Advanced pacing

Abstract

Systems, devices, and methods for providing therapy to a heart of a patient are disclosed. The system includes an implantable device to be implanted proximate the heart of the patient. The implantable device includes at least one sensing electrode configured to sense electrical activity of the heart, at least two pacing electrodes configured to deliver electrical stimulation energy to tissue of the heart, and a controller including one or more algorithms. The one or more algorithms are executable to determine a pacing strategy to terminate atrial fibrillation.

Description

Attorney Docket No.: MAX-012-PCTADVANCED PACINGRELATED APPLICATIONS

[0001] The present application claims priority to United States Provisional Patent Application Serial Number 63 / 910,304 (Docket No.: MAX-012-PR). entitled “Advanced Pacing”, filed November 3, 2025, the content of which is incorporated herein by reference in its entirety for all purposes.

[0002] This present application claims priority to United States Provisional Patent Application Serial Number 63 / 967,457 (Docket No.: MAX-012-PR2), entitled “Advanced Pacing”, filed January 24, 2026, the content of which is incorporated herein by reference in its entirety for all purposes.

[0003] This present application claims priority to United States Provisional Patent Application Serial Number 63 / 779,348 (Docket No.: MAX-012-PRA), entitled “Serpentine Epicardial Catheter Lead for Atrial Synchronization Treatment”, filed March 28, 2025, the content of which is incorporated herein by reference in its entirety for all purposes.

[0004] This present application claims priority to United States Provisional Patent Application Serial Number 63 / 780,336 (Docket No.: MAX-012-PRB), entitled “AI-Enhanced Spatial Resynchronization Therapy (SRT) and Neuromodulation System”, filed March 30, 2025, the content of which is incorporated herein by reference in its entirety for all purposes.

[0005] This application is related to United States Provisional Application Serial Number 63 / 032,687 (Docket No. MAX-003-PR), titled “RECHARGEABLE BIOMEDICAL BATTERY POWERED WIRELESS SELF-ANCHORING MICRO-PACING AND SENSING DEVICES AND CONTROL SYSTEM”, filed May 31, 2020, the content of which is incorporated by reference in its entirety.

[0006] This application is related to International PCT Patent Application Serial Number PCT / US21 / 035132 (Docket No. MAX-003-PCT). titled “PACING AND SENSING DEVICES AND CONTROL SYSTEM” filed June 1, 2021, Publication Number WO2021 / 247490, published December 9, 2021, the content of which is incorporated by reference in its entirety .

[0007] This application is related to United States Patent Application Serial Number 17 / 925,821 (Docket No. MAX-003-US), titled “PACING AND SENSING DEVICES ANDAttorney Docket No.: MAX-012-PCTCONTROL SYSTEM”, filed November 16, 2022, Publication Number 2023-0181910, published June 15, 2023. the content of which is incorporated by reference in its entirety.

[0008] This application is related to United States Provisional Application Serial Number 62 / 987,238 (Docket No. MAX-004-PR), titled “STENT, MOUNTED AND DELIVERED WIRELESS, BATTERYLESS MICROPACING CHIP SYSTEM”, filed March 9, 2020, the content of which is incorporated by reference in its entirety.

[0009] This application is related to International PCT Patent Application Serial Number PCT / US2021 / 021467 (Docket No. MAX-004-PCT), titled “CARDIAC PACING DEVICE”, filed March 9, 2021, Publication Number WO 2021 / 183487, published September 16, 2021, the content of which is incorporated by reference in its entirety.

[0010] This application is related to United States Patent Application Serial Number 17 / 908,002 (Docket No. MAX-004-US), titled “CARDIAC PACING DEVICE”, filed August 30, 2022, Publication Number 2023-0101497, published March 30, 2023, the content of which is incorporated by reference in its entirety.[Oil] This application is related to United States Provisional Application Serial Number 62 / 895,655 (Docket No.: MAX-001-PR), titled “MULTI-SIDE MICRO PACING CIRCUITS AND ALGORITHMS, INTEGRATED INTO A VENIOUSLY PLACED STENT ASSEMBLY”, filed September 4, 2019, the content of which is incorporated by reference in its entirety.

[0012] This application is related to International PCT Patent Application Serial Number PCT / US2020 / 049349 (Docket No. MAX-007-PCT), titled “CARDIAC STIMULATION SYSTEM”, filed September 4, 2020, Publication Number WO 2021 / 046313, published March 11, 2021, the content of which is incorporated by reference in its entirety.

[0013] This application is related to United States Patent Application Serial Number 17 / 637,877 (Docket No. MAX-007-US), titled “CARDIAC STIMULATION SYSTEM”, filed February 24, 2022, Publication Number 2022-0273944, published September 1, 2022, the content of which is incorporated by reference in its entirety.

[0014] This application is related to United States Continuation Patent Application Serial Number 19 / 361,316 (Docket No. MAX-007-USCON), titled “CARDIAC STIMULATION SYSTEM”, filed October 17, 2025, the content of which is incorporated by reference in its entirety.Attorney Docket No.: MAX-012-PCT

[0015] This application is related to United States Provisional Application Serial Number 63 / 221,117 (Docket No.: MAX-010-PR), titled “STIMULATION SYSTEM’; filed July 13, 2021, the content of which is incorporated by reference in its entirety.

[0016] This application is related to United States Provisional Application Serial Number 63 / 326,190 (Docket No.: MAX-010-PR2), titled “STIMULATION SYSTEM”, filed March 31, 2022, the content of which is incorporated by reference in its entirety.

[0017] This application is related to United States Provisional Application Serial Number 63 / 336,517 (Docket No.: MAX-010-PR3), titled “STIMULATION SYSTEM”, filed April 29, 2022. the content of which is incorporated by reference in its entirety.

[0018] This application is related to International PCT Patent Application Serial Number PCT / US2022 / 036926 (Docket No. MAX-010-PCT), titled “STIMULATION SYSTEM”, filed July 13, 2022, Publication Number WO 2023 / 287859, published January 19, 2023, the content of which is incorporated by reference in its entirety.

[0019] This application is related to United States Patent Application Serial Number 18 / 578,882 (Docket No. MAX-010-US), titled “STIMULATION SYSTEM”, filed January 12, 2024, Publication Number 2025-0161691, published May 22, 2025, the content of which is incorporated by reference in its entirety.

[0020] This application is related to United States Provisional Application Serial Number 63 / 389,094 (Docket No.: MAX-011-PR), titled “ADVANCED PACING”, filed July 14. 2022, the content of which is incorporated by reference in its entirety.

[0021] This application is related to United States Provisional Application Serial Number 63 / 453,570 (Docket No.: MAX-011-PR2), titled “ADVANCED PACING”, filed March 21, 2023, the content of which is incorporated by reference in its entirety.

[0022] This application is related to International PCT Patent Application Serial Number PCT / US2023 / 027740 (Docket No. MAX-011-PCT), titled “ADVANCED PACING”, filed July 14, 2023, Publication Number WO 2024 / 015555, published January 18, 2024. the content of which is incorporated by reference in its entirety.

[0023] This application is related to United States Patent Application Serial Number 19 / 543,132 (Docket No. MAX-011 -US-CON), titled “ADVANCED PACING”, filed February 18, 2026, the content of which is incorporated by reference in its entirety.Attorney Docket No.: MAX-012-PCT

[0024] This application is related to United States Patent Application Serial Number 18 / 976,825 (Docket No. MAX-011-US), titled "ADVANCED PACING’; filed December 11, 2024, Publication Number 2025-0108220, published April 3, 2025, the content of which is incorporated by reference in its entirety.FIELD OF INVENTIVE CONCEPTS

[0025] The present inventive concepts relate generally to stimulation systems, and in particular systems that stimulate tissue of a patient’s heart.BACKGROUND

[0026] The heart is a critical muscle in humans and other animals that is responsible for circulating blood through the circulatory system. The human heart is made up of four chambers, two upper atria, and two lower ventricles, organized into a left and right pairing of an atrium and a ventricle. In a healthy heart, the chambers contract and rel x in a synchronized fashion, referred to as a “beat,” in order to force blood through the network of veins and arteries.

[0027] Irregular heartbeats can pose a health risk, and in some cases normal beating can be restored via electrical stimulation. Implantable devices called “pacemakers” are devices which can stimulate the muscle tissue, causing it to contract. By methodically and accurately applying stimulation as needed, normal heart rhythm can be restored.

[0028] There is a need for improved systems for treating irregular heartbeats.SUMMARY

[0029] According to an aspect of the present inventive concepts, a system for treating a cardiac arrhythmia of a patient comprises: an implantable device comprising an electrode array including one or more sensing electrodes and one or more pacing electrodes; and a controller comprising a memory configured to store instructions for one or more algorithms. The one or more algorithms are executable to: (i) operate the system in a therapy category selected from the group consisting of: Diagnostic Monitoring Mode (DMM); Tissue Conditioning Therapy (TCT); Acute Therapy (AcTh); Multi-Chamber Synchronization Therapy (MCST); and combinations thereof; (ii) process diagnostic data collected by the system; (iii) select and configure the therapy provided by the system; and (iv) automatically transition the system between therapy and / or monitoring modes.Attorney Docket No.: MAX-012-PCT

[0030] In some embodiments, TCT further includes Pace Conditioning Mode (PCM), Conditioning Monitoring Mode (CMM), or both; and AcTh further includes: Preventative Pacing Mode (PPM); Pace Termination Mode (PTM); Left- Atrial Reset Mode (LRM);Arrhythmia Disruption Mode (ADM); and combinations thereof; and MCST further includes: Atrial Synchronization Mode (ASM); AV Synchronization Mode (AVSM); Atrial Overdrive Stabilization Mode (AOSM); Synchronization Therapy Monitoring Mode (STMM); and combinations thereof.

[0031] In some embodiments, the system is configured to improve hemodynamic function by reducing delay of activation of the left-atrial appendage (LAA) via pacing from an electrode positioned in the distal reach of the Vein-of-Marshall, and the system is further configured to synchronize activation of the left ventricle.

[0032] In some embodiments, the system is configured to deliver nerve stimulation to shift autonomic tone toward inhibition of AF.

[0033] In some embodiments, the system is configured to analyze data collected from multiple patients to identify similarities, differences, and / or patterns, and the system is further configured to recommend and / or enact parameter updates based on the collected data.

[0034] In some embodiments, the one or more algorithms are executable to deliver pacing stimuli across the electrode array to advance and / or block cardiac activation wavefronts and synchronize atrial activation to a spatiotemporal pattern of stimulation, and the pacing stimuli is configured to automatically stop upon restoration of normal rhythm. The timing of the delivered pacing stimuli can be in response to electrical activity sensed at one or more electrodes of the electrode array. Delivery of the pacing stimuli can be simultaneous and / or asynchronous, and delivery of the pacing stimuli can be regular and / or irregular. Delivery' of the pacing stimuli can be imperceptible or minimally perceived by the patient. The one or more sensing electrodes and / or the one or more pacing electrodes can be spatially distributed. The system can be configured to execute in a Preventative Pacing Mode (PPM). The system can be configured to execute in a Pace Termination Mode (PTM) including Simultaneous PTM and Consensus PTM. Delivery of the pacing stimuli can be configured to maximize, over a given time interval, the area of tissue in a depolarized state. Delivery of the pacing stimuli can be configured to maximize, over a given time interval, the area of tissue in a repolarized state.Attorney Docket No.: MAX-012-PCT

[0035] According to another aspect of the present inventive concepts, a system for providing a left-atrial reset therapy comprises the implantable device and controller as described herein, and such that the implantable device is further configured to deliver a limited sequence of pulses that abruptly depolarize the targeted area, and such that the pulses are delivered asynchronously to fibrillatory activity in the treated chamber and synchronously to non-fibrillating chambers. The sequence of pulses can be delivered in rapid succession and each pulse can comprise engineered phases.

[0036] According to another aspect of the present inventive concepts, a system for preventing induction of atrial fibrillation comprises the implantable device and controller as described herein, such that the implantable device is configured to detect premature atrial contractions (PACs) and / or pro-arrhythmogenic conditions, and such that the implantable device is further configured to deliver simultaneous and / or strategically staggered multisite pacing across distributed electrodes to compress activation times and reduce depolarization and / or repolarization gradients to prevent AF initiation.

[0037] In some embodiments, the system further comprises functional modules selected from the group consisting of: Therapy Monitoring Module (Ml); Configuration Management Module (M2); Sensing Module (M3); Pacing Control Module (M4); Pacing Module (M5); and combinations thereof. The therapy monitoring module (Ml) can be configured to: classify SR / PAC patterns; identify first beats of AF; estimate PAC origin from activation timing / morphology; and / or adapt PAC criteria with feedback provided to the configuration management module (M2). The configuration management module (M2) can be configured to: set PAC timing windows; account for SR variance; and / or select unipolar and / or bipolar configurations; and the sensing module (M3) can be configured to detect local activation at each electrode.

[0038] According to another aspect of the present inventive concepts, a system for treating atrial fibrillation of a patient comprises a stimulation device for delivering energy to tissue of the patient’s heart, such that delivery of the energy is configured to at least reduce atrial fibrillation without ablating the heart tissue.

[0039] In some embodiments, the system is configured to reduce the use of blood thinners taken by the patient.

[0040] According to another aspect of the present inventive concepts, a method of treating atrial fibrillation of a patient comprises delivering energy to tissue of the patient’sAttorney Docket No.: MAX-012-PCTheart, such that the method is configured to at least reduce atrial fibrillation without ablating the heart tissue.

[0041] In some embodiments, the method is configured to reduce the use of blood thinners taken by the patient.

[0042] According to another aspect of the present inventive concepts, a system for providing post operative therapy to a patient is provided. The system comprises: an implantable device and a controller. The implantable device comprises an electrode array including one or more sensing electrodes and one or more pacing electrodes. The controller comprises a memory configured to store instructions for one or more algorithms. The one or more algorithms are executable to: (i) monitor for post operative atrial fibrillation, and (ii) cause the implantable device to deliver therapy configured to prevent and / or otherwise treat post operative atrial fibrillation. The implantable device can be configured to be explanted following a post operative monitoring period.

[0043] The technology described herein, along with the attributes and attendant advantages thereof, will best be appreciated and understood in view of the following detailed description taken in conjunction with the accompanying drawings in which representative embodiments are described by way of example.INCORPORATION BY REFERENCE

[0044] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. The content of all publications, patents, and patent applications mentioned in this specification are herein incorporated by reference in their entirety. It will be clearly understood that, if a prior art publication is referred to herein, this reference does not constitute an admission that the publication forms part of the common general knowledge in the art in any country.BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Fig. 1 illustrates a schematic view of a system for diagnosing and / or treating a patient, consistent with the present inventive concepts.Attorney Docket No.: MAX-012-PCT

[0046] Fig. 1A illustrates a partial anatomic, partial schematic view of a system of devices, consistent with the present inventive concepts.

[0047] Fig. 2 illustrates an anatomic view of an atrium showing electrical activity, consistent with the present inventive concepts.

[0048] Fig. 3 illustrates a system state diagram of a method of patient therapy selection and monitoring, consistent with the present inventive concepts.

[0049] Fig. 4 illustrates a modular state diagram of a system for providing therapy, consistent with the present inventive concepts.

[0050] Fig. 5 illustrates a flow chart of an embodiment of a method for managing postoperative atrial fibrillation, consistent with the present inventive concepts.

[0051] Figs.6A through 6C illustrate schematic views of embodiments of an implantable device configured for post-operative cardiac monitoring and therapy, consistent with the present inventive concepts.

[0052] Fig. 7 illustrates a flowchart of an embodiment of a method for closed-loop therapy selection and delivery, consistent with the present inventive concepts.

[0053] Figs.8A through 8F illustrate schematic views of embodiments of extractioncompatible fixation mechanisms for an implantable device, consistent with the present inventive concepts.

[0054] Fig. 9 illustrates a flowchart of an embodiment of a method for pre-therapeutic cardiac monitoring and preventative therapy, consistent with the present inventive concepts.

[0055] Fig. 10 illustrates a process stage diagram of an embodiment of a closed-loop process for cardiac arrhythmia management, consistent with the present inventive concepts.

[0056] Figs. 11A and 11B illustrate flowcharts of embodiments of methods for characterizing cardiac tissue state and delivering therapy based on the characterized tissue state, respectively, consistent with the present inventive concepts.

[0057] Fig. 12 illustrates a flowchart of an embodiment of a method for characterizing cardiac action potential and delivering spatiotemporal resynchronization therapy, consistent with the present inventive concepts.

[0058] Fig. 13 illustrates a flowchart of an embodiment of a method for Al-enhanced spatiotemporal resynchronization therapy, consistent with the present inventive concepts.Attorney Docket No.: MAX-012-PCT

[0059] Fig. 14 illustrates a schematic view of an embodiment of cardiac action potential characteristics, consistent with the present inventive concepts.

[0060] Figs. 15A through 15D illustrate schematic views of excitable gap characteristics and pacing in a reentrant circuit, consistent with the present inventive concepts.

[0061] Fig. 16 illustrates a flowchart of an embodiment of a method for delivering spatiotemporal resynchronization therapy via excitable gap pacing, consistent with the present inventive concepts.

[0062] Fig. 17 illustrates a flowchart of an embodiment of a method for circadian and state-aware neuro-adaptive learning and therapy window scheduling, consistent with the present inventive concepts.

[0063] Figs. 18A and 18B illustrate schematic block diagrams of embodiments of an external patient device and associated sensor assemblies, consistent with the present inventive concepts.

[0064] Fig. 19 illustrates a flowchart of an embodiment of a method for diagnosing heart failure with preserved ejection fraction (HFpEF), consistent with the present inventive concepts.

[0065] Fig. 20 illustrates a perspective view of an embodiment of an implantable device including an electrode array configured in a serpentine geometry, consistent with the present inventive concepts.

[0066] Figs. 21A through 21D illustrate sectional and perspective views of embodiments of an implantable device and a clinician device, respectively, consistent with the present inventive concepts.DETAILED DESCRIPTION OF THE DRAWINGS

[0067] Reference will now be made in detail to the present embodiments of the technology7, examples of which are illustrated in the accompanying drawings. Similar reference numbers may be used to refer to similar components. However, the description is not intended to limit the present disclosure to particular embodiments, and it should be construed as including various modifications, equivalents, and / or alternatives of the embodiments described herein.Attorney Docket No.: MAX-012-PCT

[0068] It will be understood that the words "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include") or "containing" (and any form of containing, such as "contains" and "contain") when used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0069] It will be further understood that, although the terms first, second, third, etc. may be used herein to describe various limitations, elements, components, regions, layers and / or sections, these limitations, elements, components, regions, layers and / or sections should not be limited by these terms. These terms are only used to distinguish one limitation, element, component, region, layer or section from another limitation, element, component, region, layer or section. Thus, a first limitation, element, component, region, layer or section discussed below could be termed a second limitation, element, component, region, layer or section without departing from the teachings of the present application.

[0070] It will be further understood that when an element is referred to as being "on", "attached", "connected" or "coupled" to another element, it can be directly on or above, or connected or coupled to, the other element, or one or more intervening elements can be present. In contrast, when an element is referred to as being "directly on", "directly attached", "directly connected" or "directly coupled" to another element, there are no intervening elements present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., "between" versus "directly between," "adjacent" versus "directly adjacent," etc.).

[0071] It will be further understood that when a first element is referred to as being "in", "on" and / or "within" a second element, the first element can be positioned: within an internal space of the second element, within a portion of the second element (e.g., within a wall of the second element); positioned on an external and / or internal surface of the second element; and combinations of one or more of these.

[0072] As used herein, the term ''proximate”, when used to describe proximity of a first component or location to a second component or location, is to be taken to include one or more locations near to the second component or location, as well as locations in, on and / or within the second component or location. For example, a component positioned proximateAttorney Docket No.: MAX-012-PCTan anatomical site (e g., a target tissue location), shall include components positioned near to the anatomical site, as well as components positioned in, on and / or within the anatomical site.

[0073] Spatially relative terms, such as "beneath," "below," "lower," "above," "upper" and the like may be used to describe an element and / or feature's relationship to another element(s) and / or feature(s) as, for example, illustrated in the figures. It will be further understood that the spatially relative terms are intended to encompass different orientations of the device in use and / or operation in addition to the orientation depicted in the figures. For example, if the device in a figure is turned over, elements described as "below" and / or "beneath" other elements or features would then be oriented "above" the other elements or features. The device can be otherwise oriented (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

[0074] The terms “reduce”, “reducing”, “reduction” and the like, where used herein, are to include a reduction in a quantity, including a reduction to zero. Reducing the likelihood of an occurrence shall include prevention of the occurrence. Correspondingly, the terms “prevent”, “preventing”, and “prevention” shall include the acts of “reduce”, “reducing”, and “reduction”, respectively.

[0075] The term "and / or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, "A and / or B" is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein.

[0076] The term “one or more”, where used herein can mean one, two, three, four, five, six, seven, eight, nine, ten, or more, up to any number.

[0077] The terms “and combinations thereof’ and “and combinations of these” can each be used herein after a list of items that are to be included singly or collectively. For example, a component, process, and / or other item selected from the group consisting of: A; B; C; and combinations thereof, shall include a set of one or more components that comprise: one, two, three or more of item A; one, two, three or more of item B; and / or one, two, three, or more of item C.

[0078] In this specification, unless explicitly stated otherwise, “and” can mean “or”, and “or” can mean “and”. For example, if a feature is described as having A, B, or C, the feature can have A, B, and C, or any combination of A, B, and C. Similarly, if a feature is described as having A, B, and C, the feature can have only one or two of A, B, or C.Attorney Docket No.: MAX-012-PCT

[0079] As used herein, when a quantifiable parameter is described as having a value "betw een" a first value X and a second value Y. it shall include the parameter having a value of: at least X, no more than Y, and / or at least X and no more than Y. For example, a length of between 1 and 10 shall include a length of at least 1 (including values greater than 10), a length of less than 10 (including values less than 1), and / or values greater than 1 and less than 10.

[0080] The expression configured (or set) to” used in the present disclosure may be used interchangeably with, for example, the expressions “suitable for”, “having the capacity to”, “designed to”, “adapted to”, “made to” and “capable of’ according to a situation. The expression “configured (or set) to” does not mean only “specifically designed to” in hardware. Alternatively, in some situations, the expression “a device configured to” may mean that the device “can” operate together with another device or component.

[0081] As used herein, the term “threshold” refers to a maximum level, a minimum level, and / or range of values correlating to a desired or undesired state. In some embodiments, a system parameter is maintained above a minimum threshold, below a maximum threshold, within a threshold range of values, and / or outside a threshold range of values, such as to cause a desired effect (e.g., efficacious therapy) and / or to prevent or otherwise reduce (hereinafter “prevent”) an undesired event (e.g., a device and / or clinical adverse event). In some embodiments, a system parameter is maintained above a first threshold (e.g.. above a first temperature threshold to cause a desired therapeutic effect to tissue) and below a second threshold (e.g., below a second temperature threshold to prevent undesired tissue damage). In some embodiments, a threshold value is determined to include a safety margin, such as to account for patient variability, system variability, tolerances, and the like. As used herein, “exceeding a threshold” relates to a parameter going above a maximum threshold, below a minimum threshold, within a range of threshold values and / or outside of a range of threshold values.

[0082] As described herein, “room pressure” shall mean pressure of the environment surrounding the systems and devices of the present inventive concepts. Positive pressure includes pressure above room pressure or simply a pressure that is greater than another pressure, such as a positive differential pressure across a fluid pathway component such as a valve. Negative pressure includes pressure below room pressure or a pressure that is less than another pressure, such as a negative differential pressure across a fluid component pathway such as a valve. Negative pressure can include a vacuum but does not imply aAttorney Docket No.: MAX-012-PCTpressure below a vacuum. As used herein, the term “vacuum” can be used to refer to a full or partial vacuum, or any negative pressure as described hereabove.

[0083] The term “diameter” where used herein to describe a non-circular geometry is to be taken as the diameter of a hypothetical circle approximating the geometry being described. For example, when describing a cross section, such as the cross section of a component, the term “diameter” shall be taken to represent the diameter of a hypothetical circle with the same cross sectional area as the cross section of the component being described.

[0084] The terms “major axis” and “minor axis” of a component where used herein are the length and diameter, respectively, of the smallest volume hypothetical cylinder which can completely surround the component.

[0085] As used herein, the term “functional element” is to be taken to include one or more elements constructed and arranged to perform a function. A functional element can comprise a sensor and / or a transducer. In some embodiments, a functional element is configured to deliver energy and / or otherw ise perform a treatment on tissue (e.g., a functional element configured as a treatment element). Alternatively, or additionally, a functional element (e.g., a functional element comprising a sensor) can be configured to record one or more parameters, such as a patient physiologic parameter; a patient anatomical parameter (e.g., a tissue geometry' parameter); a patient environment parameter; and / or a system parameter. In some embodiments, a sensor or other functional element is configured to perform a diagnostic function (e.g., to gather data used to perform a diagnosis). In some embodiments, a functional element is configured to perform a therapeutic function (e.g., to deliver therapeutic energy' and / or a therapeutic agent). In some embodiments, a functional element comprises one or more elements constructed and arranged to perform a function selected from the group consisting of: deliver energy; extract energy (e.g., to cool a component); deliver a drug or other agent; manipulate a system component or patient tissue; record or otherwise sense a parameter such as a patient physiologic parameter or a system parameter; and combinations of one or more of these. A functional element can comprise a fluid and / or a fluid delivery system. A functional element can comprise a reservoir, such as an expandable balloon or other fluid-maintaining reservoir. A “functional assembly” can comprise an assembly constructed and arranged to perform a function, such as a diagnostic and / or therapeutic function. A functional assembly can comprise an expandable assembly. A functional assembly can comprise one or more functional elements.Attorney Docket No.: MAX-012-PCT

[0086] The term “transducer’ where used herein is to be taken to include any component or combination of components that receives energy or any input, and produces an output. For example, a transducer can include an electrode that receives electrical energy, and distributes the electrical energy to tissue (e.g., based on the size of the electrode). In some configurations, a transducer converts an electrical signal into any output, such as: light (e.g., a transducer comprising a light emitting diode or light bulb), sound (e.g., a transducer comprising a piezo crystal configured to deliver ultrasound energy); pressure (e.g., an applied pressure or force); heat energy; cryogenic energy; chemical energy; mechanical energy (e.g., a transducer comprising a motor or a solenoid); magnetic energy: and / or a different electrical signal (e.g., different than the input signal to the transducer). Alternatively, or additionally, a transducer can convert a physical quantity (e.g.. variations in a physical quantity) into an electrical signal. A transducer can include any component that delivers energy and / or an agent to tissue, such as a transducer configured to deliver one or more of: electrical energy to tissue (e.g., a transducer comprising one or more electrodes); light energy to tissue (e.g., a transducer comprising a laser, light emitting diode and / or optical component such as a lens or prism); mechanical energy to tissue (e.g., a transducer comprising a tissue manipulating element); sound energy to tissue (e g., a transducer comprising a piezo crystal); chemical energy; electromagnetic energy; magnetic energy7; and combinations of one or more of these.

[0087] As used herein, the term “fluid” can refer to a liquid, gas, gel, or any flowable material, such as a material which can be propelled through a lumen and / or opening.

[0088] As used herein, the term ’‘material” can refer to a single material, or a combination of two, three, four, or more materials.

[0089] It is appreciated that certain features of the inventive concepts, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the inventive concepts which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. For example, it will be appreciated that all features set out in any of the claims (whether independent or dependent) can be combined in any given way.

[0090] It is to be understood that at least some of the figures and descriptions of the inventive concepts have been simplified to focus on elements that are relevant for a clear understanding of the inventive concepts, while eliminating, for purposes of clarity, other elements that those of ordinary7skill in the art will appreciate may also comprise a portion ofAttorney Docket No.: MAX-012-PCTthe inventive concepts. However, because such elements are well known in the art, and because they do not necessarily facilitate a better understanding of the inventive concepts, a description of such elements is not provided herein.

[0091] Terms defined in the present disclosure are only used for describing specific embodiments of the present disclosure and are not intended to limit the scope of the present disclosure. Terms provided in singular forms are intended to include plural forms as well, unless the context clearly indicates otherwise. All of the terms used herein, including technical or scientific terms, have the same meanings as those generally understood by an ordinary person skilled in the related art, unless otherwise defined herein. Terms defined in a generally used dictionary should be interpreted as having meanings that are the same as or similar to the contextual meanings of the relevant technology and should not be interpreted as having ideal or exaggerated meanings, unless expressly so defined herein. In some cases, terms defined in the present disclosure should not be interpreted to exclude the embodiments of the present disclosure.

[0092] Provided herein are systems, devices, and methods for providing therapy to a heart of a patient. The system can comprise one or more implantable devices. In some embodiments, the system includes one or more external devices, such as external devices that deliver power and / or data to one or more implantable devices. An implantable device can comprise: an anchor configured to maintain the position of the implantable device; at least one sensor configured to record electrical activity of the heart; and / or one, two. or more pacing electrodes configured to deliver stimulation energy to tissue of the heart, such as to treat an arrhythmia such as atrial fibrillation (AF). The system can include a controller that comprises one or more algorithms, such as an algorithm that initiates and / or adjusts delivery of energy to treat an arrhythmia of the patient.

[0093] Referring now to Fig. 1, a schematic view of a system for diagnosing and / or treating a patient is illustrated, consistent with the present inventive concepts. System 10 can comprise one or more devices (e.g., devices for a clinician to perform a procedure, devices for a patient to position proximate their body, and / or devices for implantation in the patient) which can be configured to monitor one or more patient parameters, diagnose one or more patient conditions, and / or to treat one or more patient conditions, such as to treat a condition based on one or more patient diagnoses determined by system 10. For example, system 10 can be configured to monitor, diagnose, and / or treat ("‘treat’ ’ herein) an arrhythmia such asAttorney Docket No.: MAX-012-PCTatrial fibrillation (AF), a category' of abnormally fast and / or “highly irregular” rhythm due to improper electrical activity in the atrial chambers of the heart, such as by monitoring the electrical activity7of the patient’s heart, and by pacing the muscular tissue in either or both the atrial chambers of the heart to restore sinus rhythm when fibrillation is detected. In another example, system 10 can be configured to treat supraventricular tachycardia (SVT), a category7of abnormally fast and / or “regular or quasi-regular” rhythms due to improper electrical activity in the atrial chambers of the heart, such as by monitoring the electrical activity of the patient’s heart, and by pacing the muscular tissue in either or both the atrial chambers of the heart to restore sinus rhythm when SVT is detected. In another example, system 10 can be configured to treat atrial tachycardia (AT), a common abnormally fast and regular arrhythmia in the category of SVT due to improper electrical activity in the atrial chambers of the heart, such as by monitoring the electrical activity of the patient’s heart, and by pacing the muscular tissue in either or both the atrial chambers of the heart to restore sinus rhythm when AT is detected. In another example, system 10 can be configured to treat both the typical and atypical forms of atrial flutter (AFL), which are common abnormally fast and regular arrhythmias in the category of SVT due to improper electrical activity in the atrial chambers of the heart, such as by monitoring the electrical activity of the patient’s heart, and by pacing the muscular tissue in either or both the atrial chambers of the heart to restore sinus rhythm when AFL is detected. System 10 can include one or more devices configured to be implanted, implantable device 100 (also referred to as ID 100 herein), which can be implanted into the patient for an extended period of time (e.g., at least 1 month, at least 3 months, and / or at least 6 months), such as when implanted by a clinician during a clinical procedure. In some embodiments, implantable device 100 comprises a short-term implant, such as when implantable device 100 is configured to be implanted for no more than 6 months, no more than 3 months, and / or no more than 1 month (e.g., implantable device 100 can be implanted for two or three weeks following cardiac surgery). In some embodiments, ID 100 is configured to be implanted during a cardiac surgical procedure (e.g., an open chest procedure), and ID 100 is configured to be placed on the epicardial surface and adhered thereto, such as with suture, compression, and / or surgical glue.

