Tricuspid conduction protection

Abstract

A method of machine-assisted setting up of a procedure for tricuspid valve implantation in a patient with a heart, comprising: (a) identifying a conduction system location on an image data set of said heart, said image acquired using data collection from outside the heart; and (b) providing machine-assisted guidance of a tricuspid valve implantation and / or selection based on a risk to the conduction system from valve implantation.

Description

[0001] TRICUSPID CONDUCTION PROTECTION

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of priority and under 35 USC § 119(e) of US Provisionals Nos. 63 / 736,640 filed on December 20, 2024; 63 / 809,084 filed on May 20, 2025; 63 / 809,778 filed on May 21, 2025 and 63 / 918,500 filed on November 16, 2025. It also claims priority of PCT Patent Application No. IB2025 / 059358 filed on September 18, 2025. The contents of all applications are incorporated herein by reference in their entirety.

[0004] This application is also related to the following applications: PCT IB 2024 / 057540; PCT IB2024 / 057541; PCT IB2024 / 057539; US 63 / 531,063; US 63 / 530, 724;US 63 / 532,995; US 63 / 664,786; US 63 / 656,164; US 63 / 621,140; and US 63 / 6 95,905.

[0005] These applications also include methods and apparatus which may be used for carrying out some acts in accordance with some embodiments of the invention.

[0006] FIELD AND BACKGROUND

[0007] The present invention, in some embodiments thereof, relates to performing cardiac procedures using conduction system information and, more particularly, but not exclusively, to TTVR (Transcatheter Tricuspid Valve Replacement).

[0008] The article “Cardiac Conduction System: Delineation of Anatomic Landmarks With Multidetector CT”, Indian Pacing Electrophysiol J. 2009 Nov-Dec; 9(6): 318-333, states: “Major components of the cardiac conduction system including the sinoatrial node (SAN), atrioventricular node (AVN), the His Bundle, and the right and left bundle branches are too small to be directly visualized by multidetector CT (MDCT) given the limited spatial resolution of current scanners. However, the related anatomic landmarks and variants of this system as well as the areas with special interest to electrophysiologists can be reliably demonstrated by MDCT. Some of these structures and landmarks include the right SAN artery, right atrial cavotricuspid isthmus, Koch triangle, AVN artery, interatrial muscle bundles, and pulmonary veins. In addition, MDCT has an imperative role in demarcating potential arrhythmogenic structures. The aim of this review will be to assess the extent at which MDCT can outline the described anatomic landmarks and therefore provide crucial information used in clinical practice.”

[0009] US patent 8,634,896 describes “A method for 3D reconstruction of the positions of a catheter as it is moved within a human body, comprising: (a) ascertaining the 3D position of a point on a catheter for insertion into the body; (b) acquiring fixed-angle, single-plane fluoroscopic image data of the body and catheter; (c) transferring the image data and catheter-point position to a computer; (d) determining 2D image coordinates of the point on the catheter; (e) changing the insertion length of catheter by a measured amount; (f) acquiring additional single-plane fluoroscopic image data of the body and catheter from the same angle, transferring the length change and image data to the computer, and determining image coordinates of the point on the catheter; (g) computing the 3D position of the catheter point; and (h) repeating steps e-g. A 3D model is constructed by assembling the plural 3D positions of the catheter point.”

[0010] US patent 9,986,931 describes “A method for automatically determining the 3D position and orientation of a radio-opaque medical object in a living body using single-plane fluoroscopy comprising capturing a stream of digitized 2D images from a single-plane fluoroscope (10), detecting the image of the medical object in a subset of the digital 2D images, applying pixel-level geometric calculations to measure the medical-object image, applying conical projection and radial elongation corrections (31) to the image measurements, and calculating the 3D position and orientation of the medical object from the corrected 2D image measurements.”

[0011] SUMMARY

[0012] Following is a non-exclusive list including some examples of embodiments of the invention. The invention also includes embodiments which include fewer than all the features in an example and embodiments using features from multiple examples, also if not expressly listed below.

[0013] Example 1. A method of a machine-assisted cardiac procedure (e.g., TTVR), comprising:

[0014] (a) identifying a conduction system location on an image data set of said heart, said image acquired using data collection from outside the heart; and

[0015] (b) providing machine-assisted guidance of a tool for TTVR to a target location associated with said conduction system location.

[0016] Example 2. The method of example 1, comprising following said guidance to bring said tool to said target location.

[0017] Example 3. The method of example 1 or example 2, wherein said procedure comprises interacting with said conduction system at or adjacent said target location.

[0018] Example 4. The method of any of examples 1-3, wherein said procedure comprises avoiding interacting with said conduction system at or adjacent said target location.

[0019] Example 5. A method of navigating a tool with a marker on a real or synthetic fluoroscopic image, comprising:

[0020] (a) overlying on the fluoroscopic image at least one anatomical marker annotation having 3D coordinates;

[0021] (b) guiding a user to use or showing the user one or both of: (i) a first image with the tool marker and the annotation inline and appearing overlapping or near overlapping; and

[0022] (ii) a second image with the tool marker and the annotation in a same plane with no foreshortening.

[0023] Example 6. The method of example 5, wherein said overlaying comprises overlaying at two areas or over an area extending at least 3% of a width of the image and wherein said second image shows both areas in a same plane.

[0024] Example 7. Apparatus for planning a cardiac procedure, comprising:

[0025] (a) a conduction system estimator programmed to receive a 3D data set of the heart and generate an estimation of a location of a conduction system near a tricuspid valve annulus and having a length of at least 3 cm;

[0026] (b) a GUI configured to show a proposed target location and a proposed path for said procedure.

[0027] Example 8. Apparatus according to example 7, comprising one or more of a cardiac electrical activity simulator, a geometric simulator and a search engine.

[0028] Example 9. Apparatus for supporting a cardiac procedure, comprising:

[0029] (a) an overlayer which overlays a 3D annotation on a fluoroscopic image;

[0030] (b) a view generator which generates one or both of an imager viewing angle recommendation and one or more synthetic views.

[0031] Example 10. A method of visualization, comprising: a. registering a conduction system landmark detected at a prior time in a first coordinate set to a second coordinate set; and b. visualizing a live treatment tool together with said conduction system landmark in said second coordinate set.

[0032] Example 11. The method of example 10, wherein registering a conduction system landmark is in a first imaging modality; and said visualizing a live treatment tool is in a second modality.

[0033] Example 12. The method of any of examples 10-11, comprising also visualizing a treatment path and / or a treatment target, associated with said landmark.

[0034] Example 13. A method of visualization, comprising: a. automatically identifying and measuring at least one dimension of at least one tool or associated anatomy on a fluoroscopic image of the heart; and b. displaying said dimension.

[0035] Example 14. The method of example 13, wherein said displaying is on said fluoroscopic image. Example 15. The method of example 13 or example 14, wherein said automatically identifying comprises identifying a ventricular septum and displaying a distance associated with a travel of said at least one tool.

[0036] Example 16. The method of example 15, comprising displaying a distance not along a trajectory of said at least one tool.

[0037] Example 17. A method of visualization, comprising: a. generating a 2D or 3D image from a 3D image data set of the heart; b. acquiring an image of a tool using a 2D imager; and c. displaying said tool on said generated image.

[0038] Example 18. A method of registering an object in a fluoroscopy image to a 3D data set, comprising:

[0039] (a) mapping the 3D data set to the fluoroscopy image;

[0040] (b) identify a contact of said object in the fluoroscopy image with an anatomical constrain of a tissue imaged in the fluoroscopy image;

[0041] (c) using the contact information to constrain the possible mappings from the fluoroscopy image back to the 3D image.

[0042] Example 19. A method of guiding a cardiac procedure, comprising:

[0043] (a) receiving a 3D data set of the heart;

[0044] (b) acquiring a live image of the heart including at least one interventional tool;

[0045] (c) generating one or more 3D views of the heart which include an indication of said interventional tool; and

[0046] (d) displaying said one or more views or one or more projections thereof to an operator.

[0047] Example 20. The method of example 19, comprising (e) navigating said tool by said user using said displayed one or more views or projections thereof.

[0048] Example 21. The method of example 19 or example 20, comprising using said acquired live image for less than 20% of the time that said displayed one or more views are used, during navigating said tool in said heart.

[0049] Example 22. A system comprising circuitry configured to carry out the methods of one or more of examples 10-21.

[0050] Example Al. A method of implanting a prosthetic tricuspid valve in a heart of a patient, comprising:

[0051] (a) estimating a relative location of at least a portion of a conduction system of the patient and a tricuspid valve region; and (b) implanting a prosthetic tricuspid valve in said region, while reducing risk of damage to said conduction system, preemptively preparing for such damage and / or avoiding implantation, based on said estimating damaging said conduction system at said estimated location.

[0052] Example A2. A method according to example Al, wherein said implanting comprises positioning said valve using a marker of said valve.

[0053] Example A3. A method according to any of examples A1-A2, wherein said implanting comprises displaying overlaid on an in-procedure image, one or more of said conduction system, an indication to avoiding implantation and an indication where implantation is allowed.

[0054] Example A4. The method according to any of examples A1-A3, wherein said reducing risk comprises aligning said valve with said estimating.

[0055] Example A5. The method according to any of examples A1-A4, wherein said preemptively preparing comprises implanting a pacemaker in anticipation of said damage.

[0056] Example A6. A method of implanting a prosthetic valve in a heart of a patient, comprising:

[0057] (a) estimating a risk of conduction system damage due to the implantation of said valve; and

[0058] (b) avoiding implantation of said valve if the risk is above an allowed risk level set for the patient.

[0059] Example A7. The method of example A6, wherein said risk is determined by a computing circuitry based on an estimation of conduction system location.

[0060] Example A8. A method of implanting a prosthetic tricuspid valve in a heart of a patient, comprising:

[0061] (a) estimating a relative location of at least a portion of a conduction system of the patient and a tricuspid valve region; and

[0062] (b) displaying an indication of the at least a portion of a conduction system of the patient, a planning indication and / or a risk indication when implanting a prosthetic tricuspid valve in said region.

[0063] Example A9. The method of example A8, wherein said displaying comprises displaying over a 2D image acquired during the implanting procedure.

[0064] Example A10. The method of example A8 or example A9, comprising implanting a prosthetic tricuspid valve in said region, while avoiding damaging said conduction system at said estimated location.

[0065] Example Al l. The method according to any of examples A8-A10, wherein said estimating comprises imaging said heart and estimating said location based on said imaging.

[0066] Example A12. The method according to example Al l, wherein said estimating and said imaging are performed prior to a tricuspid implantation procedure. Example A13. The method according to any of examples A8-A12, wherein said estimating comprises estimating a portion of a non-branching bundle.

[0067] Example A14. The method according to any of examples A8-A13, comprising estimating one or more areas where said prosthetic valve might apply pressure which risks damaging said conduction system.

[0068] Example A15. The method according to example A14, wherein said areas are estimated relative to an annulus of a tricuspid valve of said heart.

[0069] Example A16. The method of example A15, wherein said estimating one or more areas comprises generating a risk score based on a distance between a part of a conduction system and an expected point of applied pressure by the valve.

[0070] Example A17. The method according to any of examples A8-A15, comprising selecting a prosthetic valve or generating a suggestion for said prosthetic valve according to said estimating a relative location.

[0071] Example A18. The method according to any of examples A8-A17, comprising selecting a valve orientation according to said estimating a relative location.

[0072] Example A19. The method according to any of examples A8-A18, comprising selecting a valve rotation according to said estimating a relative location.

[0073] Example A20. The method according to any of examples A8-A19, comprising selecting a valve elevation according to said estimating a relative location.

[0074] Example A21. The method according to any of examples A8-A20, comprising generating an implantation plan based on said estimating a relative location.

[0075] Example A22. A system for supporting implantation of a prosthetic tricuspid valve in a heart of a patient, comprising:

[0076] (a) a conduction system identifier which receives an anatomical image of the heart and generates an estimate of a conduction system location;

[0077] (b) a processor programmed to generate at least one indication related to a portion of the conduction system adjacent a tricuspid annulus; and

[0078] (c) an overlayer which overlays said indication on a 2D or 3D representation of the heart.

[0079] Example A23. The system according to example A22 wherein said processor is programmed to provide a planning mode and wherein said overlayer overlays said indication during said planning mode of the system.

[0080] Example A24. The system according to example A22, wherein said overlayer is configured to overlay said indication on a live image. Example A25. The system according to example A22, wherein said overlayer is configured to overlay said indication on a synthetically generated image based on real time data collection during an operating procedure on said patient.

[0081] Example A26. The system according to any of examples A22-A25, wherein said indication includes one or more of a safe zone for implantation, a danger zone to avoid, a plan for implantation and a conduction system adjacent said annulus.

[0082] Example A27. The system according to any of examples A22-A26, wherein said processor is programmed to measure at least one distance between said annulus and said conduction system.

[0083] Example A28. A prosthetic tricuspid valve, comprising: a body; and one or more anchoring elements, wherein said anchoring elements are arranged around said body and define a gap of between 20 and 60 degrees where they do not apply radial pressure in a direction away from said body on cardiac tissue, when implanted.

[0084] Example A29. A prosthetic tricuspid valve according to example A28 comprising at least one radio-opaque marker for identifying said gap.

[0085] Example A30. A prosthetic tricuspid valve according to example A28 or example 29A, wherein said anchors are non-penetrating.

[0086] Example A31. A prosthetic tricuspid valve according to any of examples A28-A30, wherein said valve is rotationally symmetric or mirror symmetric other than said gap.

[0087] Example A32. A method of selecting a valve and / or valve implant location for a prosthetic tricuspid valve, comprising:

[0088] (a) receiving a location of a conduction system adjacent an annulus of a tricuspid valve in a patient;

[0089] (b) selecting one or more of a valve geometry, valve size, valve rotation, valve orientation and / or valve elevation which reduces a risk of damage to said conduction system when said valve is implanted according to said selection.

[0090] Example A33. The method according to example A32, performed by a computer.

[0091] Example A34. A computer-implemented method of operation of circuitry for supporting implantation of a prosthetic tricuspid valve in a heart of a patient, comprising:

[0092] (a) receiving an anatomical image of the heart;

[0093] (b) generating an estimate of a conduction system location based on said image;

[0094] (c) generating at least one indication related to a portion of the conduction system adjacent a tricuspid annulus; and (d) overlaying said indication on a 2D or 3D representation of the heart.

[0095] Example B l. A method of planning an implantation procedure of a prosthetic tricuspid valve in a heart of a patient, comprising:

[0096] (a) acquiring at least one relative geometry of a conduction system and one or more parts of a prosthetic valve which move during deployment;

[0097] (b) estimating a risk of conduction system damage due to implantation of said prosthetic valve based on said acquired relative geometry.

[0098] Example B2. The method according to example B l, wherein said estimating comprises taking into account one or more of the following damage mechanisms: stretching or compression of a conduction system section due to expansion of a body of the prosthetic valve; pressure by an anchor section of the prosthetic valve; pinching between an anchor and a body of said prosthetic valve; and pressure or shearing during a movement of an anchor of said prosthetic valve during deployment.

[0099] Example B3. The method according to example B 1 or example B2, wherein said estimating is based on a simulation of a deployment and mechanical interaction thereat.

[0100] Example B4. The method according to any of examples B1-B3, wherein said estimating is based on a fixed danger zone defined by such motion.

[0101] Example B5. The method according to any of examples B1-B4, wherein said estimating is based on at least one distance between said conduction system and a native valve annulus.

[0102] Example B6. The method according to example B5, wherein said at least one distance comprises a minimal distance, a maximal distance and / or an average distance.

[0103] Example B7. The method according to example B5 or example B6, wherein said at least one distance is a distance calculated by projection onto a plane.

[0104] Example B8. The method according to any of examples B5-B7, wherein said at least one distance comprises at least two or at least three distances.

[0105] Example B9. The method according to any of examples B5-B8, wherein said at least one distance comprises a minimum lateral distance.

[0106] Example B IO. The method according to any of examples B5-B9, wherein said at least one distance comprises a vertical distance.

[0107] Example B l l. The method according to any of examples B5-B 10, wherein said at least one distance comprises an Euclidian distance. Example B 12. The method according to example B7, wherein said plane is defined using three points along a tricuspid annulus.

[0108] Example B13. The method according to any of examples B 1-B 12, comprising displaying said risk to a user.

[0109] Example B 14. The method according to example B13, wherein said risk is shown as binary.

[0110] Example B 15. The method according to example B 13 or example B 14, comprising displaying to a user the option to modify one or more valve or procedure parameter and show a risk for the updated parameter.

[0111] Example B 16. The method according to any of examples B1-B15, comprising selecting a patient for therapy based on said risk.

[0112] Example B 17. The method according to any of examples B1-B16, planning a pacemaker implantation based on said risk.

[0113] Example B18. The method according to any of examples B 1-B 17, changing a valve selection or recommendation based on said risk.

[0114] Example B 19. The method according to any of examples B 1-B 18, generating procedure guidance and / or overlay markings based on said risk.

[0115] Example B20. The method according to any of examples B 1-B 19, wherein the valve comprises a plurality of anchors that bend back during deployment.

[0116] Example B21. The method of example B20, comprising selecting a valve orientation according to said risk and / or said relative geometry.

[0117] Example B22. The method of example B20 or example B21, comprising selecting an interanchor gap geometry according to said risk and / or said relative geometry.

[0118] Example B23. The method of any of examples B20-B22, comprising selecting an anchor geometry and / or body geometry according to said risk and / or said relative geometry.

[0119] Example B24. The method of any of examples B1-B23 being computer implemented, for at least providing an automatic recommendation.

[0120] Example B25. A preplanning and / or intra-operative computer system configured to support and / or carry out the methods of any of examples B 1-B24.

[0121] Example Cl. A method of planning an implantation procedure of a prosthetic tricuspid valve implant in a heart of a patient, comprising:

[0122] (a) receiving at least one relative geometry of a conduction system and (i) a native tricuspid valve annulus; and / or (ii) one or more parts of a prosthetic valve which move during deployment; and

[0123] (b) estimating a risk of conduction system damage due to implantation of said prosthetic valve based on said received relative geometry. Example C2. The method according to example Cl, wherein said estimating comprises taking into account one or more of the following damage mechanisms: stretching or compression of a conduction system section due to expansion of a body of the prosthetic valve; pressure by an anchor section of the prosthetic valve; pinching between an anchor and a body of said prosthetic valve; pressure or shearing during a movement of an anchor of said prosthetic valve during deployment; and timing and force of contact between the valve and a central fibrous body near the conduction system.

[0124] Example C3. The method according to example Cl or example C2, wherein said estimating is based on a simulation of a deployment and mechanical interaction thereat.

[0125] Example C4. The method according to any of examples C1-C3, wherein said estimating is based on a fixed danger zone defined by such motion.

[0126] Example C5. The method according to any of examples C1-C4, wherein said estimating is based on at least one distance between said conduction system and a native valve annulus.

[0127] Example C6. The method according to example C5, wherein said at least one distance comprises a minimal distance, a maximal distance and / or an average distance.

[0128] Example C7. The method according to example C5 or example C6, wherein said at least one distance is a distance calculated by projection onto a plane.

[0129] Example C8. The method according to any of examples C5-C7, wherein said at least one distance comprises at least two or at least three distances.

[0130] Example C9. The method according to any of examples C5-C8, wherein said at least one distance comprises a minimum lateral distance.

[0131] Example CIO. The method according to any of examples C5-C9, wherein said at least one distance comprises a vertical distance.

[0132] Example Cl l. The method according to any of examples C5-C10, wherein said at least one distance comprises an Euclidian distance.

[0133] Example C12. The method according to example C7, wherein said plane is defined using three points along a tricuspid annulus.

[0134] Example C13. The method according to any of examples C1-C12, wherein said estimating is based on an exposure of said conduction system near said annulus to manipulation by said implant.

[0135] Example C14. The method according to any example C13, wherein said estimating is based on a slope of a conduction system near and relative to said annulus. Example C15. The method according to any example C13, wherein said estimating is based on an exposure angle of conduction system near said annulus.

[0136] Example C16. The method according to any of examples C1-C15, wherein said estimating is based on a perimeter or other indication of a size of said annulus.

[0137] Example C17. The method according to any of examples C1-C12, wherein said estimating is based on a pre-existing damage to the conduction system.

[0138] Example C18. The method according to any of examples C1-C12, wherein said estimating is based on a procedural parameter or indication thereof.

[0139] Example C19. The method according to example Cl 8, wherein said procedural parameter comprises a valve design and / or size.

[0140] Example C20. The method according to example C18 or example C19, wherein said procedural parameter comprises a lateral offset of implantation in an annulus plane.

[0141] Example C21. The method according to any of examples C18-C20, wherein said procedural parameter comprises an angulation of implantation relative to an annulus plane.

[0142] Example C22. The method according to any of examples C18-C21, wherein said procedural parameter comprises a rotational position of implantation in said annulus plane.

[0143] Example C23. The method according to any of examples C18-C21, wherein said procedural parameter comprises a height of implantation relative to said annulus plane.

[0144] Example C24. The method according to any of examples C18-C21, wherein said procedural parameter comprises a CFB height of implantation relative to said annulus plane.

[0145] Example C25. The method according to any of examples Cl-12, comprising displaying said risk to a user.

[0146] Example C26. The method according to example C25, wherein said risk is shown as binary or ternary.

[0147] Example C27. The method according to example C25 or example C26, comprising displaying to a user the option to modify one or more valve or procedure parameter and show a risk for the updated parameter.

[0148] Example C28. The method according to any of examples C1-C27, comprising selecting a patient for therapy based on said risk.

[0149] Example C29. The method according to any of examples C1-C28, planning a pacemaker implantation based on said risk.

[0150] Example C30. The method according to any of examples C1-C29, changing a valve selection or recommendation based on said risk. Example C31. The method according to any of examples C1-C30, generating procedure guidance and / or overlay markings based on said risk.

[0151] Example C32. The method according to any of examples C1-C31, wherein the valve comprises a plurality of anchors that bend back during deployment.

[0152] Example C33. The method of example C32, comprising selecting a valve orientation according to said risk and / or said relative geometry.

[0153] Example C34. The method of example C32 or example C33, comprising selecting an interanchor gap geometry according to said risk and / or said relative geometry.

[0154] Example C35. The method of any of examples C32-C34, comprising selecting an anchor geometry and / or body geometry according to said risk and / or said relative geometry.

[0155] Example C36. The method of any of examples C1-C35 being computer implemented, for at least providing an automatic recommendation.

[0156] Example C37. A preplanning and / or intra-operative computer system configured to support and / or carry out the methods of any of examples C1-C36.

[0157] Example C38. a computing device, comprising: a processor operatively coupled to a data storage device storing code, the code comprising instructions for executing a model that generates a prediction of risk for pacemaker implantation in response to an input of tricuspid and conduction system geometry.

[0158] Example C39. The computing device of example C38, wherein the model is a machine learning model trained on a training dataset comprising patient tricuspid and conduction system geometries labeled with need for pacemaker.

[0159] Example C40. A method of training a machine learning model for predicting pacemaker implantation after tricuspid valve implantation, comprising: generating a training dataset of a plurality of records, wherein a record comprises: an indication of an exposure of a conduction system to forces applied during and / or after valve implantation and a ground truth label of need for a pacemaker after implantation; and training the machine learning model on the training dataset for predicting a need for a pacemaker in response to an input of the indication of exposure.

[0160] Example C41. a processor coupled to a memory having thereon a model trained by the method of example C40.

[0161] Example C42. A method for predicting the need for a pacemaker after a tricuspid valve implantation, comprising: feeding a combination of an indication of an exposure of a conduction system to forces applied during and / or after valve implantation into a model; and executing the model to obtain a prediction of conduction system damage which may require implanting a pacemaker.

[0162] Example C43. A method for planning a cardiac procedure, optionally a tricuspid manipulation procedure, such as TTVR, comprising:

[0163] (a) modeling at least a portion of the heart mechanically;

[0164] (b) simulating said procedure on said modeled heart portion; and

[0165] (c) identifying, in a result of said simulation, a potential interaction between said heart or said procedure and a conduction system of the heart.

[0166] Example C44. A method according to example C43, wherein said simulating comprises using a finite element and / or a finite volume simulation.

[0167] Example C45. A method according to example C43 or example C44, wherein said modeling comprises modeling a CFB (central fibrous body) of the heart, optionally with at least one mechanical parameter differently from that used for other modeled tissue, if any.

[0168] Example C46. A method according to any of examples C43-C45, wherein said simulating comprises simulating multiple points along the procedure.

[0169] Example C47. A method according to any of examples C43-C45, wherein said simulating comprises simulating a static state.

[0170] Example C48. A method according to any of examples C43-C47, comprising repeating said method for multiple procedural parameter values.

[0171] Example C49. A method according to example C48, wherein said parameter comprises one or more of implant design, implant size, implant location and implant expansion timing.

[0172] Example C50. A method according to any of examples C43-C49, comprising generating instructions to an operator based on said simulating and said identifying.

[0173] Example C51. A method, optionally computer- implemented, of in-procedure annotation of an ultrasound image, comprising:

[0174] (a) identify, on a structural image, elements of a cardiac valve;

[0175] (b) in an acquired ultrasound image, identify matching elements of the valve; and

[0176] (c) map one or more annotation from a space of the structural image to a coordinate system of the ultrasound image; and

[0177] (d) annotate the ultrasound image with markings corresponding to the one or more annotations.

[0178] Example C52. The method of example C51, wherein (a) comprises identifying elements of a conduction system adjacent said valve. Example C 53. The method of example C51 or example C52, wherein (c) comprises identifying a slice of said ultrasound image aligned with an annulus of said valve.

[0179] Example C54. The method of any of examples C51-C53, wherein said elements of the cardiac valve comprise one or more of CFB (central fibrous body) portions, one or more commissures and an annulus section.

[0180] Example C55. The method of any of examples C51-C54, wherein said cardiac valve comprise a tricuspid valve.

[0181] Example C56. A method of supporting navigation and / or guidance of an implantation procedure of a prosthetic tricuspid valve implant in a heart of a patient, comprising:

[0182] (a) determining at least one relative geometry of a conduction system portion of the patient, relative to the patient’s heart; and

[0183] (b) showing, on an ultrasound image acquired during the procedure, markings corresponding to the conduction system of the patient.

[0184] Example C57. A method according to example C56, wherein said determining comprises determining from a CT image of said heart.

[0185] Example C58. A method according to example C56 or C57 wherein said markings comprise one or more templates of a part of the conduction system.

[0186] Example C59. A method according to any of examples C56-C58, wherein said showing is in real-time, better than 5 frames per second.

[0187] Example C60. A method according to any of examples C56-C59, wherein said showing comprises showing a relative location of said conduction system portion and a tricuspid annulus.

[0188] Example C61. A method according to any of examples C56-C60, wherein said showing comprises showing a distance between said conduction system portion and a tricuspid annulus.

[0189] Example C62. A method according to any of examples C56-C61, wherein said showing comprises showing an angle of exposure.

[0190] Example C63. A method according to any of examples C56-C62, wherein said showing comprises showing at least an indication of an angle of a nonbranching bundle and / or a bundle of His relative to a tricuspid annulus.

[0191] Example C64. Apparatus for supporting navigation and / or guidance of an implantation procedure of a prosthetic tricuspid valve implant in a heart of a patient, comprising:

[0192] (a) a conduction system input which receives at least one relative geometry of a conduction system portion of the patient, relative to the patient’s heart;

[0193] (b) an ultrasound input which receives a stream of ultrasound data; and (c) an overlayer configured to overlay markings corresponding to at least a portion of the conduction system of the patient on said ultrasound data, at a rate of at least 5 frames per second.

