first pulse of energy generated by the manifold assembly into a second pulse of energy; (ii) a catheter comprising a fluid channel operably connected to the output end of the connector and configured to transmit the second pulse of energy; and (iii) a cardiac tissue compliant element configured to receive the second pulse energy transmitted through the fluid channel of the catheter to apply pulsatile energy to the cardiovascular tissue; and The system is engaged in a manner such that the cardiac tissue compliant element transfers energy to the cardiovascular tissue.

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