[0094] In some embodiments, system 10 comprises one or more externally-placed devices, external patient device 200, which can comprise one or more devices that are configured to monitor, diagnose, and / or treat a patient, such as from one or more locations outside the patient’s body. Alternatively, or additionally, external patient device 200 (alsoAttorney Docket No.: MAX-012-PCTreferred to as EPD 200) can be configured to communicate (e.g., wirelessly communicate) with implantable device 100 (also referred to as ID 100), such as to transfer data between EPD 200 and ID 100, and / or to transfer pow er from EPD 200 to ID 100. In some embodiments, ID 100 comprises two devices, such as a first device, ID 100a, configured to be implanted proximate the patient’s heart, as described herein, and a second device, ID 100b, configured to be implanted at another location under the patient's skin (e.g., subcutaneously). In some embodiments, the second implantable device, ID 100b (implanted subcutaneously) is configured similar to EPD 200 described herein, such as to transmit power and / or data to the first implantable device, ID 100a (implanted proximate the patient’s heart). In these embodiments, system 10 may include, or may not include, EPD 200. Alternatively, or additionally, system 10 may include at least two IDs 100 (such as ID 100a and 100b shown in Fig. 1A), where a second implantable device, ID 100b is configured as EPD 200 and to transmit power and / or data to a first implantable device, ID 100a, and also include an EPD 200, such as when EPD 200 is configured to transmit pow er to the second implantable device, ID 100b, for example, to recharge a power supply (e.g., a battery and / or a capacitor) of the ID 100b. In some embodiments, one or more IDs 100 and / or EPDs 200 can be operably connected via one or more conduits, not shown, but such as an electrical conduit that is tunneled beneath the skin of the patient (e.g., to connect a subcutaneously implanted ID 100b and / or EPD 200 to an ID 100a implanted proximate the heart).

[0095] System 10 can be configured to monitor for and / or to detect irregular or otherwise undesirable (“irregular” or “undesirable” herein) electrical conduction signals or patterns (“patterns” herein) in tissue and / or to deliver energy to the tissue to restore a desirable regular (e.g., “healthy”) electrical conduction pattern. In some embodiments, system 10 is configured to detect undesirable conduction patterns comprising repeated but rapid patterns. In some embodiments, system 10 is configured to analyze conduction patterns based on timing characteristics of electrical signals recorded by system 10 (e.g., from one or more electrodes 111 described herein). In some embodiments, electrical signals comprise signals recorded from one or more locations (e.g., separate anatomical locations). Recorded signals can be analyzed by system 10 to identify one or more spatiotemporal conduction patterns that correlate to how electrical activity propagates across cardiac tissue. In some embodiments, the timing characteristics can be determined by identifying one or more fiducial features of the recorded signals (e.g., local maxima, local minima, positive slope peaks, and / or negative slope peaks). System 10 can be configured to analyze electrical timing as absolute timesAttorney Docket No.: MAX-012-PCTrelative to a reference time and / or as time intervals detected between events (e.g., intervals between successive activations at a single electrode, and / or intervals between activations at different electrodes). Additionally, or alternatively, system 10 can be configured to analyze conduction patterns based on morphological characteristics of the electrical signals measured from one or more locations. System 10 can be configured to monitor the electrical activity of the heart (e.g., conduction patterns proximate the left and / or right atrium of the heart), and to detect the presence of irregular conduction patterns, such as conduction patterns indicative of AF, SVT, ventricular tachycardia, ventricular fibrillation, and / or other abnormal arrhythmias. Additionally, or alternatively, system 10 can deliver electrical energy (e.g., pacing pulses) to tissue exhibiting irregular conduction patterns, as well as to tissue surrounding that tissue, to alter the irregular conduction patterns. In some embodiments, system 10 is configured to deliver '‘multi-site” pacing, where pacing energy is delivered from two, three, four, or more electrodes positioned at different locations, such as different locations proximate the left atrium and / or the right atrium. For example, system 10 can be configured to deliver multisite left-atrial pacing (i.e., delivery of energy’ to two left atrial tissue locations) configured to restore sinus rhythm in patients exhibiting irregular conduction patterns. In some embodiments, system 10 is configured to ablate tissue, such as by delivering energy configured to thermally ablate and / or irreversibly electroporate tissue. In these embodiments, system 10 can be further configured to also deliver pacing energy to tissue, such as multi-site pacing energy and / or other pacing energy, such as is described herein. In some embodiments, system 10 is configured to deliver therapy without ablating tissue. System 10 can be configured such that one or more parameters (e.g., current amplitude, pulse width, total energy per pulse) are maintained below thresholds for thermal ablation and / or irreversible electroporation. In some embodiments, a method for treating atrial fibrillation comprises delivering energy to tissue of the patient’s heart without ablating the heart tissue. For example, the method can comprise maintaining stimulation parameters (e.g., current amplitude, pulse width, total energy per pulse) below thresholds for thermal ablation and / or irreversible electroporation. The method can further comprise reducing AF burden without lesion formation. The method can comprise delivering pacing energy in ranges typical of conventional cardiac pacemakers (e.g., which are insufficient to cause permanent tissue damage yet effective for cardiac rhythm management).

[0096] In some embodiments, system 10 is configured to deliver energy to the patient’s heart (e.g., to treat a regular and / or an irregular arrhythmia such as atrial fibrillation, and / orAttorney Docket No.: MAX-012-PCTother irregular heartbeat) at a level such that the energy deliver}' is not perceived by the patient, or at least minimally perceived by the patient (e.g., at a level below a pain threshold, such as a threshold of approximately 0.75 J). For example, system 10 can be configured to deliver energy at a level similar to the energy delivered by a pacemaker, such as between 5mA and 20mA, and / or less than 0.1 J. In some embodiments, this energy delivery comprises multiple site energy delivery as described herein (e.g., spatially distanced energy delivery). For example, multiple electrodes (e.g., at least three, four, or five electrodes) can be placed on the epicardium for delivery of the stimulation energy. These multiple electrodes can be spatially distributed to gain sufficient coverage of the heart chamber to achieve effective therapy (e.g., to effectively pace terminate atrial fibrillation and / or other arrhythmia). In some embodiments, less than 6mJ (e.g., less than 5mJ or less than 4mJ) of energy can be delivered at each epicardial site (e.g., over a period of approximately one second), such as to terminate atrial fibrillation in the patient.

[0097] System 10 can include one or more devices for use by a clinician during a clinical procedure, clinician device 300. Clinician device 300 (also referred to as CD 300) can comprise one or more delivery devices, such as a kit of devices configured to enable the clinician to perform an implantation procedure for implanting ID 100 into the patient. For example, CD 300 can comprise one or more deliver}' catheters, such as when ID 100 is configured to be implanted during a minimally invasive procedure, such as an interventional procedure performed in a catheterization laboratory (often referred to as a “cath lab”). For example, CD 300 can comprise one or more tools for percutaneous delivery of ID 100 in the patient's vasculature, and one or more tools for transvascular deliver}' of ID 100 into locations outside of the patient’s vasculature (e.g.. into the pericardial space, such as onto the epicardial surface). Alternatively, or additionally. CD 300 can comprise one or more surgical tools (e.g., minimally invasive tools) for surgically implanting ID 100 (e.g., a surgical access kit for use in an operating room). For example, CD 300 can comprise one or more surgical tools for percutaneous deliver}' of ID 100 (e.g., a needle-based tool for insertion of ID 100 into the pericardial space). In some embodiments, ID 100 comprises a first geometry where ID 100 is in an undeployed state, such as a geometry comprising a collapsed, folded, or otherwise undeployed geometry configured to allow ease of insertion into the patient. ID 100 can be configured to transition from the first geometry into a second geometry in which ID 100 is in an expanded or otherwise deployed state. In some embodiments, ID 100 is configured to be deployed from a coronary vessel (e.g., through the tissue wall) andAttorney Docket No.: MAX-012-PCTimplanted along the epicardial surface (e.g., during an interventional procedure), such as is described in detail herein. For example. ID 100 can be deployed from a vessel (e.g., a coronary vessel) selected from the group consisting of: the coronary sinus; the Great Cardiac Vein; the Vein of Marshall; the Azygos vein; a side-branch that anastomoses the coronary sinus, for example, side branches that he proximate a desired deployment location such as the epicardial surface of the left atrium; and combinations of these. In some embodiments, ID 100 can be configured to be deployed by a robotic delivery device, such as a magnetically-driven robotic device.

[0098] In some embodiments, CD 300 includes one or more tools for providing epicardial access (e.g., subxiphoid percutaneous epicardial access), such as to allow a clinician to implant ID 100 on or otherwise proximate an epicardial surface. CD 300 can be configured to prevent (or at least limit the likelihood) of ventricular puncture. CD 300 can be constructed and arranged to enable the clinician to perform a ‘‘dry tap” of the epicardial space (e.g., without allowing the needle to penetrate the ventricular tissue). In some embodiments, CD 300 includes one or more devices for positioning a visualizable device, such as a visuahzable portion of guidewire or a lead (e.g., a visuahzable lead, such as a lead visualizable under fluoroscopy or ultrasound) proximate the lateral margin of the roof of the right atrium (RA). In some embodiments, CD 300 includes a needle and mechanical or other stopping mechanism configured to prevent the needle from advancing into ventricular tissue. After placement, this visuahzable device can assist the clinician by providing a visuahzable marker indicating the location of the lateral RA boundary. In some embodiments, CD 300 includes one or more devices for positioning a visualizable device proximate the posterior wall of the left atrium (LA). After placement, this visualizable device can assist the clinician by providing a visualizable marker indicating the location of the posterior LA boundary. In some embodiments, CD 300 includes one or more devices for positioning a visualizable device proximate the interatrial septum between the RA and LA. After placement, this visuahzable device can assist the clinician by providing a visualizable marker indicating the location of the interatrial septum. In some embodiments, CD 300 includes one or more devices for positioning a visuahzable device proximate the apex of the right ventricle (RV). After placement, this visualizable device can assist the clinician by providing a visualizable marker indicating the location of the RV boundary. In some embodiments, CD 300 includes one or more devices for positioning a lead (e.g., a visualizable lead, such as a lead visualizable under fluoroscopy or ultrasound) proximate the apex of the left ventricle (LV).Attorney Docket No.: MAX-012-PCTAfter placement, this lead can assist the clinician by providing a visualizable marker indicating the location of the LV boundary’. In some embodiments, system 10 is configured to image the RV, such as with an angiogram or other visualization method (e.g., as provided by imaging device 60 described herein), such as to assist the clinician by providing one or more images that show the border of the RV and the pericardial space. In some embodiments, system 10 is configured to image the LV, such as with an angiogram or other visualization method (e.g., as provided by imaging device 60 described herein), such as to assist the clinician by providing one or more images that show the border of the LV and the pericardial space.

[0099] In some embodiments, CD 300 includes a device (e.g., a needle) configured to provide a signal used to identify the pericardial juncture (e.g.. by providing a bioimpedance signal). For example, the needle can include an electrode proximate the distal end of the needle. Alternatively, or additionally, the needle can comprise an electrically conductive material, and at least a proximal portion of the needle can be insulated such that the distal tip of the needle comprises the electrode. In some embodiments. CD 300 comprises one or more devices configured to be positioned within the coronary sinus, perforate the coronary sinus, and enter the pericardial space. System 10 can comprise one or more visualizable agents, agent 80 shown. In some embodiments, CD 300 is constructed and arranged to inject agent 80 (e.g., a radiopaque material such as contrast) into the pericardial space. For example, device 300 can be configured to inject approximately lOmL of a contrast-based agent 80 into the pericardial space.

[0100] In some embodiments, clinician device 300 comprises a programmer configured to transfer a set of parameters (e.g., a “program"’) to one or more of implantable device 100 and / or external patient device 200. In some embodiments, external patient device 200 can transfer programs to implantable device 100. A program can comprise a set of parameters, such as stimulation parameters which implantable device 100 will follow when stimulating the patient, such as described herein. In some embodiments, one or more algorithms of system 10 (e.g., algorithm 500 described herein) can be configured to cause implantable device 100 to stimulate the patient based on a program received from EPD 200 and / or clinician device 300. As described herein, system 10 can include one or more algorithms. Various algorithms of system 10 can be referred to singly or collectively herein as algorithm 500 (e.g., an algorithm performed via instructions stored on a memory storage element of system 10).Attorney Docket No.: MAX-012-PCT

[0101] System 10 can include one or more consoles, console 400 shown. Console 400 can operably connect to CD 300 and can be configured to facilitate one or more processes, energy deliveries, data collections, data analyses, data transfers, signal processing, and / or other functions (“functions” herein) of system 10. In some embodiments, system 10 is constructed and arranged to map electrical activity within the body of a patient (e.g., to map electrical activity of the patient’s heart), such as when CD 300 comprises a mapping catheter and console 400 comprises mapping module 420. Mapping module 420 can be configured to record and process mapping signals recorded by CD 300. For example, mapping module 420 can be configured to characterize conduction patterns and / or signal morphologies, such as to classify them (e.g., via algorithm 415 described herein) into arrhythmia types, such as AF, AT, AFL, and the like, both typical and atypical. In some embodiments, implantable device 100 and / or EPD 200 are similarly configured to characterize conduction patterns and / or signal morphologies, for example, by processing signals recorded by one or more electrodes and / or electrode arrays of system 10 (e.g., processing via algorithms 135 and / or 215 signals recorded from electrode array 110 described herein). In some embodiments, system 10 is constructed and arranged to ablate tissue (e.g., ablate cardiac tissue to treat AF). In these embodiments, console 400 comprises energy delivery module 430. Energy delivery module 430 can be configured to deliver ablative energy7to tissue, such as via one or more energy delivery- elements (e.g., electrodes, ultrasound transducers, light-emitting elements, and the like) of CD 300. In some embodiments, system 10 is constructed and arranged to stimulate tissue, for example, by delivering stimulation energy via one or more electrodes and / or other energy delivery elements of clinician device 300 (e.g., such as electrodes 311 described herein). Energy- delivery module 430 can be configured to deliver energy in the form of stimulation pulses that stimulate tissue. Energy delivery module 430 can deliver stimulation pulses via any one or more single electrodes, and / or via one or more sets (e.g., pairs) of electrodes at any given instant and / or at any frequency. In some embodiments, stimulation pulses are delivered as a sequence of pulses, such as a sequence of pulses that are delivered simultaneously and / or asynchronously, and / or regularly and / or irregularly. The stimulation pulses can be delivered across a plurality of operably connected electrodes, where each electrode can be positioned at prescribed (e.g., clinician and / or system 10 determined, as described herein) locations about a chamber and / or chambers of the heart. These sequences of pulses can be controlled either manually and / or by an algorithm (e.g., algorithm 415 described herein), such as an algorithm that determines the location and the instances in timeAttorney Docket No.: MAX-012-PCTto deliver stimulation, such as a determination that is based on the measured state of a prescribed chamber’s conduction pattern. Console 400 can include processing unit 410, which can be configured to perform one or more functions of console 400 (e.g., as described hereabove). Processing unit 410 can include processor 411, memory 412, and / or algorithm 415, each as shown. In some embodiments, memory7412 stores instructions to perform algorithm 415. Processing unit 410 can be constructed and arranged to execute algorithm 415 and to thereby execute one or more functions of console 400. In some embodiments, console 400 includes one or more user interfaces, user interface 450. In some embodiments, console 400 includes one or more functional elements, functional element 499 shown.Functional element 499 can include one or more sensors and / or transducers.

[0102] In some embodiments, console 400 is configured to perform a diagnostic interrogation of the morphology of cardiac activity of the patient, such as to provide a diagnostic interrogation of AF and / or SVT. For example, algorithm 415 can analyze electrical activity of the patient’s heart to determine a treatment plan including selection and configuration of one or more components of system 10 to optimize treatment of the patient. In some embodiments, algorithm 415 is configured to process one or more electrograms (e.g., electrograms recorded by system 10 and / or imported into system 10) to produce a 3D model of the electrical activity7of at least a portion of the heart. For example, algorithm 415 can produce 3D models that can be displayed (e.g., via user interface 450) to show the electrical conduction patterns and / or conduction timing of a portion of the heart (e.g., one or more chambers of the heart).

[0103] In some embodiments, algorithm 500 is configured to determine a treatment plan, such as to identify one or more portions of cardiac tissue to be treated by system 10, such as tissue to be ablated by clinician device 300. In some embodiments, one or more treatment locations determined by algorithm 500 are based on future therapy to be delivered by system 10, such as spatiotemporal resynchronization therapy (SRT) that will be delivered by ID 100. In some embodiments, algorithm 500 determines the treatment plan based on signals recorded from ID 100, such as when ID 100 is implanted prior to an ablation step and / or prior to an ablation procedure, for example when ID 100 is implanted in a first clinical procedure, and a second clinical procedure (e.g., an ablation procedure) is performed at a later date, such as at least one month, or at least six months later. In some embodiments, the treatment plan is based on signals recorded between the first procedure and the second procedure.Attorney Docket No.: MAX-012-PCT

[0104] As used herein, “SRT” can refer to spatial resynchronization therapy and / or spatiotemporal resynchronization therapy. SRT can include delivery of pacing energy from a plurality of electrodes in a spatially coordinated manner, and optionally with timing coordination, to restore synchronized atrial activation and / or to suppress arrhythmogenic conduction patterns. In some embodiments, SRT is implemented using one or more algorithms described herein, including Al-enhanced embodiments in which machine learning and / or other artificial intelligence techniques are used to improve sensing, prediction, classification, therapy selection, and / or therapy parameter selection.

[0105] In some embodiments, one or more Al algorithms described herein (e.g., algorithm 500) can be implemented using one or more agent-based architectures. For example, the Al algorithm can implement a multi-agent system (MAS) comprising one or more agents configured to perform one or more tasks selected from the group consisting of: signal interpretation; arrhythmia classification; therapy selection; therapy timing determination; spatial electrode selection; adaptive control of pacing delivery; and combinations of these. In some embodiments, the one or more agents are configured to operate collaboratively and / or hierarchically, can share state information, and / or can coordinate actions to achieve system-level objectives including stabilization of cardiac rhythm and restoration of synchronized activation.

[0106] The implantation locations of each of the electrodes 111 can be: determined automatically by system 10, determined by a clinician, and / or determined in a semiautomated way based on clinician and system 10 input. In some embodiments, one or more electrodes 111 are positioned at one or more locations on and / or within the heart, including epicardial, endocardial, intramural, sub-epicardial, and / or trans-septal locations. The one or more electrodes 111 can be delivered via a surgical approach, a minimally invasive approach, a percutaneous approach, a transvascular approach, and / or a hybrid approach. In some embodiments, one or more electrodes 111 are placed in proximity to and / or along one or more conduction structures or pathways (e.g., Bachmann’s bundle), interatrial conduction pathways, and / or in regions associated with preferential conduction and / or arrhythmogenic substrate. In some embodiments, electrode placement is guided by and / or refined using electroanatomic mapping, imaging (e.g., CT, MRI, ultrasound), computational modeling, real-time electrophysiological feedback, and / or data-driven approaches, including Al-based approaches as described herein. In some embodiments, a pacing diagnostic procedure is performed in which energy is delivered by an electrode (e.g., an electrode 311 of clinicianAttorney Docket No.: MAX-012-PCTdevice 300, an electrode 111 of ID 100, and / or other electrode) that is positioned in a tissue location temporarily, such as to assess the impact (the pacing impact) of the energy delivery at that location (e.g., an epicardial or other cardiac location). In these embodiments, a set of electrode 111 implant locations can be determined. In some embodiments, additional criteria can be used to determine the electrode 111 implant locations, such as clinical criteria, anatomical criteria, geometric criteria, criteria derived in simulations, and / or other criteria. These additional criteria can be used cooperatively with the criteria collected in the pacing diagnostic procedure to determine the implant locations for the electrodes 111.

[0107] System 10 can include one or more imaging devices, imaging device 60. Imaging device 60 can comprise an imaging device selected from the group consisting of: an X-ray device such as a fluoroscopy device; a CT scanner device; an MRI device; an ultrasound imaging device; and combinations of these.

[0108] ID 100 can comprise one or more arrays of functional elements (e.g., sensors and / or transducers), electrode array 110, comprising one, two or more elements, electrodes 111. Electrode array 110 can comprise multiple configurations. Electrode array 110 can be constructed and arranged to be implanted on the epicardial surface of the heart, for example, on the epicardial wall proximate the left atrium. Alternatively, or additionally, at least a portion of electrode array 110 (e.g., at least one electrode 111) can be implanted in a vessel (e.g., a coronary vessel), such as the coronary sinus, the Vein of Marshall, the Azygos vein, and / or another vessel proximate the heart. In some embodiments, at least a portion of electrode array 110 is implanted on the endocardial surface, such as within the left atrium or right atrium of the heart, for example on the septum between the left and right atrium. In some embodiments, at least a portion of electrode array 110 is positioned within the left atrial appendage (e.g., as part of a left atrial appendage closure device). Electrodes 111 can comprise pacing electrodes configured to deliver electrical stimulation energy to patient tissue (e.g.. tissue of the heart). Additionally, or alternatively, electrodes 111 can comprise sensing electrodes configured to record electrical activity of tissue (e.g., electrical activity of the heart). Electrodes 111 can be configured to deliver electrical stimulation and / or to sense electrical activity in unipolar and / or multipolar (e.g., bipolar) configurations, such as when two electrodes 111 comprise a pair of electrodes configured to operate in a source and sink arrangement. In some embodiments, electrode array 110 is fixedly attached to one or more flexible membranes, substrate 102. In some embodiments, substrate 102 comprise a single layer membrane. In some embodiments, substrate 102 comprises two or more membraneAttorney Docket No.: MAX-012-PCTlayers. Substrate 102 can comprise an elastomeric material, for example, a material selected from the group consisting of: poly(lactic-co-glycolic) acid (PLGA); silicone (PDMS); liquid crystal polymers; polyimide; polyurethane (PU); thermoplastic polyurethane (TPU); and combinations of these. In some embodiments, substrate 102 comprises a fabric mesh, such as a polyester mesh. In some embodiments, substrate 102 comprises a flexible material. In some embodiments, substrate 102 comprises a stretchable material, for example, a material that can stretch at least 5% and / or a material that stretches no more than 200%. In some embodiments, substrate 102 can comprise one or more holes constructed and arranged to cause and / or enhance capillary' action of tissue into substrate 102.

[0109] In some embodiments, one or more components of ID 100 (e.g., the components on the outer surfaces of ID 100 which will be exposed to the environment within the body when implanted) comprise biocompatible materials. In some embodiments, one or more components of ID 100 are at least partially encapsulated within substrate 102, for example, electrode array 110 can be positioned between two or more layers of substrate 102. In some embodiments, at least a portion of each electrode 111 of electrode array 110 extends through a layer of substrate 102 (e.g., an outer layer) such that at least a surface portion of electrode 111 is exposed to the body when ID 100 is implanted (e.g., such that ID 100 can be positioned with one or more electrodes 111 (e.g., all electrodes 111) in contact with the epicardial wall). In some embodiments, electrode array 110, and / or other electronic components of ID 100 can comprise one or more elastomeric materials. Alternatively, or additionally, electrode array 110, and / or other electronic components of ID 100 can comprise one or more non-elastomeric materials. In some embodiments, substrate 102 comprises an elongate tubular geometry, such as when substrate 102 comprises a shaft similar to a catheter shaft with one or more electrodes positioned thereon.

[0110] In some embodiments, electrodes 111 comprise a coating and / or a surface treatment (either or both, “coating’’ herein), such as a coating that is configured to enhance the recording ability7of ID 100 via electrodes 111. For example, electrode 111 can comprise one or more coatings, such as coating 104 described herein, that are configured to increase the surface area of electrodes 111, such as to enhance the recording ability of electrodes 111, such as by lowering the source impedance of electrodes 111. Coatings can reduce the impedance and effects of the half-cell potential that occur from large surface areas of noble metals. A balance of low input impedance and reduced capacitive effects are needed here. Consider that small electrodes are noisy due to high source impedance. In someAttorney Docket No.: MAX-012-PCTembodiments, electrodes 111 can comprise a coating configured to reduce the electrodetissue interface impedance, for example to improve recorded signal integrity and / or to improve energy transfer efficiency.

[0111] Electrode array 110 can comprise an array surface area (e.g., the surface area defined by the outside boundary of array 110, and / or the convex hull of electrodes 111 of ID 100) of at least 6.5cm2. In some embodiments, electrode array 110 can comprise a surface area greater than or equal to at least 12% of the epicardial surface of the right atrium of the heart and / or the left atrium of the heart. System 10 can comprise multiple implantable devices 100 in various sizes and shapes (e.g., various array 110 sizes), such as when provided in a kit form such that a clinician can select which implantable device 100 of a kit of implantable devices 100 to implant. The selection made can be based on one or more patient parameters, such as the size of the patient's heart (e g., the size of an atrium and / or a ventricle of the patient’s heart) and / or one or more target anatomical placement sites (e.g., proximity to conduction structures and / or pathways, and / or proximity to arrhythmogenic substrate). In some embodiments, the size of array 110 of a particular ID 100 is proportional to the amount of tissue through which ID 100 can manipulate the electrical activity of the heart (e.g., to control and / or direct the propagation of cardiac activation of the tissue). In some embodiments, ID 100 comprises a conformable and / or an adjustable construction, for example when electrode array 110 is configured to transition from a compact geometry' to an expanded geometry'. In some embodiments, one or more ID 100 can be implanted at a location selected to treat a particular disease or ailment. For example, ID 100 can be implanted proximate the left atrium (e.g., on the epicardial surface) to deliver stimulation energy to treat atrial fibrillation. Alternatively, or additionally, ID 100 can be implanted proximate a ventricle of the heart (e.g., on the epicardial surface) to deliver stimulation energy to treat ventricular tachycardia and / or ventricular fibrillation, such as via antitachycardia pacing (ATP), cardioversion, and / or defibrillation therapy. In some embodiments, at least one electrode I l l is implanted in each chamber of the heart (e.g., at least one ID 100 is implanted in each chamber of the heart), such that system 10 can sense and / or pace from within each chamber.

[0112] In some embodiments, ID 100 comprises multiple devices, such as at least 5, or at least 10 devices. In these embodiments, multiple implantable devices 100 can be configured to be implanted in a distributed manner, for example, evenly distributed across one or more portions of the epicardial surface. In some embodiments, multiple devices 100 areAttorney Docket No.: MAX-012-PCTconfigured to treat the patient in a coordinated fashion, such as to deliver energy to the cardiac tissue in a pattern based on the location of each individual ID 100 (e.g., relative to each other and / or the cardiac tissue). In some embodiments, ID 100 can comprise multiple devices, such as two, three, or more implantable devices 100. In some embodiments, multiple devices 100 are configured to collectively treat a patient with multiple arrhythmias in a coordinated fashion, such as to deliver energy to the right and / or the left atrium to treat AF and / or SVT, and / or to deliver energy to the right and / or the left ventricle to treat other arrhythmias. For example, the multiple devices 100 can each deliver energy as needed (e g., as determined by a treatment plan of system 10, described herein), such as when the device 100 closest to the source of an arrhythmia is selected to deliver energy to treat that arrhythmia. In some embodiments, at least one of a set of multiple implantable devices 100 can be configured to be implanted in one or more locations selected from the group consisting of: within the right atrium, such as affixed to the endocardial wall of the right atrium; within the left atrium, such as affixed to the endocardial w all of the left atrium; within the left and / or right ventricle; proximate one or more pulmonary veins, such as within and / or partially surrounding a pulmonary vein; on the endocardial surface proximate the left and / or right atrium, the left and / or right ventricle, a pulmonary vein, and / or another anatomic landmark; within a coronary' vessel; embedded into cardiac tissue, such as betw een the endocardial and epicardial surface; and combinations of these.

[0113] In some embodiments, one or more conductive portions (e.g., conductive surfaces) of ID 100 (e.g., conductive portions of electrode array 110) are positioned on device 100 to be directed towards tissue to be stimulated when ID 100 is implanted (e.g., directed towards cardiac tissue), and one or more nonconductive portions of ID 100 are positioned on device 100 to be directed toward tissue to be insulated from stimulation energy’ delivered by ID 100 (e.g., directed toward the pericardium). For example, ID 100 can be configured to be implanted on the epicardial surface with the “bottom” of ID 100 directed towards the epicardial surface, and electrodes 111 can be positioned on the bottom of ID 100 and insulated from the top of ID 100, such as to prevent unintended stimulation of the phrenic nerve, the pericardium, and / or other electrically active thoracic structures. In some embodiments, ID 100 can comprise a cover configured to insulate one or more portions of ID 100 from tissue.

[0114] ID 100 can comprise controller 130, which can be configured to perform various functions of ID 100. Controller 130 can comprise a microprocessor, memory, and otherAttorney Docket No.: MAX-012-PCTcomponents that can be constructed and arranged to control, perform, and / or otherwise enable one or more functions of ID 100. In some embodiments, controller 130 comprises one or more algorithms, algorithm 135 shown. In some embodiments, controller 130 comprises a memory for storing instructions to perform algorithm 135. Controller 130 can be constructed and arranged to execute algorithm 135 and to thereby execute one or more functions of ID 100. In some embodiments, each electrode 111 of electrode array 110 is independently addressable (e.g., electrically connected to at least two wires, such as ground and power or data, between each electrode and controller 130), such that signals (e.g., data and / or power) can be transmitted between controller 130 and each electrode 111 individually or collectively. Alternatively, or additionally, controller 130 and / or electrode array 110 can be configured in a multiplexed arrangement, such that each electrode 111 can be individually addressed via a multiplexing component.

[0115] In some embodiments, controller 130 is configured to record electrical activity from one or more electrodes 111 (e.g., one or more electrodes 111 configured as sensing electrodes). Additionally, or alternatively, controller 130 can be configured to provide stimulation signals to be delivered to the patient via one or more electrodes 111 (e.g., one or more electrodes 111 configured as pacing electrodes). In some embodiments, electrode array 110 comprises a set of electrodes 111 configured as pacing electrodes, and a set of electrodes 111 configured as sensing electrodes. Alternatively, or additionally, controller 130 can be configured to alternate between pacing and sensing from an electrode 111 of electrode array 1 10 (e g., in a multiplexed arrangement). In some embodiments, controller 130 is configured to simultaneously sense and pace from a given electrode 111. In some embodiments, multiple electrodes 111 can be multiplexed such as to sense (e.g., record signals) from one electrode 111 relative to a plurality’ of other electrodes 111 that collectively serve as a sensing reference. For example, the collective reference can be formed by the distance-weighted average of each of the electrodes 111 in the collected-reference (the collective signalreference) relative to the one measurement electrode (the onesignal-measurement). Additionally, or alternatively, a similar arrangement can be provided for electrodes 111 delivering stimulation energy, such as when stimulation energy is delivered between a set of electrodes 111 (e.g., configured as an anode or a cathode) and a single electrode 111 (e.g., configured as a cathode or anode, respectively).