[0194] Example C65. Apparatus according to example C64, comprising an image display configured to display an ultrasound image based on said data and said overlay.

[0195] Example C66. A computer implemented method of generating a display for supporting implanting a prosthetic tricuspid valve in a heart of a patient, comprising:

[0196] (a) estimating a relative location of at least a portion of a conduction system of the patient and a tricuspid valve region; and

[0197] (b) displaying an indication of the at least a portion of a conduction system of the patient, a planning indication and / or a risk indication when implanting a prosthetic tricuspid valve in said region.

[0198] Example C67. A system for generating a display for supporting implantation of a prosthetic tricuspid valve in a heart of a patient, comprising:

[0199] (a) a conduction system identifier which receives an anatomical image of the heart and generates an estimate of a conduction system location;

[0200] (b) a processor programmed to generate at least one indication related to a portion of the conduction system adjacent a tricuspid annulus; and

[0201] (c) an overlayer which overlays said indication on a 2D or 3D representation of the heart.

[0202] Example C68. A prosthetic tricuspid valve, comprising: a body; and one or more anchoring elements, wherein said anchoring elements are arranged around said body and define a gap of between 20 and 60 degrees where they do not apply radial pressure in a direction away from said body on cardiac tissue, when implanted.

[0203] Example C69. A computer-implemented method of selecting a valve and / or valve implant location for a prosthetic tricuspid valve, comprising:

[0204] (a) receiving a location of a conduction system adjacent an annulus of a tricuspid valve in a patient;

[0205] (b) selecting one or more of a valve geometry, valve size, valve rotation, valve orientation and / or valve elevation which reduces a risk of damage to said conduction system when said valve is implanted according to said selection.

[0206] Example C70. A computer- implemented method of operation of circuitry for supporting implantation of a prosthetic tricuspid valve in a heart of a patient, comprising:

[0207] (a) receiving an anatomical image of the heart; (b) generating an estimate of a conduction system location based on said image;

[0208] (c) generating at least one indication related to a portion of the conduction system adjacent a tricuspid annulus; and

[0209] (d) overlaying said indication on a 2D or 3D representation of the heart.

[0210] Example C71. A method of machine-assisted setting up of a procedure for tricuspid valve implantation in a patient with a heart, comprising:

[0211] (a) identifying a conduction system location on an image data set of said heart, said image acquired using data collection from outside the heart; and

[0212] (b) providing machine-assisted guidance of a tricuspid valve implantation and / or selection based on a risk to the conduction system from valve implantation.

[0213] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0214] As will be appreciated by one skilled in the art, some embodiments of the present invention may be embodied as a system, method or computer program product. Accordingly, some embodiments of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, some embodiments of the present invention may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon. Implementation of the method and / or system of some embodiments of the invention can involve performing and / or completing selected tasks manually, automatically, or a combination thereof. Moreover, according to actual instrumentation and equipment of some embodiments of the method and / or system of the invention, several selected tasks could be implemented by hardware, by software or by firmware and / or by a combination thereof, e.g., using an operating system.

[0215] For example, hardware for performing selected tasks according to some embodiments of the invention could be implemented as a chip or a circuit. As software, selected tasks according to some embodiments of the invention could be implemented as a plurality of software instructions being executed by a computer using any suitable operating system. In an exemplary embodiment of the invention, one or more tasks according to some exemplary embodiments of method and / or system as described herein are performed by a data processor, such as a computing platform for executing a plurality of instructions. Optionally, the data processor includes a volatile memory for storing instructions and / or data and / or a non-volatile storage, for example, a magnetic hard-disk and / or removable media, for storing instructions and / or data. Optionally, a network connection is provided as well. A display and / or a user input device such as a keyboard or mouse are optionally provided as well.

[0216] Any combination of one or more computer readable medium(s) may be utilized for some embodiments of the invention. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable readonly memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.

[0217] A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0218] Program code embodied on a computer readable medium and / or data used thereby may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.

[0219] Computer program code for carrying out operations for some embodiments of the present invention may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the “C” programming language or similar programming languages. The program code may execute entirely on the user’s computer, partly on the user’s computer, as a stand-alone software package, partly on the user’s computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user’s computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).

[0220] Some embodiments of the present invention may be described below with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0221] These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function / act specified in the flowchart and / or block diagram block or blocks.

[0222] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0223] Some of the methods described herein are generally designed only for use by a computer, and may not be feasible or practical for performing purely manually, by a human expert. A human expert who wanted to manually perform similar tasks, such as planning or guiding a procedure, might be expected to use completely different methods, e.g., making use of expert knowledge and / or the pattern recognition capabilities of the human brain, which would be vastly more efficient than manually going through the steps of the methods described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0224] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings and images. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0225] In the drawings:

[0226] Fig. 1 is a cross-sectional view of a heart showing substantially all parts of a conduction system;

[0227] Fig. 2 is a top level flowchart of a method of treating and / or diagnosing a heart, in accordance with some embodiments of the invention;

[0228] Fig. 3 is a top level block diagram of a pre-procedure system usable for treating and / or diagnosing a heart, in accordance with some embodiments of the invention;

[0229] Fig. 4 is a top level block diagram of a navigation system usable for treating and / or diagnosing a heart, in accordance with some embodiments of the invention;

[0230] Fig. 5 is a more detailed flowchart of a method for treating and / or diagnosing a heart, in accordance with some embodiments of the invention;

[0231] Fig. 6 is a flowchart of a method for treating a structural heart disease, such as by TAVR or TTVR, in accordance with some embodiments of the invention;

[0232] Figs. 7A-7D are various synthetic views showing a conduction system or portion thereof, potentially for display to a user in accordance with some embodiments of the invention;

[0233] Fig. 8 is a flowchart of a method for carrying out an operational stage of treating and / or diagnosing a heart, in accordance with some embodiments of the invention;

[0234] Fig. 9 shows several views of a pacemaker lead positioned relative to an LBB, in accordance with some embodiments of the invention;

[0235] Fig. 10A shows a transverse view DRR image showing a tool layout in the RV, in accordance with some embodiments of the invention;

[0236] Figs. 10B-10D are synthetic view sets at various stages of septum penetration, in accordance with some embodiments of the invention;

[0237] Fig. 10E shows matching real and synthetic views, in accordance with some embodiments of the invention;

[0238] Fig. 11A is a flowchart of a method of bi-directional registration, in accordance with some embodiments of the invention; Fig. 11B shows a 3D view showing an interventional tool, in accordance with some embodiments of the invention;

[0239] Fig. 12 shows guide annotations for valve implantation, in accordance with some embodiments of the invention;

[0240] Fig. 13 shows 3D model views of an undesirable interaction between a valve implantation and the conduction system, which may be avoided in accordance with some embodiments of the invention;

[0241] Fig. 14 is a flowchart outlining general stages of a procedure of implantation of a tricuspid valve prosthesis, according to some embodiments of the invention; and

[0242] Fig. 15 shows a schematic representation of a tricuspid annulus in relation to the conduction system;

[0243] Fig. 16 shows a schematic representation of a tricuspid annulus and anatomical structures comprising a conduction system;

[0244] Fig. 17 shows various measured distances between a conduction system and a tricuspid annular line, according to some embodiments of the invention;

[0245] Fig. 18A shows a Venn diagram depicting the intersection between the device, its theoretical locations for implantation and the conduction system, in accordance with some embodiments of the invention;

[0246] Fig. 18B shows a tricuspid valve replacement implant in its designated anatomical location in the heart and in relationship to a conduction system, indicating potential risk in accordance with some embodiments of the invention;

[0247] Fig. 19 shows a detailed flowchart of a procedure of implantation of a tricuspid valve prosthesis with preplanning, according to some embodiments of the invention;

[0248] Fig. 20 shows a detailed flowchart of a procedure of implantation of a tricuspid valve prosthesis without preplanning, according to some embodiments of the invention;

[0249] Fig. 21 shows an image of a heart, using synthetic reconstruction of CT data, using methods of some embodiments of the invention;

[0250] Fig. 22 shows an image of a heart, using synthetic reconstruction of CT data, according to some embodiments of the invention;

[0251] Fig. 23 shows schematic representations of safe (red) and danger (purple) zones for implantation of a tricuspid valve, for various anatomical situations, which can be added or projected onto an image of the heart during a tricuspid valve implantation planning and / or procedure, in accordance with some embodiments of the invention; Fig. 24 shows a modified tricuspid valve prosthesis with a gap which can be aligned with the area of close proximity of valve to the conduction system, according to some embodiments of the invention;

[0252] Fig. 25 shows the modified tricuspid valve of Fig. 24, with a variation according to some embodiments of the invention, of affixing a radiopaque marker used for alignment;

[0253] Figs. 26 is flowchart of a method of valve selection, in accordance with some embodiments of the invention;

[0254] Fig. 27 depicts a heart valve with its anchors extended outwards from the body of the device, before the device is anchored to its implantation location;

[0255] Fig. 28 depicts the movement (e.g., change in angle and / or direction) of a single anchor during deployment of the valve of Fig. 27;

[0256] Fig. 29 is a visualization depicting a plurality of implant anchors, a tricuspid valve annulus and a conduction system portion at risk as well as projections, in a patient where a pacemaker implantation was required due to conduction system damage, in accordance with some embodiments of the invention;

[0257] Fig. 30 depicts a visualization of a single anchor in relation to a tricuspid annulus, conduction system at risk, as well as projections, in a patient where a pacemaker implantation was required due to conduction system damage, in accordance with some embodiments of the invention;

[0258] Fig. 31 depicts a representation of the tricuspid annulus, its projection and its plane of projection, in spatial relation to a conduction system, showing a method of defining a safety zone, in accordance with some embodiments of the invention;

[0259] Fig. 32 is similar to Fig. 31, but for a different patient, with an A-B line below a frame height and no pacemaker implantation required (e.g., due to conduction system damage);

[0260] Fig. 33 is a depiction of yet another patient’s tricuspid annulus and conduction system at risk, where pacemaker implantation was required, in accordance with some embodiments of the invention;

[0261] Fig. 34 shows a different view of Fig. 33;

[0262] Fig. 35 shows a pair of view and projection similar to Figs. 33 and 34, for a different patient, in accordance with some embodiments of the invention;

[0263] Figs. 36 and 37 shows such pairs as in Fig. 35 for two other patients, in accordance with some embodiments of the invention;

[0264] Fig. 38 depicts a representation of the tricuspid annulus, its projection and its plane of projection, in spatial relation to the conduction system for another patient in which a pacemaker implantation was not required due to conduction system damage, in accordance with some embodiments of the invention; Fig. 39A and 39B depict 3D renderings of deployed valves with relationship to a conduction system (e.g., as extracted from CT data sets), in 39A pacemaker implantation was required and in 39B no pacemaker implantation was required, possibly due to relative locations of anchors and conduction system, in accordance with some embodiments of the invention;

[0265] Figs. 40A-40D are schematic representations of valve delivery in accordance with some embodiments of the invention;

[0266] Fig. 41 is a summary histogram showing the distribution of cases where a pacemaker was needed as a function of minimum lateral distance between the conduction system and the projection of the annulus on the tricuspid plane, in accordance with some embodiments of the invention;

[0267] Figs. 42A-42B are charts showing the probability for needing a pacemaker depending on conduction system geometry, in view of additional experimental data;

[0268] Fig. 42C is a chart relating PPI (predicted probability of requiring a pacemaker after valve implantation) as a function of nearest distance to the conduction system and also as a function of device size;

[0269] Fig. 42D is a chart showing sensitivity and specificity of a predictor created using data in accordance with some embodiments of the invention;

[0270] Fig. 43A is a Forest chart for a predictor based on multiple components in accordance with some embodiments of the invention, in standard deviation units;

[0271] Fig. 43B is a Forest chart for a predictor based on multiple components in accordance with some embodiments of the invention, in clinical units;

[0272] Fig. 43C is a chart showing sensitivity and specificity of a predictor created using data in accordance with some embodiments of the invention;

[0273] Figs. 43D-F are scatter plots showing the relationship between slope, distance and annulus permitted and prediction of pacemaker need (PPI), for a predictor according to some embodiments of the invention;

[0274] Fig. 43G is a set of three charts showing a risk map relating angle and lateral offset, in accordance with some embodiments of the invention;

[0275] Fig. 43H is a set of two charts showing relationships between tricuspid annulus and a section of the conduction system, in accordance with some embodiments of the invention;

[0276] Fig. 431 schematically shows an exposure angle, in accordance with some embodiments of the invention;

[0277] Fig. 43J is a set of three charts showing CTA-based predictors of PPI in a study sample in accordance with some embodiments of the invention: observed (bars) and predicted (trendlines) risk of PPI, error bars are 95% confidence intervals (Wilson method); Fig. 43K is a chart showing sensitivity and specificity of a predictor created using data in accordance with some embodiments of the invention;

[0278] Fig. 43L shows a confusion matrix for the predictor of the chart of Fig. 43J

[0279] Fig. 43M shows an exposure angle in a real patient, requiring pacemaker implantation, in accordance with some embodiments of the invention;

[0280] Fig. 43N shows an exposure angle in a real patient, not requiring pacemaker implantation, in accordance with some embodiments of the invention;

[0281] Fig. 44A is a top view of a partially dissected heart, showing a triangle of Koch, parts of the conduction system and a tricuspid valve;

[0282] Fig. 44B is a top view of a CFB (central fibrous body relative to conduction system components and valves;

[0283] Fig. 44C is a perspective view showing the CFB and a part of the conduction system adjacent the aortic and tricuspid valve;

[0284] Fig. 44D is a set of charts showing a force applied by, and strain generated by, valve expansion on cardiac tissue depending on early or late contact with CFB

[0285] Fig. 44E is a chart showing PPI risk as a function of vertical offset of a CFB and lateral gap between the conduction system and the CFB;

[0286] Fig. 45A shows an annotation of a TEE image with a portion of the conduction system, according to some embodiments of the invention;

[0287] Fig. 45B shows an annotated ultrasound image slice with a conducti system and leaflet locations annotated thereon;

[0288] Fig. 45C shows an overlaying of a 3D model of a tricuspid implant, overlaid on an acquired ultrasound slice; and

[0289] Fig. 45D shows side views of such overlaid model, in accordance with some embodiments of the invention.

[0290] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0291] The present invention, in some embodiments thereof, relates to performing cardiac procedures using conduction system information and, more particularly, but not exclusively, to using such data for Transcatheter Tricuspid Valve Replacement.

[0292] Overview

[0293] A broad aspect of some embodiments of the invention relates to treating and / or diagnosing a heart while taking into account the location of parts of the conduction system of the heart. In some embodiments, the location of the conduction system parts is determined by analyzing a pre-operative image, such as a cardiac CT image and not by EP (electrophysiological) mapping methods. It is noted that some aspects and embodiments described herein, such as mapping tool locations from a fluoroscopic image to a 3D data set and navigation and selection of views, do not need to involve conduction system data.

[0294] An aspect of some embodiments of the invention relates to machine-assisted guiding of a cardiac procedure, where the machine-guiding takes into account the locations of parts of the conduction system. In some embodiments, the procedure comprises a cardiac treatment by treatment of a conduction system portion. In some embodiments, the cardiac procedure comprises implanting tricuspid valves. In some embodiments, the cardiac procedure comprises cardiac pacing and / or ablation, possibly applied after valve implantation (e.g., according to some methods and apparatus for implantation shown herein). Pacing after valve implantation may make use of a determination or estimation of where the conduction system was damaged (or may become damaged, if pacing is prophylactic) and therefore which pacing locations may be best suited (e.g., close to a location of damage but not above such location of damage), “above” is in a direction towards the AV node.

[0295] In some embodiments, CS system detection is based on a pre-operative image, such as a CT image. Optionally, guiding during the procedure uses a fluoroscopic image, optionally annotated based on the 3D image, CS location, procedure guides and / or other data. In some embodiments, guiding during the procedure uses (additionally or alternatively) synthetic images which include information from the procedure, for example, based on data extracted from the fluoroscopic image. In some embodiments, surface ECG data is used for guiding and / or verification.

[0296] In some embodiments, the procedure has two stages, a first stage, whereby a 3D image such as a CT is analyzed and a treatment plan is determined (e.g., manually, automatically and / or semi- automatically) and a treatment stage where the plan is carried out and modified as needed. In some embodiments a plan is generated in the first stage and used during the second stage.

[0297] An aspect of some embodiments of the invention relates to pacemaker implantation for valve implantations, for example aortic and / or tricuspid implantation. The process of valve implantation can damage the conduction systems, and in some cases, this cannot be avoided. The risk and / or location of such damage is optionally determinable during a planning phase. In some embodiments, based on location of damage, a pacing lead is implanted below a block or damage caused (or expected to be caused) by the valve implant (or other structural heart intervention). In some embodiments, the pacing is within 29 mm, 10 mm, 5mm or smaller or intermediate distances from such expected location of damage. An aspect of some embodiments of the invention relates to a procedure planning phase of a cardiac intervention, in which the planning takes into account a location of at least a part of a cardiac conduction system. Optionally the planning takes into account additional information, such as one or more of tissue viability (e.g., scar tissue), ischemia, geometry and location of important blood vessels and / or nerves.

[0298] In some embodiments, the planning includes a simulation, for example, a functional simulation and / or a geometric simulation. The simulation may be, for example, for one beat, for part of the heart and / or for a series of beats and / or all of the heart.

[0299] In some embodiments, the functional simulation comprises simulating the effect on electrical activity (e.g., action potential propagation, surface ECG, intracardiac electrogram and / or cardiovectorgram) and / or mechanical activity (e.g., muscle contraction, contraction wave, intracardiac pressures, stroke volume and / or cardiac output). In some embodiments the simulation includes pacemaker parameters and / or logic.

[0300] In some embodiments, a geometric simulation includes simulating one or more of possible access paths and how a lead (or implant such as leadless pacemaker) will lie after implantation.

[0301] In some embodiments a simulation includes a search function whereby one or more parameters are varied and for each parameter set variation a score or result may be collected. This may be used, for example, to display a map or range of possibilities and / or find one or more working solution. This search may be wholly automatic, for example, or manual or semi-automatic.

[0302] In some embodiments the search is used to find solutions for the procedure which normalize (e.g., vary by less than 30%, 20%, 10% or intermediate percentages relative to a baseline value) one or more cardiac-related parameters, such as systolic duration, cardiac output and surface ECG (e.g., time-aligned traces vary by average intensity by less than 30%).

[0303] An aspect of some embodiments of the invention relates to a procedure plan for a cardiac procedure. In some embodiments the procedure plan includes one or more of imaging angulation angles, tool angulation settings, expected images, expected in-procedure results, one or more dangers to be avoided and / or one or more alert parameter for an automated system to present. In some embodiments, the plan is generated with the help of simulation and includes both parameters and expected results of following such parameters. Optionally alternatively or additionally, the plan includes one or more alternatives with expected results for such alternatives.

[0304] In some embodiments, the plan relates to one or more specific tools, for example a lead and / or a sheath and images and / or guidance based on using such specific tools.

[0305] An aspect of some embodiments of the invention relates to parallel views in fluoroscopy, in which views objects of interest may be foreshortened. In some embodiments a navigation system is used which detects such foreshortening and alerts a user and / or suggests imaging angles which prevent the parallax and foreshortening. In some embodiments, the system recommends viewing angles where there is no foreshortening if the tools are correctly arranged, as per plan.

[0306] In some embodiments of the invention, the system generates a synthetic view in which the foreshortening is corrected, based on the foreshortened view.

[0307] In some embodiments, two views are shown, a first view in which a tool and / or its trajectory lie flat, and a second view aligned along an axis of the tool or trajectory thereof.

[0308] An aspect of some embodiments of the invention relates to an augmented fluoroscopy image showing annotations generated based on a 3D data set such as a CT. In some embodiments, the image includes both a tool, as imaged, and annotations, for example, of anatomical features that are not directly delineated on the image (e.g., conduction system) and / or of guides for a procedure, such as target locations.

[0309] In some embodiments, a user navigates using such an image, in which the user can see, for example, two points of a tool and one or more target indications. In some embodiments, one or both of two images are shown, a first image in which the tool and / or trajectory are aligned with the target(s). A second image is shown along the axis of the tool. In use, the first image shows distances and if the tool is in a correct distance and / or trajectory. In a “correct” situation, all the markers may lie along a single line. The second image, when in a “correct” position, optionally shows all the markers colocated.

[0310] It is noted that if the annotations includes two markers, then the alignment method can be used to guide a tool and / or verify that the tool is oriented correctly and optionally positioned correctly as well.

[0311] In some embodiments, one or both of the image sis synthetically created, but includes both a tool indication and the annotations.

[0312] An aspect of some embodiments of the invention relates to mapping from a fluoroscopic image to a CT data set (or other 3D data set) and optionally back to a 2D image such as a fluoroscopic image. In some embodiments, the 2D image has a marking or an object not found in the CT image. Optionally the object’s location in 3D space is deducted from the fluoroscopic image with the help of a physical constraint, such as contact between the object and an anatomical structure (which can be detected in various ways, for example, as described herein, and for example, by detecting a change in the shape of the tool when it contacts tissue). In some embodiments of the invention, the system includes a database or a programmed ML system with a set of typical layouts of a tool in the heart. This may be used to deduce the layout, for example, by selecting a closest layout or by interpolation of by ML generated output trained on such layouts. Optionally, an indication of the object position, or an annotation relative to such position, such as a reference location thereon or a current or future interaction of the object or a geometry thereof (e.g., a trajectory) with the anatomy is shown on the 3D image or a derivative thereof. In some embodiments of the invention, the reference location of the tool used for annotation is not on the tool itself, but tracks the tool position and / or orientation. Knowledge of the tool position may be used to calculate the location of this annotation and show it.

[0313] In some embodiments of the invention, the 2D image is used to generate a theoretical space of possible locations of the tool and the contact is used to contract the space. Optionally or additionally, anatomical constraints and / or limits on how the device might fit in the body, for example, the heart are used for constraining the set of possible positions.

[0314] In some embodiments, the 3D data set is shown as a synthetic two-dimensional image, for example, a simulation of a fluoroscopic image. It is noted that such images may also be shown during a preoperational stage or during operation, when the tool is not yet in the visualization space, but plan for such tool can be shown.

[0315] Such mapping may be especially useful for conduction system-related cardiac procedures. First, it allows one to see the conduction system (and / or other annotations) and a tool on the same image. Second, it allows a synthetic view / image to be created, allowing a physician to avoid moving the fluoroscopic imager, while still seeing the tool and target form a desired view. In some embodiments, a plurality of views is shown, for example views perpendicular to each other and / or which align a tool with a target or other marker.

[0316] In some embodiments, the view is shown from a point of view of the tool.

[0317] Optionally alternatively or additionally, as the tool is mapped back to the 3D data set, a physician can optionally perform the procedure in 3D space, possibly with a 3D imager, the fluoroscope may be relegated for data collection and / or verification, for at least 20%, 30%, 40%, 60% or more of a duration of the procedure where the tool is in the heart.

[0318] Optionally alternatively or additionally to a 3D view or a 2D synthetic fluoroscopic view a simplified view is shown, for example, based on segmentation of the CT data and / or the fluoroscopic data. In some embodiments, the view is a wireframe view. In some embodiments of the invention, the coordinates used to show the images are coordinates of the ultrasonic system (e.g., if any, e.g., a transesophagus imager), with one axis being the LV axis and the other axes defining the base of the LV. This has the potential advantage of invariance over changes in the cardiac orientation.

[0319] An aspect of some embodiments of the invention relates to showing an operator a simulated fluoroscopic image from a view which is physically difficult or impossible to obtain. In particular, a transverse view image may be provided. Such image may be useful when showing how a lead is penetrating a ventricular septum. In some embodiments multiple views are shown simultaneously, optionally with a “real” fluoroscopic view.

[0320] An aspect of some embodiments of the invention relates to protecting the CS (conduction system) when implanting a tricuspid valve prothesis. In some embodiments of the invention, the implant is selected and / or positioned in a way that is less likely to damage the CS. In some embodiments of the invention, the portions of the CS near the tricuspid annulus are selected for protection. In some embodiments of the invention, CS protection takes into account the particular CS layout of a patient, optionally portions thereof near the tricuspid annulus, for example, the nonbranching bundle. In some embodiments of the invention, protection comprises displaying information to an implanting physician, for example, location of a conduction system segment, a location where implantation is safe and / or a location where implantation is less safe. In some embodiments of the invention, the safety level of a location depends on the specific implant design and / or model being used and / or a planned implantation location and / or orientation. In some embodiments of the invention, implantation is made safer by selecting an implant of a size and / or shape and / or type less likely to cause damage. In some embodiments of the invention, the damage to be avoided is pressure application on the conduction system or overlying tissue, for example pressure against the conduction system and / or pinching between parts of the implant. In some embodiments of the invention, a location and / or orientation of the implant are selected to avoid such pressure. In some embodiments, the damage to be avoided is caused by the act of deployment of the implant, specifically the movements the device (or parts thereof) makes in the course of implantation and the various anatomical locations it interacts with on its way to the final implantation location and / or orientation.

[0321] Referring to risk of needing a pacemaker after tricuspid valve implantation, in some embodiments of the invention, risk is reduced from 25-35% risk or more (naive risk) to 10-15% or less, by one or more of patient selection, valve selection and valve alignment in rotation, height and / or orientation (tilt).

[0322] In some embodiments of the invention, a desired implant and / or location and / or orientation of the implant are selected, during a planning phase, according to an estimation of the CS location.

[0323] In some embodiments of the invention, the implanting method is modified, for example to manipulate the relative locations and / or angles of the valve and the tricuspid annulus, in order to reduce risk of damage to the conduction system. In some embodiments of the invention, such modification is informed by the description herein of damage mechanisms (e.g., using a simulation) and / or by methods described herein of assessing risk and / or safety / danger zone.

[0324] In some embodiments, the planning phase comprises at least one simulation, simulating at least one feature of the implantation procedure and / or of the device in its designated implantation location. In some embodiments of the invention, the simulation is in the form of an (optionally geometrically static) visualization of the conduction system relative to the annulus.

[0325] In some embodiments of the invention, the simulation includes one or more geometric projections and / or measurements to help identify safe / danger zones and / or otherwise evaluate implantation risk.

[0326] In some embodiments, the simulation comprises simulating the implantation procedure, specifically, for example, the movement caused by the movement of the anchors of the device as the device is implanted. In some embodiments, this movement is termed “scooping” as it scoops across and / or against nearby tissue (which may include conduction system components). In some embodiments, “scooping” is defined as a bending of the anchors and the device is being localized and secured in its implantation location. In particular, in some valves, anchors which are initially extended towards the ventricle, bends sideways and then fold back. In some embodiments of the invention, simulation takes into account resistance of tissue and / or other device / tissue geometric interactions. In some embodiments, the tissue is assumed to be infinitely pliable and non-resistant to anchor movement and / or device expansion and / or other device geometry changes which include interacting with tissue.

[0327] In some embodiments, the simulation comprises simulating the movement of the anchors in the course of the implantation process. In some embodiments, this step in the simulation comprises determining the location of the anchors in relation to the anatomy of the patient, at each stage of the movement of the device in some embodiments, this is done so as to ascertain whether the anchors damage at least one part of the conduction system at any point during the full arc of movement of the anchors.

[0328] In some embodiments, rather than simulating, a path of the anchors (or danger zone based thereon) is determined based on geometric characteristics of the valve and / or anchors and overlaid on an image of the valve area.

[0329] It is noted that in some embodiments of the invention, rather than simulating the scooping, previous cases are analyzed to determine one or more geometrical characteristic of the conduction system which predict the negative effects (if any) on the conduction system, of scooping.

[0330] For example, if the A-B conduction line is below the valve implant, it is optionally expected that there be less or no damage to the conduction system.