[0116] In some embodiments, ID 100 comprises a membrane or other material, coating 104, which can surround at least a portion of the surface of one or more componentsAttorney Docket No.: MAX-012-PCTpositioned on and / or within substrate 102. Coating 104 can comprise a biocompatible material, for example, a coating selected from the group consisting of a silicone (PDMS) coating; a parylene coating; a water-based coating; a resin coating; a chemical coating; a steroidal coating; and combinations of these. Coating 104 can be configured to prevent irritation of the tissue onto which ID 100 is implanted, for example, to prevent an allergic reaction. In some embodiments, coating 104 comprises a bio-adhesive configured to permanently and / or semi-permanently adhere ID 100 to tissue (e.g., to the epicardial wall). For example, coating 104 can comprise a hydrogel (e.g., a hydrogel adhesive). Alternatively, or additionally, system 10 can include adhesive 70, configured to be applied between ID 100 and tissue. In some embodiments, adhesive 70 is electrically conductive. In some embodiments, adhesive 70 comprises a UV activated adhesive. Adhesive 70 can comprise an injectable adhesive, for example, an injectable adhesive comprising a durometer under a threshold (e.g., a sufficiently soft adhesive). Adhesive 70 can comprise a biocompatible adhesive. In some embodiments, coating 104 can comprise a hollow tube, sheath 1041, configured to surround shaft 1021 of ID 100. Sheath 1041 can comprise one or more openings, openings 1042 through which electrodes 111 can contact tissue.

[0117] In some embodiments, ID 100 comprises one or more securing and / or stabilizing elements, anchoring element 105. Anchoring element 105 can be configured to secure, affix, stabilize, prevent (or at least limit) migration of. or otherw ise prevent or limit unwanted motion of ID 100 (“secure7’ herein) before, during, and / or after implantation of device 100. In some embodiments, anchoring element 105 comprises a releasable and / or re-securable securing mechanism, such that ID 100 can be repositioned and / or removed (e.g., repositioned by a clinician using clinician device 300). Anchoring element 105 can be configured to interact with an anatomical feature to secure ID 100, such as by pushing against the pericardial sac to force ID 100 onto the epicardial wall. In some embodiments, anchoring element 105 comprises a material configured to promote tissue ingrowth and / or tissue overgrowth, such as to secure ID 100 as tissue growth interacts with anchoring element 105. For example, anchoring element 105 can comprise a fabric mesh.

[0118] In some embodiments, the various components of ID 100 are interconnected by one or more conduits, wires 112. In some embodiments, one or more wires 112 are included in and / or comprise a portion of a lead, lead 1121 herein. In some embodiments, wires 112 comprise conductive routing filaments, for example, one or more conductive traces, such as one or more traces within and / or on a circuit board (e.g., a flexible circuit board). In someAttorney Docket No.: MAX-012-PCTembodiments, wires 112 comprise traces within and / or on substrate 102. In some embodiments, electrode array 110 comprises one or more wires 112, for example, when electrodes 111 are electrically interconnected by wires 112. Wires 112 comprising conductive routings can each comprise a liquid metal routing, for example, a routing liquid phase eutectic gallium. In some embodiments, conductive traces are applied to substrate 102 (e.g., during a manufacturing process) with methods that include the manipulation of nanoparticles. For example, conductive traces can be formed such that wires 112 comprise nano wires consisting of graphene and / or silver. In some embodiments, wires 112 (configured as conductive traces of substrate 102) comprises a geometry configured to minimize Van der Waals, tensile, compressive, and / or other undesired forces, such as when wires 112 comprise a wavelike geometry (e.g.. a sinusoidal geometry). The geometry of wires 112 can be configured such that wires 112 maintain a high level of conductivity, such when under strain.

[0119] In some embodiments, controller 130 and electrode array 110 are operably coupled via lead 1121. Lead 1121 can include one or more conductors (e.g., wires 112) and can electrically couple electrode array 110 (e.g.. one or more electrodes 111) to controller 130 and / or one or more other components of system 10. In some embodiments, lead 1121 is configured to be tunneled through tissue and / or exteriorized through a skin exit site, such as for temporary coupling to external patient device 200 and / or clinician device 300 (e.g., during a trial and / or implantation workflow). For example, clinician device 300 can be configured to couple to lead 1121 during implantation and / or during a trial procedure, such as to perform one or more sensing tests, pacing tests, mapping procedures, and / or parameter programming.

[0120] ID 100 can include transceiver 120. Transceiver 120 can be configured to communicate (e.g.. wirelessly communicate) with one or more other components of system 10, for example, one or more additional implanted devices 100 (e.g., when ID 100 comprises two or more devices, such as ID 100a and ID 100b), as well as EPD 200, CD 300, console 400, and / or another component of system 10. Transceiver 120 can comprise a receiving and / or transmitting interface, antenna 125. Antenna 125 can be positioned on and / or embedded within substrate 102. In some embodiments, electrode array 110 comprises antenna 125, for example, when wires 112 of electrode array 110 are constructed and arranged to function as an antenna. Antenna 125 can comprise various shapes, for example, antenna 125 can comprise planar micro coils configured in various shapes.

[0121] ID 100 can include power module 140. Power module 140 can include one or more power-generating, power-harvesting, power-storing, power- transferring (e.g., viaAttorney Docket No.: MAX-012-PCTwireless power transfer) and / or other power-supplying components configured to deliver energy to ID 100. Power module 140 can be configured to provide power to one or more components of ID 100. In some embodiments, power module 140 comprises one or more batteries, capacitors, and / or other power-storing devices. In some embodiments, power module 140 comprises a solid-state battery, such as a miniature solid-state battery. In some embodiments, power module 140 comprises a rechargeable battery. In some embodiments, power module 140 comprises one or more capacitors. In some embodiments, power module 140 comprises at least one battery and at least one capacitor. In some embodiments, ID 100 does not include a battery (i.e., a source of power that is generated by an electrochemical reaction), a “battery-less design"’ herein, for example, when power module 140 is configured to harvest power (e.g., configured to harvest power transmitted wirelessly from EPD 200). and power module 140 is configured to store and directly provide the harvested power to power the various components of ID 100. Power module 140 can be constructed and arranged to “harvest"’ power from kinetic motion, for example, from kinetic motion of heart tissue when at least a portion of ID 100 is positioned on and / or within the heart. In some embodiments, power module 140 comprises one or more piezo electric components configured to convert kinetic energy to electrical energy.

[0122] In some embodiments, ID 100 can comprise patient sensor 160 shown. Patient sensor 160 can comprise one, two or more sensors selected from the group consisting of: an electrical sensor, such as a sensor configured to record an electrogram; a temperature sensor; accelerometer; position sensor; gravimetric sensor; pressure sensor; strain gauge; acoustic sensor; and combinations of these. System 10 can be configured to monitor one or more patient parameters based on information recorded by patient sensor 160, such as heartbeat, patient position, and / or patient activity.

[0123] In some embodiments, system 10 is configured to monitor for fluid in the lungs of the patient. For example, patient sensor 1 0 can comprise an impedance sensor and / or an ultrasonic sensor configured to measure the level and / or detect the presence of fluid in the lungs.

[0124] In some embodiments, system 10 is configured to measure thoracic bioimpedance. System 10 can measure bio-impedance between one or more electrodes 111 and one or more reference electrodes (e.g., skin surface electrodes, subcutaneous electrodes, or other electrodes operably attached to system 10). Thoracic bio-impedance measurements canAttorney Docket No.: MAX-012-PCTbe used by system 10 to assess fluid status, pulmonary congestion, and / or respiratory function.

[0125] In some embodiments, system 10 is configured to monitor local tissue impedance, such as to assess tissue state. Algorithm 500 can be configured to analyze impedance measurements between one or more electrodes 11 1 and / or other electrodes of system 10. Algorithm 500 can be configured to analyze impedance changes over time. In some embodiments, algorithm 500 is configured to distinguish between impedance changes attributable to electrode-tissue contact quality and impedance changes attributable to tissue inflammation and / or edema. Tissue inflammation can occur as part of a post-operative inflammatory response. Edema can alter local tissue impedance characteristics. In some embodiments, impedance measurements are used to estimate left atrial (LA) function, such as function including mechanical and / or electromechanical properties. Impedance variations (e.g., cyclic impedance variations) associated with atrial contraction can be analyzed to derive one or more metrics indicative of atrial contractility, compliance, and / or synchrony. In some embodiments, the derived LA function metric(s) are used by system 10 to guide and / or optimize therapy delivery' (e.g., pacing timing, spatial electrode selection, and / or therapy mode).

[0126] In some embodiments, algorithm 500 is configured to adjust one or more therapy parameters (e.g., therapy intensity) based on detected tissue inflammation and / or edema (or other detected patient parameters). Algorithm 500 can be configured to adjust one or more therapy parameters selected from the group consisting of: reversible electroporation voltage; reversible electroporation pulse duration; elevated-output pacing energy; standard pacing output; and combinations of these. For example, algorithm 500 can be configured to reduce reversible electroporation voltage when impedance measurements indicate reduced tissue inflammation. In some embodiments, algorithm 500 incorporates impedance trend data to optimize therapy delivery' timing.

[0127] In some embodiments, system 10 is configured to distinguish electrode-tissue coupling changes associated with lead position and / or mechanical disturbance from tissuestate changes associated with inflammation and / or edema. For example, algorithm 500 can be configured to analyze one or more impedance measurements (e.g., electrode-to-reference impedance, el ectrode- to-electrode impedance, and / or impedance trend over time) together with one or more electrical signal quality metrics (e.g., electrogram amplitude, baseline stability, artifact contamination, capture verification, and / or pacing threshold trend) toAttorney Docket No.: MAX-012-PCTclassify an observed change as a lead-position condition or an inflammation and / or edema condition. In some embodiments, a lead-position condition is associated with an abrupt and / or localized impedance change at a subset of electrodes and reduced local signal quality and / or capture reliability, while an inflammation and / or edema condition is associated with a gradual and / or multi-electrode impedance trend and correlated changes in one or more physiologic indicators (e.g., temperature and / or hemodynamic trend). Based on the classification, algorithm 500 can be configured to adjust therapy delivery (e.g., adjust energy level, adjust waveform parameters, switch electrode configuration, increase sensing redundancy, and / or withhold escalation) and / or generate an alert indicating a suspected lead-position issue.

[0128] ID 100 can include one or more functional elements, functional element 199 shown. Functional element 199 can comprise one, two, or more sensors selected from the group consisting of: pressure sensor such as blood pressure sensor; acoustic sensor; respiration sensor; gas sensor such as blood gas sensor; flow sensor such as blood flow sensor; temperature sensor; pH sensor; optical sensor; impedance sensor; and combinations of these. In some embodiments, functional element 199 comprises one, two, or more transducers, such as an optical transducer (e.g., an LED).

[0129] System 10 can be configured to both monitor one or more patent parameters and to treat the patient based on the monitored parameters (e.g., based on an analysis of the monitored parameters). For example, system 10 can be configured to monitor (e.g., via electrode array 1 10) and analyze (e g., via controller 130) electrograms recorded by ID 100, (e.g., unipolar and / or multipolar, for example, bipolar, modes of electrogram recording) and to pace and / or otherwise stimulate tissue if atrial fibrillation is detected, for example as described herein. In some embodiments, system 10 is configured to monitor and / or record one, two, or more of electrophysiological activity, patient temperature, heartbeat information, and / or another patient parameter. In some embodiments, ID 100 is configured to stimulate tissue based on data recorded and / or analyzed by mapping module 420 of console 400. For example, mapping module 420 can be configured to identify irregular conduction patterns within one or more locations of cardiac tissue, as described herein, and to determine a set of stimulation parameters to be delivered by ID 100 to stimulate the tissue to treat (e g., correct) the irregular conduction patterns.

[0130] In some embodiments, electrode array 110 is positioned along (e.g., on and / or within) shaft 1021. such as a shaft 1021 configured in a spiral geometry. Additionally, orAttorney Docket No.: MAX-012-PCTalternatively, shaft 1021 can comprise a resiliency biased geometry, such as when shaft 1021 is configured in a resiliently biased spiral geometry. In some embodiments, substrate 102 comprises a nickel titanium alloy and / or other shape memory material, such as when substrate 102 comprises a shape memory inner layer surrounded by one or more layers of polymers or other flexible materials. In some embodiments, substrate 102 comprises an elongate geometry (e.g., shaft 1021), and the one or more wires 112 extend along (e.g., on the surface and / or within) substrate 102, for example, connecting each electrode 111 to controller 130 positioned at one end of shaft 1021. In some embodiments, controller 130 comprises various other components of ID 100, such as transceiver 120, power module 140, patient sensor 160. and the like.

[0131] In some embodiments, wires 112 and / or a portion of substrate 102 are configured as at least a portion of antenna 125, such as when shaft 1021 is configured in a spiral geometry' (such as a spiral geometry described herein). For example, substrate 102 can comprise a conductive portion (e.g., an inner core of shaft 1021), such as a portion with a gold conductive core with a nickel titanium cladding, or a nickel titanium core with a platinum iridium cladding. In these embodiments, this conductive core of shaft 1021 can be electrically insulated, such as when the core is surrounded by an insulative material, such as an insulative polymer.

[0132] In some embodiments, one or more portions of ID 100 (e.g., one, two, or more components of ID 100) can be bioabsorbable and / or bioresorbable ("“bioabsorbable7’ herein). For example, ID 100 can comprise a device including two or more electrodes 111 operably attached to antenna 125, that is configured to harvest RF energy' (e.g., RF energy' transmitted from EPD 200) and directly stimulate tissue by providing the harvested energy to electrodes 111 and electrodes 111, antenna 125 and / or the associated electrical traces of ID 100 can comprise a bioabsorbable conductive material, such as tungsten-coated magnesium (W / Mg). ID 100 can comprise one or more other components that comprise bioabsorbable magnesium. In some embodiments, electrodes 111, antenna 125, and / or the associated electrical traces of ID 100 are positioned on and / or within a bioabsorbable patch, such as a bioabsorbable patch configured to be attached to the epicardial surface with bioabsorbable suture.

[0133] In some embodiments, external patient device 200 includes one or more sensor assemblies, sensor assembly 270 shown. Sensor assembly 270 can include one or more sensors configured to provide one or more signals related to a patient parameter, an environmental parameter, and / or other parameter, such as described herein. In someAttorney Docket No.: MAX-012-PCTembodiments, sensor assembly 270 comprises one or more sensors such as are described in reference to Figs. 18A and 18B herebelow.

[0134] External patient device 200 (EPD 200) can be constructed and arranged to be worn by the patient, such as when positioned on the skin of the patient (e.g., when EPD 200 is temporarily adhered or otherwise temporarily attached to the patient’s skin), and / or when inserted in and / or otherwise attached to the patient’s clothing. Alternatively, or additionally. EPD 200 can be held against the patient, such as when held against the patient's skin and / or clothing (e.g., by the patient and / or by a patient attachment device). For example, EPD 200 can be configured to be held against the patient, proximate ID 100, while EPD 200 communicates with ID 100 (e.g., for a brief period of time, such as less than 60 seconds). In some embodiments, EPD 200 includes attachment assembly 280. Attachment assembly 280 can include an adhesive, such as an adhesive patch, configured to adhere EPD 200 to the patient’s skin for at least 6 hours, such as at least 12 hours, or at least 24 hours (e.g., before the adhesive patch must be replaced). Alternatively, or additionally, attachment assembly 280 can comprise a harness, clip, specialized garment, or other non-adhesive based tool for positioning EPD 200 proximate the patient (e.g., proximate the location where ID 100 is implanted in the patient). For example, attachment assembly 280 can comprise a chest strap constructed and arranged to hold EPD 200 over the patient’s heart, for example, when ID 100 is implanted onto the epicardial surface of the patient's left atrium. In some embodiments, EPD 200 comprises a device that is implanted subcutaneously or at another internal body location. Alternatively, one or more portions of EPD 200 are implanted in the patient and one or more portions are positioned external to the patient.

[0135] EPD 200 can include transceiver 220. Transceiver 220 can be configured to communicate (e.g.. wirelessly communicate) with one or more components of system 10, for example, one or more implanted devices 100, and / or one or more additional external patient devices 200’, as well as CD 300, console 400, and / or other components of system 10.Transceiver 220 can comprise a receiving and / or transmitting interface, antenna 225. EPD 200 can be constructed and arranged to transmit power and / or data to one or more implantable devices 100. such as by transmitting a radio frequency (RF) energy from antenna 225, through the skin of the patient, towards ID 100, and ID 100 can be constructed and arranged to harvest the RF energy and / or receive the RF data via antenna 125 (e.g., a powerharvesting antenna). In some embodiments, EPD 200 is constructed and arranged to receive data from one or more implantable devices 100. such as when transceiver 120 is constructedAttorney Docket No.: MAX-012-PCTand arranged to transmit RF data to EPD 200. In some embodiments, transceiver 220 comprises one or more wireless communication interfaces, such as one or more interfaces selected from the group consisting of: Bluetooth (e.g., Bluetooth Low Energy ); near-field communication (NFC); Wi-Fi; cellular; and combinations of these.

[0136] EPD 200 can include one or more user interfaces, user interface 250 shown. User interface 250 can include one or more user input and / or user output components, for example, one or more: displays, indicators (e.g., LEDs), speakers, buttons, microphones, and / or other user interface components. In some embodiments, EPD 200 includes one or more functional elements, functional element 299 shown. Functional element 299 can include one or more sensors and / or transducers. User interface 250 can display a visual representation of the heart chambers (e.g.. a digital model) including one or more electrical conduction patterns (e.g., AF conduction patterns and / or sinus rhythm conduction patterns) that are displayed relative to the representation of the heart anatomy. In some embodiments, user interface 250 can display a representation of one or more portions of ID 100 (e.g., one or more electrodes 111) relative to the representation of the heart. In some embodiments, the conduction patterns displayed include pre-treatment and / or post-treatment (e.g., post pacing) conduction patterns. In some embodiments, the conduction patterns are displayed relative to each electrode 111 that is displayed on the representation of the heart. In some embodiments, user interface 250 can display various simulations of conduction patterns resulting from a proposed therapy to be delivered to treat the arrhythmia (e.g.. AF) of the patient.

[0137] In some embodiments, functional element 299 of EPD 200 comprises one or more sensors that are used to record a patient parameter, such as a patient EEG. For example, functional elements 299 can comprise one, two, or more sensors (e.g., electrodes) that are positioned on EPD 200 such that the patient can place their thumbs or other fingers to contact the sensors, to provide an ECG recording (e.g., an additional ECG recording collected by system 10). For example, system 10 can perform diagnostic monitoring (e.g., ECG recording) on a predetermined schedule, but also allow for additional diagnostic monitoring (e.g., ECG recording) as determined by the patient (e.g., at any time). In some embodiments, the patient may choose to perform additional monitoring based on a physiologic condition, such as feeling dizzy, feeling faint, having palpitations, having shortness of breath, feeling tired, and the like. In some embodiments, the monitoring of the one or more patient parameters can be initiated by the patient. For example, the one or more patient parameters to be monitored (as initiated by the patient) can comprise at least an ECG, and the system canAttorney Docket No.: MAX-012-PCTbe configured to adjust the therapy provided (e.g., initiate stimulation energy delivery ) based on detection of an arrhythmia via the monitored ECG. In some embodiments, the patient, clinician, and / or other user of system 10 can adjust the monitoring of one or more patient physiologic parameters, such as to establish a time-interval for monitoring of these parameters.

[0138] In some embodiments, functional element 299 of EPD 200, and / or another functional element of system 10. comprises one or more sensors that are configured to record EMG, EEG, and / or ECG, and system 10 is configured to analyze the recorded signals in order to perform a diagnosis and / or prognosis (“diagnosis” herein) of sleep apnea of the patient. EPD 200 can be configured to monitor one or more parameters related to the detection of sleep apnea selected from the group consisting of: movement, such as chest movement; snoring; body position; heart rate; 02 saturation; and combinations of these. In some embodiments, system 10 is configured to provide a sleep analysis. Analysis performed by system 10 (e.g., sleep apnea and / or other patient diagnosis such as a diagnosis of atrial fibrillation) can be accessible via an online portal (e.g., a patient portal hosted by server 600), and / or automated reports can be provided to the patient’s managing physician.

[0139] Additionally, or alternatively, analysis performed by system 10 includes one or more autonomic risk stratification outputs and / or preventative screening outputs. In some embodiments, the online portal and / or automated reports include an autonomic-cardiac interaction summary, one or more risk scores and / or phenotype outputs, and one or more recommendations for additional monitoring, repeating one or more provocation sessions, and / or repeating one or more diagnostic workflows (e.g., the workflows described in reference to Fig. 17 and / or Fig. 19).

[0140] In some embodiments, external patient device 200 can comprise a patient wearable device (e.g., a wrist-wom device and / or a wearable band). External patient device 200 can be configured to produce one or more “wearable signals”. For example while external patient device 200 is worn by the patient, sensor assembly 270 can be configured to sense one or more patient and / or environmental parameters and / or conditions and to produce one or more “wearable signals” relating to the parameters and / or conditions. In some embodiments, sensor assembly 270 is constructed and arranged as described in reference to Figs. 18A and 18B herebelow.

[0141] Attorney Docket No.: MAX-012-PCT

[0142] EPD 200 can include processing unit 210 which can be configured to perform one or more functions of EPD 200. Processing unit 210 can include one or more algorithms, algorithm 215 shown. In some embodiments, processing unit 210 comprises a memory for storing instructions to perform algorithm 215. Processing unit 210 can be constructed and arranged to execute algorithm 215 and to thereby execute one or more functions of EPD 200. In some embodiments, processing unit 210 analyzes data (e.g., via algorithm 215) received from ID 100. For example, EPD 200 can receive data from ID 100, process (e.g., mathematically process) the information received via algorithm 215 (e.g., to determine if pacing should be performed, and to determine the parameters of stimulation energy' to be delivered), and send information and / or power to ID 100 based on the processed information.

[0143] EPD 200 can include power module 240. Power module 240 can include one or more power-generating, power-harvesting, power-storing, and / or other power-supplying components configured to deliver energy to EPD 200, and / or to deliver power to ID 100 via wireless power transfer. Power module 240 can be configured to provide power to one or more components of EPD 200. In some embodiments, power module 240 comprises one or more batteries, capacitors, and / or other power-storing devices. Power module 240 can be constructed and arranged to “harvest” power from kinetic motion. In some embodiments, power module 240 comprises one or more piezoelectric components configured to convert kinetic energy to electrical energy.

[0144] CD 300 can include one or more catheters and / or or one or more surgical tools for delivering ID 100 into the patient. Additionally, CD 300 can include one or more devices configured to diagnose and / or treat the patient, such as to perform a diagnosis and / or a treatment during a clinical procedure in which ID 100 is implanted into the patient. For example, CD 300 can comprise a cardiac mapping catheter which can be used to collect data (e.g., data to be processed by console 400) such as to map the cardiac electrical activity of the heart. Additionally, or alternatively, CD 300 can comprise an ablation catheter which can be used to ablate tissue (e.g., cardiac tissue). In some embodiments, system 10 can include one or more clinician devices 300 that are constructed and arranged to enable the clinician to perform: a mapping procedure, a tissue treatment procedure (e.g., an ablation procedure or other tissue treatment procedure), and / or an ID 100 implantation procedure (e.g., for continued, post procedural treatment of the patient).

[0145] In some embodiments, CD 300 comprises electrode array 310 shown, which can comprise one or more arrays of electrodes that can be inserted into the patient. ElectrodeAttorney Docket No.: MAX-012-PCTarray 310 can comprise one or more electrodes, electrodes 311. CD 300 can include user interface 350 shown. User interface 350 can include one or more user input and / or user output components, for example, one or more: displays, indicators (e.g., LEDs), speakers, buttons, levers, microphones, and / or other user interface devices. In some embodiments, user interface 350 comprises a handle (e.g., a catheter handle) including one or more controls, such as a steering control.

[0146] In some embodiments, CD 300 includes transceiver 320. Transceiver 320 can comprise an assembly configured to communicate (e g., wirelessly communicate) with one or more components of system 10, for example, one or more implanted devices 100, one or more external patient devices 200, console 400, and / or other components of system 10. Transceiver 320 can comprise a receiving and / or transmitting interface, antenna 325. In some embodiments, CD 300 includes one or more functional elements, functional element 399 shown. Functional element 399 can include one or more sensors and / or transducers.

[0147] In some embodiments, system 10 is configured to perform an acute assessment and / or treatment of the cardiac substrate, such as when one or more recordings of cardiac signals are recorded by clinician device 300, such as when electrode array 310 is positioned within a chamber of the heart and / or positioned intravascularly within a cardiac vessel, and / or when clinician device 300 is used to treat the cardiac substrate (e.g., when pacing energy' is delivered via electrode array 310). Additionally, or alternatively, ID 100 can be configured to monitor and / or treat the cardiac substrate temporarily (e.g.. acutely) or chronically. For example, ID 100 can be temporarily implanted (e.g., as described herein), such as to temporarily provide substrate monitoring and / or SRT. In some embodiments, ID 100 can be removed and / or otherwise stop monitoring and / or providing therapy (e.g., when ID 100 is configured to remain implanted after a temporary battery has been exhausted). In some embodiments, ID 100 is chronically implanted, such as to provide substrate monitoring and / or SRT chronically.

[0148] In some embodiments, clinician device 300 is configured for percutaneous access and / or transvascular access to a location proximate the heart, such as a cardiac vessel, a cardiac chamber, and / or the pericardial space. Clinician device 300 can be configured to access various cardiac locations using various methods, such as percutaneous to transvascular, transvascular to a location outside the heart (e.g., when clinician device 300 is configured to exit the vessel into the pericardial space), and / or transvascular to a location within the heart.Attorney Docket No.: MAX-012-PCT

[0149] In some embodiments, system 10 includes a data storage and processing device, server 600. Server 600 can comprise an "off-site” server (e.g., outside of the operating room or other clinical site in which ID 100 is implanted), such as a server maintained by the manufacturer of system 10. Alternatively, or additionally, server 600 can comprise a cloudbased server. Server 600 can include processing unit 610 shown, which can be configured to perform one or more functions of server 600. Processing unit 610 can include one or more algorithms, algorithm 615. In some embodiments, processing unit 610 includes a memory for storing instructions to perform algorithm 615. Processing unit 610 can be constructed and arranged to execute algorithm 615 and to thereby execute one or more functions of server 600. Server 600 can be configured to receive and store various forms of data, such as: patient, procedural, device, and / or other information, data 620. Data 620 can comprise data collected from multiple patients (e.g., multiple patients treated with system 10), such as data collected during and / or after clinical procedures where ID 100 was implanted into the patient. For example, data can be collected from ID 100, transmitted to EPD 200, and sent to server 600 for analysis. In some embodiments, one or more devices of system 10, such as EPD 200 and server 600, can communicate over a network, network 50, for example, a wide area network such as the Internet. In some embodiments, system 10 includes a virtual private netw ork (VPN) through which various devices of system 10 transfer data.

[0150] Algorithm 615 can be configured to analyze data 620. For example, algorithm 615 can be configured to analy ze data 620 collected from multiple patients to identify similarities and / or differences in treatment parameters and patient results. In some embodiments, algorithm 615 comprises a machine learning and / or other artificial intelligence algorithm ('‘Al algorithm” herein) that can be configured to identify patterns in the correlations between treatment parameters and results based on data collected from multiple patients. In some embodiments, algorithm 615 analyzes patterns to determine better treatment parameters for one or more patients to be treated using system 10. For example, algorithm 615 can identify one or more patterns in the data (e.g., one or more patterns associated with efficacy of the treatment being delivered to the patient) by analyzing data 620 collected from many patients (e.g., tens of thousands of patients). Algorithm 615 can be further configured to use these patterns to determine whether a patient (e.g., in the set of patients from which the data was collected and / or in a new patient) is receiving sub-optimal treatment (e.g., the parameters associated with pacing and / or other energy being delivered could be modified to improve efficacy). System 10 (e.g., via algorithm 615) can beAttorney Docket No.: MAX-012-PCTconfigured to alert the clinician of a patient receiving sub-optimal treatment, and to recommend (e.g., via CD 300, such as the clinician’s phone or computer) the parameters to be adjusted. In some embodiments, the clinician may schedule an appointment to adjust the parameters (e.g., in person), or the parameters can be adjusted remotely, for example, when CD 300 is configured to adjust the parameters remotely via network 50. Alternatively, or additionally, server 600 can adjust the parameter automatically (e.g., via network 50). In some embodiments, one or more parameters are automatically adjustable (e.g., within certain thresholds), while other parameters require clinician approval. In some embodiments, system 10 is configured to enable remote monitoring of one or more implanted devices 100 and / or remote modification of one or more therapy parameters (e.g., timing, amplitude, electrode selection, and / or therapy mode), such as by a clinician using CD 300 and / or another computing device in communication with server 600 via network 50. In some embodiments, remote commands are executed subject to device-side safety checks and / or authorization requirements, including verification of programmed limits and / or physiological conditions. In some embodiments, system 10 generates alerts and / or recommendations for clinician review. System 10 can be configured to operate in a closed-loop and / or semi-closed-loop manner combining remote input with local sensing and algorithmic control.

[0151] As described herein, system 10 can comprise one or more algorithms, such as algorithms 135, 215, 415 and / or 615 shown in Fig. 1. As described hereabove, the various algorithms of system 10 can be referred to singly or collectively herein as algorithm 500 (e.g., an algorithm performed via instructions stored on a memory’ storage element of system 10). In some embodiments, algorithm 500 comprises a machine learning and / or other artificial intelligence algorithm (“Al algorithm” herein). Any algorithmic process described herein may be performed by any algorithm of system 10 (e.g., algorithms 135, 215, 415, and / or 615). The various processors and / or controllers of system 10 can each comprise memory configured to store instructions for performing the algorithms described herein.

[0152] In some embodiments, algorithm 500 can comprise a set of algorithms configured to identify the presence of atrial fibrillation and deliver (e.g., automatically deliver via ID 100) pacing stimuli across a spatially distributed array of electrodes placed on the left atrium (e.g., electrodes 111 of electrode array 110). The pacing stimuli delivered by ID 100 can be imperceptible to the patient. The pacing stimuli can be precisely timed at each electrode 111 to advance and / or block fibrillation wavefronts, for example as described in reference to Fig.2 and otherwise herein. Delivery' of pacing stimuli by ID 100 can be configured toAttorney Docket No.: MAX-012-PCTsynchronize atrial activation to the pattern of stimulation and can be configured to automatically stop upon restoration of normal rhythm, for example as described herein.

[0153] System 10 can be configured to record electrical activity, such as cardiac electrical activity, and algorithm 500 can be configured to analyze the recorded electrical activity. For example, electrical activity can be recorded via one or more electrodes 111 of electrode array 110. The recorded electrical activity can be transmitted, via transceiver 120, to EPD 200. Algorithm 215 of EPD 200 can be configured to analyze the received data, and to determine if stimulation is required to treat the patient. Algorithm 215 can determine a set of stimulation parameters to be delivered by ID 100 based on the received electrical data (e.g., based on a recorded pattern of conduction within the cardiac tissue). For example, algorithm 215 can determine the location and instances in time to deliver stimulation energy (e.g., via electrodes 111). Alternatively, or additionally, the recorded electrical data can be transmitted to console 400 and / or server 600, such that algorithms 415 and / or 615 can analyze the data and determine stimulation parameters. The stimulation parameters determined by algorithm 500 can be transmitted back to implantable device 100, via transceiver 220, to ID 100. In some embodiments, the stimulation parameters prescribe stimulation pulses to be delivered as a sequence of pulses to be delivered simultaneously and / or asynchronously, and / or regularly and / or irregularly. The stimulation pulses can be delivered from one or more electrodes 111. In some embodiments, algorithm 135 is configured to process stimulation parameters received from EPD 200 and stimulate via electrodes 111 based on the processed parameters. Alternatively, or additionally, ID 100 does not comprise an algorithm, and is configured to stimulate based on power and / or data received from EPD 200 (e.g., stimulation power is received by transceiver 120 and provided to an electrode 111 based on data received with the transmitted power).

[0154] In some embodiments, system 10 is configured to stimulate cardiac tissue by providing electrical stimulation such that any pain and / or discomfort caused by the delivery of the electrical stimulation is below a threshold, such as below a perception threshold (e.g., provide ‘“shock-free” stimulation where patient does not feel any pain or discomfort caused by the delivery of the electrical stimulation).

[0155] In some embodiments, one or more sensors (e.g., functional element 199 comprising one or more sensors and / or one or more electrodes 111 configured as a sensor) of ID 100 (e.g., an ID 100 comprising one or more implantable devices) are positioned at one or more locations proximate heart tissue and are configured to produce signals from which aAttorney Docket No.: MAX-012-PCTcalculation of pressure within a chamber (e.g.. pressure of the blood within the left atrium) can be determined (e.g., by one or more of algorithms 500). such as is described in reference to Fig. 1 herein. In some embodiments, the signals are recorded from (e.g., ID 100 and the associated sensors are implanted at) a location outside of the chamber of the heart for which the chamber pressure is determined (e.g., outside of the left atrium when left atrial pressure is determined). For example, one, two or more electrodes 111 of ID 100 (e.g., an ID 100 comprising one, two, or more implantable devices) can be configured to record signals to determine a chamber pressure, such as when an impedance measurement is performed to identify impedance characteristics of tissue surrounding a heart chamber (e.g., the left atrium) that can be correlated (e.g., by an algorithm 500) to the chamber pressure (e.g., left atrial pressure). Alternatively, or additionally, functional element 199 of ID 100 (e.g., an ID 100 comprising one, two, or more implantable devices) can comprise one, two, or more sensors configured to produce a signal (e.g., record a physiologic parameter) that can be used to determine the pressure of a heart chamber. In some embodiments, at least one, two, or more of these sensors are positioned within the chamber for which the chamber pressure is determined. In some embodiments, at least one, two, or more of these sensors are positioned on tissue that is proximate, but outside the chamber for which the chamber pressure is determined (e.g., on the epicardial wall), such as when no sensors are present within that chamber. Applicable sensors for producing a signal used by system 10 (e.g., an algorithm 500) to determine a chamber pressure include but are not limited to: a pressure sensor; a strain gauge (e g., to measure strain in tissue that can be correlated to the chamber pressure proximate the tissue on which the sensor is positioned); an accelerometer (e.g., to measure tissue motion that can be correlated to chamber pressure proximate the tissue on which the sensor is positioned); an ultrasound sensor and / or other acoustic sensor, such as a doppler ultrasound sensor (e.g., configured to measure one or more blood flow parameters which can be correlated to the chamber pressure); an optical sensor (e.g., configured to measure one or more tissue and / or blood properties which can be correlated to the chamber pressure); and combinations of these.

[0156] In some embodiments, system 10 is configured to deliver pacing stimulation during sinus rhythm, such that the stimulation is configured to synchronize activation of the left ventricle. This stimulation can improve the timing and volume filling of the left ventricle and can increase cardiac output. Since the 1990’s, it has been shown that a natural variability¬ in heart-rate reduces vulnerability of the cardiac substrate to initiation and / or re-initiation ofAttorney Docket No.: MAX-012-PCTarrhythmia. Nonlinear pacing can be defined as delivery of pacing energy that is irregular, aperiodic, and / or otherwise varying (e.g., in level, frequency, modulation, and the like). System 10 can be configured to deliver nonlinear pacing. In some embodiments, such as during nonlinear pacing, the timing of delivered pulses is determined by one or more algorithms, such as algorithm 500 described herein. In some embodiments, Algorithm 500 can be configured to determine timing of delivered pacing pulses based on electrical activity sensed at one or more electrodes 111, where the delivered pacing pulses can be responsive to the sensed electrical activity (e.g., creating a feedback loop between cardiac electrical activity and the delivered nonlinear pacing). Alternatively, or additionally, system 10 can be configured to deliver spatiotemporal resynchronization therapy, SRT. SRT shall include the ability to control a fibrillating substrate by strategically pacing into the narrowed excitable gap present during AF, such as from a well distributed set of electrodes. Once each electrode has gained control of the adjacent substrate, system 10 selectively advances the pacing to achieve alignment across electrodes, prolonged, and inhibited to allow normal sinus rhythm to return. Accordingly, after delivery of SRT via system 10 has terminated AF, another algorithm (e.g., algorithm 500) can be applied to device 100 in which the baseline sinus rhythm is nonlinearly (e.g., deterministically) varied with “irregularly-early” pacing pulses that impose said deterministic variation in heart rate. In another embodiment, this can be achieved by first deriving the mean and standard deviation (or median and IQR) of heart rate for a predetermined period of time. Based on these parameters, stimuli can then be delivered according to a “fractal” or other appropriate nonlinear function that paces the heart at a time that is “earlier” than the mean cycle-length (e.g., inverse of heart-rate) to deterministically impose a variation in said beat, as compared to the previous beat. Similarly, subsequent beats can be at differing durations of “earliness” to impose a desired variability in the heart rate over time. Such a configuration can also include occasional inhibition of pacing to achieve the “intrinsically -longest” cycle-length, as a part of the overall range of variation that occurs over time. Such a configuration can also include periodic cessation of pacing to re-assess the mean and standard deviation (or median and IQR) of heart rate. In such a configuration, the algorithm (e.g., algorithm 500) can follow the natural variation in heart rate and enhance the natural variation (or lack thereof) with “variably-early stimulation”. The overall goal of such a pacing algorithm (e.g., algorithm 500) is to achieve a level of variation that optimizes the probability of reducing vulnerability to initiation and / or re-initiation of arrhythmia. In someAttorney Docket No.: MAX-012-PCTembodiments, system 10 can deliver multiple different forms of energy delivery', such as to treat different medical conditions of the patient (e.g., at least AF).

[0157] During AF ablation procedures, AF is terminated into sinus rhythm during the delivery of ablation in approximately 35% of procedures. In approximately 10% of these 35% of procedures, the SA-node fails to automatically re-initiate a baseline (‘‘normal”) sinus rhythm. In such cases, the SA-node appears to have been electrically remodeled into a quiescent state that is presumably due to the rapid impingement of activation upon it during the ongoing AF. It has also been observed that such instances of cessation are temporary', wi th SA-node activation gradually “waking-up” and resuming the maintenance of baseline sinus rhythm. Such wake-up periods generally range from a few minutes to about 30 minutes. At this point in the procedure, the laboratory’ stimulator is applied to address the bradycardia and maintain a normal baseline heart rate, while the SA-node is recovering its ability to maintain sinus rhythm. This is performed by the support staff (e.g., laboratory) at the request of the clinician (e.g., physician), by pacing through existing catheter-electrodes that are already placed in the heart. Accordingly, after nonlinear pacing (e.g., spatiotemporal resynchronization therapy, SRT, as defined herein) via system 10 has terminated AF, another algorithm (e.g., algorithm 500) can be applied by ID 100 in which the baseline sinus rhythm is temporarily maintained at a “ty pically normal” rate. In another embodiment, this can be achieved by first deriving the mean heart rate over a short period of time (e.g., several beats). In accordance with a maximum threshold of cycle-length, stimulation can be delivered (including “immediately”) in the “AAI” pacing mode (Atrial sensing / Atrial pacing / Inhibited). Such a configuration can comprise periodically inhibiting pacing, while pacing is inhibited re-assessing the intrinsic heart rate and determining if the SA-node has recovered; if recovery' is determined, pacing can remain inhibited. Additionally, such a configuration can also include variation in the pacing rate, as disclosed hereinabove, with the goal of reducing the vulnerability^ of the cardiac substrate to initiation and / or re-initiation arrhythmia. Another embodiment can consider application of the VVI pacing mode (Ventricularsensing / V entricular pacing / Inhibited). This mode can be considered less desirable than atrial pacing for aiding in the recovery of the SA-node, as it depends on adequate retrograde conduction through the AV-node. Conversely, atrial pacing is directly “in-line” with the SA-node, and such conduction characteristics may play a positive role in recovery' of the SA-node. Ventricular pacing, on the other hand, directly addresses the undesired slow heart rate (e.g., bradycardia) without any consideration on the “health” of AV-node conduction.Attorney Docket No.: MAX-012-PCTRegardless, ventricular pacing is inherently less desirable than atrial pacing, as an additional device (e.g., ID 100) must be applied upon the ventricle to fulfill this embodiment. In the rare instance where the SA-node remains quiescent for a prolonged period of time, then the clinician (e.g., physician) can be notified through the device upload. In such rare cases, the patient enters a separate category that requires another type of therapy. In that case, there would likely be implantation of a pacemaker to address bradycardia caused by a “sick sinus node’; In the less-rare instance of AV -node conduction disease, the patient may have been identified as having various levels of AV-block at a much earlier time in their treatment history. In that case, implantation of a pacemaker may likely have already been performed to address bradycardia caused by abnormal AV -node conduction. In either case, as described hereinabove, implantation of a pacemaker can be symbiotic with implantation with ID 100.

[0158] In some embodiments, system 10 is configured to provide treatment for left atrial pre-conditioning (e.g., pre-conditioning for a patient with atrial fibrillation prior to an ablation procedure). Pre-ablation pacing therapy, implanting the device 3 months prior to ablation to maximize the likelihood of maintaining sinus rhythm after the ablation procedure. Delivered over some months, pre-ablation pacing can result in enough reverse-remodeling to regain some level of organization that reveals demarcated, putative ablation targets in a future ablation procedure. In some embodiments, system 10 is configured to provide treatment for left atrial re-conditioning, for example by providing a “blanking period” post ablation. Early recurrence of atrial fibrillation or atrial tachycardia (AT) after catheter ablation (CA) in AF patients is known to be a transient phenomenon. An expert consensus group recommends to measure the success of an ablation therapy from 3 months after the procedure onward. This period of time is termed the “blinding or blanking period” and is now widely adopted in both clinical routine and clinical trials. The 3-month period is often thought of as a time for the lesions to maturate and heal.

[0159] The underlying pathophysiological processes responsible for early recurrence and the delayed cure are unknown. Early recurrence is considered the consequence of ablation-induced proarrhythmic factors that are limited to the time frame of the blanking period. Whereas a delayed cure may also be the cause of an antiarrhythmic effect that develops in the course of the blanking period and that is not necessarily related to electrical isolation of the PV. A potential confounding influence is played by the use of AADs during the blinding period, as they may paradoxically act as a possible proarrhythmic factor. AADs are usually- discontinued after the 3-month period, and this may unmask the antiarrhythmic effect of theAttorney Docket No.: MAX-012-PCTablation procedure. The theoretical basis of the blanking period is based on such observations. However, the clinical implications of early recurrence may be avoided. The incidence of early AF recurrence during the 3-month blinding period following PVI ranges from 9 to 65%. It has been shown that 54% of patients have early recurrence within week 1 to 2 following ablation therapy, after which the percentage drops to 38% in weeks 2 to 4 and to 24% in weeks 4 to 6. The first episode of early recurrence occurs within month 1 of the blinding period in 81% to 91% of patients with early recurrence. This emphasizes the dynamic nature of the blinding period.

[0160] AF is a complex arrhythmia with multiple possible mechanisms underlying initiation and maintenance. Ablation is successful in 60% of paroxysmal AF patients. AF can recur during the 3-month blanking period after ablation. No therapy or interaction takes place during this 3-month blanking period.

[0161] Recent retrospective studies indicate that right atrial pacing decreases the incidence of AF. They demonstrated significant benefit for atrial pacing with improved survival and a decreased incidence of thromboembolic events, AF, and congestive heart failure, especially after longer follow-up. The hypothesis: if during the so-called blanking period, where no therapy or patient management is occurring, change this 3-month period into a left Atrial ‘'Re-Conditioning” period. System 10 can be configured to perform continuous (7 / 24) sinus rhythm pacing. This not only keeps the post ablation patient in sinus rhythm but reverse remodels the left atrium (AF remodels the left atrium to AF), reconditioning reverses this AF remodeling back to normal. Post the 3-month LA reconditioning, the ID 100 can perform normal monitoring and deliver therapy only when the patient has an AF episode. In some embodiments, reducing AF burden and / or maintaining sinus rhythm with low-energy7multi-site pacing can decrease thromboembolic risk. In some embodiments, reducing AF burden and / or maintaining sinus rhythm with low-energy multisite pacing can allow for the patient to discontinue or otherwise reduce their use of blood thinners. In some embodiments, a method of treating atrial fibrillation comprises reducing AF burden and maintaining sinus rhythm with low-energy' multi-site pacing to decrease thromboembolic risk, and furthermore, the method can allow for the patient to discontinue or otherwise reduce their use of blood thinners. In some embodiments, system 10 detects prolonged and / or sustained atrial fibrillation and generates a notification and / or alert for the patient and / or clinician to initiate and / or resume oral anticoagulant therapy' based on one or more predefined criteria.Attorney Docket No.: MAX-012-PCT

[0162] In some embodiments, system 10 is configured to deliver multisite pacing for termination of atrial fibrillation (AF), and / or supraventricular tachycardia (SVT). such as is described herein. AF can be caused by a stretch-induced infiltration of fibrosis that is progressively and broadly distributed across the left atrium. Global, simultaneous mapping of AF has revealed patient-specific confined zones of conduction that are distributed primarily across three anatomical regions of the left atrium: (1) posterior wall; (2) anterior-roof; and / or (3) anterior-septum. In the early phase of AF, categorized as “paroxysmal”, the progression of fibrosis is more confined to the muscular sleeves surrounding the pulmonary veins and the posterior wall of the left atrium. As the disease of AF progresses into the “persistent” stage, fibrosis spreads beyond the posterior wall, predominantly across patientspecific locations of the roof and septum, anteriorly, toward the mitral valve annulus. The feasibility of low-voltage shocks and multisite pacing for terminating AF has been demonstrated and can be primarily limited by: (1) the number, size, and / or distribution of electrodes placed about the left atrium; and (2) the pattern of stimulation energy7delivered (e.g., as governed by algorithm 500). The progressive nature of the disease can require matching the spatiotemporal characteristics of pacing with the patient-specific distribution of fibrosis. For example, in the early, paroxysmal phase of AF, pacing can be delivered from multiple (e.g., 3 or 4) electrodes, such as 3 or 4 electrodes distributed within the Vein of Marshall and the adjacent coronary sinus. These locations are close to the lateral border of the posterior wall and the left pulmonary veins, where stimulation can be delivered for effective interruption of fibrillatory conduction in the region of the left atrium that is relevant for paroxysmal AF. Additionally, or alternatively, in the later, persistent and long-standing phases of AF, pacing can be delivered from more electrodes (e.g., 5 or 6) electrodes distributed epicardially on the posterior wall and / or the anterior roof and / or the superior septum. These locations are close to the critical, “confined zones” of conduction that maintain AF. Stimulation can be delivered near these zones for effective interruption of fibrillatory conduction in the regions of the left atrium that are relevant for persistent AF.

[0163] In some embodiments, system 10 is configured to provide left atrial pacing therapy to improve hemodynamic function. Extensive ablation of the left atrium for treatment of AF can lead to a decrease in overall hemodynamic function. This occurs when significant delay of conduction to the left-atrial appendage is imposed by ablation lesions that are delivered between the insertion of Bachmann's Bundle, in the high septum and roof, and the appendage. Normally, the appendage is a significant contributor to the mass transport ofAttorney Docket No.: MAX-012-PCTblood from the left atrium to the left ventricle. If activation of the appendage is delayed by intervening ablation-lesions, then the timing of active pumping by the appendage is also delayed. It is possible for this delay to be long enough to be working against the closure of the mitral valve during the beginning of left ventricular contraction. In this case, filling of the left ventricle is incomplete and overall hemodynamic performance is compromised. In the long term, this effect, in combination with other factors, can lead to the gradual decline of heart failure.

[0164] System 10 can be configured to enable the placement of one or more pacing electrodes in the distal -reach of the Vein of Marshall. This region of the vein is in relatively close apposition to the posteromedial aspect of the left atrial appendage. Specifically, this is the same general location where the left-lateral branch of Bachmann's Bundle terminates and which enables timely activation of the left atrial appendage. Accordingly, after pace termination of AF by system 10, the most distal electrode in the Vein of Marshall can then be used to ensure timely activation of the left atrial appendage. This concept is analogous to ventricular resynchronization therapy, whereby the right and left ventricles are paced in specific locations and with relative timing of stimulation that are intended to synchronize activation of both ventricles for the purpose of improving and optimizing overall hemodynamic performance. In the case of delayed conduction in the left atrial appendage, the effectiveness of ventricular resynchronization therapy can be compromised or severely limited. Accordingly, left atrial appendage resynchronization pacing can improve overall hemodynamic performance, either with or without ventricular resynchronization therapy. One embodiment can include sensing the timing of activation from one or more implanted electrodes 111 and / or one or more surface ECG leads. These signals would be used to algorithmically (e.g.. via algorithm 500) sense the relative timing between the beginning of left atrial activation and the time of activation of the left atrial appendage. The algorithm (e.g., algorithm 500) can command an electrode 111 to pace at an optimal time in the attempt to promote optimal left-ventricular filling.

[0165] In some embodiments, system 10 is configured to deliver median and / or ulnar nerve stimulation for the purpose of shifting the operating-point of afferent autonomic tone toward inhibition of AF across the left-atrial substrate. Additionally, or alternatively, system 10 can be configured to deliver stimulation to nerve bundles in the feet or in the ear.Additionally, or alternatively, system 10 can be configured to deliver local neuromodulation proximate the heart, such as via one or more electrodes of implantable device 100 positionedAttorney Docket No.: MAX-012-PCTproximate Bachmann’s bundle and / or positioned proximate one or more ganglionated plexi and / or vagus nerve fibers, such as to enhance atrial conduction and / or inhibit AF. The autonomic nervous system plays a significant role in modulating the overall state of syncytial -conduction throughout the left-atrial myocardial substrate. It is challenging to access both the efferent nerve fibers, from the ganglionated plexi, as well as the distribution of afferent fibers that insert throughout the left- atrial chamber. Consequently, the objective of either ablating (e.g., destroying) these nerves or modulating (e.g., stimulating) these nerves has not been adequately effective. It has been shown acupuncture therapy that targets the Median Nerve promotes cessation of arrhythmias, notably AF. Recent clinical studies have validated this observation from the practice of acupuncture. System 10 can be extended and / or coordinated, algorithmically (via algorithm 500), together with sensing of intracardiac and / or surface ECG signals to stimulate pacing electrodes that are located on the arm, for example, within a wrist-band, that is positioned to stimulate the Median and / or Ulnar nerves and thereby mediate modulation of autonomic vagal tone in the direction of at least partial inhibition of AF. In some embodiments, non-invasive stimulation of the median nerve and / or ulnar nerve as described herein can be referred to as median-vagus nen e stimulation (mVNS), such as when stimulation of the median nerve and / or ulnar nerve is configured to influence autonomic balance and / or vagal tone.

[0166] In some embodiments, stimulation of the median nerve and / or ulnar nerve activates one or more afferent pathways that project to one or more central autonomic centers (e.g., brainstem autonomic centers and / or cortical autonomic centers) that regulate autonomic output to the heart. In some embodiments, system 10 selects one or more stimulation parameters configured to evoke one or more reflexogenic responses, such as responses configured to attenuate sympathetic overactivity and / or enhance vagal tone.

[0167] In some embodiments, during and / or following delivery of mVNS, system 10 is configured to acquire one or more response data items in addition to stimulation session parameters. For example, the response data items can include electrodermal activity signals, heart rate variability proxy metrics, and / or one or more neural feedback metrics. In some embodiments, the response data items are time-stamped and used as inputs to one or more analyses and / or learning processes described herein.

[0168] In some embodiments, system 10 includes one or more computer applications (e.g., software applications performed by a processor of system 10, where the instructions forAttorney Docket No.: MAX-012-PCTperforming the applications are stored in memory of system 10), such as cardiac simulator 4101, comprising a cardiac tissue simulator application. Cardiac simulator 4101 can include an interactive, physiologically realistic, and accurate computer simulation that allows multiple scenarios to be tested in a “live” environment (e.g., during a clinical procedure). In some embodiments, cardiac simulator 4101 is performed by processing unit 410 of console 400. Cardiac simulator 4101 can be used for the rapid development and testing of treatment strategies for atrial fibrillation. Cardiac simulator 4101 can include a model of cardiac tissue that allows the user to define the regions and zones of anisotropic conduction to test the effectiveness of a variety' of AF treatment strategies.

[0169] The model was developed using standard electrophysiologic (EP) parameters established in the literature. An advanced implementation of the Fitzhugh-Nagumo model reproduces the action potential morphology of the human atrium enabling live simulations. To reproduce the complex conduction patterns (CCP) of AF identified in the EP lab, a bilayer model was implemented to represent epi- and endocardial dissociation. The model allows the user to define regions of fibrosis, zones of slow conduction, and action potential duration (APD). The user can graphically draw these regions and zones, including gradients assigned by maximum and minimum values of conduction velocity (CV) and APD. The EP lab experience and workflow is reproduced, with CCP visualized on a 3D anatomy and signal traces of calculated potentials displayed. To test the CCPs and performance of the model, isolated, geometrically, symmetric zones of conduction were defined on a 3D left atrial model.

[0170] In some embodiments, system 10 is configured to perform autonomic risk stratification and / or preventative screening based on multimodal sensor data, including cardiac signals and one or more autonomic proxy signals, as described herein. In some embodiments, the autonomic risk stratification is configured to identify autonomic dysfunction and / or arrhythmia vulnerability in patients without known atrial fibrillation. For example, system 10 can be configured to screen one or more high-risk patient populations (e.g., heart failure with preserved ejection fraction (HFpEF) patients and / or postural orthostatic tachycardia syndrome (POTS) patients) to detect one or more Al-derived autonomic-cardiac signatures indicative of elevated risk of future arrhythmia and / or disease progression.Attorney Docket No.: MAX-012-PCT

[0171] Referring additionally to Fig. 1A, a partial anatomic, partial schematic view of a system of devices is illustrated, consistent with the present inventive concepts. In some embodiments, system 10 includes one, two, three, or more implantable devices, such as the two implantable devices 100a and 100b shown. For example, system 10 can include ID 100a, including an implantable device, including one or more electrodes Illa, positioned proximate the left atrium of the heart, for example on the epicardial surface of the left atrium or within a cardiac vessel proximate the left atrium. System 10 can also include ID 100b, including an implantable device with at least a portion positioned away from the heart, for example comprising an implantable pulse generator (IPG) that is implanted in a subcutaneous pocket. In some embodiments, ID 100b includes a lead operably connecting controller 130b to electrode 111b and / or antenna 125b implanted proximate the heart, for example implanted within the right atrium on the septal wall. Antenna 125b can be positioned proximate antenna 125a of ID 100a to minimize the transmission distance between ID 100a and ID 100b (e.g., the distance over which power is transmitted from ID 100b to ID 100a).

[0172] In addition to one, two. three, or more internal devices, system 10 can include one, two, three, or more external patient devices, such as the four external devices 200a-d shown. For example, system 10 can include EPD 200a, including a patient worn device configured to be positioned (e.g., temporarily positioned by the patient) proximate an implantable device, such as proximate ID 100b as shown, and / or proximate ID 100a (e.g., when system 10 does not include a subcutaneous implant, such as ID 100b). EPD 200a can be positioned to minimize the transmission distance between transceiver 220a and the intended ID (e.g., ID 100a and / or ID 100b). System 10 can also include one or more additional patient worn and / or handheld devices, such as EPD 200b comprising a wrist worn device (e.g., a smart watch). EPD 200c comprising an ankle worn device (e.g.. a “smart” sock, and / or a fitness tracker), and / or EPD 200d comprising a computing device (e.g., a smartphone). In some embodiments, EPD 200a,b,c,d are configured to communicate with each other, for example when one EPD 200 (e.g., EPD 200d) is configured to gather data collected by each EPD 200 and / or ID 100 and to analyze the aggregated data (e.g., via algorithm 215). In some embodiments, an EPD 200 is configured to collect data and send the aggregated data to server 600 (e g., when EPD 200d comprising a smart phone is configured to collect all patient data recorded by system 10 and transmit the data via the internet to server 600 for analysis). In some embodiments, one or more of EPD 200 can include one or more functional elements, such as functional elements 299b and 299c shown.Attorney Docket No.: MAX-012-PCT

[0173] In some embodiments, system 10 includes one or more communication components configured to provide connectivity to one or more hospital systems (e.g., hospital-based device monitoring, device control, and / or data storage systems). EPD 200 and / or console 400 can be configured to communicate with one or more hospital systems via network 50. Hospital system connectivity can be configured to perform one or more functions selected from the group consisting of: time synchronization; data export; clinical alarms; remote configuration; and combinations of these. Time synchronization can include synchronizing system 10 time with hospital time, surgical procedure time, or both. Data export can include transmitting recorded cardiac signals, therapy delivery’ logs, and / or arrhythmia episode data to hospital electronic medical records systems. Clinical alarms can include transmitting alerts to nursing stations, clinician pagers, hospital monitoring systems, or combinations or these. Remote configuration can include receiving clinician-entered parameter updates.

[0174] In some embodiments, transceiver 220 of EPD 200 is configured to transmit data 620 to server 600 via network 50. Data 620 can include cardiac signals recordings, therapy delivery logs, arrhythmia episode records, device status information, or combinations of these. Server 600 can be configured to receive data 620 from a plurality' of patients and / or a plurality' of system 10 installations. Server 600 can be configured to aggregate, analyze, and / or store received data 620. In some embodiments, server 600 is configured to transmit population-level reference data to EPD 200 (e.g., via network 50). In some embodiments, server 600 is configured to transmit algorithm 500 updates to EPD 200 (e.g., via network 50). In some embodiments, server 600 is configured to transmit alerts (e.g., alerts to one or more clinicians or other healthcare providers) to hospital systems and / or clinician devices (e.g., via network 50).

[0175] In some embodiments, EPD 200 is configured to provide therapy during a postoperative monitoring period. EPD 200 can include signal acquisition circuitry configured to receive signals from a plurality' of electrodes 111. The signal acquisition circuitry' can include multi-channel amplifiers, analog-to-digital converters, and / or signal conditioning circuitry. EPD 200 can include artifact mitigation circuitry, such as circuitry configured to reduce signal artifacts (e.g., pacing artifacts, motion artifacts, far-field artifacts). EPD 200 can include a processor configured to execute algorithm 500. The processor can execute one or more functions selected from the group consisting of: cardiac rhythm detection; arrhythmiaAttorney Docket No.: MAX-012-PCTclassification; arrhythmia prediction; tissue state assessment; therapy selection; and combinations of these.

[0176] EPD 200 can include energy delivery circuitry configured to generate and / or deliver multiple therapy modalities. The multiple therapy modalities can include standard pacing, elevated-output pacing, reversible electroporation, or combinations of these. The energy delivery’ circuitry can include one or more output stages. Each output stage can be configured to generate a different energy waveform and / or a different energy level. EPD 200 can include memory configured to store patient-specific data (e g., therapy logs, arrhythmia episode records, signal recordings). EPD 200 can include memory’ configured to store population-level reference data (e.g., baseline algorithm parameters, training data). EPD 200 can include user interface 250 configured for clinician interaction. User interface 250 can be configured for therapy configuration, real-time monitoring, and / or clinical reporting.

[0177] In some embodiments, one or more of the devices of system 10 comprises two or more batteries, such as when a device includes a primary’ power supply (e.g., one or more batteries and / or one or more capacitors) and a backup power supply (e.g., one or more batteries and / or one or more capacitors). For example, power module 140 of ID 100 can comprise a first battery’ and / or capacitor, battery’ 1401, and a second battery and / or capacitor, battery’ 1402 (as shown in Fig. 1). Battery’ 1401 can be configured as amain power source for ID 100, and battery 1402 can be configured as a backup power source, for example to be used if battery 1401 is depleted. In some embodiments, battery 1401 and / or 1402 are rechargeable. In some embodiments, battery 1402 is configured to maintain operation of ID 100 if the patient is unable to charge battery’ 1401 for a period of time (e.g., the patient is away from the charger when battery 1401 runs low on power). Batteries 1401 and 1402 can comprise batteries with similar or dissimilar battery chemistry’, for example lithium-ion batteries and / or lithium thionyl chloride batteries. In some embodiments, ID 100 comprises a single battery' 1401, and system 10 (e.g., algorithm 500 of system 10) is configured to virtually partition the single battery’ into two virtual batteries, such that ID 100 functions as if battery 1401 comprised a main battery and a backup battery. In some embodiments, batteries 1401, 1402 comprise different size batteries (e.g., batteries with different amp-hour capacity). In some embodiments, ID 100 can operate in two or more power modes, for example a first, “normal-power” mode, and a second, “low-power” mode. In some embodiments, when the main power supply of ID 100, battery 1401, is depleted, ID 100 transitions into the low power mode and operates using energy from battery 1402, for example until battery 1401 canAttorney Docket No.: MAX-012-PCTbe recharged. In some embodiments, if battery71402 is used for a period of time, for example at least 1 hour, at least 6 hours, at least 12 hours, at least 1 day, and / or at least 1 week, ID 100 and / or battery 1402 (e.g., when battery 1402 is replaceable), are replaced (e.g., in a follow-up procedure) to ensure ID 100 maintains adequate backup power supply (e.g., backup battery supply and / or backup capacitor supply) at all times. In some embodiments, power module 140 is configured to periodically test battery 1401 and / or 1402, for example to confirm battery 1402 is charged and available to provide backup power. In some embodiments, system 10 can be configured to enter an alert mode (e g., provide an alert to the user as described herein) if a power supply level (e.g., battery' level and / or capacitor charge level) is below a threshold, and / or if ID 100 transitions to a low power mode.