[0331] For example, the presence of an anchor near the conduction system is optionally expected to cause damage. For example, the presence of the conduction system in tissue being pinched between the anchor and frame (e.g., especially a radially inwards extending part thereof) is optionally expected to cause damage.

[0332] For example, if the conduction system is close to the valve frame, optionally no damage due to anchors is optionally expected (but damage due to annulus stretching in annulus-anchored valves could be possibly expected).

[0333] For example, as the distance away from the frame increases, so may the risk. It is noted that this risk starts going down after a certain distance.

[0334] It is noted that in some embodiments of the invention the outcome of planning is not a binary answer, but rather a risk value. Such risk value may inform clinical decisions, such as preemptive pacemaker implantation and / or selection of valve to use and / or selection of a patient for a certain procedure.

[0335] In some embodiments, it is desired to avoid damaging the conduction system caused by exerting physical pressure by the anchors (or any other part of the device) on cardiac tissue comprising at least one part of the conduction system. In some embodiments, the damage to the conduction system is caused in the course of the movement of the anchors (or any other part of the device) (e.g., the compression movement that anchors create when they are released) and / or by the presence of an anchor next to the conduction path (e.g., while applying forces).

[0336] In some embodiments of the invention, damage to the conduction system, to be avoided, is caused by stretching of the conduction system, for example, by stretching the tri-cuspid annulus by an implant.

[0337] Some results regarding potential safe zones follow. a. If the conduction system lies below the annulus, this indicates safety b. a vertical distance (height) between of 5-9 mm above the tricuspid annulus plane (defined by the plane interconnecting the three commissures) indicates risk c. lateral distance (minimal distance between conduction system and valve, as measured by projection unto the tricuspid annulus plane) - very close to the frame - is generally safe, for example, less than 0.5 or 1 or 2 mm or intermediate values. A maximal risk appears to be between about 2.5 mm and about 4 or 5 mm. above 6 and above 7 mm appears to be safe. It is noted that the lateral distance appears to be a strong predictor. For example, each 1 mm increase appears to increase the risk of pacemaker need by about 50%.

[0338] If distance between an anchor and a conduction system is shown to be close, risk may be reduced in some embodiments of the invention, for example, by avoiding such anchor (e.g., removal or manufacture with a gap) and / or aligning a spacing (e.g., about 40% or made larger) between anchors with such location, by device rotation. Optionally and / or alternatively eccentric positioning may be used to distance such an anchor from the conduction system, for example, 2 mm, 4 mm, 6 mm, 8 mm or smaller or intermediated distances. Optionally and / or alternatively an anchor may be modified compared to other anchors and / or the anchors currently used, for example, made shorter or longer and / or with a more gentle radius of curvature (or a set of implants with various length anchors or possibly only a few shorter anchors, such as one or two, provided. Optionally and / or alternatively pinching risk may be reduced by radially weakening or reducing the diameter of the frame (e.g., a dent) adjacent an anchor.

[0339] In some embodiments of the invention, when a special anchor is provided, a radiopaque marker may be provided for alignment during a procedure with a location (most) at risk, for example, based on conduction system geometry, such locations may be shown using the planning and / or execution systems described herein, for example, as synthetic images and / or overlayed on x-ray image(s).

[0340] The parts of the conduction system specifically considered in some embodiments of the invention (e.g., as being relevant to Tricuspid manipulation damage) are the A-B-C line - A being the AV node, B being the penetrating point so A-B is the non-branching bundle and point C is the split, for example as described herein.

[0341] Some additional definitions are used in accordance with some embodiments of the invention. Each TAVR annulus (which is typically not flat) has a bottom and top planes. The box is defied by the height of this box, also called “thickness”.

[0342] Angles are defined between a given commissure (there are three around the annulus) from each of these points to points a b c.

[0343] There are other measures that may also affect the risk, for example, the relative height of the conduction line from the TA bottom plane (=signed Vertical average “svetav”) or the shortest distance to the conduction system.

[0344] In some embodiments of the invention, such measures are used instead of simulation to determine a risk of conduction system damage.

[0345] In some embodiments of the invention, the measures are measured on a CT data set or other image of the valve area. In some embodiments of the invention, however, measurement is assisted by using projection to simplify the geometry. Such simplification may also be useful for displaying on 2D images, for example, fluoroscopy images, including defining a viewing angle where the measure is not foreshortened.

[0346] In some embodiments, the pre-operative planning step comprises projection. This projection comprises projecting the tricuspid annulus onto a plane. In some embodiments, this assists the medical professional carrying out the implantation procedure to visualize the device to be implanted in spatial relation to the patient’s anatomy, and to optionally define the danger and safety zones. In some embodiments, such visualization is provided by a graphical work station which displays such valve, tissue and / or conduction system, optionally with projections and / or measures.

[0347] In some embodiments, a “danger zone” (and / or “safe zone”) is defined, for example based on measures, predefined geometry based on the valve / valve movement and / or based on a simulation. Such zones may eb used to plan the implantation procedure. In some embodiments, the danger zone comprises an area in which the device, if implanted may compress and / or otherwise cause damage to the conduction system. In some embodiments, the danger zone is defined as the conduction system being within 3 mm of the annulus and / or within 5 mm of annulus (e.g., lateral, vertical and / or diagonal distance). It is noted that multiple zones may be provided, each reflecting a different risk level. Alternatively, only a single threshold risk is used to show a danger / safe zone. For example, the threshold may be set by a physician or other user.

[0348] In some embodiments, a simulation is used for assessing a potential device to be implanted, based on its geometric and functional characteristics. In some embodiments, these characteristics are assessed and a determination is made in regards to how these characteristics will impact the success of implanting this device in the selected implantation location. In some embodiments, a device may be selected, for example, based on how much it expands. The expansion of the device potentially affects the patient’s danger and safety zones, which have been pre-determined in order to select an appropriate device. Optionally and / or alternatively the expansion may cause direct pressure and / or stretching of the conduction system. The type of risk provided by a valve may, for example, inform a selection of valve type - according to risk and / or implantation details, such as angle or rotation.

[0349] In some embodiments, there is provided a method by which to calculate and display the variables used to carry out a pre-operative step. In some embodiments, the method comprises a submethod for collecting and storing the various data required for carrying out any of the steps of - mapping out the patient’s anatomy and determining the physiological characteristics of the various heart structures and constituents of the conduction system. In other embodiments, the method pertains to specific methods of displaying anatomical and physiological data. In other embodiments, the method pertains to specific methods of calculating the distances between the various anatomical and physiological structures. In other embodiments, the method pertains to specific methods of determining the safety and danger zones. In other embodiments, the method pertains to specific methods of superimposing an image of the device on the anatomical and physiological mapping of the specific patient. In other embodiments, the method pertains to specific methods of creating a 3D rendering of the device, in spatial relation to the anatomical and physiological landmarks of the patient, in any phase of the implantation procedure. In some embodiments of the invention, there is provided a planning, visualization and / or inoperation system for one or more of displaying the effects of an implantation procedure / valve on risk. In some embodiments, rules as described herein are implemented by a physician, optionally with the help of a system which makes, for example the conduction system, on an in-operation visualization of the heart valve.

[0350] It is noted that safety is not a binary property. Rather, different locations, orientations and valve designs have different risk levels involved. In some embodiments of the invention, the decision of a physician is simplified by selecting or preselecting an acceptable risk level and separately indicating areas which appear to be associated with a risk level above or below that level. Optionally alternatively or additionally, an indication comprises a color or gray scale or symbolic display, optionally with different colors and / or intensities and / or symbols indicating different relative and / or absolute risk.

[0351] In some embodiments of the invention, a safety display is modulated to take into account other considerations, for example, geometrical ease of access.

[0352] In some embodiments of the invention, safe location as and / or orientations are indicated as an overlay on an image used during the implantation process. In one example, the overlay is shown on an x-ray image or an ultrasound image or other real time imager. Optionally alternatively or additionally, the overlay is shown on a synthetically generated image, for example, a 3D image or a synthetically generated 2D view, optionally a physically unobtainable.

[0353] In some embodiments of the invention, computer circuitry is used for one or more of valve selection, location selection, orientation selection and / or display generation.

[0354] In some embodiments of the invention, a location is selected higher or lower relative to the annulus or the conduction system.

[0355] In some embodiments of the invention, an orientation of a valve is selected to avoid pressure on a sensitive conduction system location.

[0356] In some embodiments of the invention, the valve is selected or modified to have at least one circumferential section which applies less pressure on the heart wall and / or is otherwise less likely to damage the conduction system.

[0357] In some embodiments of the invention, risk assessment is used to veto the implantation of a particular valve design.

[0358] In some embodiments of the invention, if the risk is considered high, a pacemaker, for example a leadless pacemaker, may be preemptively implanted taking into account the potential for AV (or other) block due to the implantation. Optionally alternatively or additionally, a pacemaker is planned for implantation after the valve, if needed. An aspect of some embodiments of the invention relates to providing and / or using a tricuspid valve prothesis including a sector which is less likely to apply CS damaging forces to the heart. In some embodiments of the invention, this sector is radially less pronounced and / or is lacking radially extending elements found in other sectors. For example, a valve may include a circumferentially arranged series of anchoring legs, made smaller or absent at said sector. Such sector may extend, for example, 10-100 degrees, for example, 20-70 degrees, for example, 25-50 degrees. A valve may include one or more radio-opaque markers which may be used to identify an alignment of the valve with a safe zone of implantation.

[0359] In some embodiments of the invention, the valve is designed by taking an existing tricuspid design and removing one or more of such legs and manufacturing such modified design.

[0360] In some embodiments of the invention, the valve is implanted in a way that is aligned with the conduction system in order to reduce danger thereto.

[0361] In some embodiments of the invention, conduction system imaging or analysis is used to estimate a location of the conduction system and during implantation the valve is aligned (to the heart) in a way which reduces risk to the conduction system. Such implantation may or may not use a live image with conduction system indications or risk indications overlaid thereon.

[0362] An aspect of some embodiments of the invention relates to patient selection for tricuspid treatment. In some embodiments of the invention, a determination of the location of sensitive parts of the conduction system is used to decide if to allow a certain procedure (e.g., implanting a particular valve) to proceed and / or if to preemptively implant (or plan on implanting) a pacemaker. In some embodiments of the invention, the risk of damage to the conduction system is estimated based on the conduction system geometry and empirical results from previous patients. In some embodiments of the invention, the valve selection is optionally changed based on the risk indication.

[0363] An aspect of some embodiments of the invention relates to predicting (and / or reducing) a risk of requiring a pacemaker after tricuspid valve implantation. In some embodiments of the invention, the prediction uses a predictor trained on geometric properties of a heart, for example, lateral and / or vertical distance between a portion of the conduction system and an annulus of the tricuspid valve. In some embodiments of the invention, implant size and Euclidian distance are used for such predicting. Optionally, the distance is between the conduction system and the tricuspid valve annular spline.

[0364] It is noted that such analysis as described here may also be used for other treatments delivered in the vicinity of the tricuspid valve, for example, near a septal side thereof. In such treatments, the location of force application and / or other intervention are optionally evaluated, planned and / or changed and / or drive monitoring and / or preemptive treatment, for effect on conduction, base don the methods described herein for estimating interaction and potential impact on the conduction system. In some embodiments of the invention, lateral distance and / or exposure angle (and / or indications thereof) are used. Exposure angle is defined as the angular extent of the conduction system when viewed from the center of the tricuspid valve. This may reflect on and / or be correlated with the overall angle of the conduction system. For example, a low angle (relative to the tricuspid annulus plane) means a higher exposure angle. Optionally and / or alternatively to the angle, an indicator may be, for example, a circumferential extent of the conduction system. Optionally and / or alternatively a perimeter length of the annulus may indicate a distance to the conduction system and thus affect the exposure angle. Optionally and / or alternatively a distance (e.g., Euclidian and / or lateral) from the annulus to the conduction system may affect the exposure. More generally, a predictor in accordance with some embodiments of the invention is one that has at least an 80% correlation over a randomly selected sample of 1000 adults with a predictor using an exposure angle and lateral distance and optionally an indication of annulus perimeter length.

[0365] In some embodiments of the invention, the vertical spacing of a conduction system from the valve annulus and / or radially extending parts of the implant is considered. In some embodiments of the invention, a vertical exposure angle is defined, which reflects a length of the conduction system in the danger area (where a valve part might apply damaging forces thereto during and / or after implantation). Such vertical exposure angle (which optionally depends on the valve geometry - e.g., vertical extent above and / or below the annulus) may be used as a predictive input for a predictor and / or used to create implantation procedure guidance.

[0366] In some embodiments of the invention, risk is bimodal, for example, peaking at about zero and about 4 mm. Optionally, a minimum risk is at about 0.5-1 mm and / or risk goes down at sizes greater than 4 mm.

[0367] In some embodiments of the invention, risk increases with implant size.

[0368] In some embodiments of the invention, the risk is evaluated for a two-year period, so the predictor potentially predicts risk over such term. In other embodiments, the period is different, for example, 3 months, 1 year, 3 years or shorter, longer or intermediate periods.

[0369] In some embodiments of the invention, the risk is used to select a valve size which balances the risk of conduction system problems and the risk of lack of proper valve function.

[0370] An aspect of some embodiments of the invention relates to valve implantation and / or other structural procedures which take into account the interaction between fibrous portions of the heart, such as parts of the central fibrous body and an implant or tool. In some embodiments of the invention, damage to a conduction system portion protected by such fibrous portion is reduced by matching the size, direction and / or type of force applied to the fibrous portion so as to reduce a risk of damage to the conduction system portion. In some embodiments of the invention, the implant is a self-expanding or a balloon expanding implant and the implant is delivered in a way which encourages contact with the fibrous body during a time at which the implant applies more force and / or when the fibrous body can move with the heart. In one example, in implanting a self-expanding tricuspid valve where the force applied by an implant is higher at certain parts of expansion thereof, the valve is asymmetrically positioned to radially expand in contact with the fibrous body during times with a high force and / or during times with a low force. This may allow, for example, for the central fibrous body to move with the expansion, rather than be forced against the conducting system portion.

[0371] In some embodiments of the invention, the valve or other implant is balloon inflated and inflation rate and / or pressure may be varied in order to avoid pressure at certain times against the CFB and / or limit applied forces thereon.

[0372] An aspect of some embodiments of the invention relates to modeling an effect of force application in the heart using analytical tools such as finite element (e.g., including finite volume) analysis. In some embodiments of the invention, the modeling is used to assess the effect of mechanical forces on one or more portions of a cardiac conduction system. In some embodiments, selection of a valve, for example, size and / or implantation position and / or implantation process and / or type / design, are selected according to results of such analysis. In one example, the analysis includes an estimation of the effect of implant forces on fibrous portions, such as the central fibrous body, which forces can lead to crushing and / or otherwise damaging a portion of the conduction system.

[0373] In some embodiments of the invention, the analysis is performed generically and a particular patient is matched, based, for example, on cardiac geometry, to one or more previously performed analysis. In some embodiments, an analysis is performed per patient.

[0374] Such analysis may be used to search a solution space (e.g., of implant position, type, size and / or implantation method) for an implantation procedure less likely to cause conduction system problems. Optionally and / or alternatively such analysis is used to predict a risk of needing a pacemaker after (or prophylactically) the implantation.

[0375] An aspect of some embodiments of the invention relates to marking up an ultrasonic image, for example, a 3D image, for example, a TEE image, during tricuspid implantation, optionally in realtime (e.g., with the annotations moving with the dynamics of the imager and / or the imaged tissue, for example, with a delay of less than 300 ms, 200 ms, 100 ms or intermediate delays). In some embodiments, a TEE image is annotated using data from a pre-operative CT or other structural image.

[0376] In some embodiments of the invention, the 3D image is registered to a previously acquired structural data 3D coordinate system (e.g., based on a 3D structural image such as CT, optionally preoperative). In some embodiments of the invention, the registrations by identifying three anatomical points (or more) on the 3D image that can also be identified in the structural data. In some embodiments of the invention, the points are on a plane. Optionally and / or alternatively the points are of, or strongly coupled to, a relatively rigid part of the heart, for example, the CFB. This includes, for example, annuluses (e.g., as a curved line) of the heart valves, especially those closer to the septum and / or other valvular-adjacent structures and / or commissures (which define a single point along the annulus), papillary muscles, pulmonary veins, coronary sinus vein, coronary arteries, previously implanted body, such as a valve and / or particularly implanted elements that are stable under contraction cycle phase and / or the superior and / or inferior vena cava.

[0377] In some embodiments of the invention, one or more, for example, two or three, commissures of the tricuspid valve are identified in the TEE image and aligned with the CT data. In one example, if a 2D image or slice is used (e.g., the imaging being 2D or such slice rotated in space, for example, based on detection of the landmarks thereof), when two commissures (e.g., the anteroseptal and posteroseptal) are visible / identified in the image, it indicates that the TEE imager and / or image slice is aligned with the tricuspid annulus. Such a slice can be (e.g., automatically and / or manually) aligned with the CT data and enlarged or reduced and / or rotated in plane so the commissures are aligned in the two images. This means that any additional acquired slice and / or 3D image (e.g., if the TEE does not move) is also aligned. This allows annotations, for example, conduction system data, to be overlaid on the TEE image. Any and all of these acts may be manual and / or by a computer system, which generally uses different methods than a human to perform such acts.

[0378] In some embodiments of the invention, real time ultrasound data is used to calculate an amount of deformation and / or movement of cardiac tissues, so that a location of the conduction system and / or other annotations can be rendered correctly. Optionally and / or alternatively changes in registration may indicate an effect on the CFB, which effects may indicate safety and / or danger to the conduction system, for example. Optionally, tissue deformation is calculated using a finite element analysis. In some cases, the FEA is carried out before a procedure, optionally with various parameter settings, such as deployment method, and image matching is used to select which simulation is more correct. Such simulation may indicate danger and / or be linked to guidance to provide to a practitioner during implantation. More generally, potentially this provides a non-rigid registration.

[0379] It is noted that plane alignment and / or other three-point alignment may be used for ultrasound images and / or other images also not during tricuspid-related procedures and / or for not implantation procedures, such as structural procedures and / or electrophysiology procedures (e.g., conduction system pacing, Bachman bundle pacing). For example, a matching plane can be defined based on the three tricuspid commissures. One or more aortic nadirs and / or commissures and / or an annulus thereof, based on mitral valve annulus and / or one or more commissure), based on the location of the SVC / IVC

[0380] RA junctions and the fossa ovalis or Coronary sinus ostium.

[0381] It is noted that in general, each of these aspects may be practiced separately without other aspects. In implantation, for example, according to embodiments described below, features not relating to a particular aspect being practiced may be omitted. For example, geometric simulation need not use conduction system detection and 3D navigation need not show annotations of the conduction system.

[0382] It is noted that the terms “physician”, “operator” and “user” are used herein substantially interchangeable and relate to a person operating and / or receiving guidance form the system, which are typically physicians but may be technicians or other operators. Also, while CT data is used for some embodiments of the invention, it is noted that CT data can be replaced by MRI data or other 3D imaging data, at least for some embodiments.

[0383] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and / or methods set forth in the following description and / or illustrated in the drawings and / or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0384] Fig. 1 is a front cross-sectional view of a patient (not shown) 104 having a heart 100 with a conduction system 102, for diagnosis and / or treatment in accordance with some embodiments of the invention. In particular, the heart includes a septum 106, a left ventricle 108 and a right ventricle 110. Also indicated are a membranous septum 112, left atria 114 and right atria 116. As to the conduction system, indicated are an SA node 118, an AV node 120, a bundle of His 122, a LBB 124 (optionally including fascicles 125), a RBB 126, Purkinje fibers 130, fibers of Mahaim 128, Bachmann’s bundle 132, a fast pathway 134 and a slow pathway 136. In view of the process for marking them, the following letter annotation is used as well - AV node: A, Penetrating bundle: B, Branching bundle: C, LBB: D, RBB: E. The letters may be used to designate, for example, the start, middle or end of such conduction system component, along the conduction pathway.

[0385] Fig. 2 is a flowchart of a method 200 of diagnosing and / or treating such heart 100, taking into account conduction system 102, in accordance with some embodiments of the invention.

[0386] At 202, data indicating the layout of at least part of conduction system 102 of heart 100 are provided. While several ways of such providing are envisioned, in a particular set of embodiments, a cardiac CT is analyzed to generate this layout. This cardiac CT is typically acquired and / or analyzed before active intervention with the body of patient 104. In some embodiments such acquisition and / or analysis is during intervention, such as during catheterization. At 204, a tool, such as a catheter is guided in and / or to heart 100 to a location selected (e.g., targeted) according to the provided conduction system layout.

[0387] At 206, optionally, the guided tool or other tool is used to diagnose the patient and / or treat the patient.

[0388] Fig. 3 is a top level block diagram of a pre-procedure system 300 which may be used for CT image acquisition and / or analysis to provide the data of act 202, in accordance with some embodiments of the invention. It should be noted that other apparatus may be used to provide such data, for example, as described below. In some embodiments of the invention, system 300 may also be used for planning. It is noted that such planning may be beneficial, for example, in generating guidance for an actual procedure. However, such planning prior to a procedure is optional and may instead (if at all) be carried out during a procedure.

[0389] Fig. 4 is a top level block diagram of a system 400 which may be used for said guiding during act 204 in accordance with some embodiments of the invention.

[0390] Referring first to Fig. 3, a CT imager 302 is shown as an example of an anatomical imager. Other imager types may be used as well. The image acquired by imager 302, for example, a 3D data set, may be analyzed by an anatomical landmark / gross anatomy features finder 302 to identify anatomical landmarks. After anatomical landmark finding, a conduction system estimator 304 may be used to identify the location of at least a portion of conduction system 102 on the 3D image. In some embodiments of the invention, modules 302 and 304 are combined into a single module, for example, a machine learning model which maps anatomical images to conduction system layouts. The output of estimator 304 may include conduction system layout coordinates for use before and / or during a procedure.

[0391] For structural interventions it may be useful to identify, automatically, e.g., of the CT data, various anatomical portions. For example, TTVR it may be useful to automatically identify the tricuspid annulus and / or the CFB (central fibrous body). Such identification may be, for example, on the CT data, for example, by pattern matching (e.g., based on the shape of the annulus) or Al segmentation or object recognition and / or based on segmentation of the 3D data set of the heart into anatomical portions. In some embodiments of the invention, identification of the annulus, for example, is manual, by a technician or other user. Such identification may be provided by module 304 for example and / or a separate module, noting that module 304 may also utilize cardiac anatomy identification and / or segmentation.

[0392] An optionally planner module 306 (which may include a simulator) may be used to help plan a diagnostic and / or therapeutic procedure, based on conduction system 102. Module 306 may output plan data, which can include, for example, instructions to machines and / or humans. In some embodiments of the invention, planner module 306, conduction system estimator 304 and / or an anatomical module may be programed to measure, calculate and / or estimate anatomical distances, for example, as used for predicting conduction system damage, for example, as described below. Optionally and / or alternatively planner module 306 or a separate risk estimation module may be programmed to calculate a risk, for example, using a ML model and / or classifier and / or other estimator, for example, as described herein. Optionally and / or alternatively planner module 306 or a separate simulation module may be programmed to run simulations, for example, FEA type simulations, for example of mechanical forces and / or movements, for example to evaluate a risk and / or suggest one or more structural treatment parameters.

[0393] More generally, in some embodiments of the invention, the methods described herein which include calculations, image / 2D / 3D data processing and simulations and other machine-type operations are optionally carried out on circuitry configured for such operations that may be contained in separate modules and / or integrated two or more functions in a single module.

[0394] Referring now to Fig. 4, a tool 402, for example, a catheter is guided to a target location, for example a particular location in conduction system 102 or a part of the heart structure, for example, a tricuspid valve annulus (e.g., for TTVR). Tool 402 and / or heart 100 may be tracked during the procedure, for example, using an optional imager 404 (e.g., x-ray fluoroscopy and / or ultrasound). Data may be collected from the heart, for example, using an ECG 406. A registration module 416 is optionally used for calculating registration of a fluoroscopic (or other in-procedure) image to the conduction system data and / or CT image. Guidance to the user and / or portions of the conduction system may be presented on an optional display 408, for example, as markup on a fluoroscopy image, for example, as a color overlay. Optionally, a transform and overlay module 410 is used to calculate position and / or generate an overlay for display 408. Optionally or additionally, a management module 412 is used to help guide the procedure, for example, by generating indications and / or alerts and / or responding to user requests. Optionally, an arm control module 418 controls a position of a C-arm or other imager according to said guidance. Also shown is an optional guide sheath 414 which is optionally manufactured, controlled, and / or manually manipulable to help guide tool 402 to the target location, for example as described in PCT application IB2025 / 059358. In some embodiments of the invention, system 400 may also be used for planning. A testing / planning module 420 is optionally provided for guiding testing of an ongoing procedure and / or in-procedure planning and calculations relating to the procedure itself, for example, paths and / or simulation of effects. In this application, the term “system” is used to describe system 300 and / or system 400 (which can be implemented, for example, as a single configuration, two separate subsystem and / or as multiple components, possibly some remote). In some embodiments of the invention, processes such as image analysis, simulation, guidance generation, image generation and / or guidance providing are performed by the system. In some embodiments, the performance is semi-automatic - with a user requesting an action and / or in response to user action and / or with a user providing significant input (e.g., for locating a conduction system or suggesting a treatment). However, automated methods are described as well (e.g., for conduction system data extraction, target selection and / or plan evaluation) and may be used in some embodiments of the invention.

[0395] Referring now to Fig. 5, which is a more detailed flowchart 500 of a method of diagnosing and / or treating patient 100 (e.g., as an example of Fig. 2), in accordance with some embodiments of the invention. The acts in this flowchart will serve as the backbone of a part of the detailed description of this disclosure, with each act described in greater detail in separate sections below. Details in one section may be applied in other sections as well.

[0396] Flowchart 500 focuses on a particular procedure cardiac procedure, for example, conduction system pacing or TTVR.

[0397] Referring now back to Fig. 5, the acts are described briefly and as a prelude for the below, noting that the order of the acts can change, some cats are optional and the contents of the acts can be different.

[0398] At 502, a patient is selected, for example, for CS (conduction system) pacing or TTVR.

[0399] At 504, a cardiac CT image (or other anatomical image) is acquired of heart 100.

[0400] At 506, the CT image is analyzed to identify a layout of at least part of conduction system 102. Optionally, such layout is displayed on the CT image (507).

[0401] At 508, a more detailed diagnosis may be performed, for example, combining data from the CT image and ECG data.

[0402] At 510, a treatment is planned, for example, based on relative position of the conduction system and the tricuspid annulus.

[0403] At 512, potential effects of such treatment are optionally simulated and / or treatment changed accordingly.

[0404] At 514, geometrical access to the valve annulus and / or a CS location are optionally selected and / or simulated optionally resulting in changes in treatment planning and / or target locations.

[0405] At 516, a plan for the procedure is optionally generated.

[0406] At 518, the patient is set up for treatment, for example, in a cath-lab. It is noted that in some embodiments, one or more of acts 502-516 are done after such setup.

[0407] At 520, system 400 is optionally calibrated to actual patient conditions.

[0408] At 522, tool 402 is guided to the heart, optionally a sheath, optionally to the tricuspid annalus. In some embodiments of the invention, such guiding may include indications shown on a fluoroscopic image and / or machine control of tool 402. Optionally or additionally, such guiding includes one or more alerts and / or warnings.

[0409] At 524, a simulation of the effectiveness of the treatment may be made based on actual location of tool 402 and / or data measurements, optionally using a simulation.

[0410] At 526, the procedure is performed, for example, TTVR. Such performance may be under monitoring of system 400.