[0178] In some embodiments, ID 100 is configured to deliver both life-saving therapy (or life-sustaining therapy, either or both "‘life-saving therapy” herein) as well as symptom relief therapy and / or quality-of-life therapy. As used herein, “symptom relief therapy” and / or quality-of-life therapy can comprise therapy7configured to reduce and / or alleviate one or more symptoms (e.g., palpitations, shortness of breath, fatigue, and / or exercise intolerance) without necessarily being limited to and / or coextensive with long-term disease modification. In these embodiments. ID 100 can be configured to provide multiple forms of therapy, such as a first form of therapy (e.g., a life-saving therapy) and / or a second form of therapy (e.g., a quality-of-life therapy), and ID 100 can be configured to deliver (e.g., only deliver) a particular ty pe of therapy based on the amount of energy stored in ID 100 (e.g., the energy- stored in battery 1401 and / or battery 1402). In these embodiments. ID 100 can be configured to provide only life-saving therapy when the energy stored in battery 1401 and / or battery 1402 is below a threshold (e.g., below a pre-determined amount of energy). In some embodiments, ID 100 can be configured to provide life-saving therapy comprising cardiac pacing (e.g., pacing of the ventricle, such as when complete AV node block is present), and ID 100 can be further configured to provide quality-of-life therapy comprising providing stimulation energy to treat AF. In some embodiments, ID 100 is configured to deliver atrial pacing that is configured to: address bradycardia due to sinus node dysfunction; maintain normal heart rate variability; and / or to reduce the vulnerability to re-initiation of AF. ID 100 can also be configured to perform non-therapy -related tasks, as described herein, such as communicate with external devices (e.g., EPD 200), perform self-diagnostics, monitor patient parameters, and / or other non-life-saving tasks. In some embodiments, where ID 100 is configured to operate (e.g., sequentially operate) in a regular-power mode and a low-powerAttorney Docket No.: MAX-012-PCTmode, when ID 100 enters a low-power mode, only life-saving therapy is provided to the patient, such as to allow ID 100 to continue to operate (e.g.. as long as possible) until a normal or otherwise improved power mode can be re-initiated (e.g., when batten' 1401 is charged). Alternatively, or additionally, ID 100 can comprise a first battery and / or capacitor, battery 1401, that is used to power a first set of operations, and a second battery' and / or capacitor, battery 1402, that is used to power a second set of operations. For example, battery 1401 can be used to power life-saving operations, such as cardiac pacing (e.g., when ID 100 is configured as a pacemaker), and battery 1402 can be used to pow er quality-of-life therapy operations, for example operations of ID 100 which monitor for and treat AF.

[0179] In some embodiments, one or more algorithms 500 are configured to assess the cardiac electrical activity of one or more regions of a patient’s heart, such as by analyzing one or more signals recorded by system 10, as described herein. In some embodiments, a region comprises a single chamber of the heart, for example when algorithm 500 is configured to assess the electrical activity of the left atrium or the left ventricle (e.g., to assess the recorded electrical activity from a chamber collectively). In some embodiments, a region comprises a portion of a chamber, such as when algorithm 500 is configured to assess a portion of the tissue of an atrium or ventricle (e.g., to assess the recorded electrical activity of only a portion of the chamber). In some embodiments, algorithm 500 is configured to automatically and / or semi-automatically (e.g., semi-automatically with input from the user of system 10) divide a chamber into two or more regions, such as by assigning a first set of electrodes 111 to a first region, and a second set of electrodes 111 to a second region. In some embodiments, algorithm 500 is configured to define one or more sets of electrodes 111 by assessing the signals recorded from the electrodes and grouping the electrodes based on the recorded signals (e.g., grouping the electrodes 111 based on common frequencies in the recorded signals).

[0180] In some embodiments, ID 100 is configured to deliver stimulation energy configured to defibrillate cardiac tissue. In some embodiments, one or more defibrillation pulses are delivered via tw o or more groups of electrodes 111 of ID 100. In some embodiments, one or more defibrillation pulses are delivered prior to pacing, such as SRT pacing described herein. In some embodiments, defibrillation pulses delivered via electrodes 111 of ID 100 comprise a lower energy than similar pulses configured to be delivered via one or more external electrodes. Additionally, or alternatively, defibrillation pulses delivered via electrodes 111 of ID 100 can comprise pulses that are imperceptible to the patient.Attorney Docket No.: MAX-012-PCT

[0181] Referring now to Fig. 2, an anatomic view of an atrium showing electrical activity is illustrated, consistent with the present inventive concepts. In some embodiments, algorithm 500 of system 10 described herein is configured to determine a pacing strategy to terminate AF. In some embodiments, the pacing strategy includes providing stimulation energy intended to advance and / or block one or more wavefronts (e.g., cardiac activation wavefronts) to increase the region of refractoriness. In some embodiments, pacing is initiated ahead of an approaching wavefront which can both advance the wavefront beyond the pacing site and block the wavefront behind the pacing site, as shown.

[0182] Referring now to Fig.3, a system state diagram illustrating an embodiment of a method of patient therapy selection and monitoring is show n, consistent with the present inventive concepts. System 10 and / or other components described in reference to Fig. 3 can be of similar construction and arrangement to the similar components described in reference to Fig. 1, Fig. 1 A, and otherwise herein. Fig. 3 shows a comprehensive therapy management workflow where system 10 can be configured to provide multiple therapeutic approaches based on patient diagnostic data that can be collected by patient monitoring also performed by system 10.

[0183] System 10 can be configured to operate within a set of one or more operational modes, as described herein. The workflow of Fig. 3 illustrates an embodiment of the interaction and / or transition between the various operational modes. System 10 can be configured to operate in two or more operational modes simultaneously and / or can be configured to switch between operational modes in the methods described herein and / or in any other arrangement configured to provide therapy as described herein. In some embodiments, system 10 comprises Diagnostic Monitoring Mode (DMM). In diagnostic monitoring mode, one or more sensors (e.g., electrodes 111 of electrode array 110) can be configured to record cardiac electrical activity from the patient. System 10 can be configured to process the recorded diagnostic data using one or more algorithms, such as algorithm 500, to determine an appropriate therapy selection based on the patient’s cardiac condition. In some embodiments, based on data collected during therapy (e.g., data collected while operating in a monitoring mode and therapy mode simultaneously), system 10 is configuredAttorney Docket No.: MAX-012-PCTto adjust the therapy, stop the therapy, initiate a different therapy delivery' mode (e.g., start a different therapy) and / or return to diagnostic monitoring mode.

[0184] System 10 can be configured to provide therapy that can be grouped into one or more categories, such as Tissue Conditioning Therapy (TCT), Acute Therapy (AcTh), and / or Multi-Chamber Synchronization Therapy (MCST). Each therapy category can comprise one or more specific therapeutic modes configured to address one or more cardiac conditions such as atrial fibrillation (AF), atrial flutter (AFL), atrial tachycardia (AT), and / or supraventricular tachycardia (SVT). System 10 can be configured to transition between different therapy modes and / or monitoring modes based on an assessment of patient data (e.g., areal-time assessment of patient data performed by system 10, as described herein) and / or can be configured to operate in one or more therapy modes and monitoring modes simultaneously.

[0185] In some embodiments, system 10 is configured to provide tissue conditioning therapy comprising one or more modes of tissue conditioning. Tissue conditioning therapy can comprise delivering stimulation energy configured to condition cardiac tissue (e.g., left atrial tissue) to improve electrical conduction properties, and / or to reduce arrhythmia occurrence. In some embodiments, system 10 is configured to operate in Pace Conditioning mode (PCM) shown, where system 10 is configured to deliver continuous and / or periodic pacing to condition the cardiac tissue (e.g., to reduce the likelihood of arrhythmia and / or other cardiac condition). In some embodiments, PCM comprises nonlinear pacing (described hereabove). Nonlinear pacing can comprise delivering pacing pulses configured to impose a desired variation in heart rate during sinus rhythm (e.g., irregularly -early pacing pulses that deterministically vary cardiac cycle length to reduce arrhythmia vulnerability). In some embodiments, PCM comprises pacing configured to reverse unhealthy remodeling of the cardiac substrate of one or more cardiac chambers, or “reverse-remodeling pacing”.Reverse remodeling pacing can comprise pre-conditioning pacing and / or re-condition pacing, (described hereabove). Reverse remodeling pacing can be delivered to one or more cardiac chambers selected from the group consisting of: the right atrium; the left atrium; the right ventricle; the left ventricle; or combinations of these. In some embodiments, PCM comprises pacing delivered from one or more electrodes 111 configured to coordinate activation of cardiac tissue. Coordinating activation of cardiac tissue can comprise shortening the time span over which cardiac tissue is depolarized and / or repolarized (e.g., reducing activation time dispersion across one or more regions of a cardiac chamber). By coordinating activationAttorney Docket No.: MAX-012-PCTof cardiac tissue, system 10 can be configured to reduce the ability of the tissue to initiate, support, and / or maintain an arrhythmia. In some embodiments. PCM comprises “sinus-assisted synchronization pacing’’ configured to coordinate activation of cardiac tissue while normal sinus node activation is detected. Sinus-assisted synchronization pacing can comprise delivering pacing energy from one or more electrodes 111 to shorten a time span over which cardiac tissue is depolarized and / or repolarized, such as to reduce ability of the tissue to initiate, support, and / or maintain an arrhythmia. During sinus-assisted synchronization pacing, cardiac activation rate can be determined by sinus node activation, while timing and / or pattern of activation across one or more cardiac chambers can be augmented by pacing from one or more electrodes 111 (e.g., modifying the timing, direction, and / or progression of conducting wavefronts). Sinus-assisted synchronization pacing can be configured to activate regions of cardiac tissue in the chamber earlier than would occur via wavefront propagation of un-paced sinus beats alone. By activating tissue regions earlier, sinus-assisted synchronization pacing can compress the distribution of activation times across portions of the cardiac chamber, reducing the spatiotemporal gradients of depolarization and / or reducing the spatiotemporal gradients of repolarization. Compression of activation times and / or reduction of depolarization and / or repolarization gradients can reduce opportunities for reentry7, thereby reducing the likelihood of AF initiation, AF recurrence, and / or AF maintenance. Additionally, or alternatively, within the TCT category of operational modes, system 10 can be configured to operate in Conditioning Monitoring Mode (CMM), shown. In some embodiments, system 10 is configured to operate in Pace Conditioning Mode and Conditioning Monitoring Mode simultaneously, such as to monitor the conditioning progress of the pacing therapy performed. Algorithm 500 can be configured to analyze the distribution of activation times across two or more electrodes 111 during un-paced cardiac activity and to analyze the distribution of activation times on two or more electrodes 111 (e.g., the same electrodes 111) during paced cardiac activity7. Algorithm 500 can be configured to compare the un-paced activation time distribution to the paced activation time distribution to determine whether pacing is achieving the desired therapeutic effect (e.g., shortening the span of time over w hich the cardiac tissue is depolarized and / or repolarized). Alternatively, or additionally, algorithm 500 can be configured to analyze the morphological characteristics of cardiac signals and / or quiescence of cardiac signals following delivery7of pacing pulses to assess tissue condition and / or pacing effectiveness. The cardiac signals can comprise bipolar electrograms and / or unipolar electrograms recorded from one or moreAttorney Docket No.: MAX-012-PCTelectrodes 111. Algorithm 500 can be configured to determine one or more of the conditions of tissue; the effectiveness of pacing to capture tissue; blockage of delayed activation; and / or to prevention of fractionated electrograms.[01861 System 10 can be configured to deliver acute therapy configured to provide one or more therapeutic interventions in response to one or more detected arrhythmia events (e.g., therapy delivered within the AcTh category of operation modes). Acute therapy can comprise one or more therapeutic approaches selected based on one or more factors such as type, complexity, and / or other characteristics of the detected arrhythmia. In some embodiments, system 10 is configured to operate in Preventative Pacing Mode (PPM) shown, where system 10 is configured to deliver preventative pacing when AF initiation is determined to be probable (e.g., determined by system 10, for example as determined during diagnostic monitoring mode). In some embodiments, while system 10 is operating in PPM, pacing energy is delivered from one or more electrodes 111 to coordinate activation of cardiac tissue when a pro-arrhythmogenic condition is detected. Coordinating activation of cardiac tissue can comprise shortening the time span over which the cardiac tissue is depolarized and / or repolarized, such as to reduce the ability of the tissue to initiate, support, and / or maintain an arrhythmia. In some embodiments, PPM can be triggered by detection of a pro-arrhythmogenic event, such as a premature beat. Premature atrial contractions (PACs) can originate from the pulmonary vein (PV) regions of the left atrium and / or from non-PV regions of the heart and can be triggers of AF initiation. PACs can occur with shortened timing relative to normal sinus beats (e.g.. occurring earlier or later than expected based on normal sinus rhythm timing). PACs and / or other AF -triggering events can be identified by system 10 as pro-arrhythmogenic based on one or more factors selected from the group consisting of: the timing interval between beats (e.g., between sinus beats, between PACs, and / or between sinus beats and PACs); the location and direction of wavefronts propagating from these beats; the spatial distribution of tissue substrate that affects the conduction dynamics across the cardiac chamber; the spatiotemporal gradients of depolarization across the substrate; the spatiotemporal gradients of repolarization across the substrate; and combinations of these. These factors can establish an environment with potential pathw ays of conduction re-entry that can initiate AF and / or other arrhythmias (e.g., AFL that can degenerate to AF). In some embodiments, pacing delivered during PPM is configured to augment the timing and / or pattern of activation across the cardiac chamber (e.g., modifying the timing, direction, and / or progression of conducting wavefronts) that might otherwise leadAttorney Docket No.: MAX-012-PCTto a pro-arrhythmogenic environment. Pacing can be delivered to activate regions of cardiac tissue earlier than would otherwise occur via wavefront propagation of un-paced beats. Early activation of tissue regions can produce one or more therapeutic effects selected from the group consisting of: blocking pathways of re-entry; compressing the distribution of activation times across portions of the cardiac chamber; reducing the spatiotemporal gradients of depolarization; reducing the spatiotemporal gradients of repolarization; and combinations of these. By compressing activation times and / or reducing gradients of depolarization and / or repolarization, the opportunities for re-entry can be reduced and the likelihood of AF initiation, AF recurrence, and / or AF maintenance can be reduced. In some embodiments, PACs may be detected by sensing cardiac activity outside of a range of expected heart rate variation.

[0187] Algorithm 500 can be configured to detect a pro-arrhythmogenic condition by analyzing the timing and / or pattern of activation across two or more electrodes 111. In some embodiments, for example where two or more electrodes 111 are distributed across a portion of the heart, the time interval spanning activations across the set of electrodes 111 for a non-arrhythmogenic beat can be shorter than the time interval spanning activations across the set of electrodes 111 for a pro-arrhythmogenic beat. In some embodiments, the spatiotemporal pattern of activation events across electrodes 111 for a pro-arrhythmogenic beat can be substantially different from a spatiotemporal pattern for a non-arrhythmogenic beat, where the difference can be detectable by analyzing correlation between subsequent beats and / or correlation to a template pattern. In some embodiments, algorithm 500 is configured to detect a pro-arrhythmogenic condition based on one or more signal characteristics selected from the group consisting of: morphology of one or more electrical signals; amplitude of one or more electrical signals; frequency content of one or more electrical signals; fractionation of one or more electrical signals; and combinations of these. In non-arrhythmogenic conditions, electrograms can be large, sharper, and / or less fractionated than pro-arrhythmogenic conditions. In some embodiments, certain sites of origin and / or directions of origin for premature beats can be associated with higher pro-arrhythmogenic risk, where these events can be detected by analyzing the activation times on two or more electrodes 111 to estimate site of origin and / or direction of origin for each beat. In some embodiments, when pro-arrhythmogenic conditions and / or events are detected, system 10 is configured to deliver pacing energy to counteract such conditions. Counteracting pacing can comprise delivering pacing energy with strategically staggered timing across multiple electrodes 111 toAttorney Docket No.: MAX-012-PCTdisrupt conduction conditions of the substrate (e.g., preventing formation of reentrant circuits).

[0188] Additionally, or alternatively, within the AcTh category of operational modes, system 10 can be configured to operate in Pace Termination Mode (PTM) shown, where system 10 is configured to terminate atrial fibrillation (e.g., to restore sinus rhythm) when AF is detected.

[0189] Additionally, or alternatively, within the AcTh category of operational modes, system 10 can be configured to operate in Left- Atrial Reset Mode (LRM) shown, where system 10 is configured to provide atrial reset therapy when AF is detected (e.g., left atrial reset therapy, right atrial reset therapy, or both), and abrupt, asynchronous cardioversion is indicated to restore cardiac rhythm (e.g., cardioversion comprising stimulation configured to reset the atrial electrical activity). In some embodiments, system 10 is configured to deliver reset therapy comprising one or more pulses configured to abruptly cardiovert a portion of the heart. The portion of the heart cardioverted can comprise a single cardiac chamber (e.g.. the left atrium) and / or two or more cardiac chambers (e.g., the left atrium and the right atrium). In some embodiments, the one or more pulses are delivered asynchronously with fi bri 11 atory cardiac activity in the chamber being reset. Additionally, or alternatively, the one or more pulses can be delivered asynchronously with the fibrillatory activity in a first cardiac chamber and synchronously with electrical activity in one or more non-fibrillating cardiac chambers (e.g., synchronously with ventricular activity), such as to prevent fibrillation in the one or more non-fibrillating chambers. In some embodiments, reset therapy pulses are delivered between a first set of one or more electrodes 111 and a second set of one or more electrodes 111, where the first set and the second set span an area of cardiac tissue to be depolarized. The delivered pulses can be configured to electrically depolarize the targeted area of tissue abruptly (e.g., to simultaneously reset electrical activity across the targeted tissue area). Additionally, or alternatively, reset therapy pulses can be delivered from a set of one or more electrodes 111 positioned in the vicinity of the chamber being reset to a return electrode 111 positioned at a location further from the heart (e.g., a subcutaneous return electrode, and / or an electrode positioned in a remote cardiac chamber). In some embodiments, the reset therapy pulses are configured with one or more phases, where each phase comprises a defined amplitude, timing, and / or morphology. The amplitude, timing, and / or morphology of each phase can be configured to achieve one or more objectives selected from the group consisting of: deliver a uniform electric field across targeted tissue; deliver optimal current output toAttorney Docket No.: MAX-012-PCTtargeted tissue; deliver optimal voltage output to targeted tissue; minimize electrode degradation; minimize electrode corrosion; maximize battery life; or combinations of these. In some embodiments, system 10 is configured to deliver a sequence of pulses in rapid succession, where the structure of each pulse and the timing between pulses can be configured to maximize efficacy of depolarizing the targeted tissue area.

[0190] Additionally, or alternatively, within the AcTh category7, system 10 can be configured to operate in Arrhythmia Disruption Mode (ADM) shown, where system 10 is configured to disrupt organized, regular arrhythmias such as with AFL and / or AT. In some embodiments, system 10 can be configured to deliver ADM therapy to terminate AFL and / or AT. Additionally, or alternatively, system 10 can be configured to deliver ADM therapy to induce AF when AFL and / or AT is detected, such as to convert an organized arrhythmia into a disorganized arrhythmia that can be more readily terminated using a different therapy mode (e.g., SRT as described herein). In some embodiments, algorithm 500 is configured to detect AFL and / or AT by measuring the cycle length between successive activations detected on one or more electrodes 111. In AFL and / or AT arrhythmias, the cycle length can fall within a narrow range (e.g., between approximately 10ms to 30ms). Additionally, or alternatively, algorithm 500 can be configured to detect AFL and / or AT by analyzing the morphology and / or timing pattern across a set of electrodes 111 between successive beats. In AFL and / or AT arrhythmias, the morphology' or timing pattern across a set of electrodes 111 can remain consistent over multiple beats. In some embodiments, algorithm 500 can be configured to compare the morphology and / or timing pattern across electrodes 111 for each beat using one or more analytical methods selected from the group consisting of: correlation analysis; wavelet decomposition analysis; or combinations of these. In some embodiments, when AFL or AT is detected, system 10 can be configured to deliver pacing energy7at one or more electrodes 111 at a rate faster than the AFL and / or AT cycle length (e.g., pacing at a rate configured to capture and / or entrain the existing arrhythmia). Pacing energy can be configured to be delivered simultaneously from two or more electrodes 1 11. The pacing energy' can be configured to be delivered with staggered timing across two or more electrodes 111. The pacing energy can be configured to capture and / or entrain the existing arrhythmia and accelerate the arrhythmia into AF. Once the organized arrhythmia is disrupted into AF, system 10 can be configured to transition to a different therapy mode configured to terminate AF (e.g., transition to PTM as described herein).Attorney Docket No.: MAX-012-PCT

[0191] In some embodiments, within the AcTh category, system 10 is configured to operate in Acute Therapy Monitoring Mode (ATMM) shown, where system 10 is configured to assess the effectiveness of one or more acute therapeutic interventions. In some embodiments, system 10 is configured to operate in one or more AcTh modes (e.g., PPM, PTM, LRM, and / or ADM) and Acute Therapy Monitoring Mode simultaneously, such as to monitor the progress and effectiveness of the acute therapy performed. In some embodiments, algorithm 500 is configured to assess effectiveness of pacing-based therapy by analyzing the distribution of activation times across two or more electrodes 111. Algorithm 500 can be configured to analyze the distribution of activation times during un-paced cardiac activity and / or to analyze the distribution of activation times during paced cardiac activity. Algorithm 500 can be configured to compare the un-paced activation time distribution to the paced activation time distribution to determine whether pacing is achieving a desired therapeutic effect (e.g., shortening the span of time over which the cardiac tissue is depolarized and / or repolarized). Alternatively, or additionally, algorithm 500 can be configured to analyze one or more morphological characteristics of recorded cardiac signals and / or quiescence of the cardiac signals following the delivery of a pacing pulse to assess tissue condition and / or the pacing effectiveness. Recorded cardiac signals can comprise unipolar electrograms and / or bipolar electrograms recorded from one or more electrodes 111. Algorithm 500 can be configured to determine one or more pacing effectiveness parameters selected from the group consisting of: successful tissue capture: blockage of delayed activation; prevention of fractionated electrograms; reduction in electrogram fractionation; and combinations of these. In some embodiments, algorithm 500 is configured to classify one or more arrhythmias based on characteristics of electrical signals recorded from one or more electrodes 111. Algorithm 500 can be configured to perform arrhythmia classification when therapy delivery is enabled and / or when therapy delivery is disabled. Additionally, or alternatively, algorithm 500 can be configured to assess changes in one or more arrhythmia characteristics during therapy delivery, such as changes in cycle length of individual electrical signals and / or groups of electrical signals recorded from one or more electrodes 111. Changes in cycle length can be assessed at a single electrode 111, across a subset of electrodes 111 within a region of cardiac tissue, and / or across electrode array 110. In some embodiments, a decrease in cycle length variability in one or multiple regions of a cardiac chamber can indicate positive therapeutic effect (e.g., transition from chaotic AF activation to more organized activation patterns). Alternatively, or additionally, an increase in cycleAttorney Docket No.: MAX-012-PCTlength in one or more regions of a cardiac chamber can indicate positive therapeutic effect (e.g., slowing of rapid arrhythmia rate toward normal sinus rhythm). In some embodiments, algorithm 500 is configured to assess the degree of pace capture at each electrode 111 where pacing is delivered. Algorithm 500 can be configured to assess pace capture by analyzing one or more characteristics of electrical signals recorded from one or more electrodes 111 following pacing pulse delivery. The one or more characteristics can comprise morphological features of the electrical signals and / or detected activation events in the electrical signal (e.g., signal peaks, sharp deflections, and / or rapid voltage changes). In some embodiments, algorithm 500 is configured to identify successful pace capture based on detection of a tissue activation event within a time window following a delivered pacing pulse followed by a quiescent period in the electrical signal (e.g., absence of additional activation events for a duration of time following the detected activation). In some embodiments, algorithm 500 is configured to assess the degree of pace control across a set of electrodes 111. Algorithm 500 can be configured to assess pace control by identifying one or more electrodes 111 that have successfully captured cardiac tissue and / or by detecting an absence of uncaptured electrical activity in the time intervals between delivered pacing pulses. An increase in pace control spanning across a greater number of electrodes 111 can indicate a positive therapeutic effect. In some embodiments, algorithm 500 is configured to compute a ‘‘Control Index"’ for a time window surrounding each delivered pacing pulse. The control index can be calculated by subtracting a first count from a second count, where the first count comprises a number of electrodes 111 detecting electrical activity preceding the delivered pacing pulse, and where the second count comprises a number of electrodes 111 detecting electrical activity following the delivered pacing pulse. A higher control index value can indicate that pacing energy is leading cardiac electrical activity in the chamber (e.g., indicating positive therapeutic effect), while a lower control index value can indicate that pacing energy is following behind cardiac electrical activity in the chamber.

[0192] System 10 can be configured to deliver multi-chamber synchronization therapy comprising operational modes configured to provide coordinated pacing of multiple cardiac chambers to optimize cardiac function. Various modes of therapy within the Multi-Chamber Synchronization Therapy category of therapy can comprise addressing conduction delays and / or optimizing cardiac output through coordinated stimulation provided across multiple chambers and / or stimulation provided to one or more chambers based on signals recorded from one or more other chambers. In some embodiments, system 10 is configured to operateAttorney Docket No.: MAX-012-PCTin Atrial Synchronization Mode (ASM) shown, where system 10 is configured to pace the heart to synchronize left and right atrial activation.

[0193] Additionally, or alternatively, within the MCST category, system 10 can be configured to operate in AV Synchronization Mode (AVSM) where system 10 is configured to pace the heart to synchronize atrial and ventricular activation (e g., 2, 3, and / or 4 chamber synchronization).

[0194] Additionally, or alternatively within the MCST category, system 10 can be configured to operate in Atrial Overdrive Stabilization Mode (AOSM), where system 10 is configured to deliver pacing at a rate that is faster than the patient’s intrinsic atrial rate, such as to stabilize cardiac activation patterns and reduce arrhythmia vulnerability.

[0195] In some embodiments, when system 10 is configured to operate in an AOSM configuration, system 10 is further configured to establish an intrinsic atrial baseline rate by analyzing cardiac signals over a period of time (e.g., a predetermined time period). In some embodiments, algorithm 500 is configured to determine the intrinsic atrial rate from the analyzed cardiac signals. The intrinsic atrial rate can be determined from mean cycle length, median cycle length, and / or other statistical measures of the analyzed cardiac signals.

[0196] In some embodiments, when system 10 is configured to operate in an AOSM configuration, system 10 is further configured to detect atrial instability and / or atrial vulnerability. Atrial instability can include one or more conditions selected from the group consisting of: increased cycle length variability; increased activation time dispersions across two or more electrodes 111; detection of PACs with arrhythmogenic characteristics; changes in electrogram morphology indicative of conduction abnormalities; and combinations of these. In some embodiments, algorithm 500 is configured to determine that atrial instability is present when one or more instability' criteria are satisfied.

[0197] In some embodiments, when atrial instability is detected, system 10 is configured to initiate overdrive atrial pacing at a rate exceeding the intrinsic atrial rate by an overdrive rate OR1. In some embodiments, OR1 is at least 1%, at least 3%, at least 5%, at least 7%, and / or at least 10% greater than the intrinsic atrial rate. In some embodiments OR1 is no more than 20%, no more than 15%, no more than 10% and / or no more than 7% greater than the intrinsic atrial rate. In some embodiments, OR1 is between approximately 5% and 10% greater than the intrinsic atrial rate. In some embodiments, the overdrive atrial pacing is configured to stabilize cardiac activation patterns while avoiding pro-arrhythmia from pacingAttorney Docket No.: MAX-012-PCTintervention. System 10 can be configured to deliver the overdrive atrial pacing from two or more spatially distributed electrodes 111, such as to achieve spatial resynchronization of atrial activation.[01981 In some embodiments, when system 10 is configured to operate in an AOSM configuration, system 10 is further configured to optimize atrioventricular coupling while delivering overdrive atrial pacing. Optimizing atrioventricular coupling can comprise adjusting the timing relationship between atrial pacing and ventricular activation, such as to improve hemodynamic function. In some embodiments, algorithm 500 is configured to select atrioventricular timing based on one or more parameters selected from the group consisting of: hemodynamic sensor data; ventricular activation timing; cardiac output indicators; and combinations of these.

[0199] In some embodiments, when system 10 is configured to operate in an AOSM configuration, system 10 can be further configured to monitor (e.g., continuously and / or intermittently monitor) mechanical and / or electrical response (e.g., a tissue response) to the overdrive atrial pacing. Monitoring electrical response can include assessing activation patern regularity, cycle length stability, and / or pace capture effectiveness. Monitoring mechanical response can include assessing hemodynamic parameters, cardiac output indicators, and / or heart sounds. In some embodiments, algorithm 500 is configured to adjust overdrive pacing parameters, such as an adjustment that is based on the monitored response.

[0200] In some embodiments, when system 10 is configured to operate in an AOSM configuration, system 10 can be further configured to taper and / or inhibit overdrive pacing, such as when atrial stability returns. Algorithm 500 can be configured to determine that atrial stability' has returned based on one or more criteria selected from the group consisting of: decreased cycle length variability below a threshold; decreased activation time dispersion below a threshold; absence of arrhythmogenic premature beats for a predetermined duration; restoration of normal electrogram morphology; and combinations of these. In some embodiments, tapering overdrive pacing comprises gradually reducing the overdrive percentage over a period of time (a ‘‘taper period’'). In some embodiments, system 10 is configured to return to diagnostic monitoring mode when overdrive pacing is discontinued.

[0201] In some embodiments, when system 10 is configured to operate in an AOSM configuration, system 10 can be further configured to escalate therapy when overdrive pacing is insufficient to restore atrial stability. Escalating therapy can include increasing theAttorney Docket No.: MAX-012-PCToverdrive percentage, changing electrode configurations, transitioning to a different therapy mode (e.g.. PTM, LRM, ADM), and / or combinations of these. Algorithm 500 can be configured to determine that escalation is indicated based on persistence of atrial instability despite overdrive pacing.

[0202] In some embodiments, within the MCST category, system 10 is configured to operate in Synchronization Therapy Monitoring Mode (STMM) shown, where system 10 is configured to assess the effectiveness of multi-chamber synchronization therapy provided by system 10. In some embodiments, system 10 is configured to operate in one or more synchronization therapy modes (e.g., ASM and / or AVSM) and / or Synchronization Therapy Monitoring Mode simultaneously, such as to monitor the progress and effectiveness of the synchronization therapy performed. Synchronization therapy monitoring can evaluate pacing coordination across multiple chambers, monitor cardiac response, assess timing optimization between different electrode regions, adjust one or more synchronization parameters, and / or determine when transitions to alternative therapy approaches may be appropriate. In some embodiments, system 10 is configured to assess hemodynamic function of one or more cardiac chambers while operating in STMM, such as by using one or more sensors (e.g., one or more functional elements 199). The one or more sensors can be configured to directly measure hemodynamic parameters. Alternatively, or additionally, the one or more sensors can be configured to measure surrogate indicators of hemodynamic function.

[0203] In some embodiments, the Diagnostic Monitoring Mode, therapy categories (e.g., TCT, AcTh, and / or MCST) and associated monitoring modes (e.g., CMM, ATMM, and / or STMM) can operate in a coordinated fashion where transitions between operation modes can occur automatically based on system 10 (e.g., algorithm 500) determination, clinician input, and / or predetermined therapy protocols. System 10 can be configured to simultaneously monitor patient status while delivering therapy, such as to enable therapy optimization and / or adaptive treatment strategies. System 10 can be configured to transition between operational modes based on monitored therapy effectiveness, changes in patient cardiac status, detected arrhythmia events, and / or other therapeutic requirements according to patient need and / or clinician decision.

[0204] Referring now to Fig. 4, a modular state diagram of an embodiment of a system for providing therapy is illustrated, consistent with the present inventive concepts. System 10Attorney Docket No.: MAX-012-PCTand / or other components described in reference to Fig. 4 can be of similar construction and arrangement as the similar components described in reference to Fig. 1, Fig. 1A, and otherwise herein. Fig. 4 shows a state diagram depicting the operational architecture of an embodiment of system 10 that can be configured to process cardiac signals through distinct functional modules that can operate independently and / or in coordination with other modules of system 10.

[0205] In some embodiments, system 10 comprises one, two, three, four, five or more functional modules configured to work cooperatively to manage cardiac therapy provided by the system. System 10 can be configured to operate using multiple interconnected modules, where each module comprises one or more components configured to perform specific functions including cardiac monitoring, signal processing, and / or pacing therapy deliver}'. The modular architecture shown can allow system 10 to process cardiac signals through distinct functional components while maintaining operational flexibility and therapeutic effectiveness. As described herein, each module can comprise one or more components, each configured to perform one or more of: a collection of data; an analysis of data; making a determination; a method of collecting, analyzing, and / or making one or more determinations based on collected and / or analyzed data; a gating of one or more operations and / or methods of system 10; and combinations of these.

[0206] In some embodiments, system 10 comprises Therapy Monitoring Module Ml, configured to assess the effectiveness of therapy delivered by system 10. As shown in Fig. 4, Therapy Monitoring Module Ml can be configured to provide one or more signals (e.g., feedback inputs) that influence the operational flow of one or more other modules within system 10 (e.g., Configuration Management Module M2 described herebelow). Therapy Monitoring Module Ml can comprise one or more components, such as Electrode Capture Detection Unit Cl, configured to verify successful stimulation delivery and tissue response to the delivered therapy (e.g., to verify successful pacing capture). In some embodiments, algorithm 00 is configured to assess the degree of pace capture at each electrode 111 where pacing energy is delivered. Algorithm 500 can be configured to assess pace capture by analyzing one or more characteristics of electrical signals recorded from one or more electrodes 111 following pacing pulse delivery'. The one or more characteristics can comprise morphological features of the electrical signals and / or detected activation events in the electrical signals (e.g., signal peaks, sharp deflections, rapid voltage changes). In some embodiments, algorithm 500 is configured to identify successful pace capture based onAttorney Docket No.: MAX-012-PCTdetection of a tissue activation event within a time window following a delivered pacing pulse followed by a quiescent period in the electrical signal (e.g., absence of additional activation events for a duration of time following the detected activation). Additionally, or alternatively, Therapy Monitoring Module Ml can comprise Rhythm Monitoring Unit C2, configured to continuously and / or semi-continuously assess cardiac rhythm characteristics, such as to detect changes in the cardiac rhythm following therapeutic intervention and / or to assess post-therapy cardiac electrical activity. In some embodiments, algorithm 500 is configured to classify one or more arrhythmias based on characteristics of electrical signals recorded from one or more electrodes 111. Algorithm 500 can be configured to perform arrhythmia classification when therapy delivery is enabled and / or when therapy delivery is disabled. In some embodiments, algorithm 500 is configured to assess changes of an arrhythmia characteristics during therapy delivery, such as changes in cycle length of individual signals and / or groups of electrical signals recorded from one or more electrodes 111. Changes in cycle length can be assessed at a single electrode 111, across a subset of electrodes 111 within a region of cardiac tissue, and / or across electrode array 110. In some embodiments, a decrease in cycle length variability in one or more regions of the cardiac chamber can indicate positive therapeutic effect (e g., transition from chaotic AF activation to more organized activation patterns). Additionally, or alternatively, an increase in cycle length in one or more regions of the cardiac chamber can indicate positive therapeutic effect (e.g., slowing of rapid arrhythmia rate toward normal sinus rhythm). In some embodiments.Therapy Monitoring Module Ml comprises Control and Synchrony Analytics Unit C3, configured to analyze coordination between one or more electrode sites, to assess synchronization effectiveness, and / or to evaluate therapy coordination and timing effectiveness. In some embodiments, algorithm 500 is configured to assess the degree of pace control and / or the degree of synchrony across one or more electrodes 111 (e.g., across a set of electrodes 111 of electrode array 110). Algorithm 500 can be configured to assess pace control by identifying one or more electrodes 111 that have successfully captured cardiac tissue and / or by detecting the absence of uncaptured electrical activity in the time intervals between delivered pacing pulses. An increase in pace control spanning across a greater number of electrodes 111 can indicate positive therapeutic effect. In some embodiments, algorithm 500 is configured to compute a Control Index for a time window surrounding each delivered pacing pulse. The control index can be calculated by subtracting a first count from a second count, where the first count comprises a number of electrodes 111 detecting electricalAttorney Docket No.: MAX-012-PCTactivity preceding the delivered pacing pulse, and where the second count comprises a number of electrodes 111 detecting electrical activity following the delivered pacing pulse. A higher control index value can indicate that the pacing energy is leading cardiac electrical activity in the chamber (e.g., indicating positive therapeutic effect), while a lower control index value can indicate that the pacing energy is following behind the cardiac electrical activity in the chamber. In some embodiments, one or more of the components of Therapy Monitoring Module Ml are configured to provide feedback to Configuration Management Module M2 and / or other modules of system 10. For example, module Ml can provide feedback to module M2 that can be used by module M2 for parameter adjustment such as to enable adaptive therapy adjustment based on therapeutic assessment.

[0207] In some embodiments, Therapy Monitoring Module Ml is configured to assess the effectiveness of one or more pacing therapies provided by system 10 and provide feedback for adaptive therapy optimization. For example. Electrode Capture Detection Unit Cl can be configured to detect if pacing pulses are achieving intended cardiac activation, and to provide feedback that is used by system 10 to optimize the pacing being delivered to achieve the intended cardiac activation. In some embodiments, Control and Synchrony Analytics Unit C3 is configured to analyze coordination between electrode sites and / or assess synchronization effectiveness across one or more cardiac substrates and provide feedback that can be used by system 10 to determine therapy effectiveness and / or guide subsequent pacing decisions.

[0208] In some embodiments, system 10 comprises Configuration Management Module M2, configured to establish and / or maintain one or more operational parameters of system 10. As shown in Fig. 4, Configuration Management Module M2 can be configured to receive input from system settings and / or feedback from Therapy Monitoring Module Ml to adjust the configuration of one or more operational parameters of system 10. In some embodiments, Configuration Management Module M2 comprises one or more configuration components configured to manage various parameters of system 10. In some embodiments, Configuration Management Module M2 is configured to receive one or more system settings as input, where system settings can comprise initial configuration parameters, for example one or more parameters that can be modified by the one or more configuration management module components. In some embodiments, the system settings comprise default values, algorithmically-determined values, clinician-programmed values, and / or patient specific parameters determined during device manufacturing (e.g., one or more custom settingsAttorney Docket No.: MAX-012-PCTprogrammed during a bespoke manufacturing process or step), implantation and / or during a calibration and / or other initiation process. Each configuration component can be configured to optimize system 10 performance based on patient-specific requirements and / or therapeutic objectives, such as those determined during diagnostic monitoring, as described herein.

[0209] In some embodiments, Configuration Management Module M2 comprises Signal Configuration Unit C4, configured to establish and / or modify (e.g., optimize) signal acquisition and processing parameters for cardiac monitoring. Signal Configuration Unit C4 can be configured to establish signal acquisition parameters optimized for detecting activation events at one or more electrode sites. In some embodiments, Configuration Management Module M2 comprises Event Detection Configuration Unit C5, configured to define criteria and / or thresholds for cardiac event identification and / or to establish detection thresholds and / or criteria for arrhythmia detection, where such criteria and / or thresholds enable accurate identification of cardiac events while minimizing false detections.Additionally, or alternatively, Configuration Management Module M2 can comprise Algorithmic Configuration Unit C6, configured to select, parameterize, and / or tune one or more algorithms of system 10, such as algorithms 500 (e.g.. for patient-specific requirements), such as by adjusting sensitivity and / or timing parameters based on individual cardiac characteristics. Configuration Management Module M2 can comprise Pacing Configuration Unit C7, configured to establish stimulation parameters (e.g., pulse amplitude, duration, and / or timing) that can optimize therapeutic effectiveness while maintaining patient safety and comfort.

[0210] In some embodiments, system 10 comprises Sensing Module M3, configured to receive one or more cardiac signals, such as signals recorded from one or more electrodes 111 of system 10. As shown in Fig. 4, Sensing Module M3 can receive one or more configuration parameters from Configuration Management Module M2, and can provide processed signal data to Pacing Control Module M4, described herebelow. Sensing Module M3 can be configured to acquire and / or process cardiac electrical signals recorded from cardiac tissue and / or other tissue of the patient.

[0211] In some embodiments, Sensing Module M3 comprises one or more components, such as Signal Processing Unit C8, configured to process (e.g., filter, amplify, digitize, and / or otherwise process) cardiac signals, such as signals recorded via an electrode 111 of electrode array 110 as described herein. Signal Processing Unit C8 can be configured toAttorney Docket No.: MAX-012-PCTprocess cardiac signals to enable detection of various activation events and / or other cardiac events, for example local events detected proximate each electrode site. Sensing Module M3 can comprise Event Detection Unit C9, configured to identify these cardiac events (e.g., atrial activations, ventricular activations, and / or arrhythmia events) by evaluating the processed cardiac signals from Signal Processing Unit C8. Event Detection Unit C9 can be configured to identify cardiac events such as depolarizations, arrhythmias and / or other electrical activity events and / or patterns. Event Detection Unit C9 can be configured to identify' activation events (e.g., local depolarization) proximate each electrode 111, and can provide activation timing information used by subsequent modules for pacing control decisions. In some embodiments, Event Detection Unit C9 is configured to detect one or more specific signal characteristics (e.g., amplitude, frequency and / or morphology) indicative of various cardiac conditions. In some embodiments, Sensing Module M3 is configured to monitor (e.g., continuously and / or intermittently monitor) cardiac signals while system 10 operates in one or more therapeutic modes described herein, such as to provide simultaneous assessment of cardiac electrical activity while therapy is provided by system 10. Sensing Module M3 can be configured to measure and / or sense cardiac activity at one or more sites (e g., electrodes 111) and can be configured to provide real-time data for both pacing control and therapy monitoring functions of system 10.

[0212] In some embodiments, system 10 comprises Pacing Control Module M4, configured to analyze detected cardiac events and determine appropriate therapeutic responses. As shown in Fig. 4, Pacing Control Module M4 can receive processed signal data from Sensing Module M3 and / or configuration parameters from Configuration Management Module M2, and / or can provide control signals to Pacing Module M5 (described herebelow), for example if and when pacing is determined to be appropriate. Pacing Control Module M4 can be configured to analyze cardiac electrical activity and determine appropriate pacing interventions, as described herein.

[0213] In some embodiments, Pacing Control Module M4 comprises one or more algorithms configured to make decisions regarding stimulation delivery. For example.Pacing Control Module M4 can comprise Spatiotemporal Pacing Control Unit CIO, configured to implement spatiotemporal resynchronization therapy (SRT) as described herein and / or to otherwise process event detection data and determine parameters related to pacing stimulation delivery. Spatiotemporal Pacing Control Unit CIO can be configured to analyze cardiac signals and determine whether pacing conditions are satisfied. Pacing ControlAttorney Docket No.: MAX-012-PCTModule M4 can comprise one or more decision components, such as Event Trigger Cll, configured to evaluate whether events detected by one or more algorithms of Spatiotemporal Pacing Control Unit CIO should trigger pacing delivery based on one or more criteria (e.g., arrhythmia detection algorithms, timing windows, and / or therapeutic protocols). When one or more events are determined to require pacing (e.g., “Event triggers pacing” is determined to be “Yes”). Pacing Control Module M4 can initiate stimulation delivery’ via Pacing Module M5 and / or otherwise communicate instructions to Pacing Module M5 as shown by the flow arrows in Fig. 4. Pacing Control Module M4 can comprise Event History Unit C12, configured to maintain records of detected events and / or delivered therapies for subsequent analysis. Pacing Control Module M4 can be configured to implement algorithmic control (e.g., closed loop control) of where and / or when pacing pulses are delivered (e.g., in optimal locations and / or at optimal times). Spatiotemporal Pacing Control Unit CIO can be configured to analyze detected cardiac events and to determine when pacing should be delivered in response to detected events that meet specific criteria (e.g., output is “triggered” when specific conditions are satisfied). The decision-making process of Pacing Control Module M4 can allow system 10 to operate in a closed loop manner based on cardiac activity, where system 10 can be responsive from beat-to-beat. In some embodiments, Pacing Control Module M4 is configured to monitor cardiac activity’ compared to various criteria and respond according to multiple operational strategies, such as: to maintain and / or increase synchrony of depolarized tissue by delivering pacing at the same time as depolarization in other parts of the cardiac chamber; to maintain and / or increase synchrony of excitable tissue by widening and consolidating excitable gaps; and / or to optimize pacing output delivery’ during excitable gaps to improve therapeutic effectiveness.

[0214] In some embodiments, system 10 comprises Pacing Module M5, configured to provide one or more electrical pacing pulses to cardiac tissue via one or more electrodes 111. As shown in Fig. 4, Pacing Module M5 can receive control signals from Pacing Control Module M4 and / or configuration parameters from Configuration Management Module M2, and can be configured to deliver therapeutic stimulation to cardiac tissue. Pacing Module M5 can be configured to generate and deliver electrical stimulation energy to cardiac tissue.

[0215] In some embodiments, Pacing Module M5 comprises one or more components, such as Waveform Generator C13, configured to generate one or more pacing pulses comprising one or more specified parameters (e.g.. amplitude, duration, and / or morphology). Additionally, or alternatively, Pacing Module M5 can comprise Pacing Output ControllerAttorney Docket No.: MAX-012-PCTC14, configured to route generated pacing pulses to one or more selected electrodes 111 of electrode array 110 and / or to control stimulation timing across one or more electrode sites. Pacing Output Controller C14 can be configured to route pacing energy to selected electrodes 111 based on control signals received from Pacing Control Module M4. In some embodiments, Pacing Control Module M5 is configured to deliver spatially distributed stimulation energy, where stimulation is delivered from one or more electrode 111 locations with precise temporal coordination to achieve one or more therapeutic objectives (e.g., AF termination, arrhythmia prevention). Pacing Module M5 can be configured to deliver stimulation energy simultaneously and / or sequentially across one or more electrodes 111, enabling multisite pacing therapies such as spatiotemporal resynchronization therapy (SRT) described herein. Pacing Module M5 can be configured to deliver pacing pulses to cardiac tissue to provide therapeutic stimulation based on instructions received from Pacing Control Module M4, with the delivered therapy monitored by Therapy Monitoring Module Ml. In some embodiments, Pacing Module M5 is configured to deliver pacing pulses where effectiveness can be optimized based on timing relative to tissue refractoriness, such as when pulses are delivered with timing that avoids ineffective delivery (e.g., pulses delivered too quickly relative to last depolarization when tissue is still refractory) and / or timing that avoids minimal tissue capture (e.g., pulses delivered too delayed relative to next depolarization).

[0216] In some embodiments, system 10 is configured such that criteria to pace on a given electrode can use one or more factors selected from the group consisting of: activation event (e.g.. local depolarization) at the given electrode; previous activation event at the given electrode; most recent pacing delivered at the given electrode; activation event (e.g., local depolarization) at any other electrode; previous activation event at any other electrode; most recent pacing delivered at any other electrode; and combinations of these. The modular architecture of sy stem 10 can enable Pacing Control Module M4 to process these multiple criteria simultaneously across all electrodes 111, allowing for spatiotemporal pacing strategies that can adapt to complex cardiac electrical dynamics in real-time.

[0217] System 10 can be configured such that cardiac signals from the patient’s heart can be processed through the interconnected modular architecture in a coordinated workflow following the flow relationships shown in Fig. 4. In some embodiments, system 10 is configured to operate multiple modules simultaneously, enabling continuous cardiac monitoring while delivering one or more therapeutic interventions. For example, Therapy Monitoring Module Ml can be configured to assess ongoing therapy effectiveness whileAttorney Docket No.: MAX-012-PCTpacing is being delivered, and can provide feedback that can influence one or more pacing control decisions. Additionally, or alternatively, Configuration Management Module M2 can be configured to adjust operational parameters based on therapy monitoring results. The modular architecture of system 10 can enable flexible therapeutic approaches where different modules can be activated, deactivated and / or reconfigured based on patient needs and / or clinical requirements. In some embodiments, system 10 is configured to operate in simplified configurations where only essential modules are active, and / or in comprehensive configurations where all modules can operate simultaneously to provide maximum therapeutic capability' and / or monitoring coverage.

[0218] In some embodiments, system 10 is configured to operate in Preventative Pacing Mode (PPM) as described in reference to Fig. 3, where system 10 is configured to deliver preventative pacing therapy to prevent AF initiation. As described herein, PPM can comprise an operational mode within the Acute Therapy (AcTh) category- yvhere system 10 can be configured to deliver preventative pacing when AF initiation is determined to be probable. PPM can comprise a simultaneous pacing approach, yvhere each pacing pulse can be delivered on all electrodes 111 simultaneously. In some embodiments, one or more detected cardiac events can trigger preventative pacing initiation. For example, system 10 can be configured to detect premature atrial contractions (PACs) and deliver pacing (e.g., simultaneous pacing) across one or more electrodes 111 to prevent AF initiation.

[0219] In some embodiments, when system 10 is configured to operate in PPM, Therapy Monitoring Module Ml is configured to assess the effectiveness of preventative pacing interventions and / or monitor the efficacy of AF prevention through comprehensive PAC and SR pattern analysis (e.g., using one or more algorithms 500). Therapy Monitoring Module Ml can be configured to monitor SR and PAC activation patterns, where monitoring can include tracking sinus rhythm characteristics and / or identifying premature atrial contraction patterns that can indicate increased AF risk. Additionally, or alternatively, Therapy Monitoring Module Ml can be configured to approximate PAC site of origin by analyzing activation timing and / or morphology' across one or more electrodes 111. In some embodiments, system 10 uses PAC origin identification to enable targeted preventative pacing strategies. Therapy Monitoring Module Ml can be configured to classify one or more PAC characteristics that induce AF frequently. Therapy Monitoring Module Ml can be configured to record and identify the first “beats” of AF (e.g.. the initiation of AF). for example if AF is induced despite preventative pacing. In some embodiments, TherapyAttorney Docket No.: MAX-012-PCTMonitoring Module Ml is configured to adjust PAC criteria if PACs inducing AF are missed by the detection algorithms (e.g., algorithm 500) of system 10. For example. Therapy Monitoring Module Ml can be configured to modify (e.g., increase) specificity for specific PAC characteristics (e.g., site of origin, activation pattern) that are associated with AF initiation. Additionally, or alternatively, Therapy Monitoring Module Ml can provide adaptive feedback to Configuration Management Module M2 for preventative pacing parameters based on observed PAC-AF relationships and / or therapeutic outcomes.

[0220] In some embodiments, when system 10 is configured to operate in PPM, Configuration Management Module M2 is configured to establish one or more operational parameters specifically optimized for preventative pacing therapy. Configuration Management Module M2 can configure system 10 to record and / or analyze unipolar and / or bipolar signals. For example, Configuration Management Module M2 can configure system 10 to analyze unipolar signals to assess capture (e.g., control of the cardiac substrate via pacing provided by system 10). In some embodiments, Configuration Management Module M2 can configure system 10 to perform activation detection using bipolar signals.Configuration Management Module M2 can be configured to track SR interval rate and / or can be configured to adjust for SR variance. In some embodiments. Configuration Management Module M2 is configured to set one or more timing windows for PAC detection, and can be configured to adjust the one or more PAC timing windows, for example over time as more PACs are observed. Configuration Management Module M2 can configure system 10 to use unipolar pacing configurations and / or bipolar pacing configurations.

[0221] In some embodiments, when system 10 is configured to operate in PPM, Sensing Module M3 is configured to acquire and process cardiac electrical signals, which may include SR signals and / or signals which include premature beats. Sensing Module M3 can be configured to process bipolar and / or unipolar signals and can be configured to perform various signal filtering, as described herein. Sensing Module M3 can be configured to detect local tissue activation at each electrode 111. Sensing Module M3 can be configured to determine when premature beat has occurred (e.g., a premature beat correlating to a PAC). Additionally, or alternatively, Sensing Module M3 can be configured to classify PACs by activation pattern across electrodes, by origin, and / or by timing of the PAC compared to SR patterns and timing.Attorney Docket No.: MAX-012-PCT

[0222] In some embodiments, when system 10 is configured to operate in PPM, Pacing Control Module M4 can be configured to analyze activations at each electrode 111. Pacing Control Module M4 can be configured to determine if activation time is premature (e.g., compared to SR). Additionally, or alternatively. Pacing Control Module M4 can be configured to determine if a recorded activation pattern is different (e.g., different from the preceding activation and / or any previously recorded activation). In some embodiments, Pacing Control Module M4 is configured to trigger pacing when premature beat is detected. Additionally, or alternatively, Pacing Control Module M4 can be configured to trigger pacing only when a specific type of PAC and / or specific criteria are met (e.g., including site or activation pattern criteria). In some embodiments, detected PACs are classified into one or more classes (e.g., simultaneously classified into one or more classes). Some classes may exhibit a higher occurrence rate and / or probability’ of initiating AF, while other classes may exhibit a lower occurrence rate and / or probability of initiating AF. In some embodiments, system 10 can be configured to trigger Pacing only when detected PACs are determined to belong to one or more classes associated with higher AF initiation probability (e.g., when real-time PAC classification indicates high-risk PAC classes). In some embodiments, PAC classification is based on one or more parameters selected from the group consisting of: estimated site of origin; estimated direction of origin; pattern of activations across one or more electrodes 111; and combinations of these. In some embodiments, system 10 is configured to perform real-time PAC classification based on the earliest detected activations on a subset of electrodes 111, such as to enable rapid classification and responsive pacing delivery. In some embodiments, algorithm 500 is configured to reduce PAC classification to a simplified set of differentiating criteria between classes, such as to improve the real-time responsiveness of the delivered pacing. In some embodiments, algorithm 500 is configured to use machine learning and / or artificial intelligence to establish the distinctive classes of PACs. In some embodiments, algorithm 500 is configured to use machine learning and / or artificial intelligence to reduce and / or optimize the differentiating criteria between classes for responsiveness. In some embodiments, Pacing Control Module M4 is configured to use a subset of electrodes 111 to sense activations, for example approximately five electrodes 111. In some embodiments, only a subset of electrodes 111 of electrode array 110 are configured for both sensing and pacing, and / or a first subset of electrodes 111 are configured for sensing only and a second subset of electrodes 111 are configured for pacing only. In some embodiments, electrodes 111 configured to perform a single function (e.g.. sensing or pacing)Attorney Docket No.: MAX-012-PCTrequire less wires and / or other enabling elements and / or properties (e.g., electrode size) than multi -function electrodes. In some embodiments, the majority of electrodes 111 of electrode array 110 are configured as pacing electrodes.

[0223] In some embodiments, one or more algorithms of system 10 (e.g.. algorithm 500 described herein) comprise a bias. For example, system 10 can comprise a bias toward false positive detection of a patient state (e.g., the predicted onset of AF), such that the system is configured to tend toward the unnecessary delivery of preventative therapy in order to limit the likelihood of “missing’" a window of necessary therapy delivery, resulting in the otherwise preventable onset of AF. Alternatively, or additionally, system 10 can comprise a bias toward false negative detection of a patient state, such that the system is configured toward not delivering therapy, for example therapy with larger patient affect (e.g., LRM therapy).

[0224] In some embodiments, when system 10 is configured to operate in PPM, Pacing Module M5 is configured to use a unipolar pacing configuration. Additionally, or alternatively, Pacing Module M5 can be configured to utilize biphasic and / or triphasic waveforms. In some embodiments, Pacing Module M5 is configured to deliver biphasic and / or triphasic waveforms comprising a phase duration of approximately 4ms per phase and / or 8ms per phase. In some embodiments, Pacing Module M5 is configured to deliver pacing to all electrodes 111 simultaneously, such that all electrodes 111 pace in unison. Alternatively, or additionally, pacing can be delivered in a staggered pattern similar to SR activation timing (e.g., to promote SR control). In some embodiments, if PAC induces AF frequently, staggered timing is introduced to counteract the pattern of the first few beats of AF.

[0225] In some embodiments, system 10 is configured to operate in one or more Pace Termination Modes (PTM), as described in reference to Fig. 3. PTM can comprise one or more modes, such as Simultaneous Pace Termination Mode, where system 10 is configured to terminate ongoing atrial fibrillation through coordinated pacing delivered across electrode array 110. As described herein, simultaneous PTM can comprise an operational mode within the Acute Therapy (AcTh) category. Simultaneous PTM can be configured to deliver each pacing pulse on a set of electrodes 111 (e g., all electrodes 111) simultaneously to interrupt fi bri llatory conduction patterns and restore organized cardiac rhythm (e.g., SR).Attorney Docket No.: MAX-012-PCT

[0226] In some embodiments, when system 10 is configured to operate in Simultaneous PTM, system 10 is configured such that any activation event detected on any electrode 111 during AF can trigger pacing. In some embodiments, an activation event can trigger pacing only after a specified time interval has elapsed since any previous pacing output. This specified time interval can be referred to herein as a “minimum pacing period” (MPP).Triggering pacing only following an MPP can improve cardiac response to pacing delivered during fibrillatory conduction while preventing extraneous pulses that could perpetuate arrhythmia and / or cause re-induction following successful termination.

[0227] In some embodiments, when system 10 is configured to operate in Simultaneous PTM, Therapy Monitoring Module Ml is configured to assess therapeutic effectiveness specifically for AF termination. Therapy Monitoring Module Ml can be configured to monitor one or more cycle length characteristics to determine if ongoing AF requires termination therapy. In some embodiments, one or more components of Therapy Monitoring Module Ml, such as Rhythm Monitoring Unit C2, are configured to determine if AF is ongoing and / or if electrical signals have successfully converted to one or more organized rhythms (e.g., sinus rhythm and / or atrial flutter). In some embodiments, Therapy Monitoring Module Ml is configured to detect successful AF termination to SR and can trigger cessation of PTM and / or transition to one or more monitoring modes. Alternatively, or additionally, Therapy Monitoring Module Ml can be configured to detect conversion from AF to AFL (e.g., transition from a chaotic rhythm to a rapid but organized rhythm) and can trigger transition to a different therapy mode configured to treat AFL. One or more components of Therapy Monitoring Module Ml, such as Control and Synchrony Analytics Unit C3, can be configured to assess whether simultaneous pacing delivery is successful. In some embodiments, Therapy Monitoring Module Ml is configured to use one or more indices, such as Synchrony Index and / or Control Index to determine if AF has been altered.

[0228] In some embodiments, when system 10 is configured to operate in Simultaneous PTM, Configuration Management Module M2 is configured to establish parameters specifically optimized for AF termination. In some embodiments, one or more components of Configuration Management Module M2, such as Pacing Configuration Unit C7, are configured to establish minimum pacing period parameters based on one or more AF cycle length characteristics. For example, a minimum pacing period can be set to the median cycle length of the detected AF. Alternatively, or additionally, a minimum pacing period can be set to a percentage of median AF cycle length (e g., such as between approximately 70% andAttorney Docket No.: MAX-012-PCT120%, such as between approximately 75% and 95%). In some embodiments, Configuration Management Module M2 is configured to define one or more unipolar pacing configurations and / or bipolar pacing configurations.

[0229] In some embodiments, when system 10 is configured to operate in Simultaneous PTM, Sensing Module M3 is configured to acquire and process cardiac electrical signals, for example signals that comprise chaotic AF signals for which Simultaneous PTM is indicated for treatment. Sensing Module M3 can be configured to process bipolar and / or unipolar signals. In some embodiments, Sensing Module M3 is configured to perform filtering of the acquired cardiac signals. Sensing Module M3 can be configured to detect local tissue activation at each electrode 111. In some embodiments, Sensing Module M3 uses peak detection or detection of steepest slope (e.g., negative slope) to detect local tissue activation.

[0230] In some embodiments, when system 10 is configured to operate in Simultaneous PTM, Pacing Control Module M4 is configured to analyze activations at each electrode 111 and / or determine if pacing should be triggered. In some embodiments, one or more components of Pacing Control Module M4, such as Spatiotemporal Pacing Control Unit CIO, are configured to analyze irregular activation events detected across electrode array 110 and determine whether termination pacing should be delivered, for example based on the timing of the activation and / or one or more minimum pacing period constraints. In some embodiments, Pacing Control Module M4 is configured such that any fibrillatory activation event detected on any electrode 111 can trigger simultaneous pacing delivery, for example, once sufficient time has elapsed since the last pacing output (e.g., as long as system 10 is not within an MPP). In some embodiments. Pacing Control Module M4 is configured to use a subset of electrodes 111 to sense activations, as described herein.

[0231] In some embodiments, when system 10 is configured to operate in Simultaneous PTM, Pacing Module M5 is configured to pace using a unipolar pacing configuration.Additionally, or alternatively, Pacing Module M5 can be configured to pace using biphasic and / or triphasic waveforms. In some embodiments, Pacing Module M5 is configured to deliver pacing energy to one or more (e.g., all electrodes 111, or all pacing electrodes 111) simultaneously, such that electrodes 111 pace cardiac tissue simultaneously. In some embodiments, one or more components of Pacing Module M5, such as Pacing Output Controller C14, are configured to route generated pacing pulses to a set of one or more (e.g., all) electrodes 111 simultaneously, such as to promote alignment of excitable gaps andAttorney Docket No.: MAX-012-PCTcoordinated depolarization and / or repolarization across the cardiac substrate. In some embodiments, "‘simultaneous'’ pacing can be delivered from a set of electrodes 111 in unison, and / or temporally staggered. For example, pacing can be staggered in a pattern similar to SR activation timing (e.g., to promote SR control). In some embodiments, Pacing Module M5 is configured to introduce staggered pacing when system 10 detects that pacing has modified AF characteristics toward a ‘nearly macro-reentrant pattern’. For example, a macro reentry pattern may be detected on a majority of electrodes 111, while a minority of electrodes 111 continue to record fibrillating cardiac signals. In some embodiments, the staggered pacing is utilized to terminate and / or disrupt the reentrant circuit and facilitate restoration of normal rhythm (e.g., SR). In some embodiments, when system 10 is configured to operate in Simultaneous PTM, Pacing Module M5 is configured to pace using a bipolar pacing configuration.

[0232] In some embodiments, PTM comprises an Independent Pacing with Consensus Algorithm Pace Termination Mode (also described herein as “Consensus PTM”), where system 10 is configured to terminate ongoing atrial fibrillation through individualized pacing delivery' from electrodes 111 across electrode array 110. As described herein, Consensus PTM comprises an operational mode within the Acute Therapy (AcTh) category. Consensus PTM can be configured to deliver pacing pulses independently from each electrode 111. In some embodiments, Consensus PTM is configured to deliver independent pacing pulses when the criteria to do so for a particular electrode 111 is met (e.g., to interrupt fibrillatory conduction patterns and restore organized cardiac rhythm).