[0411] At 528, the procedure is completed. Optionally, data generated before the procedure and / or collected during the procedure are used to predict the effects on patient 104, which maybe used a monitoring physician to determine effectiveness of treatment and / or suggest follow up treatment.

[0412] Referring now to Fig. 6 which shows an example flow diagram 700 of a method of diagnosis and / or therapy in accordance with some embodiments of the invention. As can be seen, the system may be divided into two stages with corresponding hardware and / or software. First, at a pre-procedure stage 702, a CT image is acquired (706), various landmarks connected to the conduction system are noted (708) and actual conduction system portion locations may be generated (710). Second, a navigator stage 704 includes a pre-planning process 712 (which may include simulations, for example as described herein), a registration process 714 where the coordinates for the data from the CT is aligned with coordinates of the fluoroscope image (if any, or other image) and finally augmented reality display on a fluoroscopic image to help actual navigation, diagnosis and / or treatment 716. Each such process may use separate computing hardware which can be, for example, in a cath-lab, in a physician office or, at least in part, on a local or remote computing location (e.g., a cloud).

[0413] In one example type of implementations, planning is done on a remote system, for example accessed as a cloud. In some cases, the user interface and some functions run locally, for example, to enhance reaction time, but certain features, for example, conduction system detection, searches, simulations, recommendations and / or image generation, are handled remotely.

[0414] In-procedure support, for example, registration, image alignment, alerts, measurements, imager control, angulation output and / or overlay generation is optionally performed locally. This may be useful to reduce a risk of a procedure getting stuck due to a data outage. Some functions may be provided remotely, for example suggestions and / or requests for re-planning.

[0415] The plan itself may be stored locally and / or remotely.

[0416] A potential benefit of remote functionality is ease of updating functionality and / or reacting to potentially serious software problems and / or reduced hardware requirements (e.g., a capital expense). Remote access potentially supports easier protection of secret methods and data. Remote access potentially enables gatekeeping by the remote system which can be used, for example, to limit unauthorized use of the system and / or using metering methods for charging (e.g., counting number of uses and / or patients)

[0417] As noted, in some embodiments of the invention, time critical and / or clinically critical (e.g., lifesaving and / or death preventing) information is processed and / or used locally. Information which can bear time delay, requires heavier processing and / or is less clinically critical, may be done by remote.

[0418] Patient intake

[0419] Referring back to Fig. 5, at 502, a patient is selected for a procedure. In some embodiments of the invention, the patient is any patient about to undergo catheterization and / or EP procedures and / or treatment for structural heart disease, such as tricuspid regurgitation. As noted, in some particular embodiments of the invention, the procedure is a pacing lead implantation procedure. A particular potential benefit of some embodiments of the invention is in the ability to guide an implantation to a desired physical and / or functional location in the heart and patients may be selected to take advantage of such benefits. This can support conduction system pacing. In conduction system pacing a lead is delivered to the heart (e.g., through the right ventricle) with a stimulation electrode located so that it can stimulate a desired part of the conduction system. It is believed that such stimulation results in more physiological and / or effective cardiac contraction, for example, due to timing and sequencing benefits provided by using the native conduction system rather than general cell-to-cell propagation. In another example, the procedure comprises TTVR. A particular feature of some embodiments of the invention is the ability to predict and / or reduce possible side effects of TTVR and / or guide pacing lead implantation if such TTVR is expected to or seen to damage the conduction system.

[0420] Potentially, simulation, for example as described herein, can help guide the selection of an appropriate pacing mode for HF patients or at risk for HF, or bradycardia patients, for example, by comparing location of scar and conduction on the left ventricle myocardium. The presence of a scar suggests a reduced ability to reach conduction system within it and / or reduced probability of muscle recruitment in areas of scar. The selection of mode and / or location of pacing leads can therefore potentially be personalized, in accordance with some embodiments of the invention. In TTVR, simulation can be, for example, geometric and / or hydrodynamics and show, for example, one or more of potential damage to a conduction system and a geometry of implantation.

[0421] CS imaging

[0422] A CS map (or more generally, data about parts of the conduction, such as location relative to other parts of the heart) may be created in various manners. In some embodiments of the invention, a 3D structural image of the heart is used to generate such CS data. In some particular embodiments, at 504, a cardiac CT image of the heart is acquired as such a structural image. But other structural images may be used, for example, MRI and ultrasound.

[0423] At 506, the structural image (with CT as an example) is analyzed to identify the layout of conduction system 102. As will be explained below, in some embodiments, the conduction system location can be overlaid on a fluoroscopy or ultrasound (or other) image acquired during a procedure.

[0424] In some embodiments of the invention, the CT image is analyzed using a CT analysis package that suggests the location of one or more of the following portions of the conduction system, relative to gross anatomical features, for example, relative to valve annuluses, leaflets, septum and / or the membranous septum: a. SA node b. Bachman Bundle c. Slow pathway d. Fast Pathway e. AV node f. His Bundle g. Branching bundle i. Left Bundle Branch (LBB) ii. Left Anterior Fascicle (LAF) iii. Left Septal Fascicle (LSF) iv. Left Posterior Fascicle (LPF) v. Right Bundle Branch (RBB) vi. Mahaiem Fibers (MF) h. Left ventricle papillary muscle i. Right ventricle Papillary muscle

[0425] The specific conduction systems portions identified and / or anatomical features identified (and / or later visualized) are optionally selected according to the target procedure.

[0426] A potential advantage of using a CT or structural image is that the conduction system can be mapped without catheterization of the heart, especially no left ventricle or left side catheterization.

[0427] Another potential advantage of structural based mapping of a conduction system over EP electrical mapping is that structural based mapping can show the location of a blocked conduction system section, which, if suitably paced, may provide a desired conduction. In some embodiments of the invention, the structural image is analyzed to identify dead areas, in which the conduction system may be inoperative. Such areas may be identified, for example, using MRI, nuclear-medicine imaging and / or CT images (e.g., where wash-in and wash-out are analyzed).

[0428] In some embodiments of the invention, a CS map includes multiple layers, for example, anatomical-based conduction system location, electrical measurement based data and / or functional data such as perfusion or viability (e.g., from a PET or SPECT image or a contrast CT image). Such added layers may be aligned using the CT image or anatomical data extracted therefrom.

[0429] In some embodiments of the invention, the CS data is used to build a conduction model of the heart which is optionally used to predict the effect of electrical stimulation on the propagation of electrical signals in the heart and / or contraction thereof. Optionally, the model is a standard model and the CS data is used as parameters for such a model, such as more exact location of certain pathways or using anatomical data, for example, to model a more exact shape of the heart.

[0430] In some embodiments of the invention, the conduction system data is provided using methods described in PCT application IB2024 / 057540, the disclosure of which is incorporated herein by reference.

[0431] In one example embodiment of the invention, the following method is used to identify the conduction system. This method may be applied automatically, manually or semi-automatically, for example. It is noted that some parts may be skipped and some parts of the conduction system unmarked or be marked differently, the phrase “drawing” intended to convey a mathematical equivalent which may also be used for marking up an image. Any of the anatomical landmarks described herein may be identified based on location, shape and / or tissue type by image analysis of a CT data set, for example, using image segmentation methods, optionally using templates. Other methods may be used as well. In some embodiments of the invention, the methods use take into account anatomical structures which are visible, for example, as landmarks on a CT image and / or an MRI image. In some embodiments of the invention, the anatomical structures are selected because they constrain the possible locations for a portion of the conduction system and / or because they guide and / or co-develop with the conduction system during fetal development.

[0432] 1. Segment patient CT a. Identify chambers, vascular system, bones,

[0433] 2. Mark the tricuspid annulus (e.g., by identifying the plane between the RA and RV)

[0434] 3. Calculate center lines of the vascular system, e.g., one or more of: a. Subclavian b. SVC c. RA; and d. RV 4. Mark one or more of the A B C points of the conduction system: a. A - AV Node b. B - penetrating bundle; and c. C - branching bundle

[0435] 5. Mark point / area D, in one method: a. Draw a line connecting the point C to the LV apex lying on the LV septal wall b. Mark point DI at 1cm below point C on that line c. Mark point D2 at 2cm below point C on that line d. Mark point D3 at 3cm below point C on that line - this may be repeated for more points D e. Optionally place a perpendicular line through points D with a fixed width of 5mm or 10mm or any value from 3 to 12 mm. f. Optionally place a perpendicular line through points D with a non-fixed, increasing width of, for example, 5mm for DI 7mm for D2, with the line widening from a minimum of 3mm or more to a maximum of 15mm or less.

[0436] 6. Mark point / area D, in another method a. Draw a line connecting the point C to the LV apex lying on the LV septal wall - this line will be the direction the septal fascicle will be oriented for orienting the placement of the LB template (below) b. Draw a line connecting the point C to the base of the anterior papillary muscle in the LV - this line will be the direction of the anterior (superior) fascicle will be oriented for orienting the placement of the LB template (below) c. Draw a line connecting the point C to the base of the posterior papillary muscle in the LV - this line will be the direction of the posterior (inferior) fascicle will be oriented for orienting the placement of the LB template (below) d. An LB template is scaled to the real patient heart anatomy - the distance from C to LV apex, the width of the LV base based on weighing their ratio to the ratio the template describes, and overlaid on the heart, for example, curved to conform to the surface of the LV wall. In some embodiments of the invention, the LBB estimation or template is urged against the wall as the pathways are extended. For example, first the LBB is positioned against the wall and then the fascicles are positioned against the wall. In one example, an estimation process extends along the conduction pathway, one small part at a time and each part is positioned against the wall and laterally on (or in) the wall. In some embodiments of the invention, the conduction pathway is shown narrower and / or shorter than it actually is, for example, 70%, 60%, 40% or smaller or intermediate percentages. This may assist in preventing an operator from aiming to a more peripheral part of the conduction system which, due to intra-personal variations, might not exist at that location. Optionally alternatively or additionally, the showing of the conduction system is shaded or stippled or otherwise indicated to show confidence.

[0437] 7. Point D may be marked at the lower part of the LBB (before it bifurcate to the fascicles) and may be a useful target for LBB pacing

[0438] 8. Point E (RBB split from the His bundle toward the RV lumen) may also be noted; points D and E may be useful for dual chamber pacing, for example, using a single lead. In some embodiments of the invention, when two leads are used a safety distance is kept and / or monitored e.g., by the system (e.g., during planning and / or during implantation) between the contact points of the leads where they contact cardiac tissue, for example, 1, 2, 3, 4, 6, 10, 15 mm or smaller or intermediate distances. Alternatively, no safety distance is kept.

[0439] 9. Optionally parts of the atrial conduction system are marked, for example, as described herein, for example, one or more of the SA node, Bachmann’s bundle and intermodal pathways.

[0440] Another set of methods method which may be used for identifying the conduction system, together with or instead of other methods herein, comprises: a. Identifying the Inferoseptal recess, for example, by one or more of i. By its differentiated content from the rest of the adjacent tissue (fibrous tissue vs. muscle or blood) as seen by various volumetric imaging system ii. By its neighbors

[0441] 1. The roof of the inferoseptal recess is formed by an area of fibrous continuity between the leaflets of the mitral and tricuspid valves. This fibrous tissue supports the base of the atrial septum

[0442] 2. Anterior / Superior: The aortic leaflet of the mitral valve forms the anterior / superior border

[0443] 3. Posterior / Inferior: The septal surface of the left ventricle forms the posterior / inferior border 4. Right side: The right wall of the recess is formed by fibrous tissue through which the conduction axis (His bundle) typically penetrates

[0444] 5. Left side: The left ventricular cavity borders the left side of the recess. iii. By an alternative analysis of nearby anatomy:

[0445] 1. The inferoseptal recess is bounded on the atrial side by the diverging vestibules of the mitral and tricuspid valves. These vestibules are part of the atrial anatomy and play a role in the function of the atrioventricular valves

[0446] 2. The ventricular boundary of the inferoseptal recess is formed by the crest of the muscular ventricular septum. This septum is the thick, muscular wall that separates the left and right ventricles of the heart

[0447] 3. At its apex, the inferoseptal recess is marked by the inferior margin of the membranous septum. This septum typically acts as an atrioventricular partition at this level and is often overlaid by a layer of atrial vestibular myocardium. This layer separates the apex of the pyramidal space from the inferoseptal recess within the left ventricle iv. And / Or by the following set of neighboring anatomical structures:

[0448] 1. Base- The base of the IPS is located on the diaphragmatic surface of the heart. This is the bottom part of the pyramid- shaped space.

[0449] 2. Apex- The apex of the IPS is near the central fibrous body of the atrioventricular septum, close to the noncoronary sinus of the aortic root.

[0450] 3. Anterior Border- The anterior border is formed by the crest of the interventricular septum.

[0451] 4. Posterior Border- The posterior border is continuous with the diaphragmatic surface of the heart at the crossing of the left and right inferior atrioventricular and interatrial grooves.

[0452] 5. Lateral Borders - The lateral borders are defined by the two septal atrial walls. b. Infrapyramidal space may be identified, for example: i. By identifying on the volumetric imaging its differentiated content (fat and fibers as compared to surrounding muscle)

[0453] 1. For example identifying a low HUE epicardial invagination volume of cardiac CT

[0454] 2. For example identifying a high signal intensity on T1 weighted images of cardiac MRI ii. And / or based on structure, for example:

[0455] 1. Location and Shape a. The inferior pyramidal space is a pyramid- shaped fibrofatty structure located on the diaphragmatic (inferior) surface of the heart. It wedges between the four cardiac chambers from the diaphragmatic surface

[0456] 2. Its border are: a. The apex of the pyramid is located near the central fibrous body of the atrioventricular septum, close to the noncoronary sinus of the aortic root b. Inferior: The base of the pyramid is on the diaphragmatic surface of the heart c. Formed by the two septal atrial walls d. Bounded by the crest of the interventricular septum e. The space is continuous with the left and right inferior atrioventricular and interatrial grooves at their intersection on the diaphragmatic surface c. Using the infero septal recess and the infrapyramidal space identifications, one can locate the patient specific location of the conduction system axis. Using, for example, these rules: i. To understand how the infra septal recess and the infra pyramidal space relate to the cardiac conduction system, including the AV node, Bundle of His, and the left and right bundles, one takes into account their anatomical positions and their relationship with the conduction pathways. ii. The Infra Septal Recess is significant because it is close to the atrioventricular (AV) node and the Bundle of His iii. The Infra Pyramidal Space is closely related to the AV node and the initial part of the Bundle of His.

[0457] 1. AV Node - is situated within the atrioventricular septum, near the opening of the coronary sinus, and is part of the triangle of Koch, which is bounded by the tendon of Todaro, the tricuspid valve annulus, and the coronary sinus ostium, The AV node is located just above the infra septal recess, making this recess a landmark for accessing the AV node during procedures as well AV node is also adjacent to the apex infra pyramidal space, which provides a pathway for the AV node to transition into the Bundle of His.

[0458] 2. The Bundle of His originates from the AV node and travels through the floor of the membranous part of the interventricular septum

[0459] 3. The Bundle of His passes close to the infra septal recess as it descends through the septum. The Bundle of His is closely associated with the infra pyramidal space, particularly at its origin from the AV node. During the path of the bundle of His over the membranous septal floor it give rise to the right and left bundle branches.

[0460] 4. The Right Bundle originates from the branching bundle (during its path over the membranous septal floor) and travels along the right side of the interventricular septum toward the medial papillary muscle of the right ventricle

[0461] 5. The Left Bundle originates from the branching bundle (during its path over the membranous septal floor) and travels along the left side of the interventricular septum d. According to the above methodology one can localize the landmarks that describe the location of the conduction system axis of a patient. These annotations can be achieved manually or by image processing of CT or MRI using the difference between the elements attenuation properties (HUE in CT) or T1 weights in MRI, or can be generated by a ML network or a combination of 2 or more of the techniques.

[0462] For example, for a HUE based method in CT, an image processing method performing HUE filtering of the Cardiac CT and generating CT images of values of HUE that corresponds with tissue like fat, fibrous, connective tissue may be performed. For example the filtering select a window of HUE of values below 30 HUE or below 0 HUE. In some embodiments, by generating multiple images of different HUE windowing. In some embodiments by using a dual beam CT image and selecting a different HUE for each beam depending of the beam energy. In some embodiments in a dual beam image using a ratio between the two energy values of the corresponding voxels. In some embodiments using a conventional cardiac CT and processing the image into multiple HUE windows and using a derived ratio formula that enhances the difference between the above mentioned tissues and the rest of the myocardium and the blood within it.

[0463] In some embodiments of the invention, the membranous septum and the membranous septal floor are identified by searching the most proximal endocardium of RV and LV area.

[0464] In some embodiments of the invention, the membranous septal floor is identified for example by drawing a highest elevation line of the myocardium and identifying the crossing of the membranous septum (e.g., previously identified) and the myocardium highest elevation line. Once identified, the Infrapyramidal space (IPS) and the inferoseptal recess (ISR) are optionally segmented.

[0465] In some embodiments of the invention, the following points are identified and / or marked:

[0466] 1. AV node (Point A) sits at apex of IPS closest or at the intersection between IPS and ISR (in one embodiment).

[0467] 2. Point B sits on intersection of ISR and posterior border of MSF (MS floor) in (in one embodiment)

[0468] 3. The Non branching bundle of His extends from point A to Point B over the surface of the ISR.

[0469] 4. Point C sits on the MSF at, for example, 70% of MSF length (other values, for example, between 50% and 80% may be used)

[0470] 5. The Left bundle (sheath) starts emerging from the MSF and will commonly continue to extend all the way to 100% the MSF length and cover the endocardium of the LV on its common path a distance of, for example, between 1-4 times the MSF length and then the Left Bundle will break into fascicles and each will continue its path toward the anterior, posterior papillary muscles and the LV apex (superior, inferior and septal respectively).

[0471] 6. The right bundle emerges as a narrow bundle at, for example, 60% of MSF (other values, for example, between 40% and 80% may be used) In some embodiments of the invention, locations in the atrial conduction system are identified.

[0472] 1. The SA node is optionally identified by identifying the sulcus terminalis on the epicardial surface of the right atrium (e.g., fat surrounding and separating the SVC and RAA) in a CT, typically is located lateral side of the SVC.

[0473] 2. Bachmann’s bundle is optionally identified by identifying points as follows:

[0474] (a) BAC 1- Point on the SVC RA junction in a medial - posterior position. On the border between RA and RAA.

[0475] (b) BAC 2 - a point between the roof of the LUPV (Left Upper pulmonary vein) and the Left Atrial Appendage.

[0476] It is noted that for tricuspid procedures, for example as described below, it is often enough to locate just the points A, B and C and possibly assume that the conduction system is a straight line, for example in the form of a cylinder of a fixed radius between pairs of points, for example, 1, 2, 3, 4 mm (or smaller or lager or intermediate values) in diameter. In some embodiments, the conduction system is assumed to have a different cross-sectional shape.

[0477] While planning of a cardiac procedure can be started before providing conduction system data, it is a particular feature of some embodiments of the invention that planning takes into account such data. Optionally or alternatively, the execution of such a procedure uses conduction system data, for example, as will be described below.

[0478] A simplest type of planning (510) uses a visualization of the conduction system (507) for example for manual planning (e.g., a user marking possible locations related to activities and evaluating by eye).

[0479] A more sophisticated type of planning uses one or more of the following tools:

[0480] (a) combined visualization (507) showing structure, conduction system and more data, such as functional data or electrical data;

[0481] (b) simulation of effects of a proposed treatment (512);

[0482] (c) geometric planning of access and / or layout (514);

[0483] (d) automated or semi- automated search of a solution space for effects and / or geometry (516);

[0484] In some embodiments of the invention, a more in depth diagnosis is carried out after the conduction system data is available, for example, using ECG data (508). During planning, visualizations and / or other data as expected to be seen during an actual procedure may be created and shown to a user. This may allow, for example, for a user to test-run a treatment.

[0485] After planning is completed, one or more outputs may be generated. In some embodiments of the invention, the output includes one or more of:

[0486] (a) views;

[0487] (b) synthetic images showing what should be seen at various stages;

[0488] (c) synthetic data showing what might be measured during a procedure;

[0489] (d) recommended fluoroscopic viewing angles and / or other settings;

[0490] (e) data for a computer for generating indications (e.g., alerts and / or a traffic-light type indication) showing a user if a procedure is progressing as planned; and

[0491] (f) instructions for a user and / or devices to be carried out at various stages of the procedure.

[0492] At 507 a display of the heart including the conduction system is optionally provided. In some embodiments of the invention, the display is a 3D display showing the conduction system overlaid or otherwise indicated on a 3D rendering of the heart. Optionally or additionally, the display is a display of one or more 2D projection images which can be used to simulate fluoroscopic views (during a procedure, actual fluoroscopic images may be used). Optionally, views not readily available in fluoroscopy, such as a transverse view, are generated and displayed.

[0493] In some embodiments of the invention, one or more of the following components of the conduction system are indicated. It is noted that the certainty of location (or spatial extent) may not be 100% and may be different for different components or parts thereof. Optionally, the display includes not only an indication of the component location but also an indication of uncertainty, for example, a lightly shaded area or dashed line. The following list shows one possible order of certainty of location: a. Point B (penetrating bundle); b. AV Node; c. Point C (branching bundle); d. LBB; e. RBB; f. Proximal Septal fascicle; g. Proximal Superior fascicle; h. Proximal posterior fascicle; i. Distal Septal fascicle; j. Distal Septal fascicle; and / or k. Distal Superior fascicle.

[0494] For tricuspid procedures, just showing points A, B, C and / or estimated conduction system pathways therebetween (to the extent they are adjacent the tricuspid annulus) may be sufficient.

[0495] In addition other data may be overlaid, for example:

[0496] (a) Targets (such a location on the septum to penetrate and / or a location in the septum to capture;

[0497] (b) places to be avoided;

[0498] (c) less or unviable locations;

[0499] (d) previously treated locations;

[0500] (e) suspected locations of blocks or previous ablation; and / or

[0501] (f) locations that are and / or were targets of structural intervention;

[0502] (g) one or more parts of the CFB (central fibrous body); and

[0503] (h) one or more valve annulus and / or other valve parts.

[0504] In some embodiments of the invention, instead of or in addition to marking conduction system locations, what is marked is anatomical locations which may indicate conduction system pathways. While such locations may be visible on a CT image, they are often not easily and / or precisely detectable on a fluoroscopy image. Optionally, as will be described herein, marking can be used to indicate such locations during a procedure.

[0505] In some embodiments of the invention, instead of natural cardiac locations, what is marked are anatomically arbitrary locations which are otherwise selected for targeting. For example, when planning an ablation to block a reentrant loop one can identify the location on a CT image, possibly with the help previous electrical mapping. This location, however, may be in an otherwise anatomically arbitrary location on the wall of a cardiac chamber. However, the location can be identified with respect to gross anatomy. As is described herein, such location can be marked on a fluoroscopy image or other image generated during a procedure.

[0506] A particular type of arbitrary marking is guide marks for a procedure, such as locations to ablate or attach an implant or safety boxes (e.g., not to pass a line).

[0507] It is noted that the indication need not be on a cardiac structure. In one example, the indication is within a cardiac structure, for example, within a wall, such as the septum. The location may be shown with an error and / or certainty indicator and / or may be matched to a particular (or several) phases of breathing and / or cardiac cycle. In another example, an indication may be in a lumen of the heart. Such indication may be useful, for example, to show a desired path of a catheter. In a particular example, such indication may be used to indicate a location of a radio-opaque marker or electrode or other identifiable part of a catheter or other interventional tool.

[0508] As can be seen, in general, any location which can be defined relative to cardiac structure can be indicated. In some embodiments of the invention, the definition is relative to cardiac structures in a particular phase of the heart, such as diastole. This phase may be standardized and / or may depend on the cardiac procedure. The phase may also be different for different cardiac locations. In some embodiments, however, an indication is located for multiple cardiac phases. When marked, for example as described herein, such marking can move with cardiac dynamics.

[0509] In some embodiments of the invention, when abnormal cardiac dynamics are suspected (e.g., due to an arrhythmia) a marking may be indicated as tentative. Optionally or additionally, different locations will be shown for different cardiac dynamics, for example, one location for regular sinus rhythm and another for when a heart is over paced.

[0510] An indication can also include what is expected to be measured (or seen) at a location during a procedure, for example, an electrical measurement or a physical movement. Such indication can be tied to, for example, a stage in the procedure, a triggering activity (which is optionally detected automatically), a manual request and / or a tool location. One way of identifying the viability of a location is used contrast CT and looking at the difference between uptake and washout in various areas - ischemic or scar tissue is expected to have slower uptake and slower wash-out. Another way is using electrical measurement data. Another way is from nuclear medicine imaging, such as PET or SPECT or other functional imaging modalities. In some embodiments of the invention, for example for pacing, scar tissue is identified manually or automatically as a location not likely to be captured by pacing, so it is not selected as a target area and / or its effects on signal propagation otherwise taken into account. It is noted that scar tissue may be a target area for penetration into a tissue in order to electrify viable tissue laying past it. Features other than scar tissue may be identified instead or as well, for example, one or more of myocardial viability, scar, fibrosis, amyloid deposition, contractile behavior, ischemic state, and / or inflammatory conditions.

[0511] In some embodiments of the invention, the display depends on the planned procedure. Optionally, the user enters the desired procedure into a user interface of the system.

[0512] In another example, of performing atrial trans-septal puncture sites, one or more of the following can be indicated:

[0513] The RA puncture point, the LA point, and / or a line assuming one pre-planned optimal trajectory between two electrodes of a tool. For example, when using a sheath containing the needle with two radio-visible markings, have one location indication in a known position proximal to said sheath distal opening, with a second indication being a desired distal end location of the needle.

[0514] In addition to or alternatively to automatically added markings (e.g., based on preset or procedure) and semi-automatically (e.g., a user selects from a list or by name), a user can optionally modify the location of an added marking, for example, by editing a 3D location, for example by dragging on a 3D image. Optionally or additionally, a user can add a new marking, for example, by indicating a 3D location and selecting a marking type (e.g., dot, sphere, line or other geometric shape). Optionally, the marking system allows a user to snap a marking to a cardiac structure, such as a cardiac wall.

[0515] Different indications may have preset graphical properties when displayed and / or user selectable properties, for example, line shape, transparency, color, shadow, width, texture and / or variations of any of the above.

[0516] Other data can be shown as well and / or have indications added therefor in some embodiments. This includes, for example, electrical information and tissue viability and / or type.

[0517] Visualization may include a 3D image visualization. In some embodiments of the invention, 2D visualizations and, in particular, 2D projection visualizations are shown. One type of visualization shows an expected view during a procedure. A user optionally adds indications to be shown that are tied to particular visualizations. This may be useful as changes in visualizations directions may correlate with stages of a procedure, allowing data to be shown as needed.

[0518] In particular, it may be useful to show non-parallax visualizations, e.g., which have a point target on the left bundle and the right ventricle penetration point align. This can include selecting the LAO and CRA angles of the fluoroscopy such that they belong to the corresponding S curve. For example, this can include portrait and enface views of the heart. In some embodiments of the invention, an enface view is a non-parallax view of the left bundle and its fascicles viewed at the LV septum from a left lateral view where the dimensions of the left bundle and the fascicles are kept without parallax. In some embodiments of the invention, a portrait view refers to a view from the point of penetration of the septum that includes in the image the target point for pacing and the distance between the penetration to the target is kept accurate.