[0233] In some embodiments, when system 10 is configured to operate in Consensus PTM, pacing is delivered from a given electrode 111 if an activation event on any other electrode 111 has occurred, and a sufficient duration of time has elapsed since the last activation event on the given electrode where pacing is going to be delivered. In some embodiments, the elapsed time can be referred to as a “dead zone” interval where the dead zone interval (or “dead zone condition”) can act as an estimate of refractory’ period for the cardiac tissue at the electrode site. The dead zone condition can be reset each time local activation at a given electrode 111 is detected and / or each time pacing is delivered to that electrode 111. This approach can ensure that pacing occurs beyond the refractory' period of tissue proximate a given electrode 111, to improve pacing effectiveness while limiting arrhythmia perpetuation.Attorney Docket No.: MAX-012-PCT

[0234] In some embodiments, when system 10 is configured to operate in Consensus PTM, Therapy Monitoring Module Ml is configured to assess therapeutic effectiveness specifically for AF termination. Therapy Monitoring Module Ml can be configured to monitor one or more cycle length characteristics to determine if ongoing AF requires termination therapy. In some embodiments, one or more components of Therapy Monitoring Module Ml, such as Rhythm Monitoring Unit C2, are configured to determine if AF is ongoing and / or if electncal signals have successfully converted to one or more organized rhythms (e.g., sinus rhythm and / or atrial flutter). In some embodiments, Therapy Monitoring Module Ml is configured to detect successful AF termination to SR and can trigger cessation of PTM and / or transition to one or more monitoring modes. Alternatively, or additionally, Therapy Monitoring Module Ml can be configured to detect conversion from AF to AFL (e.g., transition from a chaotic rhythm to a rapid but organized rhythm) and can trigger transition to a different therapy mode configured to treat AFL. One or more components of Therapy Monitoring Module Ml, such as Control and Synchrony Analytics Unit C3, can be configured to assess whether pacing delivery is successful. Therapy Monitoring Module Ml can be configured to use one or more indices, such as Synchrony Index and / or Control Index to determine if AF has been altered.

[0235] In some embodiments, when system 10 is configured to operate in Consensus PTM, Configuration Management Module M2 is configured to establish parameters specifically optimized for AF termination. In some embodiments, one or more components of Configuration Management Module M2, such as Pacing Configuration Unit C7, are configured to establish dead zone duration parameters based on one or more AF cycle length characteristics. For example, the dead zone duration can be set to the median cycle length of the detected AF. Alternatively, or additionally, the dead zone duration can be set to a value offset from the median cycle length of AF, such as a percentage offset (e.g., such as between approximately 70% and 120% of median cycle length, such as between approximately 75% and 95%) and / or a fixed time offset (e g., between approximately -50ms and +50ms from median cycle length, such as between approximately -30ms and -10ms from median cycle length). In some embodiments, Configuration Management Module M2 is configured to define one or more unipolar pacing configurations and / or bipolar pacing configurations.

[0236] In some embodiments, when system 10 is configured to operate in Consensus PTM, Sensing Module M3 is configured to acquire and process cardiac electrical signals, for example signals that comprise chaotic AF signals for which Consensus PTM is indicated forAttorney Docket No.: MAX-012-PCTtreatment. Sensing Module M3 can be configured to process bipolar and / or unipolar signals. In some embodiments. Sensing Module M3 is configured to perform filtering of the acquired cardiac signals. Sensing Module M3 can be configured to detect local tissue activation at each electrode 111 during ongoing AF and maintain timing records for individual electrode dead zone management. Each local activation event detection (e.g., for a given electrode) can reset the dead zone timing for the given electrode 111 and / or provide triggering signals for pacing decisions at other electrodes 111.

[0237] In some embodiments, when system 10 is configured to operate in Consensus PTM, Pacing Control Module M4 is configured to analyze activations at each electrode 111 individually and / or determine if pacing should be triggered for each specific electrode 111. Pacing Control Module M4 can be configured to keep track of a dead zone time for each electrode 111 independently, where pacing based on a triggering event can occur only if the time exceeds the dead zone threshold for that specific electrode 111. In some embodiments, one or more components of Pacing Control Module M4, such as Spatiotemporal Pacing Control Unit CIO, are configured to analyze irregular activation events detected across electrode array 110 and determine whether termination pacing should be delivered on individual electrodes 111, for example based on the dead zone duration constraints specific to each electrode and / or based on the last local activation event at that electrode. In some embodiments, Pacing Control Module M4 is configured such that once sufficient time has elapsed since the last local activation event on a given electrode 111 (e.g., the dead zone condition as lapsed), the next activation event on any other electrode 111 can trigger pacing on the given electrode. Pacing Control Module M4 can be configured to reset the dead zone condition each time local activation at the electrode 111 is detected and / or each time pacing is delivered to that electrode 111. In some embodiments, Pacing Control Module M4 is configured to augment the pacing control logic by sub-grouping the sensing and pacing sites (e.g.. grouping sets of electrodes 111), where the relationships between triggering events from specific sets of electrodes 111 and the pacing from specific sets of electrodes 111 can be limited to prioritize different aspects of control and synchrony. For example, in Consensus PTM, pacing at a given electrode 111 can be triggered only by electrodes 111 within a certain distance from the given electrode. Additionally, or alternatively, pacing at a given electrode 111 can be triggered only from electrodes 111 beyond a predetermined distance away from a given electrode (such as 20mm away). One or more components of Pacing Control Module M4, such as Event History Unit Cl 2, can be configured to track individual electrodeAttorney Docket No.: MAX-012-PCTactivation patterns and / or dead zone timing for each electrode 111 independently. System 10 can perform pattern analysis to assess whether individual electrode pacing is contributing to successful control. In some embodiments, Pacing Control Module M4 is configured to use a subset of electrodes 111 to sense activations, as described herein.

[0238] In some embodiments, when system 10 is configured to operate in Consensus PTM, Pacing Module M5 is configured to pace using a unipolar configuration. Additionally, or alternatively, Pacing Module M5 can be configured to pace using biphasic and / or triphasic waveforms. In some embodiments, Pacing Module M5 is configured such that each electrode 111 can deliver pacing energy independently based on individual electrode criteria. In some embodiments, one or more components of Pacing Module M5, such as Pacing Output Controller Cl 4, are configured to route generated pacing pulses to individual electrodes 111 based on individual electrode dead zone timing criteria and / or other triggering criteria, such as to promote distributed synchrony of depolarization and alignment of excitable gaps across the cardiac substrate. In some embodiments, Pacing Module M5 is configured to implement electrode grouping variations, such as configuring groups of electrodes 111 to pace together when triggered by a single event, for example if the duration since the last activation within the group is longer than a dead zone threshold. In some embodiments, when system 10 is configured to operate in Consensus PTM, Pacing Module M5 is configured to pace using a bipolar configuration.

[0239] In some embodiments, one or more pacing parameters are selected to maximize, over a given time interval, the proportion of targeted tissue that is depolarized. For example, system 10 can be configured to coordinate stimulation timing, electrode selection, and / or pacing pulse characteristics across electrode array 110 to achieve maximal simultaneous depolarization. In some embodiments, system 10 is configured such that one or more pacing parameters are selected to maximize, over a given time interval, the proportion of targeted tissue that is repolarized. System 10 can be configured to time the delivery of stimulation energy to extend refractory’ periods across electrode array 110.

[0240] In some embodiments, system 10 is configured to operate in Left- Atrial Reset Mode (LRM), as described in reference to Fig. 3, where system 10 is configured to terminate ongoing atrial fibrillation through abrupt, asynchronous “large area depolarization” using energy delivered across electrode array 110. As described herein, LRM comprises an operational mode within the Acute Therapy (AcTh) category. LRM can be configured toAttorney Docket No.: MAX-012-PCTdeliver pulses from a group of electrodes 111 (e.g., all electrodes 111) simultaneously to depolarize large areas of tissue with a limited number of pacing pulses, such as less than five pulses (e.g., between one and three pulses). In some embodiments, pulses used for LRM can be configured to use a higher output and / or broader width than pacing pulses delivered in other pacing modes described above. In some embodiments, LRM can be configured as low-energy defibrillation (e.g., when system 10 is configured to be bipolar along a vector). In some embodiments, the LRM comprises a short pulse or set of pulses to abruptly cardiovert a portion of the heart. In some embodiments, the portion of the heart cardioverted is a single chamber (such as the left atrium) or two chambers (such as the left and right atria). In some embodiments, the pulse or pulses are delivered asynchronously to the fibrillatory cardiac activity in the chamber being reset. In some embodiments, the pulse or pulses may be delivered asynchronously to the fibrillating chamber but synchronously to other non-fibrillating chambers of the heart (such as the ventricles) to prevent fibrillation in those chambers. In some embodiments the pulses are delivered between two sets of one or more electrodes spanning an area of tissue to electrically depolarize the targeted area of tissue abruptly. In some embodiments, the pulses are delivered from a set of one or more electrodes in the vicinity of the chamber being reset to a return further from the heart. In some embodiments, the pulse or pulses are configured with one or more strategically engineered phases with amplitude, timing, and morphology of each phase designed to deliver a uniform electric field, deliver optimal current or voltage output, minimize electrode degradation or corrosion, and / or maximize battery life. In some embodiments, a sequence of pulses can be delivered in rapid succession where the structure of each pulse and the timing between pulses is designed to maximize efficacy of depolarizing the targeted tissue area.

[0241] In some embodiments, when system 10 is configured to operate in LRM, Therapy Monitoring Module Ml is configured to assess therapeutic effectiveness specifically for large area depolarization and AF termination. In some embodiments, one or more components of Therapy Monitoring Module Ml , such as Rhythm Monitoring Unit C2, are configured to assess cardiac signals for ventricular arrhythmia. In some embodiments, one or more components of Therapy Monitoring Module Ml, such as Rhythm Monitoring Unit C2, are configured to detect ventricular activity (e.g., depolarization or repolarization) and deliver therapy only during a prescribed time window relative to the ventricular activity. For example, delivering LRM therapy shortly after ventricular depolarization (e.g., when the ventricles are most likely to be in a refractory state so as not to induce ventricularAttorney Docket No.: MAX-012-PCTarrhythmia.) Therapy Monitoring Module Ml can be configured to track one or more indices, such as Organization Index, to determine the best time to deliver LRM pacing. Therapy Module Ml can be configured to deliver therapy when the one or more indices indicates a change in arrhythmia for which LRM is preferred. Therapy Module Ml can be configured to monitor AF cycle length and / or to monitor for rhythm changes to determine if AF is being modified by LA Reset therapy. Therapy Monitoring Module Ml can be configured to detect successful AF termination and can trigger cessation of LRM therapy and / or transition to one or more monitoring modes. Additionally, or alternatively, Therapy Monitoring Module Ml can be configured to detect conversion from AF to AFL and can trigger transition to a different therapy mode configured to treat AFL. One or more components of Therapy Monitoring Module Ml, such as Control and Synchrony Analytics Unit C3, can be configured to use one or more indices, such as Synchrony Index and / or Control Index to determine if AF is being altered by LRM therapy.

[0242] In some embodiments, when system 10 is configured to operate in LRM, Configuration Management Module M2 is configured to establish parameters specifically optimized for large area depolarization during chaotic fibrillatoiy conduction. In some embodiments, Configuration Management Module M2 is configured to establish one or more asynchronous pulse delivery parameters. Configuration Management Module can M2 be configured to implement ventricular synchronization to avoid ventricular arrhythmias. In some embodiments, Configuration Management Module M2 determines triggering criteria such that system 10 will not pace until organized AF is detected. Alternatively, or additionally. Configuration Management Module M2 can determine triggering criteria such that system 10 will wait for fractionated AF before delivering LA Reset therapy. In some embodiments, Configuration Management Module M2 is configured to use unipolar pulse configurations and / or bipolar pulse configurations.

[0243] In some embodiments, when system 10 is configured to operate in LRM, Sensing Module M3 is configured to acquire and process cardiac electrical signals, for example signals that comprise chaotic AF signals for which LRM is indicated for treatment. Sensing Module M3 can be configured to detect ventricular depolarization timing and / or repolarization timing to coordinate LA Reset pulse delivery' timing. Sensing Module M3 can be configured to detect local tissue activation at each electrode 111. Sensing Module M3 can be configured to process unipolar and / or bipolar signals, and / or can be configured to perform filtering of the acquired cardiac signals.Attorney Docket No.: MAX-012-PCT

[0244] In some embodiments, when system 10 is configured to operate in LRM, Pacing Control Module M4 is configured to analyze ventricular depolarization timing, ventricular repolarization timing, and / or activations at each electrode 111 to determine optimal LA Reset pulse delivery timing. Pacing Control Module M4 can be configured to pulse ‘'as soon as ready” (e.g., with no feedback required for asynchronous delivery ). Alternatively, or additionally, Pacing Control Module M4 can be configured to pulse after a delay period following a ventricular depolarization, such as to lower the likelihood of inducing ventricular arrhythmia. In some embodiments, Pacing Control Module M4 is configured to implement triggering criteria, such as waiting for AF to be sufficiently organized before LA Reset pulse delivery'. Alternatively, or additionally, Pacing Control Module M4 can be configured to wait for AF to sufficiently fractionate before delivering therapy.

[0245] In some embodiments, when system 10 is configured to operate in LRM, Pacing Module M5 is configured to deliver bipolar pulses between two subsets of electrodes 111 for vectorized (e.g., directional) electrical pulses. In some embodiments, Pacing Module M5 is configured to deliver pulses between one or more electrodes 111 and one or more external electrodes, such as one or more skin patch electrodes.

[0246] Referring now to Fig. 5, a flow chart of an embodiment of a method of managing post-operative atrial fibrillation is illustrated, consistent with the present inventive concepts. Fig. 5 shows a flowchart of an embodiment of Method 1000, a method of managing postoperative atrial fibrillation (POAF) via one or more implanted devices. Method 1000 can be performed by one or more components of system 10. The one or more components of system 10 described in reference to Fig. 5 can be of similar construction and arrangement as the similar components described in reference to Fig. 1. Fig. 1 A, and otherwise herein.

[0247] Method 1000 can comprise a method of managing POAF using a temporary' cardiac monitoring and therapy system (e.g., system 10 of the present inventive concepts). POAF can occur following cardiac surgery and can be associated with increased morbidity7, prolonged hospitalization, and / or elevated stroke risk. Method 1000 can be configured to detect and / or predict POAF; deliver therapy to prevent, limit the likelihood, and / or terminate POAF; and / or to assess therapy effectiveness. In some embodiments, Method 1000 is performed during a post-operative monitoring period following cardiac surgery. The postoperative monitoring period can comprise at least 1 day, at least 3 days, at least 5 days, atAttorney Docket No.: MAX-012-PCTleast 7 days, at least 10 days, and / or at least 14 days. In some embodiments, the postoperative monitoring period comprises no more than 14 days, no more than 10 days, no more than 7 days, and / or no more than 5 days. In some embodiments, system 10 can determine that therapy should be withheld, such as when a determination to withhold therapy is based on signal quality, hemodynamic state, predicted benefit versus risk, or combinations of these.

[0248] Method 1000 can begin with Step 1010. In Step 1010, one or more medical procedures is performed. The one or more medical procedures can be selected from the group consisting of: coronary artery bypass grafting (CABG); cardiac valve repair; cardiac valve replacement; maze procedure; septal defect repair; two or more combined procedures; or combinations of these. Patients undergoing cardiac surgery can be at an elevated risk for POAF due to surgical trauma, pericardial inflammation, autonomic imbalance, electrolyte disturbances, atrial stretch, or combinations of these.

[0249] Following Step 1010, Method 1000 can proceed to Step 1020. In Step 1020, one or more devices can be implanted in the patient. In some embodiments, Step 1020 is performed before the surgical site is closed. In some embodiments, the one or more devices implanted comprises at least implantable device 100. Implantable device 100 can be configured for temporary post-operative use (e.g., explanted hours, days, or weeks after surgery). Implantable device 100 can be operably connected to external patient device 200. Implantable device 100 can be connected to external device 200 via lead 1121 (e.g., via one or more wires 112 and / or other conduits). External patient device 200 can be configured to sen e as a therapy generator and processing unit during the post-operative monitoring period. Additionally, or alternatively, during Step 1020 implantable device 100 is configured to be electrically coupled to clinician device 300 via lead 1121 to support one or more sensing tests, pacing tests, mapping procedures, parameter programming, and / or other implantation and / or trial functions described herein.

[0250] In some embodiments, implantable device 100 is positioned during a cross-clamp period of the surgical procedure. The cross-clamp period can comprise a period during which the aorta is cross-clamped and the heart is arrested. Positioning implantable device 100 during the cross-clamp period (or otherwise while the heart is not actively beating) can provide the implanting clinician improved visualization and access to cardiac structures during the implantation. In some embodiments, implantable device 100 is positioned after the cross-clamp is removed. Positioning implantable device 100 after cross-clamp removalAttorney Docket No.: MAX-012-PCTcan allow verification of electrode positioning (e.g., electrode 111 positioning) relative to beating heart tissue. In some embodiments, a first portion of implantable device 100 is positioned during the cross-clamp period and a second portion of implantable device 100 is positioned after cross-clamp removal. In some embodiments, at least a portion of device 100 is positioned during the cross-clamp period, and following the cross-clamp removal, a diagnostic or other evaluation can be performed. In some embodiments, at least a portion of device 100 is configured to be adjusted if appropriate following removal of the cross-clamp. In some embodiments, at least a first portion of device 100 is positioned on a first portion of the heart during the cross-clamp period, and at least a second portion of device 100 is positioned on a second portion of the heart after the cross-clamp is removed.

[0251] In Step 1030, system 10 can be configured to monitor cardiac activity (e.g., to monitor the patient). System 10 can be configured to acquire (e.g., continuously and / or intermittently’ acquire) cardiac signals, assess cardiac rhythm, and / or evaluate hemodynamic status. Step 1030 can sen e as a monitoring state (e.g., a relatively continuous monitoring state) to which Method 1000 returns following therapy delivery' or when POAF is not detected.

[0252] In some embodiments, system 10 is configured to operate in an “initial learning phase” following implantation. The initial learning phase can comprise a period of time during which algorithm 500 acquires baseline patient-specific data. The initial learning phase can comprise a period of time during which algorithm 500 calibrates one or more detection thresholds, classification parameters, and / or therapy parameters based on observed patientspecific cardiac activity'. In some embodiments, the initial learning phase comprises a time period of at least 1 hour, at least 6 hours, at least 12 hours, and / or at least 24 hours. In some embodiments, the initial learning phase comprises a time period of no more than 48 hours, no more than 24 hours, and / or no more than 12 hours.

[0253] Following the initial learning phase, system 10 can transition to an autonomous monitoring mode, a pre-emptive therapy delivery mode, or both. Autonomous monitoring can comprise signal acquisition and analysis (e.g.. continuous or intermittent signal acquisition and analysis), such as when performed autonomously (e.g., without clinician intervention). In some embodiments, algorithm 500 is configured to deliver pre-emptive pacing automatically upon detection of arrhythmia precursors meeting one or more triggering criteria.Attorney Docket No.: MAX-012-PCT

[0254] In Step 1040, system 10 can predict and / or detect POAF using the signals from Step 1030. Algorithm 500 can be configured to: identify the onset of atrial fibrillation; predict imminent atrial fibrillation based on precursor patterns; classify premature atrial contractions (PACs) (e.g., by arrhythmogenicity); or perform combinations of these. Step 1040 comprises a decision step to determine whether POAF has been predicted and / or detected. If POAF is predicted and / or detected, Method 1000 can proceed to Step 1050. If POAF is not predicted and / or detected, Method 1000 can return to Step 1030 to continue monitoring. In some embodiments, Step 1040 comprises a bias toward false negatives and / or false positives, as described herein.

[0255] In Step 1050, system 10 can select and / or perform therapy. System 10 can be configured to select a therapy modality based on: cardiac rhythm classification; tissue state; hemodynamic status; prior therapy response; or combinations of these. In some embodiments, therapy modalities can include: standard pacing; elevated-output pacing; reversible electroporation; or combinations of these.

[0256] In Step 1060, system 10 can assess the effectiveness of therapy delivered in Step 1050. In some embodiments, therapy effectiveness assessed by system 10 is based on: electrical criteria; tissue mechanics or tissue motion criteria; hemodynamic criteria; or combinations of these. Electrical criteria can include: rhythm restoration (e.g., sinus rhythm restoration); capture verification; arrhythmia termination; or combinations of these.Hemodynamic criteria can include: cardiac output improvement; blood pressure stabilization; or both.

[0257] After Step 1060, Method 1000 proceeds to Step 1070. In Step 1070, system 10 determines if therapy is successful. System 10 can analyze the acquired cardiac signals to determine if sinus rhythm has been restored, if arrhythmia has been terminated, or both. In some embodiments, system 10 compares post-therapy signals to pre-therapy signals to assess: changes in rhythm regularity; cycle length stability; and / or activation patterns. In some embodiments, system 10 evaluates hemodynamic parameters (e.g., cardiac output and / or blood pressure), such as to determine if therapy has improved cardiac function. In Step 1070, if therapy has not been successful. Method 1000 returns to Step 1050, and additional therapy can be selected and / or delivered, and / or the current therapy can be continued (e.g., with or without modification to one or more therapy parameters). In some embodiments, system 10 can escalate and / or otherwise change to a different therapy modality upon returning to StepAttorney Docket No.: MAX-012-PCT1050. In Step 1070, if therapy has been successful (e.g., the arrhythmia is terminated) Method 1000 continues to Step 1080.

[0258] In Step 1080. system 10 can determine if monitoring is complete. The determination can be based on: elapsed time since surgery; clinical stability- criteria; POAF burden metrics; physician assessment; or combination of these. If monitoring is complete, Method 1000 continues to Step 1090. If monitoring is not complete, Method 1000 returns to Step 1030. In some embodiments, Method 1000 performs Step 1030 continuously or semi-continuously (e.g., intermittently) while monitoring for POAF.

[0259] In Step 1090. device 100 can be removed (e g., explanted). In some embodiments, removing the device comprises percutaneous removal of implantable device 100. The removal can be performed by applying traction to one or more exteriorized portions of implantable device 100. In some embodiments, device 100 is constructed and arranged such that its removal can be performed without reopening the chest. In some embodiments, implantable device 100 comprises extraction-compatible fixation elements, such as fixation elements that are configured to release upon application of traction force. In some embodiments, at least a portion of device 100 remains implanted, for example when system 10 is configured to continue to provide therapy beyond the POAF monitoring period described herein. In some embodiments, a portion of device 100 is disconnected from EPD 200 (e.g., an external portion of system 10), and / or connected to an implantable portion (e.g., controller 130 of device 100 that can be implanted as described herein and operably attached to electrode array 110).

[0260] In some embodiments, system 10 is configured to generate one or more reports (e.g., a monitoring and therapy report) upon completion of the post-operative monitoring period. The monitoring and therapy report can include data selected from the group consisting of: number of arrhythmia episodes detected; duration of arrhythmia episodes; arrhythmia burden metrics; number of therapy deliveries; therapy modalities delivered; therapy success rates; hemodynamic parameters recorded; alert events generated; and combinations of these. The monitoring and therapy report can be transmitted to one or more hospital systems via network 50. The monitoring and therapy report can be stored in memory 412 and / or transmitted to server 600 (e.g., for archival).

[0261] In some embodiments, upon completion of Method 1000, no permanent hardware remains implanted in the patient, such as when the patient can return to an acceptableAttorney Docket No.: MAX-012-PCTbaseline cardiac state without any chronic implanted devices. Method 1000 can enable temporary post-operative management of POAF without requiring permanent pacemaker implantation or chronic device therapy. Alternatively, or additionally, at least a portion of system 10 remains implanted in and / or is configured to otherwise continue to provide therapy to the patient. In some embodiments, one or more portions of system 10 is configured to remain implanted in the patient, with or without continued therapy from system 10 (e.g., one or more biologically inert portions of system 10 are configured to remain implanted without patient injury).

[0262] Referring now to Figs. 6A through 6C, schematic views of embodiments of an implantable device configured for post-operative cardiac monitoring and therapy are illustrated, consistent with the present inventive concepts. Fig. 6A shows an embodiment of implantable device 100 including electrode arrays 110 positioned proximate multiple cardiac chambers. Fig. 6B shows an epicardial patch embodiment and an inset showing an applied configuration. Fig. 6C shows an embodiment of an electrode array positioned for delivering posterior wall therapy vectors. In some embodiments, implantable device 100 is configured for removal (e.g., explantation) without re-opening the chest. Implantable device 100 and / or other components described in Figs. 6A through 6C can be of similar construction and arrangement as the similar components described in reference to Fig. 1, Fig. 1A, and otherwise herein.

[0263] Implantable device 100 can include one or more connecting elements, such as hub 115 shown. Hub 115 can be configured to operably connect one or more electrode arrays 110. Hub 115 can be positioned at and / or near the patient’s skin (e.g., under the skin of the patient).

[0264] In some embodiments, implantable device 100 includes one or more electrode arrays 110 extending from and operably connected to hub 115. The one or more electrode arrays 110 can be configured for placement on or near one or more chambers of the heart (e.g., for endocardial and / or epicardial placement). For example, a first electrode array (e.g., such as electrode array 110a shown) can be configured for placement on or near the right atrium (labeled as RA in Fig. 6A). Electrode array 110a can include one or more electrodes, electrode 11 la shown. Additionally, or alternatively, a second electrode array (e.g., such as electrode array 110b shown) can be configured for placement on or near the left atriumAttorney Docket No.: MAX-012-PCT(labeled as LA in Fig. 6A). Electrode array 110b can include one or more electrodes, electrodes 111b shown. Additionally, or alternatively, a third electrode array (e.g.. such as electrode array 110c shown) can be configured for placement on and / or near a ventricle, such as the left ventricle (labeled as LV in Fig. 6A). Electrode array 110c can include one or more electrodes, electrodes 111c shown.

[0265] Implantable device 100 can include one or more exteriorized portions. The one or more exteriorized portions can extend from hub 115, such as when extending through a skin exit site to external patient device 200. In some embodiments, the one or more exteriorized portions comprise a portion of lead 1121.

[0266] Implantable device 100 can include one or more strain relief elements, strain relief 106 shown. Strain relief element can be configured to reduce mechanical stress at a skin exit site. Strain relief 106 can be configured to reduce tugging forces on one or more portions of implantable device 100 (e.g., electrode array 110). In some embodiments, strain relief 106 comprises one or more elements selected from the group consisting of: a suture point; an anchoring pad; a dressing-integrated strain relief structure; or combinations of these. In some embodiments, strain relief 106 is configured to secure an exteriorized portion of device 100 to the patient’s skin and / or underlying tissue.

[0267] One or more wires, such as wires 112 shown, can extend from hub 115 to one or more electrode arrays 110. Wires 112 can be configured to provide electrical communication between electrode arrays 110 and hub 115. Additionally, or alternatively, one or more wires 112 can extend from hub 115 through strain relief 106, to external patient device 200. In some embodiments, one or more wires 112 comprise one or more conductors of lead 1121.

[0268] In some embodiments, the implantation configuration of implantable device 100 can be selected based on procedure type, diagnosis, and / or arrhythmia risk. For example, a first configuration can position electrode arrays 110 on the left atrium. Alternatively, or additionally, a second configuration can position electrode arrays 110 on the left atrium and the right atrium. Alternatively, or additionally, a third configuration can position electrode arrays 110 on the left atrium and one or more ventricles.

[0269] In some embodiments, the implantation configuration of implantable device 100 can be selected based on surgical procedure type and / or therapy objective. Different surgical procedures can provide different anatomical access to different cardiac chambers. Different surgical procedures can be associated with different arrhythmia risk profiles.Attorney Docket No.: MAX-012-PCT

[0270] For example, a CABG procedure associated with a prevention-only objective can utilize a first configuration. The first configuration can include electrode arrays 110 positioned on the right atrium and the left atrium. A valve procedure associated with a prevention-plus-termination objective can utilize a second configuration. The second configuration can include electrode arrays 110 positioned on the left atrium and one or more ventricles. In some embodiments, one or more of the implantation configurations (e.g., the second configuration) can include additional electrodes 111 that are configured for elevatedoutput therapy and / or reversible electroporation.

[0271] In some embodiments, the implantation configuration of implantable device 100 and / or one or more parameters or settings of system 10 (e.g., one or more algorithm 500 parameters) can be selected based on patient risk stratification scores. Patient risk stratification scores can include CHADS2-VASc scores, CHA2DS2-VASc scores, and / or other clinical risk indices. Patients with elevated risk stratification scores can be selected (e g., by system 10, a clinician, or both) to receive more aggressive monitoring, lower therapy thresholds, adjusted biases or bias directions, and / or expanded electrode configurations.

[0272] In some embodiments, algorithm 500 is configured to incorporate one or more procedure-specific parameter presets. Procedure-specific parameter presets can comprise one or more algorithm parameters that are configured based on the surgical procedure performed. In some embodiments, procedure-specific parameter presets include PAC-origin weighting factors. PAC-origin weighting factors can be adjusted (e.g., by system 10, a clinician, or both) based on which cardiac regions were surgically manipulated during the procedure. Surgical manipulation of a cardiac region can increase arrhythmogenicity of ectopic activity originating from that region.

[0273] For example, a procedure performed using system 10 involving manipulation of the left atrial roof can result in algorithm 500 assigning increased arrhythmogenicity scores to PACs estimated to originate from the left atrial roof region. Alternatively, or additionally, a procedure involving manipulation of the right atrial appendage can result in algorithm 500 assigning increased arrhythmogenicity scores to PACs estimated to originate from the right atrial appendage region. In some embodiments, the procedure-specific presets are selected by a clinician via a user interface (e.g., user interface 450). In some embodiments, the procedure-specific parameter presets are automatically determined by system 10 (e.g., via anAttorney Docket No.: MAX-012-PCTalgorithm 500) based on procedure type information. Procedure type information can be received from one or more hospital systems via network 50.

[0274] As shown in Fig. 6B, implantable device 100 can comprise one or more flexible substrates, substrate 102 shown. Substrate 102 can be configured to conform to an epicardial surface of the patient’s heart. Electrode array 110 can be positioned on substrate 102.Electrode array 110 can include one, two, or more electrodes 111 arranged in a distributed pattern. The distributed pattern can be selected from the group consisting of: a grid pattern; a radial pattern; a linear pattern; or combinations of these.

[0275] In some embodiments, electrode array 110 includes a high-density mapping region comprising a local grid of electrodes 111 that are positioned with relatively small inter-electrode spacing. The high-density mapping region can be configured to support “high-definition” characterization of local activation, including estimating local activation times, activation time dispersion, and / or a local conduction velocity proximate the implant location. For example, algorithm 500 can be configured to detect activation events on two or more adjacent electrodes 111, compute time differences between the detected activation events, and estimate a propagation direction and / or conduction velocity based on the time differences and known electrode-to-electrode spacing. In some embodiments, algorithm 500 generates one or more maps and / or metrics based on the high-density mapping region, such as maps of activation time, conduction slowing, and / or regions consistent with conduction block, and uses the one or more maps and / or metrics to select therapy timing, electrode configurations, and / or therapy modality.