[0519] Another type of visualization is a virtual visualization not possible to be acquired during a procedure. A particular example is a transverse view of the heart. This may be useful to help a user see a trajectory and / or amount of penetration of a pacemaker lead tip from a right side of the heart to the left side of the heart to a target pacing location. Fig. 7A shows an example template for a left bundle branch. During visualization, this template may be parameterized and overlaid on an image at a location of the left bundle block as determined, for example, by CT analysis. Other templates may be used for other parts of the conduction system.

[0520] Fig. 7B shows a 3D segmented view of a heart, for example, based on CT image data and on which the left bundle branch of Fig. 7A is overlaid. Also shown are the conduction pathway from the AV node to the LBB, including the bundle of His. This conduction pathway may be especially relevant for tri-cuspid interventions.

[0521] Fig. 7C is a zoomed in view of Fig. 7B showing the conduction system parts.

[0522] Fig. 7D is an enface view of the left ventricle showing the left bundle branch and its three fascicles, from right to left: LPF, LSF and LAF.

[0523] Some additional markings, not shown, one or more of which may be provided, especially for LBB-related treatments, include:

[0524] (a) continuation of the fascicles to the base of papillary muscles. One continuation is clockwise and the other is counterclockwise. In some embodiments of the invention, the continuation is truncated at, for example, 30%, 50%, 60%, 80% or intermediate or smaller percentages of the path connected to the papillary muscles

[0525] (b) a line connecting point C to the LV apex; and / or

[0526] (c) The right bundle, for example, shown as a path from point C to the medial papillary muscle of RV and / or a path or part thereof from the medial papillary muscle to the moderator band.

[0527] In some embodiments of the invention, marking is by taking templates (e.g., such as shown Fig. 7A), positioning them according to the conduction system location and morphing them to lie flat on the ventricular wall (or other anatomical structure). In some embodiments of the invention, such overlying of a template includes scaling the template, for example, according to the LV dimensions, such as width at base and / or vertical height to apex. Optionally, a table is maintained mapping LV geometry / measurements to template deformation. In some embodiments of the invention, scaling includes setting the apical length of the LBB to be 5% of the distance between point C and the LV apex. Other values can be used as well, for example, between 3% and 10%.

[0528] More diagnosis

[0529] In some embodiments of the invention, further diagnosis is performed during the planning stage. In some embodiments analysis of the CT image can be used on its own or with other data to better understand the condition of the patient. One example of further diagnosis involves combining electrical information with structural information. For example, ECG data can be used together with the conduction system data to better evaluate a patient situation and / or plan a more effective and / or safer procedure.

[0530] One type of diagnosis which may be useful is identifying potential locations of conduction system blocks using ECG (e.g., after valvular intervention).

[0531] For example, ECG analysis of, for example a 12 lead ECG, optionally in the form of a vectorcardiogram may be used to detect an infra or supra nodal conduction disturbance.

[0532] In some embodiments of the invention, an analysis of 12 lead ECG is used to create a vectorcardiogram by transforming the 12 lead data into data from co-planar composite leads. In some embodiments of the invention, the vectrocardiograms are analyzed to show the progress of the ventricular activation front over time. Such progress may be used to generate a rating for the wellbeing of some or all the entire Left Bundle and / or its fascicles. In some embodiments of the invention, the ranking is based on general measures, such as rate of change. Optionally alternatively or additionally, the progress is compared to normal progression rates as measured in healthy hearts or in hearts with particular pathologies. Optionally alternatively or additionally, a machine learning based classifier is used to classify the vector gram and / or its progress. Such a classifier may be trained on vector electrocardiograms collected from hearts with known pathologies.

[0533] In some embodiments of the invention, the LBB state is used to plan a location for pacing, for example manually e.g., by showing a projected state of the LBB and / or automatically, for example by calculating a blockage location in the LBB and suggesting a pacing location below such location.

[0534] In some embodiments of the invention, ECG analysis is used to identify deviations in the ECG of a patient as compared to a normal ECG, a past ECG in the patient and / or an expected ECG in a patient with such pathologies as the patient is known to have. Data generated by the analysis may be used in planning a treatment, for example, in planning a treatment which results in a smallest deviation of the resulting ECG form a target (e.g., normal) ECG.

[0535] In another example of further diagnosis, the ECG is analyzed to detect myocardial infraction locations. Such locations may be untreatable and / or may block conduction and / or may be a target of therapy. For example, methods such as discussed in the following article may be used: " Deep Learning for Detecting and Locating Myocardial Infarction by Electrocardiogram: A Literature Review" by P. Xiong, S. Ming-Yuen Lee & G. Chan, Front. Cardiovasc. Med., 25 March 2022, Sec. Coronary Artery Disease Volume 9 - 2022 doi: 10.3389 / fcvm.2022.860032.

[0536] In other examples of further diagnosis, non-ECG data may be used, optionally with ECG data. For example, location of scar tissue is used to evaluate expected ECG behavior and compared to actual measured ECG to identify potential problem parts or undiagnosed problems in the conduction system.

[0537] Geometric planning

[0538] Actual treatment of the heart typically includes two geometric -based constraint issues which may affect treatment or other access to the heart. In some embodiments of the invention, one or both of these issues are considered during planning. In general, geometric considerations can be relevant not only for treatment of the conduction system (e.g., pacing or ablation), but also for other procedures, such as "structural heart" such as implanting, replacing and / or repairing an implant such as a valve, as such interaction with the heart by the implant and / or delivery system hay cause damage to the conduction system, for example, by applying pressure or shear forces.

[0539] A first issue is access. The heart is typically accessed in one of two ways. In a first manner rigid tools are used and then care must generally be taken to avoid damaging critical structures. This limits possible access paths. In a second manner, catheters or other flexible tools are used and which can deform to follow the shapes of lumens in the heart (though some tissue penetration, such as the atrial septum, is often used). However, the geometry of the heart affects the directions from which a target can be accessed.

[0540] A second issue is success of treatment as affected by geometry. Depending on the access direction a procedure may be more or less likely to fail and / or otherwise be suboptimal. For example, penetration into tissue and / or correct coverage of a target for lead placement may depend on access direction. In another example, a pacemaker lead may be more likely to fail (or a more expensive or thicker lead needed) for certain access directions. It should be noted that combination of access direction and target location can define a bend in the catheter and / or expected movement during cardiac activity, one or both of which may have a degrading effect on such lead.

[0541] Typically, but not always, a first consideration is the location to where treatment is to be provided. A second consideration can be the location from which the tool is provided (and any limitations on tool flexibility and / or steerability. For CSP (conduction system pacing) or ablation in the right ventricle, the location from which the tool is provided is usually the tricuspid valve.

[0542] For example:

[0543] (a) for reaching the slow pathway of the AV node, the target for ablation can be more superior than the marking of the AV node (point A as marked on the right ventricular wall) ;

[0544] (b) for reaching the fast pathway of the AV node the target for ablation is more to the right and superior of point A; (c) the target may be near the point A marking of the AV node that operator, based on operator selection based on a desired intervention;

[0545] (d) for reaching a point on the left bundle that is below the conduction block a. Based on the QRS axis of the ECG the operator may decide how far below point C is appropriate to deliver the pacing; b. To reach optimal hemodynamic response to conduction pacing the operator may try to activate the left bundle as high as possible in its path toward to the inferior segments of the left ventricle;

[0546] (e) to perform biventricular pacing using a single pacing lead the operator may choose a trajectory inside the septum where a distal ring electrode of the lead (the LV electrode) is positioned within the left bundle and / or a proximal point for activation (e.g., where a proximal ring will it) is positioned next to the right ventricle endocardium; Optionally the user / operator either notifies the system regarding inter-electrode spacing or the system will suggest (e.g., based on simulation as described herein) a suitable lead for such pacing;

[0547] (f) for some types of biventricular pacing, two leads will be implanted, each with its own geometric considerations and target; and / or

[0548] (g) to perform conduction system pacing achieving both activations of the left and the right bundle the operator implants in certain qualified patients, the target location may be the highest position on the path just below the branching bundle (optionally indicated as point C); this may provide for physiological pacing of both the left bundle and the right bundle.

[0549] In some embodiments of the invention, a sheath used for delivering a treatment is a sheath with fixed curves, for example part of a set and different curves are achieved using a different member of the set. In such a case, the planning system may try out various sheaths geometries to find a sheath which provides a "correct" sheath layout, e.g., as shown. Optionally alternatively or additionally, the curve values may be outputted and a user will select a closest match.

[0550] In some embodiments of the invention, a controllable sheath is used, for example a sheath with one or two or more controllable bending locations. The output of a planning can be a set of instructions what angle to bend each sheath bend. In some embodiments of the invention, the sheath layout is selected to allow the user enough leeway in bending the sheath (at one or both bending locations) during deployment to compensate for unexpected problems and / or shape mismatches.

[0551] In a valve delivery, even if the sheath (or delivery system) is unbendable, it is optionally aimed at the annulus for a certain location and / or orientation. In some embodiments of the invention, the search angle ranges are used as an input for a process of parametric searching (by the system) for a solution for sheath layout that also provides a desired end location of the sheath.

[0552] In some embodiments of the invention, the planning system may try out several sheath options to identify one or more satisfactory combinations. In some cases, this may be done manually by a user and / or a user can place constraints, such as on target locations and / or access angles and / or sheath type and / or restrictions on allows sheath and / or lead paths.

[0553] For some treatments, there is no long-term residing sheath, so sheath considerations may be ignored. A particular type of such treatment is a leadless pacemaker. While such pacemaker has no lead, the pacemaker itself may have a non-trivial size and geometric considerations considered during planning may include avoiding inadvertent contact between a body of the leadless pacemaker and the wall of the right ventricle other than at the penetration point, chordae, leaflets and / or another RV implant such as a lead or another leadless pacemaker. Similar consideration may be involved in delivering a valve or other tool for treating structural heart disease.

[0554] In some embodiments of the invention, the output of such geometric planning can be a step by step description of the implantation process including when to bend a bend of the sheath and / or advance or retract a stylet. Each step may include one or more of instructions (e.g., visual and / or audio), expected measurements, expected tip position and / or angulations, expected layout, a synthetic version of what an image (x-ray and / or ultrasound) acquired at that stage might look like, expected position (e.g., using a positioning system such as a magnetic or impedance positioning system) of some part of the tool or sheath, actions to take (such as contrast material injection), alerts and / or conditions at which such alerts will be presented. In some embodiments of the invention, no separate positioning system is used. Rather the acquired images and optionally other constraints are used for position-detection of tools (or for enhancing the accuracy of positioning systems).

[0555] It is noted that some procedures require more than one treatment location. For example, multipoint pacing may require multiple places to implant leads and ablation may include movement along a line. Such movements may interfere with cardiac structures, such as chordae. In some embodiments of the invention, such structures are taken into account when planning a path and / or a sequence of locations to which a sheath or other tool is to be breakout.

[0556] It is noted that such analysis of geometrical considerations as described herein can be used in other parts of the heart as well. However, there is particular potential benefit in the right ventricle, being a target for lead implantation, for the conduction system, where some parts are more difficult to access and / or for trans-septal penetration (such as to the LBB) where the path includes contact with tissue, floating in a chamber and fixed inside tissue. Other targets which share one or more of the properties may also potentially benefit from such planning and / or simulation as described herein.

[0557] Treatment simulation

[0558] Treatment planning may also depend on the expected outcome of the treatment. In some embodiments of the invention, planning includes estimating, for example by simulation, what such outcome might be. The results of such determining may be used to modify treatment parameters, for example, penetration or treatment location.

[0559] In the example of simulating pacing, a pacing location and pacing parameters may determine efficacy and / or other properties of pacing. In some embodiments of the invention, a FEM (finite element model) (or other simulation, such as finite volume analysis) of conduction in the heart is used to model the heart, with each element representing a small part of the heart - e.g., muscle tissue, nonconducting tissue or the conduction system. Multiple tissue types may be provided, for example, for different muscle and / or for different parts of the conduction system and / or for various degrees of health.

[0560] In some embodiments of the invention, the model is personalized to the patient, for example, based on previous imaging or other collected data, such as data on electrical behavior, viability and / or ischemia.

[0561] In some embodiments of the invention, the model is verified, for example by comparing a virtual ECG generated by such heart to a real ECG of the patient. If needed, the model may be modified, for example by adjusting parameters (manually or automatically, for example by automated search), until the behavior of the model seems to match what is observed for the patient. Such simulation may be useful also in evaluating the effects of potential damage to the conduction system caused by, for example, TTVR.

[0562] Other models of activity of the heart may be used, including, for example, an electromechanical model which also models mechanical behavior and an abstract model which models the heart as a graph. In some embodiments of the invention, only a part of the heart is modeled, for example, the left ventricle.

[0563] An exemplary basic simulation reports the effect of a certain treatment on the heart. This may be, for example, a manually triggered function used as part of planning. In some embodiments of the invention, a user may select one or more ranges of values of parameters and / or sets of such ranges and allow the simulation to map out the results over these different values. Optionally, such mapping is used to generate a data set showing various effects. Optionally or additionally, the mapping is applied as a search function to identify a satisfactory (or better) treatment. In some embodiments of the invention, a user may compare two or more treatments. In some embodiments of the invention, a user may generate a score for each parameter value set and optionally rank the value sets based on the score.

[0564] For example, one or more of the following parameters may be controlled in the simulation (such may also be varied during geometric simulation for example as described herein):

[0565] Pacing location, pacing electrical parameters, pacing logic, electrode type, cardiac condition such as drugs, exercise status and / or hydration, ANS status (sympathetic and / or parasympathetic), breathing phase, preload, afterload and / or regurgitation.

[0566] The simulation can be used to show results of a treatment, e.g., an ECG, an activation profile of the heart, mechanical contraction behavior and / or other calculated patient physiological parameters, such as cardiac output.

[0567] In some embodiments of the invention, the simulation is used to generate statistical information which represents the results of more than one run and / or more than one set of parameters of treatment and / or underlying conditions.

[0568] In one example, the results show a distribution of success. For example, one set of parameters may result in a 90% success rate and another set may have an 80% success rate. Success may be defined, for example, based on statistics of the desired outcome, such as regurgitation, length of systole, shape of the ECG and / or how similar the resulting contraction is to a physiological contraction (e.g., in time and space).

[0569] In some embodiments of the invention, the result of the simulation is the type of failure and / or risk of failure. For example, a less risky pacing location may have a lower overall score, on the average, but be less likely to fail. For TTVR, a easier implantation process may result in higher risk of damage to a conduction system, and vice versa.

[0570] It is noted that the combination of potentially precise positioning of a lead or implant and knowledge of the conduction system location potentially make such simulations and statistics more meaningful.

[0571] In some embodiments of the invention, a sensitivity evaluation is the result of simulation. For example, such evaluation may indicate to which variable the treatment is more sensitive.

[0572] In some embodiments of the invention, a source of likely failure is determined. For example, failure can be a result of doctor skill, accuracy of the reconstruction and / or patient variability. By trying out parameter variations to model each of these options, a degree of sensitivity and expected failure mode can be determined. This may help in selecting operators. In some embodiments of the invention, a better physician (e.g., with a better record) is selected if the expected failure mode is operator related. Optionally or additionally, depending on the quality of the available doctor, a different suggested treatment is proposed. In some embodiments of the invention, the simulation is used to identify potential side effects and / or incorrect functioning of the therapy, for example as they relate to pacemaker (or other therapy) settings.

[0573] In some embodiments of the invention, such simulation is repeated and / or enhanced once the operation is in progresses and / or completed and more up-to-date data is available. Results of such simulations may include, for example, recommended pacemaker settings, expected pacemaker misoperation and / or suggested changes in setting to handle such. Such results and analysis are optionally passed on to a handling physician in charge of programming the pacemaker after the operation and / or other care of the patient. In some embodiments of the invention, such information is stored on the pacemaker itself and / or linked in a database to an ID of the pacemaker and / or the patient.

[0574] In some embodiments of the invention, the simulation simulates a single beat or multiple single beats. In some embodiments of the invention, the simulation simulates a series of beats and models the effect of electrical conduction and / or contraction in one beat on following beats. One example is modeling the effect of hemodynamic effects on cardiac behavior. Another example is modeling cardiac activity through a breathing cycle and / or during an exercise ramp up or ramp down or steady state.

[0575] Another type of time related issue relates to the lead implantation. There is often a physiological reaction which can affect the outcome of treatment or at least modify it over a time period and / or which may suggest the need for different parameters (or expect different results) according to a timeline. This timeline may be measured in weeks after implantation. Such effects may also relate to TTVR, for example - with damage to a conduction system potentially appearing or becoming more sever after implantation.

[0576] For example, one or more of the following outcomes may be simulated: electromechanical effect of lead contact, edema and / or fibrotic cap.

[0577] In some embodiments of the invention, the outcome of such timeline is provided to a followup physician that treats the patient after the procedure. In some embodiments of the invention, the timelines and / or different pacing parameter sets for different times are provide din the pacemaker memory or in a database associated with the pacemaker ID. In some embodiments of the invention, pacing parameters change automatically under pacemaker control according to changes in timeline and / or according to one or more decision rule programmed therein which takes into account expected effects of a pacing regime and different sets for different conditions, such as different points along a timeline.

[0578] In some embodiments of the invention, a goal of treatment (or at least a measurement of success) is the normalization of surface ECG (and / or cardiovectorgram) post procedure. Normalization may be, for example, to the patients own baseline ECG (e.g., form the past or from a non-arrhythmic shape), normalization to a population ECG, normalization to ECG at other physiological states of the patient and / or normalization to a physician selected / input template.

[0579] In one example, a scoring function provides a normality score for an ECG and scores the outcome of one or more sets of pacing parameters (e.g., including location) and / or uses such score in a search (e.g., manual and / or automatic) process.

[0580] While the above simulation has focused on pacing and conduction system pacing in particular, simulation may be used to score the outcome and / or search for parameter sets for other treatments, such as ablation or tricuspid treatment.

[0581] Procedure

[0582] Referring back to Fig. 4 which shows a top level block diagram of a navigator sub-system which may be used during a cardiac procedure, in accordance with some embodiments of the invention.

[0583] Fig. 8 is a flowchart of a method of an in-procedure diagnosing and / or treating a heart, optionally using the navigator of Fig. 4, in accordance with some embodiments of the invention.

[0584] At 1202 various data used during the procedure is optionally received, for example, a procedure plan, conduction system annotations and / or other data.

[0585] In some embodiments, what is received includes a pre procedure CT with annotations of anatomical sites that are important for the procedure and / or for image registration during the procedure, conduction system locations and data indicating a desired path and angulation(s) of tools during the procedure, for example, path and angulations at contact with a septum.

[0586] At 1204, a patient is arranged (e.g., on a bed in a cath-lab) and prepared for the procedure, for example, by sedation thereof. In some embodiments of the invention, the arrangement is selected to mimic the arrangement during acquisition of the CT image of the patient. If the patient is propped up, information about the propping may be used for a registration, to help align the CT image with a fluoroscopy image.

[0587] At 1206, the vascular system of the patient is accessed and interventional tools, such as a guidewire, catheter and / or sheath, are inserted.

[0588] At 1208, the patient is registered. This may include, for example, registration relative to a 3D positioning system. In some embodiments of the invention, no such separate position system is needed. Instead, registration matches an imager, such as a fluoroscope, to the pre-operational CT image (or other data).

[0589] In some embodiments of the invention, registration uses one or more of the following data types, which may be detected by analysis of one or more fluoroscopy images: (a) Momentary C arm Caudal and LAO orientation, optionally starting at 30 degrees angle for each;

[0590] (b) Location and / or movement of reference catheters and / or interventional tools, for example, radio-opaque markers thereof and / or general silhouette;

[0591] (c) Location and / or movement of contrast enhance heart compartment; and

[0592] (d) Boundary of a heart lumen enhanced with contrast.

[0593] In some embodiments of the invention, reference catheters or other tools have a fixed location relative to an anatomical feature and can be used to locate and / or track that feature and / or assist in registration (e.g., as the tool should be matching the CT image anatomy). One example is a coronary sinus catheter placed in the coronary sinus of said patient.

[0594] As an example of tracking directly an anatomical feature, a contrast enhanced sequence of fluoroscopy images can be used to track movement of anatomy such as a septal (atrial and / or ventricle) wall, a valve annulus (e.g., tricuspid, pulmonary, aortic and / or mitral), for example based on leaflet motion.

[0595] In some embodiments of the invention, the actual registration comprises finding a best (or satisfactory) match between the pre-operative CT data and the currently collected information. Such a match optionally allows for tissue deformation and affine transformations.

[0596] In some embodiments of the invention, registration includes using data about physical contact. For example, if a physician indicates that a catheter is contacting a wall, and the catheter has a radioopaque marker, then the location of this marker relative to anatomy may be known. In some embodiments of the invention, such indication may be used during the procedure to assist in determining a more exact position of a catheter or other tool relative to anatomy. An example of this is the physician indicating contact between a pacing lead and tissue with the tip of a lead, which tip has a radio-opaque electrode.

[0597] In some embodiments of the invention, the fluoroscopic image is segmented, for example, based on the 3D data set, after registration. Optionally alternatively or additionally, segmentation is before matching, for example, based on detection of chamber boundaries, anatomically linked tools and / or movements of one or both thereof.

[0598] In some embodiments of the invention, once the images are registered, the fluroscopy image is analyzed to detect features which can be identified without contrast material and move with cardiac anatomy. Thereafter, these features are optionally used for overlying anatomically-linked indications on a fluoroscopy image. In some embodiments, once the fluoroscopy image is registered to the CT image, it is assumed there is no patient movement (or movement is detected directly on the fluoroscopy image), so a same or adjusted registration may be used. It is noted that once registered, the fluoroscopy viewing angulations can be changed but the registration can be maintained, if the patient does not move or the movement is known.

[0599] In some embodiments of the invention, one feature which is registered (and possibly marked on the fluoroscopy image) is the AV ring. The AV ring may be important because it has a fixed relation to the inferoseptal recess and the conduction system. This has the potential advantage of assuring a higher accuracy of registration of important features. In some embodiments of the invention, one of the views used by a physician is an AV ring centric view (e.g., created synthetically, for example as described herein and / or generated by suggesting angulation angles for the fluoroscopy system) where movement of a catheter can be seen relative to the AV ring. For other procedures, other features may be chosen for registration.

[0600] In some embodiments of the invention, an anatomical feature which is shown on the fluoroscopy image as an annotation, possibly the only one, is the inter-ventricular septum.

[0601] At 1210, one or more views are created. One type of view is annotating a live (or frozen) image (e.g., fluoroscopy or ultrasound) with data. For example, conduction system layout (e.g., AV node position) and / or target areas and / or procedure plans or markers (including, for example, point markers, line markers and / or area markers) can be overlaid on such image. Optionally, such overlays include an indication of certainty, for example, shading, blurring and / or dashed areas being used to indicate uncertainty level.

[0602] A particular type of overlay, described in more detailed herein, is a marker intended to be aligned in a known manner with tool radio-opaque markers. For example, if the tool includes two radio-opaque markers, correct alignment with a target can be determined when, at a certain viewing angle, all three markers are aligned. Correct distance from target can optionally be determined from a view at 90 degrees, which shows the distance between the markers. Such determining may be manual. Optionally alternatively or additionally, such determining is automatic, by segmenting out the radio-opaque markers and checking their alignment with the virtual marker position.

[0603] Another type of overlay is a guidance, for example, a "corridor" for a sheath used during the procedure. This is optionally a preset (manually and / or automatically) corridor and deviations from this corridor are optionally indicated to the operator and / or generate an alert. In some embodiments of the invention, the corridor is used to suggest to an operator in which direction to advance the sheath. Optionally alternatively or additionally, the corridor is shown together with a suggested / preplanned path and / or target locations and / or trajectories. In some embodiments of the invention, the corridor indicates what the expected range of advancing of the sheath (or other tool) are. It is noted that in a procedure tools often include radio-opaque markers and these are visible on the fluoroscopic image. In some embodiments of the invention, the marker locations are extracted and used for generating indications and / or indications are anchored to such markers. It is further noted that each tool may have its own markers. Optionally, in a kit, for example, a pacemaker kit or TTVR kit, tools (e.g., delivery system, sheath, lead, implant and / or guidewire) have distinguishable markers, for example, based on shape and / or width, so the system can identify the tool based on its markers. Optionally alternatively or additionally, the tools and / or the kit have an ID, such as a QR-code or an RFID or other computer or human readable ID, which is associated with tool parameters such as location and / or shape and / or distance between radio-opaque markers. The data for such markers may be provide don the RFID or QR code instead of or in addition to an ID. Optionally or additionally, the operator selects a kit to be used (or the kit has such ID) and the system retrieves data matching such ID and optionally uses such data for registration, positioning and / or generating annotations or for other calculations which use such data, for example as described herein.

[0604] Another particular type of overlay is an outline of the heart or parts thereof, such as the ventricular septum, possibly using dashed lines to indicate when it is an estimate. If a physician contacts a part of the heart and indicates this to the system such contact may be used to increase the reliability of the marking and it may, for example, turn solid. It is noted that even when all parts of a system are estimated at a high accuracy, direct registration between parts (e.g., the septum and the sheath), often allow a higher accuracy and / or certainty of positioning.

[0605] It is noted that registration and generating views are acts which may be repeated and / or adjusted throughout the procedure.

[0606] In one example, such adjusting relates to body movements, for example, such as caused by the cardiac cycle and breathing.

[0607] In some embodiments of the invention, annotations (e.g., markings in the overlay) are moved during the fluoroscopy to match their correct cycle and / or breathing dependent location by being based on a 4D CT that is segmented at multiple phases. Annotation and / or registration may then match the correct CT data segment to the physiological state at fluoroscopy acquisition (e.g., cardiac phase and / or respiratory phase. Optionally alternatively or additionally, breathing is measured and changes in the image which occur at a breathing frequency or harmonic are corrected for. Optionally alternatively or additionally, the effect of breathing on cardiac movement is modeled, for example, by extracting such effect from a fluoroscopy image and / or based on expected effect using data about a matching population.

[0608] In some embodiments of the invention, only a single-phase cardiac CT is available and a prediction method is used to separate operator movements from physiological movements. For example, an ARMA (autoregressive moving average) model is created to classify changes in an image to Cardiac, Breathing, Operator induced and noise. The position of a lead (or anatomical marker) over a sequence of fixed phase fluoroscopy images is analyzed to show the Operator induced change only.

[0609] A particular type of view which may be created is a DRR - a digital reconstruction of a fluoroscopy image, based on CT data. This may be especially useful for showing views that are not possible, for example, a transverse view (the patient's head is blocking). A DRR view may also be useful for showing multiple live views simultaneously, when only one x-ray imager is available. Optionally alternatively or additionally, a 3D view is shown, using the data from the fluoroscopy image to annotate the CT data set with catheter (and / or other tool) positions.

[0610] In some embodiments of the invention, the view includes a synthetic 3D view, for example, as described herein. In some embodiments of the invention, the view includes two views. Optionally, one view is real (captured by an x-ray c-arm, for example) and the other view is synthetic, for example as described herein, for example a transverse view. In some embodiments of the invention, the two views are perpendicular to each other.

[0611] All these view types can be annotated. For TTVR, for example, the conduction system is shown and / or an exposure angle, for example, as described herein.

[0612] Optionally alternatively or additionally, annotations include relevant anatomical indications. For example, the tricuspid annulus and / or the CFB, optionally with distance indications.

[0613] Annotations may include stage specific annotations, for example, a recommend delivery system location path, which may include a suggestion on position and / or orientation relative to the tricuspid valve.

[0614] At 1212 the procedure is carried out, for example, attaching a lead or a pacemaker to the heart, for conduction system pacing or TTVR noting that acts like creating views and registrations may continue throughout. Also, it is noted that the system may generate guidance, indication and / or alerts at any stage, for example, automatically or per request by the user.

[0615] In one example, for example depending on the stage of the procedure and / or tool location, the system may create and project (as an overlay), a theoretical direction in line with a pre-procedure planned orientation and / or a continuation of said tool direction.

[0616] In another example, data may be presented to the user, for example, on the fluoroscopic image or at a different display, concerning, for example, the suggested angulations for the C arm to achieve a navigation-assisting view. In another example, the operator may be shown tool markets, targets and / or relative distance and / or alignments between them. In some embodiments of the invention, indications or alerts, such as alignment may be provided using a non- visual method, for example, as a sound.

[0617] In some embodiments of the invention, the stage of the procedure is automatically determined by the system, for example, based on the location of radio-opaque markers in the fluoroscopic image and their position relative to anatomical structures and / or each other (e.g., indicating replacement valve location and / or expansion state). In some embodiments of the invention, one or more rules are defined that describe a state and / or a movement between states based on the contents of the fluoroscopic image. Optionally alternatively or additionally, an operator may notify the system, for example, using a GUI or by voice.

[0618] During the procedure, the location of a sheath, delivery system and / or implant is optionally tracked, for example, manually. Optionally or additionally, the tracking is automatic, for example by comparing the radio-opaque markers of the sheath (or an internal catheter) to expected positions of such markers. Optionally or additionally, an automatic positioning system may be used.

[0619] The views used by the operator at this point may be selected to assist in navigation. For example, a view may be selected which is perpendicular to a desired path of a tool or location of an implant. As delivery system may include a bend and / or is bendable and / or implant repositioned, different views may be used at different times.

[0620] The delivery system and / or implant are optionally adjusted, for example, to follow the suggested path / positioning. In one example, positioning and / or path are configured to avoid damage to chordea.

[0621] In some embodiments of the invention, adjustment comprises axial movement of the delivery system and / or changing a bending angle at one or more joints of the delivery system.

[0622] During the procedure, the alignment of the delivery system with a desired path is optionally determined. In some embodiments of the invention, this is determined manually. In some embodiments of the invention, the location of radio-opaque markers together the known registration of the CT data to the fluoroscopic image allow such determination to be performed manually.

[0623] In some embodiments of the invention, alignment determination is assisted by using appropriate views. This may be helped by activities in a planning stage or during the procedure. In one example, during planning an S-curve showing X Ray tube orientations that will create a nonparallax images of one or more of the conduction axis, delivery system, tricuspid annulus and / or CFB is created. This indicates what images to use. If the procedure does not exactly follow the plan and / or as the tools move, new viewing directions may be determined, to avoid parallax. Optionally, two views are used, to avoid ambiguity possibly present with one view. Such viewing angles are optionally presented to the operator at one or more times during the procedure, optionally triggered by sheath location and / or determined angulations (e.g., based on foreshortening of radio-opaque marker inter-distance).

[0624] In some embodiments of the invention, the suggestion of a non-parallax view takes into account information about the delivery system and implant mechanics and flexibility. In some embodiments of the invention, such view is based on real time detection of each principal component of the delivery system and / or implant (e.g., radio-opaque markers, general outline) and checking its contributor from being in a non-parallax position, and decipher its real position. This may also be used when generating a synthetic view, for example, as described herein.

[0625] At 1214 testing may be made to see if the procedure was performed correctly (e.g., and changes made if needed). It is noted that testing may also be performed during the procedure, for example, testing a pacing location before lead attachment. One type of testing includes comparing an outcome of the treatment, such as pacing, to outcome predicted and / or desired during planning and / or stimulation.

[0626] In some embodiments of the invention, testing and / or prediction values are shown as an overlay during the procedure. For example, as a lead is used to scan pacing locations, the display may show an expected quality of pacing at that location. Optionally or additionally, an overlay indicating relative quality of locations (e.g., a heatmap) may be shown, for example, based on simulation.

[0627] At 1216, the procedure may be completed. In some embodiments of the invention, data collected during the procedure is provided to a further treating physician. In some embodiments, the data is provided in a memory of or associated with the pacemaker. For example, the pacemaker may be preprogrammed with recommend parameter sets or ranges which are expected to be effective and / or avoid side effects.

[0628] During the procedure, the operator optionally indicates to the system that contact is made between a tool and the cardiac wall, which means that the position of the tool of the catheter can be mathematically constrained to be at a surface of the heart wall, for example, the ventricular septum.

[0629] When considering a fluoroscopic image, parallax can be detected by detecting foreshortening. For example, comparing a momentary distance between two markers to actual screen markers generates a measure of foreshortening. New C-arm angulations can be calculated so there is no foreshortening. Further, a C-arm angle can be further calculated so that there is planar alignment between the line connecting the two markers and a line indicating a desired trajectory (if any) or a point on the heart. In some embodiments of the invention, parallax indicators are generated for fluoroscopy images, for example, being shown over most or all of the procedure, for example, when the lead and / or sheath is in the heart.

[0630] In this and other embodiments and / or for this and / or other uses, sensing circuitry (e.g., amplifiers) may be integrated into the system (e.g., for control and / or data transfer and / or timing) and used to detect electrical activity from inside the heart. In some embodiments of the invention, the system does not include sensing. If desired, a separate sensing system may be attached to an intrabody electrode and used for measurement. Data from such measurement is optionally entered by hand into the system.

[0631] Fig. 9 shows several views of a pacemaker lead positioned relative to an LBB, as an example of annotating multiple fluoroscopic views with a conduction system portion in accordance with some embodiments of the invention.

[0632] It is noted that a transverse view is generally not physically possible but may be helpful in some situations, such as penetrating through a septum or viewing anchoring section(s) of a tricuspid valve. The 3D CT data can be converted to a synthetic 2D projection. However, the image is more useful if it shows the implant, delivery system and / or other interventional tools. In some embodiments of the invention, tool position is identified in real time, for example, better than 1 or 5 or 10 frames per second, (using a positioning system and / or using image processing methods, for example, as described herein) and this is used to generate a synthetic view including the delivery system, implant and / or other tools. In some embodiments of the invention, the generation of tool location is by matching. For example, different possible layouts of a delivery system are tried out until a best or satisfactory match to what the fluoroscopic image shows, is found. In some embodiments of the invention, a suggested angle for the fluoroscopy imager is generated by the system to provide satisfactory or better data for such determining of delivery system position and / or layout.

[0633] In some embodiments of the invention, a two directional mapping method is provided in that 3D-aligned data, such as data aligned with a CT image, is shown on a 2D image, such as a fluoroscopic image and data extracted from the fluoroscopic image is mapped back to the 3D alignment. Once this data is mapped back, the data may be shown in 3D, or a new, synthetic, 2D image may be created from the 3D data. This results in a 2D image, for example, a DRR which can simulate a fluoroscopic image, and which shows both annotations relating to the 3D data set and annotations relating to the 2D data, for example, live annotations. In some embodiments synthetic views are shown side by side with real views. In some embodiments of the invention, the mapping back from the 2D data set to the 3D data set uses one or more constraints to restrict the possible mappings. In one example, a 3D orientation and / or shape of an object to be mapped back (or possibilities thereof) are deduced from the 2D image. Optionally or additionally, a physical interaction between the object and a structure is identified and sets a constraint on the possible mappings.

[0634] Figs. 10A-10E and 11B show various views using synthetic imaging in accordance with some embodiments of the invention and will be described in greater detail below.

[0635] Fig. 11A is a flowchart of a method of generating a synthetic image including a mapping forward and a mapping backwards, in accordance with some embodiments of the invention.

[0636] At 1902 3D data is acquired, for example, a pre-procedure CT image, for example as described herein. The data is optionally converted into an image and / or processed manually and / or automatically to create annotations, such as a conduction system.

[0637] At 1904, one or more markers are identified in the data. One type of marker which may be identified is image registration markers, e.g., used for registering to a 2D fluoroscopic image. Such markers may include, for example, vertebrae, calcification, and / or vascular markers.

[0638] Another type of marker which may be identified is tool markers which are expected to interact with a tool to be mapped back, for example, the location of the right ventricular septum wall.

[0639] At 1906, during a procedure, one or more 2D images are acquired, for example fluoroscopic monoplane (or biplane) imagers may be captured continuously using a video grabber. It is noted that while fluoroscopic images are 2D (monoplane) images they actually are a projection image. Ultrasound images, another type of 2D image which may be used for this method are generally slicelike - an image of a 2D slice of tissue. A series of images may be useful for generating more registration information, such as due to motion.

[0640] At 1908, registration markers are optionally identified in the 2D image(s). Examples of registration markers include external radiopaque markers, vertebra (or other bones), contours of the heart and / or particular anatomical landmarks such as valves and the RV wall. Additional registration data which may be acquired (or controlled) includes the orientation of the imaging machine probe relative to the patient body and / or bed coordinate systems.

[0641] At 1910 a registration of the 2D image to the 3D data may be generated, for example, using the registration markers and / or, at least as a starting point, imaging system orientation. In some embodiments of the invention, this registration defines a first transformation or mapping between the fluoroscopic image and the CT data. Such registration is optionally based on an algorithm that finds a best or satisfactory (e.g., with respect to error) matching between the co-location of the image registration markers (for example matching vertebrae) of the pre procedure volumetric image or data and the intra procedure image. Optionally, this first registration / mapping is adjusted when the imager is moved from a known angulation to a new angulation.

[0642] At 1912, a probe or other tool in the body, such as a delivery system and / or an implant is identified in the 2D image. In some embodiments of the invention, the identification is based on silhouette and / or radio-opaque section(s) and / or marker(s) thereon, for example, for a pacing lead, electrodes.

[0643] As (if) the 2D image is a projection image, the exact location in space of the tool relative to the 3D coordinates cannot generally be known from the 2D location of the tool on the image, possibly even if the distance and magnification of the imager are known (and / or at least not to a desired precision).

[0644] In some embodiments of the invention, one or more interactions between the tool and anatomical features which position is known (e.g., due to the first registration / mapping) is used. In one example, an interaction is identified (1914), for example, between a tip of a lead and the RV septal wall or between an expanding valve and an annulus. This can be detected, for example, based on resistance, deforming of the lead (or sheath and / or electrogram. The detection can be automatic by the system or manually and reported by an operator, to the system. An image may be captured when such contact is detected, for example, by the system signaling image capturing circuitry. Once identified, this interaction limits the possible locations where the tool can be. In some embodiments of the invention, more than one interaction is used, for example, one or more locations where the tool leans against tissue (e.g., the tricuspid annulus) is used.

[0645] At 1916 a set of possible locations for the tool is optionally generated. The set may be larger, for example, if computed before the contacting and contracted using the contacting, or smaller, for example generated after the contracting.

[0646] At 1918, an exact location may be determined, for example, base done the above constraints or on an additional constraint, for example, that the catheter is restricted by its flexibility and entrance point to the RV. This location can be converted into a second registration / mapping, back from the fluoroscopic image to the CT / volumetric image.

[0647] In general, in some embodiments, the system has two complementary units of information: 1. The 2D location of the indwelling tool on the intra procedure viewer monitor (e.g., based on the first registration mapping which using the transformation that was formed in the CT to fluoroscopy step) correspond to a line of possible positions within the patient body or conversely in the patient pre procedure volumetric image.

[0648] The system can detect where the line intersects the position of the RV septum (or other anatomical marker), to identify a 3rddimension of location of the tool. At 1920 one or more views can be generated (e.g., 2D and / or 3D) from the 3D data, using annotation on the data such as conduction system data and / or back projections from the fluoroscopic image. In particular, the views may be generated using a DRR (Digitally Reconstructed Radiograph) technique.

[0649] In some embodiments of the invention, the layout of the sheath (or at least its tip) in the RV is calculated using the point of entry into the heart and electrode locations from the fluoroscopic image. The following method is optionally used:

[0650] (a) Compute the registration between the CT and the current fluoroscopic image. Optionally, this registration is calculated using anatomical structures such as spinal vertebrae the diaphragm and / or the heart outline. These structures can generally be detected in fluoroscopic images their location in a CT image can also be extracted, for example, using templates followed by pattern matching or other feature identification methods.

[0651] It should be noted that in some embodiments of the invention, registration can be thought of as a function F(x,y,z)->(I,j), where (x,y,z) is a point in CT coordinates and (I,j) is a point in fluoroscopic image. One direction of registration is unambiguous - given a point (x,y,z) one can compute the point (I,j). The other direction of registration is not unambiguous but can still be useful: given a point (I,j) one can compute a straight line in CT coordinates with all locations which are mapped to (I,j).

[0652] It is noted that this registration method may also be used for the above registration at the start of a procedure. It is noted that the actual c-arm angulations provide a starting point for this registration, as a range of possible angles, assuming a generally prone (or otherwise positioned) patient.

[0653] (b) In some embodiments of the invention, it is assumed (e.g., based on a physician reporting) that the distal electrode (e.g., screw) of the pacemaker lead is in contact with RV endocardium, specifically with the septum wall. The surface of RV septum is known from CT data. Given the location (10, jO) of the screw in the fluoroscopic image, and using the registration from (a) one can construct the straight line of all locations in CT coordinates which are mapped to (10, jO). The intersection of this straight line and the RV septum surface can be assumed to be the location of the screw in 3D.

[0654] Other methods of detecting septum (or other tissue) contact can be used and / or a combination thereof, for this and other uses. For example, deformation of the sheath may be detected by image processing of a fluoroscopic image, which deformation is due to advance against the septal wall. In another example, when a lead contacts the septum, an electrogram can be detected. In another example, the lead measures an impedance which changes markedly when the lead is contact with muscle (as opposed to blood). Electrograms and impedance may also be used to detect penetration (e.g., of helix) into the septum, due to changes thereof.

[0655] (c) To compute the location of the proximal electrode (or other part of the tool, such as a side of a delivery system) in 3D, it is optionally assumed that the distance D in mm between the proximal and distal electrodes is known and fixed. Given the point (il,jl) - the location of the proximal electrode in the fluoroscopy image one can construct a straight line in 3D with all possible locations of the proximal electrode in 3D. There will be two points on this line which are at distance D from the 3D location of the screw computed in (b). Optionally, one of these possibilities is eliminated based on an understanding of possible orientations of the sheath. Specifically, in some embodiments of the invention, the location of entry into the heart (and / or other anatomical constraints such as papillary muscles and locations of RV walls) and general properties of resilience of the sheath or lead are used to calculate possible layouts of the sheath between the entry point and the septum under the constraints that the two electrodes must be in the known locations. After implantation, there is another constraint of fixed angle of the tip do to ventricular tissue engagement. Optionally alternatively or additionally, if the lead is in a sheath, the sheath constrains the layouts as well. This can result in generating an entire layout for the lead / tool and / or at least for a tip of the lead.

[0656] In some embodiments of the invention, once the lead layout is known, it can be presented as an overlay on the DRR. Before contacting the septum, the layout may be based on the sheath geometry and entry point into the heart and / or anatomical shape of the heart, which constraints layout. However, the marking may show the placement as estimated.

[0657] Fig. 10A shows a transverse view DRR image showing a tool layout of a head of lead (shown as annotation 1802) in the RV with conduction system annotations 1804 (e.g., the LBB) and optional anatomical annotations 1806 (e.g., the septal walls), in accordance with some embodiments of the invention. It is noted that a transverse view is one which physicians cannot generally generate using fluoroscopy but it shows the trajectory through the septum to great benefit. It is noted that DRR methods can be used to generate a selectively enhanced DRR, for example, enhancing anatomical boundaries which might be less visible on a natural fluoroscopic image.

[0658] Figs. 10B-10D are synthetic view sets at various stages of septum penetration, in accordance with some embodiments of the invention. While three views are shown, a different number, such as 1, 2 (e.g., perpendicular), 4 or more may be used.

[0659] At Fig. 10B, three DRR views, from different angulations, are shown when the lead is only contacting a septum (shown as annotation 1806).

[0660] At Fig. 10C, the same three DRR views are shown when lead 1802 is partly penetrating the septum on its way to the EBB (shown as annotation 1804). At 10D, the same three DRR views are shown when lead 1802 is at the target LBB, as can be seen by the overlap of lead annotations 1802 with LBB annotation 1804. It is noted that the lead annotation is shown as not crossing the septal wall annotation. In some embodiments of the invention, another annotation may be shown (not depicted) of the expected range of capture of the electrode.

[0661] Fig. 10E shows matching real and synthetic views, in accordance with some embodiments of the invention, with, for example, the annotated real fluoroscopic image corresponding to the lowest shown DRR image. Optionally, the fluoroscopic image is used for verification and / or for observing details not mapped back to the volumetric data set.

[0662] Fig. 11B shows a 3D view (as three different views) showing an interventional tool, in accordance with some embodiments of the invention. In some embodiments of the invention, instead of or in addition to a 2D view, what is shown is a 3D synthetic view based on the CT data, optionally including deformation according to cardiac and / or breathing phase. By overlaying the location of the interventional tools on this 3D image, in some embodiments of the invention, the fluoroscopy is used mainly for data collection for the system and / or verification by the operator, while the navigational process is performed on the 3D image.

[0663] It is noted that annotations and / or synthetic views may be based on and / or overlaid on an ultrasound image instead of or in addition to x-ray and CT images.

[0664] Monitoring and follow-up

[0665] A particular feature of some embodiments of the invention is the precision at which a pacing lead or other tool or implant can be placed and / or expected results simulated. In some embodiments of the invention, after the procedure is completed, the results of the planning and / or of the actual treatment are used to predict an expected time line for the patient. If the patient does not follow the time line, even if the patient is within normal parameters, this may indicate to a treating physician that something is amiss.

[0666] Optionally alternatively or additionally, the time line may include tests to be made and expected measurements to detect and / or potential signs of disorder. For example, at a certain time there may be a risk of a fibrosis cap interfering with pacing (e.g., based on actual placement and / or pacemaker settings. A patient may be tested at this time to ensure that failure is not occurring.

[0667] In some embodiments of the invention, the treatment includes programming or adjusting a pacemaker (or other implant) with parameter values, or parameter sets or allowed ranges based on the planning and / or the procedure. For example a range of intensities may be selected that are expected to capture, but not expected to cause side effects. The treating physician may then select one of these preprogrammed values, when fine-tuning treatment for the patient. Optionally or additionally, such values are stored off of the pacemaker, for example, in a database associated with the patient and / or pacemaker ID.

[0668] Some non¬

[0669] In an example, described in more detail, for example, in the above referenced applications, annotations and / or conduction system data are used to guide an implantation process for an aortic (or other, e.g., tricuspid) valve.

[0670] Fig. 12 shows guide annotations for valve implantation, in accordance with some embodiments of the invention, optionally, with a goal of setting depth of implantation so that a need for a pacemaker is avoided or reduced. A trapezoid guide 2302 indicates a danger zone outside and a safe zone inside, where valve expansion may cause damage to a conduction system section 2304. A potentially damaging overlap between the valve and the conduction system is shown in the left image, and absent in the right.

[0671] In some embodiments of the invention, these guides are shown not (only) on a fluoroscopic image but also on a synthetic image, for example a 3D image. Such image (and / or projections thereof) can enjoy a mapping back form the 2D fluoroscopic image to the CT data set coordinates. For example, the outline of the valve may be extracted and projected back to the CT image.

[0672] Fig. 13 shows 3D model views of an undesirable interaction between a valve implantation and the conduction system, which may be avoided in accordance with some embodiments of the invention. A delivery tool 2320 is shown overlapping an LBB and / or a His bundle section which suggests that valve delivery using this location will cause pressure on the LBB and potentially cause an LBB block or other conduction problem which might require a pacemaker. In some embodiments of the invention, such planning is used to avoid the need for a pacemaker and / or for allowing preemptive implantation of a pacemaker, optionally with physiological pacing close to the expected location of damage.

[0673] In other applications, the conduction system imaging is used to plan positioning of tricuspid replacement implants to spare the conduction system. It is noted that the conduction system can be very close to the tricuspid annulus, for example, within 2-4 mm, so the conduction system is at risk of damage during tricuspid implantation. Similar methods may be used as for sparing of CS damage during aortic valve implantation.

[0674] Other structural interventions and especially catheter based device implants may also cause conduction system damage, for example, devices for repair of septal defects and devices for creating a shunt between ventricles or atria. In both cases the device may press against sensitive conduction system components after implantation and / or during implantation (or the delivery system or associated tools may). Knowledge of the location of sensitive conduction system parts can be used to generate guidelines for location which should be avoided and / or for showing safe locations. The target of implantation may also be annotated, for example, on real or synthetic fluoroscopic images and / or on a 3D guiding image.

[0675] Tricuspid valve prosthesis implantation

[0676] An additional non-pacing procedure type described herein relates to an implantation of a prosthetic tricuspid valve in a heart of a patient, optionally in a particular location and / or rotation and / or orientation selected to reduce a risk of damaging the conduction system. Such reduction is optionally based on patient- specific characteristics, for example, a location of the conduction system adjacent a tricuspid annulus. Optionally, a threshold of desired risk is defined, for example, as a less than 40%, 20%, 15%, 10%, 5% (or intermediate threshold values) risk of requiring a pacemaker implantation due to conduction system damage.

[0677] In some embodiments, the procedure has two stages. During a first stage an image is analyzed to determine a location of at least part of the conduction system and a treatment plan is optionally determined. The treatment plan and / or the conduction system location may be displayed to a physician. Optionally, the treatment plan determination comprises a step of creating a representation of the patient’s heart structures and (at least part of a) conduction system, and extracting therefrom one or more specific measurements relating to the spatial geometry of the conduction system and the tricuspid annulus. In some embodiments of the invention, the representation includes a projection of the conduction system unto a plane. Optionally, the treatment plan determination comprises simulating at least one part of the implantation procedure including one or more mechanical effect thereof on the conduction system, for example, anchor movement or frame expansion.

[0678] Such determination can be, for example, manually, automatically and / or semi-automatically. During a second, treatment, stage the treatment plan is carried out and modified as needed. Carrying out the plan optionally includes a display showing an indication based on the conduction system and / or the plan.

[0679] In other embodiments, the procedure has a single stage, with the conduction system location being determined during the implantation procedure itself. A location suggested for implantation may be indicated based on such determination, and displayed to a physician.

[0680] Fig. 14 is a flowchart of a method of implanting a tricuspid valve prosthetic device whilst increasing the probability of maintaining the integrity of the conduction system, in accordance with some embodiments of the invention.

[0681] At 2402, a representation of a patient’s conduction system, or at least an indication of relevant parts thereof, is acquired. Methods as described hereinabove may be used. In some embodiments, the conduction system location is determined based on an acquired image. In some embodiments of the invention, the image is a cardiac CT image, as an example of an anatomical imager. Other imager types may be used as well. The image acquired at 2402, or, more generally, a 3D data set, may be analyzed by an anatomical landmark / gross anatomy features finder to identify anatomical landmarks. After anatomical landmark finding, a conduction system estimator may be used to identify the location of at least a portion of conduction system on the 3D image, for example, a non-branching bundle. While any way of such providing may be used, in a particular set of embodiments, a cardiac CT image is analyzed to generate this layout. This cardiac CT can be acquired and / or analyzed before active intervention with the body of patient. In some embodiments such acquisition and / or analysis is during the implantation procedure itself, for example, using an intra-operative MRI or CT or using ultrasound imaging.

[0682] At 2404 there is an optional assessment of proximity of tricuspid annulus to conduction system. In some embodiments of the invention, this assessment is optionally used to estimate regions at risk (e.g., where valve contact is to be avoided) and / or a general degree of risk. In some embodiments, said risk is defined as a predictive need for a permanent pacemaker (PPM), in the event of adverse effects to the conduction system.

[0683] In some embodiments, the regions of risk are defined as a danger zone. In other embodiments, a danger zone is defined as an area in which, if device is implanted in, pressure exerted by device, during and / or after its implantation, would cause damage to conduction system. In some embodiments of the invention, assessment is based on manual or automatic measurements (e.g., on a CT image) of distance between the conduction system and the annulus or other regions near the tricuspid valve (e.g., regions where parts of a valve are expected to press against cardiac tissue). The tricuspid annulus location may be identified on the CT image, for example, using cardiac image segmentation techniques known in the art and / or using manual input.

[0684] In some embodiments of the invention, at 2406, a tricuspid valve prosthetic device is optionally selected. Optionally, device selection is done in accordance with the assessment described in 2404, to be compatible with the anatomical characteristics of the patient’s conduction system, and to allow the valve to be implanted whilst posing reasonable and / or minimal risk to significantly damaging the conduction system. Such selection may be based on a correspondence between the valve geometry and implantation options and the body anatomy, thereby defining a safety zone for implantation of the valve, e.g., as the safety zone pertains to the valve’s implantation at the anatomical location and / or the valve’s interaction with the anatomical structures during any stage of the implantation process. The selection process comprises optionally selecting a prosthetic device which would be compatible with the danger and / or safety zones, as assessed. Said compatibility is defined as the ability of the prosthetic device to be implanted at the anatomical location which enables it to function as an endogenous valve would, without clinically damaging the conduction system.

[0685] In some embodiments, the compatibility of the device with the danger zones and / or safety zones is defined as the level of success to be expected when implanting the device at the anatomical location, with minimal damaging of any structures adjacent to the anatomical location, in the process of the implantation procedure. In some embodiments, the compatibility assessment will be used to automatically determine or recommend the model and / or other parameters of a valve to be selected to be implanted. In some embodiments of the invention, the danger and / or safety zones are defined based on the valve (e.g., geometry and / or expected implantation forces). In some embodiments of the invention, a valve is selected by searching through a space of valves and checking for valves in said space if they have a safe implantation solution and / or how easy such implantation might be.

[0686] In some embodiments, a prosthetic valve is selected according to its characteristics (e.g., geometry and / or expected implantation forces) as they would contribute to a successful implantation (i.e., the device implanted at the anatomical location) or to a successful implantation procedure (i.e., the device reaching its implantation location successfully without causing any damage in the process of being deployed and implanted). In some embodiment, “successful implantation” comprises various clinical criteria such as one or more of reduced risk of valvular leakage, reduced risk of damaging the conduction system and requiring interventional pacing. In some embodiments, a prosthetic device is modified (or selected form a set to match) according to the determined safety and danger zones. In some embodiments, a simulation of other method, such as a heuristic is used to assess if at least one anchor can be removed, in order to spare heart tissue comprising at least a part of the conduction system, in the course of the implantation procedure.

[0687] Generally, the safety zone can be characterized as cardiac tissue that is far enough away from structures of the conduction system such that forces applied to it will not damage the conduction system. In some embodiments, selection of the valve comprises requesting the manufacturer (or other actor) to modify the valve and / or otherwise provide a modified valve in accordance with the patient’ s danger (and / or safety) zone assessment. In some embodiments, the manufacturing modifications can include the removal of at least one anchor / leg. It is noted that different valve designs may have different risk / geometry profiles.

[0688] In some embodiments, the modifications to the valve include at least one missing anchor. In some embodiments, the missing anchor creates a sufficiently sized gap between anchors to spare the conduction system. Correct rotational alignment of the implant (and its gap) with the conduction system (safe zone) reduces risk to the conduction system This may drive the generation of suitable planning and / or delivery indications to show a user during implantation. In some embodiments, the design modification comprises a different anchoring mechanism through which the device is anchored to the tricuspid annulus 2502. In some embodiments, a variable depth of implantation is possible, for example enabled by a supra-annular anchoring of the device to the tricuspid annulus 2502.

[0689] In general, an asymmetrical design (of supra, infra or annulus parts of valve sections) may be safer for sparing the conduction system.

[0690] In some embodiments, a selected prosthetic heart valve is designed to not expand in a manner which exerts pressure on cardiac tissue comprising a least a part of the conduction system, due to the patient’s anatomical characteristics. In some embodiments, the patient’s anatomical characteristics comprise at least a part of the conduction system in close proximity to the tricuspid annulus. In some embodiments, “close proximity” is defined as the two structures being within 1, 2, 3 mm or smaller or intermediate values in mm of each other.