[0276] The inset of Fig. 6B illustrates implantable device 100 in an applied configuration. In the applied configuration, substrate 102 can conform to a curved tissue surface, such as a curved epicardial surface.

[0277] Implantable device 100 can include one or more fixation elements, anchoring element 105 shown. Anchoring element 105 can be configured to secure substrate 102 to cardiac tissue, such as epicardial tissue. Anchoring element 105 can comprise one or more elements selected from the group consisting of: barbs; clips; hooks; sutures; adhesive layers; adhesive patches; staples; tines; friction-fit elements; tissue-engaging protrusions; or combinations of these. In some embodiments, electrode array 110 and / or substate 102 comprises a geometry configured to frictionally and / or otherwise engage a portion of the anatomy to fixedly (e.g., temporarily fixedly) attach to the cardiac tissue, such as toAttorney Docket No.: MAX-012-PCTfrictionally engage the pericardial reflections (e.g., by wedging and / or bracing in the anatomic pocket between pericardial folds to secure contact on the epicardial surface).

[0278] Anchoring element 105 can be configured to provide temporary fixation during the post-operative period. Anchoring element 105 can be configured to release upon application of a traction force (e.g., by pulling on an exteriorized portion of implantable device 100), such as to facilitate simplified, atraumatic removal of implantable device 100.

[0279] In some embodiments, at least a portion of implantable device 100 comprises bioresorbable material. The bioresorbable material can be configured to degrade over time following implantation. In some embodiments, substrate 102 comprises bioresorbable material. In some embodiments, anchoring element 105 comprises bioresorbable material. The bioresorbable material can comprise one or more materials selected from the group consisting of: polylactic acid (PLA); polygly colic acid (PGA); polylactic-co-gly colic acid (PLGA); poly caprolactone (PCL); silk fibroin; magnesium alloys; and combinations of these. In some embodiments, the bioresorbable material is configured to substantially degrade within the post-operative monitoring period. In some embodiments, the bioresorbable material is configured to substantially degrade after the post-operative monitoring period.

[0280] Implantable device 100 can include one, two, or more functional elements, functional element 199 shown. Functional element 199 can comprise a mechanical assembly configured to enable implantable device 100 to assume a collapsed, folded, and / or rolled configuration. In some embodiments, functional element 199 can comprise one or more components with a feature selected from the group consisting of: fold regions; hinge regions; score lines; living hinges; articulation zones; flexible joints; thinned substrate regions; and combinations of these.

[0281] The collapsed, folded, and / or rolled configuration can facilitate placement and / or removal of implantable device 100. The collapsed, folded, and / or rolled configuration can facilitate conformance to curved tissue surfaces (e.g., the epicardial surface). Implantable device 100 can be removed after assuming a collapsed, folded, and / or rolled configuration (e.g., by rolling substrate 102 prior to applying traction to an exteriorized portion).

[0282] As shown in Fig. 6C, system 10 can include one or more electrode arrays positioned to span a target tissue region. A first electrode array (e.g., such as electrode array 1 lOd shown) can be positioned at or near the roof of the left atrium. Electrode array 1 lOd can include one or more electrodes, electrodes 11 Id shown. A second electrode array (e.g.,Attorney Docket No.: MAX-012-PCTsuch as electrode array 1 lOe shown), can be positioned at or near the floor of the left atrium. Electrode array 1 lOe can include one or more electrodes, electrodes 11 le shown.

[0283] Electrode arrays 1 lOd and 1 lOe can be configured to deliver energy across the posterior wall of the left atrium. Electrode arrays 1 lOd and 1 lOe can create a depolarization zone spanning the posterior wall. The depolarization zone can be configured to function as a temporary conduction obstacle. The temporary conduction obstacle can block independent wavefronts (e.g., arrhythmic wavefronts propagating across the posterior wall). One or more elevated-output pulses can be delivered in rapid succession to prolong the effect of regional depolarization. The depolarization zone can render tissue within the zone temporarily non-excitable (e.g., depolarized and / or not yet repolarized). Arrhythmic wavefronts encountering the depolarization zone can be extinguished and / or blocked from further propagation.

[0284] The electrode array arrangement illustrated in Fig. 6C (e.g., roof electrode array 1 lOd and floor electrode array 1 lOe) represent one configuration for creating a depolarization zone spanning the posterior wall. Alternative electrode array 110 arrangements can achieve similar functional obstacle effects. For example, a lateral electrode array and a septal electrode array can create a depolarization zone spanning a lateral-to-septal region.Alternatively, or additionally, an anterior electrode array and a posterior electrode array can create a depolarization zone spanning an anterior-to-posterior region. The electrode array 110 arrangement can be selected based on the patient’s arrhythmia substrate, anatomical characteristics, and / or surgical access. In some embodiments, system 10 includes electrode arrays 110 that can be positioned to enable multiple alternative depolarization zone configurations, and algorithm 500 can select the depolarization zone configuration based on real-time analysis of arrhythmia characteristics.

[0285] In some embodiments, system 10 includes one or more electrodes 111 positioned remotely from the heart, such as electrode 11 If shown. Electrode 11 If can be positioned on the skin surface, on a subcutaneous tissue surface, and / or on a pericardial surface.

[0286] In some embodiments, electrode 11 If functions as a return electrode. A return electrode can comprise a reference electrode and / or a remote conductive surface configured to complete an electrical circuit with one or more electrodes positioned on or near the heart (e.g., electrodes 11 Id and / or 11 le). Electrode 11 If can be configured to serve as an anode, a cathode, or both (e.g., for unipolar configurations). For example, unipolar configurations can be configured to provide unipolar sensing, unipolar pacing, and / or unipolar electroporation.Attorney Docket No.: MAX-012-PCTUnipolar sensing (e.g., using electrode 11 If as a reference) can provide broader field detection compared to bipolar sensing.

[0287] In some embodiments, electrode arrays 1 lOd and 1 lOe are configured to deliver elevated-output pacing. The elevated-output pacing can transiently depolarize the posterior wall of the left atrium. The elevated-output pacing can comprise an output energy level, level El. In some embodiments, level El can be at least 0.25J, at least 0.5J, at least 1 J, at least 2J, and / or at least 5J. In some embodiments, level El can be no more than 5J, no more than 2J, no more than 1 J, and / or no more than 0.5 J.

[0288] In some embodiments, transient depolarization can create a “virtual electrode effect”. The virtual electrode effect can be configured to temporarily block wavefront propagation across the posterior wall. In some embodiments, the elevated-output pacing is preceded by and / or followed by standard pacing and / or reversible electroporation.

[0289] The virtual electrode effect can arise from non-uniform distribution of electric fields during elevated-output energy delivery7. Elevated-output energy delivery by system 10 can create regions of hyperpolarization and regions of depolarization in tissue surrounding the delivery electrodes. The regions of depolarization can extend beyond the immediate vicinity of the electrodes, creating a “virtual electrode” that affects tissue at a distance from the physical electrode surface. The virtual electrode effect can enable elevated-output pacing to depolarize a larger tissue region that would be affected by standard pacing at conventional output levels. The enlarged depolarization region can increase the likelihood of interrupting arrhythmic wavefronts propagating through the affected tissue. The virtual electrode effect can be influenced by one or more factors selected from the group consisting of: output energy level; electrode geometry7; electrode spacing; tissue conductivity; tissue anisotropy; and combinations of these.

[0290] In some embodiments, electrodes 111 are configured for sensing, for energy7delivery, or for both sensing and energy delivery. For example, selected electrodes 111 can deliver energy while adjacent electrodes 111 (e.g., in close proximity) can sense local cardiac activity7. In some embodiments, the number of electrodes 111 used for sensing differs from the number of electrodes 111 used for energy delivery. In some embodiments, fewer electrodes 111 are used for sensing than for energy delivery. In some embodiments, fewer electrodes 111 are used for energy delivery than for sensing. In some embodiments, theAttorney Docket No.: MAX-012-PCTsubset of electrodes 111 used for sensing partially overlaps with the subset of electrodes 111 used for energy delivery.

[0291] In some embodiments, system 10 (e.g., via an algorithm 500) can be configured to perform and / or achieve “artifact mitigation” in which signal artifacts are reduced in the postoperative environment. Post-operative signal artifacts can arise from one or more sources selected from the group consisting of: pacing pulse delivery'; patient movement; respiratory motion; surgical site inflammation; electrode-tissue interface changes; external electrical interference; and combinations of these. System 10 can perform and / or achieve artifact mitigation using one or more techniques selected from the group consisting of: blanking windows: adaptive filtering; template subtraction; differential sensing; dynamic vector selection; signal quality7scoring; and combinations of these.

[0292] Blanking windows can include time intervals during which sensing is suspended following delivery of a pacing pulse and / or other energy7delivery. Blanking windows can reduce saturation artifacts and / or residual polarization artifacts. Adaptive filtering of system 10 can include one or more filters with parameters that are adjusted based on detected signal characteristics (e.g., noise level, frequency content, baseline drift). Template subtraction performed by system 10 can include subtracting a learned pacing artifact model from acquired signals. In some embodiments, algorithm 500 is configured to generate the learned pacing artifact model based on recorded pacing artifacts during the post-operative period. In some embodiments, algorithm 500 is configured to update the learned pacing artifact model based on recorded pacing artifacts during the post-operative period. Differential sensing performed by system 10 can include analyzing the difference between signals recorded from two or more electrodes 111 (e.g., two or more segments of a split-ring electrode, two or more adjacent electrodes). Differential sensing can be configured to reduce common-mode artifacts (e.g., far-field signals, motion artifacts). Dynamic vector selection performed by system 10 can include selecting one or more sensing vectors from among a plurality of available sensing vectors based on signal quality7. In some embodiments, algorithm 500 computes a signal quality score for each available sensing vector. In some embodiments, algorithm 500 selects the one or more sensing vectors with signal quality' scores exceeding a threshold. The signal quality7score can be based on one or more metrics selected from the group consisting of: signal-to-noise ratio; baseline stability; artifact contamination level; activation detection reliability; and combinations of these.Attorney Docket No.: MAX-012-PCT

[0293] In some embodiments, adjacent sensing electrodes 111 can be configured to detect local activation and / or to assess capture and / or tissue state. The adjacent sensing electrodes 111 can reduce saturation of sensing channels caused by energy delivery. In some embodiments, electrodes 111 comprise one or more electrode configurations selected from the group consisting of: ring electrodes; split-ring electrodes (e.g., two or more electrically separated segments arranged as a ring); directional electrodes (e.g., electrodes partially shielded with non-conductive material to bias sensing and / or delivery directionality): microelectrodes embedded within a larger electrode (e.g., micro-electrodes embedded within a ring electrode or cap electrode); and combinations of these.

[0294] In some embodiments, electrodes 111 can include one or more coatings, such as coating 104 described herein. Coating 104 can be configured to improve sensing efficacy. For example, coating 104 can reduce polarization artifacts. Coating 104 can increase the surface area of electrode 111, such as to lower source impedance and / or enhance recording fidelity. Additionally, or alternatively, coating 104 can be configured to improve energy delivery efficacy. For example, coating 104 can reduce electrode-tissue interface impedance to improve energy transfer efficiency. Additionally, or alternatively, coating 104 can be configured to increase or decrease electrode impedance. Coatings 104 can be applied selectively to specific electrodes 111 (e.g., a subset of electrodes 111). For example, a first electrode 111 can include a first coating 104, and a second electrode 111 can include a second coating 104 different from the first coating 104. Coatings 104 can be applied selectively to specific sides or portions of directional electrodes (e.g.. to the tissue-facing side of a directional electrode).

[0295] In some embodiments, one or more electrodes 111 can each include one or more integrated sensing elements. The integrated sensing elements can be selected from the group consisting of: thermistors; temperature sensors; strain gauges; accelerometers; and combinations of these. The integrated sensing elements can be embedded within an electrode housing and / or positioned adjacent to an electrode surface. In some embodiments, thermistors integrated with electrodes 111 are configured to measure local tissue temperature. Local tissue temperature can be indicative of local inflammation. Algorithm 500 can be configured to adjust therapy parameters based on local tissue temperature (e.g., adjusted based on the presence of an infection).Attorney Docket No.: MAX-012-PCT

[0296] Referring now to Fig. 7, a flowchart of an embodiment of a method for closed-loop therapy selection and delivery is illustrated, consistent with the present inventive concepts. Fig. 7 shows a flowchart of an embodiment of Method 2000, a method of selecting and delivering therapy for cardiac arrhythmia management. Method 2000 can be performed by one or more components of system 10. The one or more components of system 10 described in Fig. 7 can be of similar construction and arrangement as the similar components described in reference to Fig. 1, Fig. 1A, and otherwise herein.

[0297] Method 2000 can comprise a method of closed-loop therapy selection for postoperative cardiac arrhythmia management. Method 2000 is configured for: selecting and performing therapy; assessing therapy impact; and / or determining therapy success.

[0298] Method 2000 can be configured to analyze (e g., continuously and / or intermittently analyze) multi-site electrophysiological and physiologic data. Method 2000 can be configured to dynamically select among multiple therapy modalities. Method 2000 can be configured to determine when therapy should be delivered, when therapy should be withheld, or both.

[0299] Method 2000 can be performed during a post-operative monitoring and therapy period following cardiac surgery. In some embodiments, the post-operative monitoring and therapy period comprises at least 1 day, at least 3 days, at least 5 days, and / or at least 7 days. In some embodiments, the post-operative monitoring and therapy period comprises no more than 14 days, no more than 10 days, no more than 7 days, and / or no more than 5 days.

[0300] The multiple therapy modalities provided by system 10 can include standard pacing, elevated-output pacing, and / or reversible electroporation. The multiple therapy modalities can be delivered alone or in combination.

[0301] Method 2000 can begin with Step 2010. In Step 2010, one or more signals are acquired. Step 2010 can include acquiring one or more signals from one or more components of system 10. For example, Step 2010 can include acquiring cardiac electrograms (e g., near-field electrograms, far-field electrograms, or both) from implantable device 100.Additionally, or alternatively, Step 2010 can include acquiring body-surface ECG signals from one or more surface electrodes 111. Additionally, or alternatively, Step 2010 can include acquiring sensor data from one or more sensors of system 10 (e.g., hemodynamic data, acoustic data, accelerometer data).Attorney Docket No.: MAX-012-PCT

[0302] Step 2010 can be performed continuously, and / or periodically (i.e., intermittently) during the post-operative period.

[0303] Following Step 2010, Method 2000 can proceed to Step 2020. In Step 2020, the cardiac state is determined by system 10. Step 2020 can include analyzing the one or more signals acquired in Step 2010. In some embodiments, algorithm 500 is configured to analyze the one or more signals and determine the cardiac state. In some embodiments, determining cardiac state includes determining rhythm state. Algorithm 500 can be configured to classify rhythm state based on the acquired signals. Rhythm state can include one or more states selected from the group consisting of: normal sinus rhythm; atrial fibrillation; atrial flutter; atrial tachycardia; premature atrial contractions (PAC); premature ventricular contractions; ventricular tachycardia; and combinations of these.

[0304] In some embodiments, algorithm 500 is configured to assign an arrhythmogenicity score to one or more detected PACs. The arrhythmogenicity score can indicate the likelihood that a detected PAC will initiate and / or sustain an arrhythmia (e.g., atrial fibrillation).Algorithm 500 can be configured to determine the arrhythmogenicity score based on one or more PAC characteristics. The one or more PAC characteristics can be selected from the group consisting of: estimated origin location; coupling interval; activation pattern across two or more electrodes 111; morphological features of the PAC electrogram; historical correlation with arrhythmia initiation; and combinations of these. Estimated origin location can include pulmonary vein region, non-pulmonary region, septal region, lateral wall region, or combinations of these. Coupling interval can include the time interval between the PAC and a preceding sinus beat. Morphological features can include amplitude, width, fractionation, or combinations of these. In some embodiments, PACs with arrhythmogenicity scores exceeding a threshold trigger cause system 10 to deliver preventative therapy (e.g., preventative pacing). In some embodiments, PACs with arrhythmogenicity scores below the threshold do not trigger system 10 to deliver preventative therapy.

[0305] Algorithm 500 can be configured to refine the arrhythmogenicity scoring based on observed outcomes during the post-operative monitoring period. In some embodiments, algorithm 500 tracks which PAC characteristics are associated with subsequent arrhythmia initiation. In some embodiments, algorithm 500 tracks which PAC characteristics are not associated with subsequent arrhythmia initiation. Algorithm 500 can be configured to update one or more scoring parameters based on the tracked associations. The one or more scoringAttorney Docket No.: MAX-012-PCTparameters can include weighting factors, thresholds, classification boundaries, or combinations of these. In some embodiments, the scoring parameters are updated by algorithm 500 using one or more machine learning techniques (e.g., supervised learning, reinforcement learning, Bayesian updating). In some embodiments the scoring parameters are updated using one more generative artificial intelligence (Al) models. In some embodiments, algorithm 500 (e.g.. an Al algorithm) incorporates population-level reference data to initialize the arrhythmogenicity scoring. Population-level reference data can include baseline scoring parameters derived from historical patient outcomes (e.g., weighting factors reflecting observed correlations between PAC origin locations and arrhythmia initiation rates across a plurality of patients). In some embodiments, algorithm 500 incorporates populationlevel reference data to refine the arrhythmogenicity scoring. Population-level reference data can include data from patients with similar surgical procedures, similar arrhythmia histories, similar anatomical characteristics, or combinations of these. Population-level reference data can be received from server 600 via network 50.

[0306] In some embodiments, algorithm 500 is configured to support privacy-preserving model updates. Privacy-preserving model updates can include federated learning, differential privacy, secure aggregation, or combinations of these. Federated learning can include training algorithm 500 across multiple decentralized data sources (e.g., multiple hospitals, multiple system 10 installations) without exchanging raw patient data. In some embodiments, federated learning updates are performed by transmitting model parameters and / or gradients (rather than patient data) between one or more components of system 10 and server 600. Server 600 can be configured to aggregate federated updates from a plurality of system 10 installations. Server 600 can be configured to distribute updated model parameters to system 10 via network 50. Privacy-preserving learning can enable algorithm 500 to benefit from population-level insights while maintaining patient data privacy and regulatory compliance.

[0307] In some embodiments, algorithm 500 is configured to use reinforcement learning for therapy policy selection. Reinforcement learning can include optimizing one or more therapy parameters based on observed outcomes (e.g., therapy success, therapy failure, arrhythmia recurrence, hemodynamic response). The one or more therapy parameters optimized via reinforcement learning can be selected from the group consisting of: therapy modality; energy level; electrode configuration; timing parameters; triggering criteria; and combinations of these. Algorithm 500 can be configured to explore alternative therapyAttorney Docket No.: MAX-012-PCTparameters and / or exploit therapy parameters associated with favorable outcomes. Algorithm 500 can be configured to balance exploration and exploitation using one or more reinforcement learning techniques (e.g., epsilon -greedy, upper confidence bound, Thompson sampling). In some embodiments, the reinforcement learning policy is initialized based on population-level reference data and refined based on patient-specific outcomes during the post-operative monitoring period.

[0308] In some embodiments, determining cardiac state includes anticipating arrhythmia onset. Algorithm 500 can be configured to predict imminent arrhythmia based on precursor patterns. Algorithm 500 can be configured to classify premature atrial contractions (PACs) by arrhythmogenicity. Anticipating arrhythmia onset can include one or more arrhythmia precursors (e.g., premature atrial contractions with arrhythmogenic characteristics).

[0309] In some embodiments, determining atrial state includes detecting atrial instability. Algorithm 500 can be configured to detect atrial instability based on increased cycle length variability, increased activation time dispersion. PACs with arrhythmogenic characteristics, electrogram morphology changes, or combinations of these. Algorithm 500 can be configured to determine that atrial overdrive stabilization therapy should be delivered by system 10 when atrial instability is detected.

[0310] In some embodiments, determining cardiac state includes assessing hemodynamic state. Algorithm 500 can be configured to assess hemodynamic state based on system 10 sensor data. Hemodynamic state can be determined from pressure data, flow data, impedance-derived metrics, and / or heart sounds.

[0311] In some embodiments, determining cardiac state includes detecting a bradyarrhythmia is present. Algorithm 500 can be configured to detect one or more bradyarrhythmia conditions selected from the group consisting of: sinus bradycardia; sinus arrest; junctional rhythm; second-degree atrioventricular block; third-degree atrioventricular block; bundle branch block; and combination of these. Algorithm 500 can be configured to determine that hemodynamic support pacing should be delivered by system 10 when one or more bradyarrhythmia conditions are detected. Hemodynamic support pacing provided by system 10 can include ventricular pacing configured to increase heart rate. Hemodynamic support pacing can include atrial pacing, ventricular pacing, or both.

[0312] In some embodiments, determining cardiac state includes detecting loss of atrioventricular synchrony. Loss of atrioventricular synchrony can include junctional rhythm,Attorney Docket No.: MAX-012-PCTatrial standstill, atrioventricular dissociation, or combinations of these. Algorithm 500 can be configured to determine that multi-chamber pacing should be delivered by system 10 when loss of atrioventricular synchrony is detected. Multi-chamber pacing provided by system 10 can include pacing of two or more chambers (e.g., atrial pacing and ventricular pacing). Multi-chamber pacing of system 10 can be configured to restore timing between atria and ventricles. Multi-chamber pacing of system 10 can be configured to optimize preload and / or stroke volume.

[0313] In some embodiments, algorithm 500 is configured to detect low cardiac output based on hemodynamic sensor data. Hemodynamic sensor data can include pressure data, flow data, impedance-derived metrics, heart sounds, or combinations of these. Algorithm 500 can be configured to determine that rate optimization should be performed by system 10 when low cardiac output is detected. Rate optimization can include adjusting pacing rate. Rate optimization can include adjusting atrioventricular timing. Algorithm 500 can be configured to select pacing rate targets based on hemodynamic sensor data. Algorithm 500 can be configured to select atrioventricular timing based on hemodynamic sensor data. In some embodiments, algorithm 500 iteratively adjusts pacing parameters and evaluates hemodynamic response to optimize cardiac performance.

[0314] Following Step 2020, Method 2000 can proceed to Step 2030. Step 2030 comprises a decision step to determine whether therapy is indicated. System 10 can evaluate the cardiac state determined in Step 2020. Algorithm 500 can be configured to determine whether therapy is indicated based on the cardiac state. Therapy can be indicated (e.g., and delivered by system 10) when one or more conditions are met. The one or more conditions can be selected from the group consisting of: detection of an arrhythmia; detection of an arrhythmia precursor; prediction of impending arrhythmia onset; detection of loss of chamber synchrony; and combinations of these.

[0315] If therapy is indicated, Method 2000 can proceed to Step 2050 (Assess Tissue State). If therapy is not indicated, Method 2000 can proceed to Step 2040 (Withhold Therapy).

[0316] In Step 2040, system 10 can withhold therapy (e.g., not provide therapy). System 10 can determine that therapy should not be delivered. Algorithm 500 can be configured to determine that therapy should be withheld. In some embodiments, algorithm 500 determines that therapy should be withheld based on a tissue state (e.g., a particular portion of tissue isAttorney Docket No.: MAX-012-PCTnot excitable). In some embodiments, algorithm 500 determines that therapy should be withheld based on signal reliability (e.g., signal quality is insufficient for reliable decisionmaking). In some embodiments, algorithm 500 determines that therapy should be withheld based on a hemodynamic state (e.g., hemodynamic parameters are within acceptable limits). In some embodiments, algorithm 500 determines that therapy should be withheld based on a predicted benefit versus risk analysis (e.g., predicted benefit is insufficient when compared to the predicted risk). In some embodiments, algorithm 500 determines that therapy should be withheld based on patient safety constraints (e.g., cumulative energy exposure limits, rate limits, vulnerable timing).

[0317] In some embodiments, system 10 (e.g., in Step 2040) is configured to track cumulative energy delivered during the post-operative monitoring period. Cumulative energy can include total energy delivered via standard pacing, elevated-output pacing, reversible electroporation, or combinations of these. Algorithm 500 can be configured to compare cumulative energy to one or more safety thresholds. In some embodiments, algorithm 500 determines that therapy should be withheld when cumulative energy exceeds a safety threshold. In some embodiments, algorithm 500 generates an alert when cumulative e...

Claims

1. Attorney Docket No.: MAX-012-PCTWHAT IS CLAIMED IS:

1. A system for treating a cardiac arrhythmia of a patient, the system comprising: an implantable device comprising an electrode array including one or more sensing electrodes and one or more pacing electrodes; anda controller comprising a memory configured to store instructions for one or more algorithms, wherein the one or more algorithms are executable to:(i) operate the system in a therapy category selected from the group consisting of: Diagnostic Monitoring Mode (DMM); Tissue Conditioning Therapy (TCT); Acute Therapy (AcTh); Multi-Chamber Synchronization Therapy (MCST); and combinations thereof;(ii) process diagnostic data collected by the system;(iii) select and configure the therapy provided by the system; and(iv) automatically transition the system between therapy and / or monitoring modes.

2. The system according to claim 1 and / or any one or more other claims herein, wherein TCT further includes Pace Conditioning Mode (PCM), Conditioning Monitoring Mode (CMM), or both;wherein AcTh further includes: Preventative Pacing Mode (PPM); Pace Termination Mode (PTM); Left- Atrial Reset Mode (LRM); Arrhythmia Disruption Mode (ADM); and combinations thereof; andwherein MCST further includes: Atrial Synchronization Mode (ASM); AV Synchronization Mode (AVSM); Atrial Overdrive Stabilization Mode (AOSM); Synchronization Therapy Monitoring Mode (STMM); and combinations thereof.

3. The system according to claim 1 and / or any one or more other claims herein, wherein the system is configured to improve hemodynamic function by reducing delay of activation of the left-atrial appendage (LAA) via pacing from an electrode positioned in the distal reach of the Vein-of-Marshall; andAttorney Docket No.: MAX-012-PCTwherein the system is further configured to synchronize activation of the left ventricle.

4. The system according to claim 1 and / or any one or more other claims herein, wherein the system is configured to deliver nerve stimulation to shift autonomic tone toward inhibition of AF.

5. The system according to claim 1 and / or any one or more other claims herein, wherein the system is configured to analyze data collected from multiple patients to identify similarities, differences, and / or patterns, and wherein the system is further configured to recommend and / or enact parameter updates based on the collected data.

6. The system according to claim 1 and / or any one or more other claims herein, wherein the one or more algorithms are executable to deliver pacing stimuli across the electrode array to advance and / or block cardiac activation wavefronts and synchronize atrial activation to a spatiotemporal pattern of stimulation, and wherein the pacing stimuli is configured to automatically stop upon restoration of normal rhythm.

7. The system according to claim 6 and / or any one or more other claims herein, wherein the timing of the delivered pacing stimuli is in response to electrical activity sensed at one or more electrodes of the electrode array.

8. The system according to claim 6 and / or any one or more other claims herein, wherein delivery of the pacing stimuli is simultaneous and / or asynchronous, and wherein delivery of the pacing stimuli is regular and / or irregular.

9. The system according to claim 6 and / or any one or more other claims herein, wherein delivery of the pacing stimuli is imperceptible or minimally perceived by the patient.Attorney Docket No.: MAX-012-PCT10. The system according to claim 6 and / or any one or more other claims herein, wherein the one or more sensing electrodes and / or the one or more pacing electrodes are spatially distributed.

11. The system according to claim 6 and / or any one or more other claims herein, wherein the system is configured to execute in a Preventative Pacing Mode (PPM).

12. The system according to claim 6 and / or any one or more other claims herein, wherein the system is configured to execute in a Pace Termination Mode (PTM) including Simultaneous PTM and Consensus PTM.

13. The system according to claim 6 and / or any one or more other claims herein, wherein delivery of the pacing stimuli is configured to maximize, over a given time interval, the area of tissue in a depolanzed state.

14. The system according to claim 6 and / or any one or more other claims herein, wherein delivery of the pacing stimuli is configured to maximize, over a given time interval, the area of tissue in a repolarized state.

15. A system for providing a left-atrial reset therapy, the system comprising:the implantable device and controller according to claim 1, wherein the implantable device is further configured to deliver a limited sequence of pulses that abruptly depolarize the targeted area, and wherein the pulses are delivered asynchronously to fibrillatory activity in the treated chamber and synchronously to non-fibrillating chambers.

16. The system according to claim 15 and / or any one or more other claims herein, wherein the sequence of pulses is delivered in rapid succession and wherein each pulse comprises engineered phases.

17. A system for preventing induction of atrial fibrillation, the system comprising: the implantable device and controller according to claim 1. wherein the implantable device is configured to detect premature atrial contractions (PACs) and / or pro-arrhythmogenic conditions, and wherein the implantable device isAttorney Docket No.: MAX-012-PCTfurther configured to deliver simultaneous and / or strategically staggered multisite pacing across distributed electrodes to compress activation times and reduce depolarization and / or repolarization gradients to prevent AF initiation.

18. The system according to claim 17 and / or any one or more other claims herein, wherein the system further comprises functional modules selected from the group consisting of: Therapy Monitoring Module (Ml); Configuration Management Module (M2); Sensing Module (M3); Pacing Control Module (M4); Pacing Module (M5); and combinations thereof.

19. The system according to claim 18 and / or any one or more other claims herein, wherein the therapy monitoring module (Ml) is configured to: classify SR / PAC patterns; identify first beats of AF; estimate PAC origin from activation timing / morphology; and / or adapt PAC criteria with feedback provided to the configuration management module (M2).

20. The system according to claim 18 and / or any one or more other claims herein, wherein the configuration management module (M2) is configured to: set PAC timing windows; account for SR variance; and / or select unipolar and / or bipolar configurations; and wherein the sensing module (M3) is configured to detect local activation at each electrode.

21. A system for treating atrial fibrillation of a patient, the system comprising:a stimulation device for delivering energy to tissue of the patient’s heart, wherein delivery of the energy is configured to at least reduce atrial fibrillation without ablating the heart tissue.

22. The system according to claim 21 and / or any one or more other claims herein, wherein the system comprises the system according to any of claims 1 through 20.

23. The system according to claim 21 and / or any one or more other claims herein, wherein the system is configured to reduce the use of blood thinners taken by the patient.Attorney Docket No.: MAX-012-PCT24. A method of treating atrial fibrillation of a patient, the method comprising:delivering energy to tissue of the patient’s heart,wherein the method is configured to at least reduce atrial fibrillation without ablating the heart tissue.

25. The method according to claim 24 and / or any one or more other claims herein, wherein the energy is delivered using the system according to any of claims 1 through 22.

26. The method according to claim 24 and / or any one or more other claims herein, the method is configured to reduce the use of blood thinners taken by the patient.

27. A system for providing post operative therapy to a patient, the system comprising:an implantable device comprising an electrode array including one or more sensing electrodes and one or more pacing electrodes; anda controller comprising a memory configured to store instructions for one or more algorithms, wherein the one or more algorithms are executable to:(i) monitor for post operative atrial fibrillation, and(ii) cause the implantable device to deliver therapy configured to prevent and / or otherwise treat post operative atrial fibrillation; wherein the implantable device is configured to be explanted following a post operative monitoring period.

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