[0691] Some valves are anchored using anchors (or skirts or other elements which do not relay on the annulus for anchoring), for example, the Evoque® by Edwards Lifesciences. In such valves, conduction system damage due to expansion is optionally ignored, unless, for example, the conduction system is very near the annulus (e.g., less than 3 or 2 mm). However, damage due to pressure and / or movement of other anchoring sections is considered, for example, using simulations and / or other methods as described herein. Other valves anchor by expanding the native annulus. Such valves may be at risk of damaging the conduction system if it is stretched (due to annulus expansion) or compressed (e.g., between the frame and other tissue).

[0692] In some embodiments, the safety zone is larger, i.e., the conduction system is located at a greater distance from any part of the device. In such an example, an appropriate valve to be selected is optionally Evolut™ by Medtronic.

[0693] Optionally alternatively or additionally to selecting a valve, an implantation location and / or orientation which reduces risk to the conduction system may be selected at this step. Optionally, the selection is based on the valve geometry which may determine the risk of conduction system damage at various locations (e.g., heights and / or orientations).

[0694] For example, a supra-annular design may have less risk of directly applying pressure to the conduction system (though an atrial portion thereof may eb designed asymmetrically to recede radially in a way that can be aligned with the conduction system. However, the supra-annular valve may be implanted by a mechanism of annulus distention. Such distension may apply pressure through the annulus to conduction system components (if not deep enough) or cause tearing of the conduction system (e.g., if distention is large enough). Safe implantation parameters may thus include not only valve type, position, rotation and orientation, but also (or instead) an allowed expansion diameter and / or allowed expansion force. It should be noted that the terms “device”, “prosthesis”, “prosthetic device”, “prosthetic valve” and “valve” are generally used interchangeably when referring to tricuspid valve implantation, unless explicitly indicated to the contrary and / or by context and also noting that other prothesis devices than vales may be implanted t the tricuspid area and are may be used to practice some embodiments of the invention.

[0695] In some embodiments of the invention, the orientation of the implant (e.g., a radially asymmetrically extending part thereof is selected so that the height of the implant at the side of the conduction system avoids / reduces risk of damage to the conduction system. Other parts of the implant may be at a height which provides better anchoring or prevents regurgitation. This may be referred to as “tilt”. It is noted that in some embodiments, the tilt is relative to the conduction system location.

[0696] At 2408, the device is implanted, optionally informed by the data collected in the assessment of the conduction system, any plan and / or the selection of the prosthetic device.

[0697] In some embodiments of the invention, if the risk of damage to the conduction system and / or overall state of the patient is deemed too high, the valve is not implanted or a pacemaker may be preemptively implanted.

[0698] At 2410, following the implantation, the patient is optionally examined. If adverse effects arising from an incorrect alignment of the prosthetic device are identified, the location of the device is optionally adjusted.

[0699] Fig. 15 depicts various structures of a conduction system 2504, schematically represented in relation to a tricuspid annulus 2502. Any of the structures depicted can potentially, directly or indirectly, be damaged by an inopportune positioning of the prosthetic device. In particular, the following structures appear most at risk to damage by pressure or other interaction with a tricuspid valve implant: an AV node 2506, a non-branching bundle 2508, and / or a branching bundle 2510.

[0700] Fig. 16 gives an additional perspective of the structures surrounding tricuspid annulus 2502 and conduction system 2504. These include an aortic annulus 2602, the mitral annulus node 2608, the AV node 2506, the branching bundle 2510, the non-branching bundle 2508, the left bundle branch 2612 and the right bundle branch 2614. One or more such structures may be shown during a procedure, for example, for orientation purposes.

[0701] Fig. 17 shows the conduction system 2704 and the tricuspid annulus 2702, and the measured distances 2708 between them, as reconstructed from a CT image of a particular patient, characterized by having the conduction system located (e.g., in its closest aspect) at the postero-septal commissure. These measurements optionally give the physician (and / or a planning system) an indication of the safety and danger zones regarding the placement of the prosthetic device. In some embodiments of the invention, the danger zone is defined as the area of close proximity between the tricuspid annulus 2502 and the conduction system. One factor to be considered when measuring the proximity of the conduction system to the annulus, is the specific anatomical location and / or spatial orientation of the conduction system. If the conduction system is located above the annulus, there may be a decreased risk of damaging it in the course of implanting an infra-annulus or annulus valve. If the conduction system is in an orientation which is aligned with the annulus, the proximity which is defined as embodying the danger zone can be, for example, within a range of 2 mm laterally of the annulus. Other ranges may be used as well and / or a score calculated based on the range. Optionally or additionally, the range is not lateral but total distance between a location where pressure will be applied to the cardiac tissue and the closest part of the conduction system.

[0702] In some embodiments, the danger zone is, for example, an area where the prosthetic device, if placed, would exert pressure on the cardiac tissue comprising the conduction system, in a manner which might damage the conduction system.

[0703] In some embodiments, conduction system location is classified to be posterior, postero - septal or septal location. In some embodiments, in accordance with said classification of conduction system locations, an asymmetrical design of a valve and alignment thereof therewith potentially poses less risk of adversely affecting the conduction system.

[0704] In some embodiments of the invention, a proximity index is generated per patient and / or patient valve combination and / or patient-valve-implantation parameters combination. Such an index may be used, for example, to assess risk and / or to search for solutions. In some cases, a procedure will be avoided if no suitable solution (set of parameter values yielding a low enough indexed value) can be found.

[0705] In some embodiments of the invention, the index is not merely of risk to the conduction system but rather to effect on cardiac output or other cardiac functionality parameters and / or overall effect on the patient. Such effect may be measured, for example, in QALY (Quality adjusted life years) or in expected change to a heart failure index, such as the NYHA index. For example, in a patient where (potential) cardiac functionality due damage to the conduction system is more than offset by improvement due to (expected) regurgitation reduction, implantation may proceed. In another patient, the risk profile may be such that while patient improvement is likely in some cases, in others, the risk of rapid patient decline is unacceptable.

[0706] Further, it is noted that for many patients, damage to the RBB is less damaging than a similar (or smaller) risk of damage to the NBB or the LBB. As a result, in some case, implantation may be designed to be likely to damage the RBB (which is typically more easily treated using a standard pacemaker methodology), while decreasing the risk to the NBB (which is typically more difficult to treat using a standard pacemaker methodology). In one example of an index, the risk index is based on the cumulative risk of damage to each point on a conduction system adjacent the tricuspid annulus. For example, for each point closer than (for example) 20 mm to the tricuspid annulus, the distance between the point and a location where pressure will be applied to tissue (e.g., by a valve) and / or according to distance form the annalus, is considered. Each distance has a risk value attached and / or there may be a threshold distance, for example, 5 mm, 4mm, 3mm or smaller or intermediate values which define “at risk” or “no risk”. In some embodiments of the invention, points may be selected based on general location of the conduction system - e.g., 90 degrees or 120 degrees (around the axis of the tricuspid annulus) on either side of a zero location; the zero location being the point of the tricuspid annulus closest to the aortic annulus. The score may also be based on the angular width of a gap in a valve being used for implantation. For example, a spatial convolution between the gap and the area where the conduction system lies can identify how much of the valve must be pressed against tissue at risk, even at a best positioning of the valve.

[0707] In some embodiments of the invention, what is considered are only points that meet threshold definitions (e.g., distance below threshold). In others points are evaluated by a graded scale. It is noted that distance may be lateral distance only, but in some embodiments is total distance including height, which is optionally weights lower than lateral distance.

[0708] Fig. 18A shows a Venn Diagram illustrating the concepts behind the appropriate placement of the prosthetic device according to some embodiments of the invention. The diagram depicts the interaction between three elements of the embodiments provided herein; these elements are the conduction system 2504 (which should generally not be damaged), the geometrical features of the device 3506 (which should generally be suitable for clinical treatment but may affect damage to conduction system and anchoring options) and the anatomical characteristics of a patient’s heart 3106 (which help determine how the implant might sit and operate).

[0709] When the device is within the range of theoretical locations for implantation, whilst at the appropriate orientation, elevation and rotation and in an appropriate margin from the conduction system (e.g., 2-4 mm or more), that area is an area appropriate for implantation (the “appropriate area”). The safe zone is a superset area including also areas where the implantation as such might not work. In operation, one or both of the appropriate area and the safe zone may be displayed.

[0710] Fig. 18B depicts a tricuspid prosthetic device 2802 implanted in an anatomical location which impinges on the conduction system. Reference 2806 highlights a location of potential adverse physical interaction between the device 2806 and the conduction system 2804, the latter being aligned with the tricuspid annulus 2802. According to some embodiments of the present invention, the implantation location should targeted to specific orientational, rotational and elevational coordinates (relative to the annulus, for example) and / or valve design. The orientation (or tilt) of the device is defined angulation relative to the axis of the tricuspid and in particular which causes a height on the side of the conduction system to be different from the height at an opposite side. The rotation of the device is defined as Rotation around the axis of the device. The elevation of the device is defined as axial distance along the tricuspid valve, relative to annulus.

[0711] Fig. 19 is a more detailed flowchart, illustrating the steps of the procedure, according to some embodiments of the invention. Fig. 19 provides additional detail on Fig. 14 regarding methods for implanting a tricuspid valve prothesis in accordance with some embodiments of the invention. Fig. 19 represents embodiments where there is a pre-operative planning step and optional guidance during the operative procedure itself.

[0712] The acts described in this flowchart overview a part of the detailed description of this disclosure, with each act described in greater detail in separate sections below. Details in one section may be applied in other sections as well.

[0713] At 2902, a patient may be selected, for example according to criteria defining a need for tricuspid valve replacement.

[0714] At 2904, the patient undergoes an imaging protocol, for the acquisition of an image from which a location and / or other properties of conduction system 2504 can be estimated; more generally, CS (conduction system) data is determined. In some embodiments of the invention, an image used for assessing patient need for a tricuspid procedure is used for determining CS data.

[0715] At 2906, The CS data is assessed to formulate a procedure plan 2908. The plan optionally includes a schematic representation of implantation location and / or indication thereof and / or safe and / or danger zones.

[0716] At 2910 the prosthetic device is optionally selected or implantation canceled due to risk. In some cases, risk may prompt pacemaker implantation prior to valve implantation and / or be used to indicate a desired pacemaker (and / or lead and / or electrode) implantation location and / or operational logic.

[0717] At 2912, an implantation procedure is initiated.

[0718] At 2914, an image of at least part of the heart is procured mid-procedure, upon which the preoperative schematic representation of the planned implantation location and / or other guiding data is optionally superimposed.

[0719] At 2916, the device is implanted.

[0720] At 2918, the patient is optionally examined for any adverse effects arising from an imagining of prosthetic device on conduction system, and if such effects are identified, the location of the device is adjusted. Patient intake

[0721] Referring back to Fig. 19 at 2902, a patient is selected for a procedure. In some embodiments of the invention, the patient is any patient about to undergo implantation of a prosthetic tricuspid valve. In some embodiments, the person in need of a prosthetic tricuspid valve implantation is characterized by a clinical profile of having a conduction system which is anatomically very deep relative to the target implantation area of the prosthetic tricuspid valve. This may make the patient more suitable (and at lower risk of conduction system damage). Such patients (or the converse, patients at high risk) may be identified at 2906. It is noted that patients with lower risk may be suitable for a wider (or different) range of devices and / or may be implanted without or with less guidance during the operative procedure, for example, without overlays of conduction system indications or derivations on the live images. Some patients may be referred to open heart surgery due to potential risks of percutaneous implantation of valves.

[0722] A particular potential benefit of some embodiments of the invention is in the ability to tailor the implantation procedure to the specific anatomical characteristics of the patient, in order to potentially maximize the beneficial effects of the procedure while reducing potential risks, such as conduction system damage and a resultant need for pacemaker implantation.

[0723] Conduction System (“CS”) imaging

[0724] A CS map (or more generally, data about parts of the conduction system, such as location relative to other parts of the heart) may be created in various manners. In some embodiments of the invention, a 3D structural image of the heart is used to generate such CS data. Methods as described herein may be used.

[0725] In some particular embodiments, at 2402 a cardiac CT image of the heart is acquired as such a structural image. But other structural images may be used, for example, MRI or ultrasound.

[0726] At 2404, the structural image (with CT as an example) is analyzed to identify the layout of conduction system 2504. As explained above, in some embodiments, the conduction system location can be overlaid on a fluoroscopy or ultrasound (or other) image acquired during a procedure.

[0727] In some embodiments of the invention, the CT image is analyzed using a CT analysis package that suggests the location of one or more of the following portions of the conduction system, relative to gross anatomical features: the AV node 2506 and the non-branching bundle 2508. If additional procedures are planned, such as pacing, or for other reasons, it may be useful to determine the location and / or show additional parts of the conduction system.

[0728] In some embodiments of the invention, a CS map includes multiple layers, for example, anatomical-based conduction system location, electrical measurement-based data and / or functional data such as perfusion or viability (e.g., from a PET or SPECT image or a contrast CT image). Such added layers may be aligned using the CT image or anatomical data extracted therefrom.

[0729] The procedure provided in accordance with some embodiments of the invention, optionally comprises a pre-operative planning step. In some embodiments of the invention, the physician and / or a computer program assess the conduction system data. Based on the anatomical characteristics of the conduction system 2504 and its proximity to the tricuspid annulus 2502, an indication is optionally formulated regarding the safety and danger zones for the planned implantation procedure. In some embodiments of the invention, the danger and / or safety zones are schematically represented and displayed to the physician, assisting the physician in selecting an appropriate prosthetic device. In some embodiments of the invention, the size and / or shape of such zones may be modified if the physician changes the prothesis selection. According to some embodiments, the physician can also select a target location for the positioning of the prosthetic device and optionally visualize anatomical interactions between the prothesis and / or delivery system thereof and the heart. In some embodiments of the invention, additionally or alternatively to showing zones, the physician is shown preferred and / or possible low risk implantation settings, for example, as ranges of locations or as ghost images of a valve overlaid on cardiac anatomy. The orientation and location of the device are optionally planned in accordance with the anatomical layout of the conduction system, meaning that the device is targeted for implantation with parameters values that do not impinge on the conduction system. Such planning may, for example, maximize the distance from the CS to the implant in general or maybe used to suggest an implantation height (relative to tricuspid annulus) which reduces such distances.

[0730] In some embodiments, a pre-operative planning step comprises simulating one or more steps of the implantation process. In some embodiments, the simulation comprises visualizing the device, or any of its constituent parts, in its implantation location, rendered onto images (e.g., CT images and / or extrapolations of images) of the patient’s heart structures and / or conduction system. In some embodiments, the simulation comprises visualizing the device, or any of its constituent parts, in various stages during the implantation process, optionally including one or more projections and / or measurements and / or estimated danger / safe zones. In some embodiments of the invention, simulation comprises simulating movement of device parts and / or mechanical effects of such movements on the conduction system.

[0731] Fig. 26 is a flowchart of a method of device / valve compatibility assessment in accordance with some embodiments of the invention. At 3602, various data regarding a patient’s anatomy and / or physiology are collected. In some embodiments, this data comprises images of the heart structures and the conduction system.

[0732] At 3604, conduction system portions at risk are optionally determined. Optionally, an initial valve is used for such evaluation.

[0733] If the default device appears problematic and / or if there is no default device and / or for other reason a plurality of different device types and / or parameters may be evaluated (e.g., for compatibility based on geometry, size and / or deployment method). Optionally, a search through device and implantation parameters is conducted to find a device with a lowest risk and / or a lowest type of certain risk and / or other matching of a device with risk parameters and / or desired clinical outcome.

[0734] In some devices, the movement includes non-linear movements, such as scooping and evaluation takes into account the effect of such scooping on the conduction system.

[0735] In some embodiments, a simulation and / or other evaluation methods, for example as described herein is used to assess potential damage which could be caused to the conduction system during the scooping phase.

[0736] At 3608, the device may be visualized in situ, for example, showing tissue which may be stretch, compressed, pinched and / or otherwise damaged. The visualization may be, for example, static and / or may show the deployment as a series of images.

[0737] At 3610, the results of simulation and / or visualization are used to provide an overall assessment and / or recommendation. Such assessment and / or recommendation may eb manual, fully automatic and / or semi-automatic, for example, a user selecting some parameter(s) and the system showing a best setting for one or more other parameters (e.g., based on available devices) and / or a comparison. The order of acts in Fig. 26 may be modified and acts may be merged.

[0738] Fig. 27 depicts a heart valve (e.g., the Evoque® by Edwards) with a plurality of anchors 3706 anchors extended outwards from the body of the device, before the device is anchored to its implantation location. A proximal end of the device 3702, faces upwards of the left ventricle, into the aorta. A body of the device 3704, shown fully expanded, generally describes a circular cross-section, however this is not essential (noting that in some embodiments body 3704 includes a radially inwards dent to prevent pinching between an anchor 3706 and body 3704). An example diameter is about 32 mm, however, larger and smaller sizes are possible, for example, between 20 and 45 mm, for example, between 27 and 35 mm.

[0739] In some embodiments of the invention, there are between 6 and 16 anchors, for example, between 8 and 12 anchors, for example, 9 or 10 anchors. In some embodiments of the invention, an anchor is between 6 and 15 mm long, for example, between 8 and 12 mm, for example, about 10 mm long. Fig. 28 depicts the angle and direction in which the anchor bends back towards the body of the device during movement of the anchors in the course of an exemplary implantation process. The anchors are shown in both the bent back position 3802, and the radially extended position 3706, between which is the arc of the movement arc 3804. This movement can cause damage to tissue as it passes by and / or by pinching such tissue against body / frame 3704 and / or by applying pressure to tissue.

[0740] Typically, anchors are delivered when the are straight and pointing distally on the sheath covered implant.

[0741] Referring now to Figs. 40A-40D which show a mechanism of deployment in a schematic form.

[0742] In Fig. 40A all the anchors are pointed distally, being constrained by a sheath.

[0743] In Fig. 40B the sheath is partially retracted relative to the valve and the anchors extend out radially, for example as shown also in Fig. 27.

[0744] In Fig. 40C movement of a single anchor is shown, including a scooping movement, to point proximally.

[0745] In Fig. 40D the anchors are deployed and the sheath may be retracted more to release the body of the valve. Damage to the conduction system may occur during this stage as well, due, for example, to pinching between an anchor and device body.

[0746] The effect of such placement and / or movement is optionally reported to a physician, for example, during planning and / or just before deployment. In some cases, this may lead the physician to pre-treat a patient by implanting a pacemaker therein. It is noted that it may be easier to implant a pacemaker after valve installation (passing the lead through the valve). With a wireless pacemaker it may not matter. In general however, patients at risk may be more closely monitored during a procedure and / or temporary pacing provided thereto. In some cases, this may lead to selection of a more suitable valve and / or design of a new valve or modification of an existing valve.

[0747] Fig. 29 shows a visualization of a conduction system, and a tricuspid valve annulus region and also showing three anchors 3912, in accordance with some embodiments of the invention. The visualization is of a patient who required a pacemaker implantation due to conduction system (3908, 3910) damage due to valve implantation. Section 3908 of the conduction system generally corresponds to the non-branching bundle and section 3910 to the B-C section (between the penetrating bundle and branching bundle), for example as described herein.

[0748] The markers on the tricuspid annulus (TA) (shown as white dots) are optionally connected with a spline to define the annulus. The plane which also serves as the lower boundary of the valve box is a plane passing through the most anterior-inferior three points on the TR annulus, which may be the commissures - all the commissures are marked in this figure. The commissures of the leaflets are named Anterior-Septal commissure, Inferior-Septal commissure and the Anterior- inferior commissure. Angles between points A, B and C to these points may be measured, for example as described below

[0749] While this image shows a treated patient, such a display is optionally shown in a planning (or other pre-treatment) stage and / or during treatment.

[0750] In some embodiments, the risk posed to the patient is determining pre procedure, by assessing various criteria. In some embodiments, the location of the conduction system is estimated in relation to the height of the tricuspid annulus. In some embodiments, selecting an implantation location beneath the tricuspid annulus, is deemed safe. In some embodiments, “beneath the tricuspid annulus” is defined as being more than -0.5 mm distal to the tricuspid annulus. In some embodiments, an implantation location within a range of 5-9 mm above the tricuspid annulus plane (e.g., as explained below) is indicated to be an implantation location within the danger zone. In some embodiments, an implantation location over 6 mm laterally from the tricuspid annulus itself (in the plane) is indicated to be an implantation location within the safety zone, and therefore suitable for implantation. A lateral location very close to the annulus may also be considered safe.

[0751] Another criterion to be optionally assessed when determining the safety and danger zones, and therefore an appropriate implantation location, is the position of at least one anchor in spatial relation to the conduction path. In some embodiments, the angle between the anchors is about 40°, though at least one larger gap, such as 50, 60, 70, 80 degrees or more or intermediate values may be provided in accordance with some embodiments of the invention. In some embodiments, the device can be rotated so as to align the position of the anchors with cardiac tissue which has been determined to not comprise the conduction path and / or is less at risk (e.g., based on distance considerations). In some embodiments, the device includes at least one larger gap (e.g., by anchor removal and / or uneven circumferential spacing) and such gap can be aligned by rotation.

[0752] In some embodiments, the movement of the anchors in the course of the implantation procedure is one mechanism by which the patient’s conduction system can be damaged. In other embodiments, the mechanism by which the patient’s conduction system can be damaged is the presence of an anchor next to the conduction path, as depicted for example in figures 39A and 39B.

[0753] Fig. 30 depicts a visualization of a single anchor in relation to a tricuspid annulus, conduction system at risk, as well as projections, in a patient where a pacemaker implantation was required due to conduction system damage, in accordance with some embodiments of the invention and is also used to explain projections shown also in Fig. 29. The locations of the tricuspid annulus 3906 and conduction system 3908 are optionally determined using image data, such as CT or ultrasound data, for example, acquired using transthoracic echocardiography and / or transesophageal echocardiography. Other imaging types such as EEG-gated fluoroscopy (e.g., multi-angle), MRI, PET, SPECT and CMR may be used as well. In some embodiments of the invention, CT and ultrasound images are preferred.

[0754] It is noted that while projections are not required they may help regularize what is a complex geometry and make it more amenable to visualization, display and / or explanation and / or to assist in defining rules for safe / danger zones.

[0755] A projection 3904 is a projection of the annulus onto a plane 3902 defined, for example, by the lower points of the annulus. The location of conduction system 3908 (and / or 3910) is determined, for example as described above. It is then possible to calculate a projection 3914 of the conduction system onto tricuspid annulus plane 3902. A vertical distance 4002 between this projection and the conduction system is then optionally assessed, and may provide information, for example, on the potential for conduction system damage, for example, based on whether anchors 3912 of the device would impinge on the conduction system at any stage during the implantation of the device.

[0756] Fig. 31 depicts a representation of the tricuspid annulus, its projection and its plane of projection, in spatial relation to a conduction system, showing a method of defining a safety zone, in accordance with some embodiments of the invention.

[0757] Fig. 32 is similar to Fig. 31, but for a different patient, with an A-B line below a frame height (annulus) and no pacemaker implantation required (e.g., due to conduction system damage).

[0758] Fig. 38 depicts a representation of the tricuspid annulus, its projection and its plane of projection, in spatial relation to the conduction system for another patient in which a pacemaker implantation was not required due to conduction system damage, possibly due to vertical height of the conduction system and / or small lateral distance, in accordance with some embodiments of the invention.

[0759] Figs. 31, 32 and 38 also depict the measurement of distances between the tricuspid annulus 3906 (in this example defined by a spline interconnecting points shown as white markers and which include the three commissures of the tricuspid valve) and the conduction system 3908, termed the “minimal lateral distance” 4104. The distance between the conduction system 3908 and the projection of the conduction system 3914 onto the tricuspid annulus plane 3902 is termed “minimal height” 4102.

[0760] In some embodiments, measurements which are relevant to determination of a safe implantation location, are the with measurements of the lateral distance between the conduction system (A,b,C line) to the tricuspid annulus 3906.

[0761] In some embodiments, an important measurement for determining a safe implantation location is the Euclidian min lateral distance. In some embodiments, for each 1 mm of the Euclidian min lateral distance, the probability of complete atrioventricular block (CAVB) increases by 50%. In other embodiments, additional measurements are known to increase the probability for CAVB. In some embodiments, such an additional measurement relates to the relative height of the conduction line from the bottom plane of tricuspid annulus 3906 (denoted as Vertical average (svetav). More detailed findings are presented below.

[0762] Figs. 33-37 are additional examples of patients shown as visualizations. The notation on the images of “thickness” relates to the vertical height of a minimal box enclosing the tricuspid annulus and is a measure of the non-planarity of this annulus.

[0763] In Fig. 33 (and also Fig. 34 which adds a view of a top projection), a pacemaker was required. The vertical height was 3.5 mm and the minimum lateral distance was 1.19 mm.

[0764] In Fig. 35, a pacemaker was required, the vertical height was 4.6 mm and the lateral distance was 2.79 mm.

[0765] In Fig. 36, no pacemaker was required, the minimum height was 2.76 mm and the lateral distance was close to zero, which may protect the conduction system from damage form the anchor.

[0766] In Fig. 37, a pacemaker was required, the minimum height is 2.77 mm and the lateral distance is 2.18 mm.

[0767] As can be appreciated these are retrospective results, however, the measurements therein may be used on a patient before implantation to determine risk.

[0768] In some embodiments, a patient’s risk of damage to the conduction system is assessed by utilizing the data collection, calculation and display described herein.

[0769] In some embodiments, as noted, a way to reduce risk of damage is correct rotational orientation of the implant. In some embodiments of the invention, the implant includes a radio-opaque marker adjacent (or on) an anchor or a part of the frame near an anchor, which anchor or frame location defines, for example, a gap in anchors, a radial recess (or missing section or softer part) in a frame and / or a shorter (in some cases a longer anchor and / or an anchor which defines a larger radius of curvature, such as 2 mm, 3 mm, 5 mm, 8 mm or smaller or intermediate radiuses, which may allow for less stress son tissue captured between the anchor and the valve body) or weaker anchor. The intraoperative visualization system may show an indication of where to align such marker or markers with.

[0770] In some embodiments, the mechanism of compression of the tricuspid valve prosthesis is assumed to be effected by anchors 3912 and body of device 3704. In order to minimize or prevent injury to the conduction system, particularly the conduction member closest to tricuspid annulus 3906, several protective strategies are provided.

[0771] Optionally, the implant may be positioned eccentrically, e.g., further away from the conduction system (or closer, e.g., depending on which risk measure is easier to achieve), by altering the spatial orientation of the device during deployment (optionally with permanent effect) to reduce proximity to vulnerable tissues. Optionally, the implant is positioned eccentrically within the tricuspid annulus. In some embodiments, the system allows for exertion of a lateral force on the implant, so that the lateral force can be applied to move the implant further away from the conduction system. In one embodiment, the part of the conduction system from which the implant is laterally moved is the bundle of His. In one embodiment, an eccentric positioning of the implant is achieved by utilizing a valve delivery system having an offsetter and / or any other mechanism which allows for the eccentric positioning of the implant. In one example, the delivery system includes a joint at a distance from the distal and bending of this joint changes the angle and / or lateral position of the implant. If the distance is larger, the main effect will be on lateral position. If the distance is shorter, there will be a greater effect on the angle. In some embodiments of the invention, a delivery system configured to controllably bend in an S shape is used to move the valve laterally without significant change in angle. In some embodiments of the invention, the joint or other deformation acts in a plane and the delivery system is rotated so that this plane will coincide with a desired direction to move the implant laterally, for example, with a plane defined by the delivery system and the sensitive parts of the conduction system.

[0772] In one embodiment, the implant is placed in an eccentric position in a range of 1-8 within the tricuspid annulus. For example, the center of the implant is offset, in the plane of the annulus from the center of the annulus, for example, at least 1 mm, 2 mm, 4 mm, 6mm or intermediate or greater amounts. In some embodiments, this offsetting is provided during delivery and the eccentricity is changed during delivery, for example, as one or more anchors (e.g., the one likely to damage the conduction system) is deployed and avoids causing damage. In one embodiment, the eccentric position of the implant is 2 mm and within the tricuspid annulus. In one embodiment, the eccentric position of the implant is 4 mm and within the tricuspid annulus. In one embodiment, the eccentric position of the implant is 6 mm and within the tricuspid annulus.

[0773] In some embodiments of the invention, the implant itself is eccentric, for example, having an elliptical or dented frame (e.g., in the annulus plane) and this eccentricity is aligned so as to be less likely to damage the conduction system.

[0774] In one embodiment, the lateral force amount and / or direction to be exerted on the implant in order to move it away from the conduction system (and possibly deform other tissue and / or needed to resist forces caused during expansion which may tend to recenter the implant), is calculated and displayed as a vector. It is noted that the direction of lateral offset may not be exactly away from the sensitive parts of the conduction system. In some embodiments the direction will be towards the conduction system and in some cases a safe direction and / or a possible direction (e.g., due to interfering tissue) may be at an angle. Optionally, a simulation of possible movement directions is used to automatically suggest or select a direction of movement of the valve and / or a timing thereof, which is expected to reduce risk of damage to the conduction system. In some embodiments of the invention, the precision of the direction is greater than the precision of force, for example, due to the availability of offset (or position) as feedback.

[0775] In a particular embodiment of the invention the direction in which the valve is to be moved is shown on the display (during planning and / or during delivery). In some embodiments of the invention, the system calculates an x-ray (or ultrasound) viewing angle which allows to see that the valve is being moved in a correct direction and / or a correct amount, for example, so the desired movement in in the image plane. Such indications can be calculated and / or displayed, for example as described elsewhere in this disclosure for overlay markings. In some embodiments of the invention, also a maximum allowed travel is shown. In some embodiments of the invention, the amount of lateral force being applied by the system is given to the user as feedback, for example, extracted by identifying deformation of tissue and / or based on an amount of movement as compared to an expected movement due to deformation forced (e.g., based on a geometrical mechanical simulation of the tissue).

[0776] In some embodiments, the vector of the lateral force, coupled with the eccentric position of the implant within the tricuspid annulus, is beneficial in securing a safe location for the implant and its parts, in relation to the conduction system. In some embodiments, there is provided a method for positioning the implant in an eccentric location, the method comprising: mapping the patient’s anatomical and physiological characteristic, specifically - the layout of the patient’s tricuspid annulus and conduction system. The method further optionally comprises, for example as detailed herein, creating a projection of the tricuspid annulus and extrapolating from it a tricuspid annulus plane, based on which distances between the tricuspid annulus and various constituents of the conduction system can be calculated. The method comprises planning the implantation procedure, optionally comprising selecting an appropriate implant and its desired implantation location, and optionally modifying the implant to be suitable for implantation at the selected implantation location. For example, as provided above, an optional act of the method comprises the eccentrically positioning the implant. The method may further comprise calculating a vector (e.g., at least a direction) of a lateral force to be exerted, followed by exerting the lateral force on the implant in the course of the implantation to accommodate the previously mapped conduction system, thereby ensuring a safe implantation.

[0777] In some embodiments, there is provided a method for positioning the implant at an angle, the method comprising: mapping the patient’s anatomical and physiological characteristic, specifically - the layout of the patient’s tricuspid annulus and conduction system. The method optionally further comprises, for example as detailed herein, creating a projection of the tricuspid annulus and extrapolating from it a tricuspid annulus plane, based on which distances between the tricuspid annulus and various constituents of the conduction system can be calculated. The method optionally comprises an act of planning the implantation procedure, this act optionally comprising selecting an appropriate implant and its desired implantation location, and optionally modifying the implant to be suitable for implantation at the selected implantation location. An optional step of the method comprises positioning the implant at an angle. The method further optionally comprises calculating a direction in which to bend the delivery system to achieve the desired angle. Examples of desired angles include between 10 and 20 degrees, between 20 and 30 degrees and between 30 and 40 degrees. This angle may be optionally provided only during part of the delivery process and changed, for example, as the deployment avoids damaging the conduction system.

[0778] Optionally, the implant is positioned within the tricuspid annulus, in an angle in relation to the tricuspid annulus, meaning that the implant and the tricuspid annulus are not on the same plane. Optionally the implant is also positioned eccentrically, for example as described herein.

[0779] In one embodiment, the implant is placed in a position which is at an angle to the tricuspid annulus, in a range of 1-8 within the tricuspid annulus. In one embodiment, the angled position of the implant, with respect to the tricuspid annulus, is 2 mm within the tricuspid annulus. In one embodiment, the angled position of the implant, with respect to the tricuspid annulus, is 4 mm within the tricuspid annulus. In one embodiment, the angled position of the implant, with respect to the tricuspid annulus, is 6 mm within the tricuspid annulus.

[0780] In one embodiment, the desired angle is calculated and displayed, for example using display methods as described herein. In one example, markers for a deployment stage are shown, for example, on an x-ray image. In one example, a marker includes a line to which a part of the implant is to be aligned. Optionally, a viewing angle is calculated and optionally an x-ray or other imager follows, to help an operator better ascertain the correct angulation.

[0781] In some embodiments, the vector of the lateral force, coupled with the angled position of the implant within the tricuspid annulus, is beneficial in securing a safe location for the implant and its parts, in relation to the conduction system.

[0782] In some embodiments, optionally and / or alternatively, alternatively, one or more anchors 3912 may be omitted from the implant structure. In an embodiment, the implant includes nine anchors 3912 distributed evenly about body of device 3704. A specific rotation marker or other visual alignment indicator may be used to orient the implant such that the region closest to the conduction system lacks an adjacent anchor, thereby reducing mechanical stress in this critical area.

[0783] Optionally, one or more anchors may be modified. In one embodiment, selected anchors are shortened in length. In another embodiment, an anchor is omitted, creating an open zone 106 that may be navigated to align with the conduction-sensitive area, for example, such that eucmin (minimal Euclidian distance between anchors and conduction system) and / or other distance measures is made larger.

[0784] Optionally and / or alternatively, anchors may be structured (e.g., predefined to deploy at an angle away from the vertical and / or be bent away from the vertical) or oriented to prevent intrusion into zones identified as conduction lines, based on lateral displacement and height mapping from the tricuspid annulus plane.

[0785] In some embodiments, body of device 3704 includes a C-shaped dent or similar discontinuity such that the area proximate to the conduction line remains free of implant material, reducing the risk of compression-related injury.

[0786] It is noted that multiple such features may be provided. In some embodiments of the invention, a set of implants is provided matching various parameter values, for example as noted - such as anchor spacing, anchor length and / or dents.

[0787] Each of the above strategies and / or other risk reducing methods described herein may be employed individually or in combination, and selection may be based on patient- specific anatomical features and procedural requirements.

[0788] Multiple measurements were made in patients with a pre-implantation CT and which did or did not require a pacemaker after tricuspid valve implantation (e.g., of the Evoque type).

[0789] Of these measurements, four appear to be statistically significant, each on its own, in predicting the need for a pacemaker. In some embodiments of the invention, prediction of such need is by comparing measurements to these results. Optionally and / or alternatively a classifier is created by training on data of measurements and with labeling as per actual need for a pacemaker. Such a classifier may be used (e.g., run on the system described herein) instead of using individual measurements and rules. Such a classifier may use projection or not. In some examples, rather than measurements, such a classifier is trained on actual shape of the annulus and locations of each of points A, B and C. That the method provides good predictions using simple measurements and projections strongly suggest a more complex classifier would work at least as well if not better.

[0790] In some embodiments of the invention, training or otherwise generating such a classifier or predictor (and / or others as described herein) comprises providing an indication of an exposure of a conduction system to forces applied during and / or after implantation. In some embodiments of the invention, such indication includes geometry of the conduction system and / or valve annulus (e.g., exposure angle). Optionally and / or alternatively such indication comprises expected movements and / or expected forces applied by a prosthetic valve. In some embodiments of the invention, additional data may be provided, for example as described herein, for example, previous conduction issues. Various training methods, may be used, for example, reinforcement learning or other methods, for example known in the art, that use labeled data (e.g., with a binary labeling or a non-binary labeling) to create a parametric or other model that transforms input data into a predicted label.

[0791] In some embodiments of the invention, the most predictive (statistically significant) measures are as follows:

[0792] Eucmin. Euclidean minimum distance to the a-b-c line.

[0793] Nearest. Shortest distance to any point of the a-b-c line

[0794] Latmin. Lateral minimum distance to a-b-c line

[0795] Vertav. Absolute Vertical distance from the floor to a-b-c line - average of all distances

[0796] Svertav. Signed vertical distance from floor to all a-b-c points

[0797] In table form - values predicting risks:

[0798] Other measures which may be used, for example in a classifier, include valve box height, average lateral distance, maximum lateral distance, vertical minimum and maximum distances and averaged signed minim and maximum vertical distances.

[0799] It is noted that predictors using other features are described herein as well. It is assumed that the predictors based on more data and / or using more than one measure are more accurate, but this may not be the case.

[0800] Fig. 41 is a summary histogram showing the distribution of cases where a pacemaker was needed as a function of minimum lateral distance between the conduction system and the projection of the annulus on the tricuspid plane, in accordance with some embodiments of the invention. It is noted that this histogram is based on a certain implant size (e.g., Evoque). It is not believed that implant diameter should significantly affect these results. Anchor length however, may, especially if the height of the conduction system will now fall within or without the changed anchor length.

[0801] It should be noted that at very small lateral separations, risk appears low, and as lateral separation increases, there are both more cases (human anatomical distribution, perhaps), but also a significantly higher risk, about 2.5 mm appears to be the lateral separation with maximal risk, risk then goes down and when separation is sufficient, for example, above 6 or 7 mm, risk (and population distribution) goes down. As noted above, other geometrical considerations, such as vertical separation can also affect risk. Possibly patients with under 2.5 mm separation are both more numerous and at a relatively lower risk of conduction system damage.

[0802] Further experimental data

[0803] Additional subjects, from a different site were added and further processed to generate a new predictor.

[0804] Consecutive patients undergoing TTVR with pre-operative CTA at two high volume referral centers in New York (NY, USA) and Freiburg (Germany), were analyzed. Using previously established methods (e.g., as described herein), the CSA (conduction system) was visualized. Measurements of lateral, vertical, and Euclidean distances from the retraced spline of the tricuspid valve (TV) annulus were made for the nearest (minimum), averaged, and farthest (maximum) points of CSA elements. The occurrence of PPI at 30 days follow-up was recorded. Simple binary logistic regressions were performed to elucidate the effects of the measured distances, implanted device size, and clinical-demographic characteristics on the occurrence of PPI. Significant predictors were assessed in a multiple binary regression. Generalized additive models (GAM) with integrated smoothness estimation (quadratic) were used to assess non-linear relationships. It is believed that 30 days is a time period which reflects damage to the conduction system that can be attributed to the implantation process and / or the implant.

[0805] A total of 105 patients from centers A (n = 42) and B (n = 63) were included. Patients were on average 80 years old (SD 6.5), 77% were female. The medical history included atrial fibrillation (89%), hypertension (70%), chronic kidney disease (63%), coronary artery disease (42%), and diabetes mellitus (16%). The mean (SD) baseline LVEF was 56.6 % (9.3), and the median [IQR] NYHA functional class was 3 [0]. Pre-operative ECG indicated RBBB and LBBB in 27% and 7%, respectively. The median [IQR] implanted device size was 52 mm [4].

[0806] Based on pre-operative CTA analysis, the averaged distances from TV spline to CSA elements were: lateral - 2.77mm [1.52], vertical 3.92mm [3.65] (above the spline), Euclidean (direct) - 4.95 mm [1.58]. Distances to nearest CSA elements were: lateral - 1.47mm [1.48], vertical - 0.05mm [4.02], Euclidean - 2.2mm [1.5], and to farthest elements were: lateral - 5.11 mm [2.16], vertical - 7.46mm [4.11], and Euclidean - 8.76mm [3.78], respectively. As can be seen the variation in anatomy is considerable.

[0807] Figs. 42A and 42B show the effect of vertical distance and lateral distance. As will be seen in Fig. 42C, these measures appear to miss important characteristics of risk. In simple logistic models, among clinical, demographic, and anatomical measurements, only nearest Euclidean distance and implanted device size were significant predictors of requiring PPI at follow up, such that increasing nearest Euclidean distance was associated with 53% increased odds for every 1 mm (OR 1.53, 95% CI [1.07-2.26], p = 0.023), and increasing device size doubled the odds with each size (OR: 2.15, 95% CI [1.18-4.26], p = 0.018). When mutually adjusted, both predictors retained their independent effects (nearest Euclidean distance adjusted OR: 1.46, 95% CI [1.02-2.19], p = 0.049, and device size adjusted OR: 2.03, 95% CI [1.11-4.04], p = 0.03).

[0808] To more closely approximate the observed distribution of PPI risk, a general additive model with integrated smoothness estimation was fitted to the data, with the eventual knots placed at nearest Euclidean distances 0mm, 0.5mm, 5mm, and 6mm favoring superior fit, and adjusting for the effect of device size.

[0809] Fig. 42C shows the relationship between nearest Euclidean distance and PPI risk. Separate approximations are provided for different device sizes. The Fig. shows the probability of PPI post- TTVR as a function of the nearest Euclidean distance from TV annular spline in 1mm increments. The grey bars with 95% CI reflect the observed risk per nearest distance bin, whereas the colored lines (whose vertical sequence matches the devices sizes in increasing size) stand for predicted risk.

[0810] The model suggested that along the closest Euclidean distance, the PPI odds decreased slightly until 0.5mm- 1mm, followed by a considerable increase at 4mm, in turn followed by a rapid decline (non-linear relationship significant at p = 0.0396; model’s effective degrees of freedom: edf = 2.58, UBRE = 0.093, AIC = 114). Device size remained an incremental risk, doubling the odds with every size up (OR: 2.08, 95% CI [1.09-3.98], p = 0.027).

[0811] Fig. 42D illustrates that this model demonstrated good discriminatory performance, with AUC = 0.76 (95% CI [0.65-0.85])

[0812] As noted regarding previous prediction methods, there appears to be a bimodal distribution in PPI risk across the nearest Euclidean distance between TV annular spline and the CSA elements, such that a small risk ‘bump’ was seen near 0 mm, potentially indicating the heightened risk among patients with more superficially located CSA, possibly due to an effect of the TTVR device body rubbing against the wall in the process of insertion. Importantly, the greatest risk is observed at ~4mm depth. This suggests that a common mode of damage may be as a result of extending the device anchors, which press into and scrape tissue overlying the CSA elements and which tissue conveys the forces to the CSA elements. Optionally and / or alternatively, it may be a result of the anchor elements which extend past the annulus in an anchoring state. Moreover, largest devices were found to exert the greatest harm; PPI odds doubled with every size larger. In some embodiments of the invention, a different device design is used to avoid one or more of these risks. A predictor created using this method can be, for example, a non-linear regression model based on Euclidean distance and device size. Optionally and / or alternatively different predictors are provided are provided for different device sizes.

[0813] Predictor for PPI risk based on geometry and data from still more patients

[0814] The previous experimental results were buttressed by adding patients from another study center and reanalyzing the data as a whole and generating new predictor(s). This shows a range of predictors can be generated using the data. In some embodiments of the invention, but not in these data, a predictor is built using additional data, for example, data on implantation (which can be used to predict the risk if a certain implantation procedure detail is not followed). Example data on implantation which can be used includes the depth of the implant, the orientation of the anchor to the conduction system, the angulation of the implant itself and / or the implant eccentricity at deployment.

[0815] While the predictor may be device-neutral (the data reflects a single device, the EVOQUE tricuspid valve), it is noted that device size, for example affects risk as may anchor deployment. This suggests that providing device details may result in a more reliable predictor, for example for device variants, for example, with different anchor-legs spacing. Similar predictors can be created for other device design. In some embodiments of the invention, the predictions for each device type are used to decide which device to recommend for a particular patient.

[0816] It is noted that some patient clinical data is optionally taken into account in prediction, specifically existence of existing conduction system damage, for example, presence of left bundle block and / or other data as may be detected, for example, on an ECG.

[0817] The patients were part of an international multicenter single-arm observational study of 181 consecutive patients undergoing TTVR (using the Edwards Evoque™ system; prosthesis sizes ranged from 44 mm to 56 mm in diameter) without prior pacemakers. Pre-procedural CTA was annotated for a conduction spline (AV node to His) and a tricuspid annulus reconstruction. The CTA was contrast- enhanced cardiac computed tomography angiography (CTA) of the heart prior to TTVR for procedural planning and anatomical assessment. The CTA datasets were post-processed to reconstruct a 3D model of the tricuspid valve annulus and the adjacent septal structures. The three tricuspid commissures (antero-septal, postero-septal, and antero-posterior commissures) were identified on CTA to delineate the tricuspid annular ring and define the annular plane. The course of the cardiac conduction system was approximated on CTA by identifying the region of the atrioventricular (AV) node (at the apex of the triangle of Koch near the septal tricuspid annulus) and the point of His bundle bifurcation in the interventricular septum. These two landmarks were connected with a smooth spline (in some embodiments, other approximation methods may be used, for example, piecewise linear) to represent the path of the conduction system from the AV (point A) node through the penetrating bundle of His (point B) to its branching point (point C).

[0818] The data was analyzed twice. First, only 179 patients were used and their analysis will be described. Thereafter analysis of a partially different type for all 181 patients is described.

[0819] Referring first to the 179-patinet set of data. The CTA was analyzed to derive:

[0820] (i) the conduction-annulus angle (°)(e.g., see Fig. 43H);

[0821] (ii) the lateral offset (mm; minimal lateral distance from the conduction spline to the septal annulus segment) (e.g., see Fig. 31); and

[0822] (iii) tricuspid annulus perimeter-derived diameter (PDD, mm) (Perimeter shown in Fig. 31, for example).

[0823] Pre-procedural left bundle branch block (LBBB) and planned device size were included; implant depth / direction were excluded by design, but one or both may be provided in some embodiments of the invention.

[0824] The primary endpoint of this study was the incidence of new PPI during the index hospitalization (e.g., 30 days). Multivariable logistic regression with 5-fold out-of-fold (OOF) ROC / AUC assessed performance.

[0825] The study population had a mean age of 77.0+9.9 years, 72% were female, and 82% were in atrial fibrillation / flutter. Pre-existing conduction disturbances were: right bundle branch block 20%, left anterior fascicular block 15%, left bundle branch block 3%, and left posterior fascicular block 3%. The primary endpoint occurred in 44 / 179 patients (24.6%).

[0826] The following independent pre-procedural CTA-based predictors (adjusted OR [95% CI]) were generated:

[0827] (i) conduction-annulus angle (per °: 1.04 [1.01-1.08], p=0.02) with greater angle corresponding to higher risk;

[0828] (ii) lateral offset (per mm: 0.82 [0.70-0.98], p=0.02) with farther distance from septum corresponding to lower risk; and

[0829] (iii) annulus PDD (per mm: 1.09 [1.01-1.18], p=0.03) with larger annulus corresponding to higher risk.

[0830] Pre-existing left bundle branch block trended toward higher risk (OR=2.0; p = non-significant).

[0831] Model AUC was 0.68-0.70. Practical thresholds which may be applied when deciding if PPI is expected (and perhaps to implant before a procedure) in this cohort were a 25° to 30° conductionannulus angle (which may indicate the exposure angle of the conduction system to the implant) and a 4-5 mm lateral offset (which may indicate a nearness which increases risk of CS damage by implant contact or forces. A high- sensitivity setting (e.g., -80% sensitivity) captured most PPI patients at the cost of more false positives, whereas a balanced setting detected -50% with fewer false positives.

[0832] Using single component predictors to asses risk as high or low, the following separation are found. Slope of the conduction system, in degrees can be considered high risk of 35% PPI when slope is below 22.2 degrees and low (17%) when slope is above 22.0 degrees. Fig. 43D is a scatter plot of slope degrees and need for PPI.

[0833] Lateral distance smaller than 3.99 mm is high risk (32%) and low risk (12%) at higher values. Fig. 43E is a scatter plot of minimal (lateral) distance and need for PPI.

[0834] Annulus perimeter of above 142.4 is high risk (39% PPI) and low below (14%). Fig. 43F is a scatter plot of annulus perimeter and need for PPI.

[0835] In some embodiments of the invention, a predictor is generated (e.g., using linear logistic methods, decision trees, AdaBoost and / or machine learning methods, such as reinforcement learning using labeled data) using multiple components and may yield a higher AUC.

[0836] More generally, this multi-variant predictor takes into account a previous physiological state (e.g., existing LBBB) as well as anatomical considerations (slope of conduction system, lateral distance and valve annulus perimeter).

[0837] Fig. 43A is a Forest chart for a predictor based on multiple components in accordance with some embodiments of the invention. This forest chart shows how a change (in standard deviation of each predictor component) affects the predictor behavior.

[0838] Fig. 43B is a Forest chart for a predictor based on multiple components in accordance with some embodiments of the invention. This chart shows how changes in various components affect the predictor outcome.

[0839] Fig. 43C is a chart showing sensitivity and specificity of such a predictor, showing an AUC of 0.714.

[0840] Fig. 43G is a set of three charts showing a risk map relating angle and lateral offset, in accordance with some embodiments of the invention. The 2x2 chart shows an overall predicted risk based on the combination of predictors for angle and lateral offset. The two single charts on the right show the predicted risk for just angle (e.g., with lateral offset from septal annulus at 4.5 mm) and offset (e.g., at 28 degree angle).

[0841] Fig. 43H is a set of two charts showing relationships between a tricuspid annulus 5302, 5322 and a section of the conduction system 5304, 5324, in accordance with some embodiments of the invention.

[0842] In the top chart, a distance 5306 between conduction system 5304 and annulus 5302 is shown.

[0843] It is noted this distance is a 3D distance and the annulus is used as is, rather than as a projection onto a plane. Distance 5306 is 4.2 mm and the slope angle of conduction system 5304 to an annulus plane (aligned with a projection of the conduction system) is 4.4 degrees. A pacemaker was required. It is noted that, general, a low angle generally means that more of the conduction system is a zone of danger of force applied (directly or indirectly) by the implant. The slope angle is optionally an average angle of the two parts of the conduction system shown point A to B and point B to C. Optionally and / or alternatively a predictor may use both angles (of AB and BC to the plane). Optionally and / or alternatively other indicators of slope angle may eb used, for example, length of the projection of the CS onto the tricuspid plane. In some embodiments of the invention, the predictor takes into account the parts of the AB and BC lines that are in the danger area. For example, parts that are high enough above the tricuspid plane may be outside of such zone. In some embodiments of the invention, during implantation, the implant is positioned so that parts of the CS are outside such danger zone.

[0844] In the top chart, a distance 5326 between conduction system 5324 and annulus 5322 is shown. It is noted this distance is a 3D distance and the annulus is used as is, rather than as a projection onto a plane. Distance 5326 is 9 mm and the slope angle of conduction system 5304 to annulus plane is 40.2 degrees. A pacemaker was not required.

[0845] In some embodiments of the invention, an indication of danger is based on the angle (circumferential angular displacement) between a conduction axis from the anterior- septal commissure (in the direction of the posteroseptal commissure). In some embodiments of the invention, such angle is marked on a display as a danger zone, for example, relative to commissure locations. In some embodiments of the invention, this danger zone relates to location of infra-annular anchors, for example, of an Evoque device. In some embodiments of the invention, the angle is an angle (difference) relative to the Anterio septal commissure or the posterior septal commissure. In some embodiments of the invention, the danger zone is defined by an anchor located in a danger circumferential zone, for example, defined as the projection of the bundle of His (A-C line) and / or or the infra annular part of the A-C line on the annalus.

[0846] Referring now to an analysis of the full 181 results.

[0847] Fig. 431 schematically shows an exposure angle, in accordance with some embodiments of the invention. Fig. 431 shows a 2D projection of a 3D model, which quantifies the geometric relationship between the conduction system (line A-B-C) and the tricuspid annulus (including line A’-B’-C’) for each patient, in accordance with some embodiments of the invention. Specifically, a conduction system exposure angle (shown as epsilon), defined as the angle (in degrees) occupied by the conduction system path on plane of the tricuspid annulus, is measured, optionally at the centroid. This angle indicates how “exposed to injury” the His bundle and / or other parts of the conduction system is on the annular plane (with a larger angle typically indicating a conduction system ‘wrapped around’ the annulus plane). The model is optionally also used to measure the lateral offset distance, defined as the minimal distance (in millimeters) between the farthest conduction system element and the tricuspid annulus. This distance represents how far away the His bundle runs from the tricuspid annular ring laterally - a smaller distance typically means the conduction bundle courses closer to (or along) the annulus. In addition, the tricuspid annulus size is optionally quantified by the perimeter- derived diameter (PDD), optionally calculated from the measured annular circumference (perimeter) on CTA (in millimeters). A larger PDD reflects a larger tricuspid annular size and typically necessitates a larger TTVR prosthesis, which may result in larger forces and / or further anchor reach.

[0848] It is noted that as the exposure angle gets smaller, it becomes easier to align the implant (e.g., rotationally) so that the anchors do not overlap with the exposure angle and / or particular parts thereof. Optionally, this is provided as operator guidance, optionally on a display and / or used to predict risk if instructions are followed. More generally, simulation may be used to determine risk and / or suitable instructions and / or risk if such instructions are followed. Such information may be shown to an operator.

[0849] The study results are analyzed to generate a predictor for new-onset high-grade atrioventricular (AV) block (and / or other CS damage) necessitating permanent pacemaker implantation (PPI) within 30 days of the TTVR procedure. This includes complete heart block and / or advanced second-degree AV block that was clinically indicated for pacemaker placement. Patients were continuously rhythm-monitored during the index hospitalization, and any new PPI required (either during the initial hospitalization or upon early follow-up within 1 month) was recorded as an event. The decision to implant a pacemaker was made by the treating electrophysiology / cardiology team based on standard guidelines (e.g., persistent high-grade AV block, symptomatic bradyarrhythmias). Patients were followed through 30 days post-procedure for detection of delayed conduction issues.

[0850] All data were analyzed using R Studio and respective statistical packages. Continuous variables are reported as mean ± standard deviation or median [interquartile range] as appropriate, and categorical variables as counts and percentages. Group comparisons (e.g., patients with vs. without PPI) utilized Student’s Z-test or Mann-Whitney U test for continuous data and chi-square or Fisher’s exact tests for categorical data, as appropriate. Multivariable logistic regression was performed to identify independent pre-procedural predictors of new PPI. The candidate predictor variables entered into the model were the conduction system exposure angle, lateral offset distance, tricuspid annulus PDD, the presence of baseline abnormalities on ECG, and the planned TTVR device size. Implantation depth or technique-related variables were not included in this model by design, focusing only on pre-procedural factors. As noted, in some embodiments of the invention, such data is optionally used for generating a predictor. All candidate predictors were entered simultaneously given the hypothesized importance of each, and backward selection was applied. The logistic regression results are presented as odds ratios (OR) with 95% confidence intervals (CI) and p-values. Model discrimination was evaluated with receiver-operating characteristic (ROC) analysis. To guard against overfitting, a 5-fold cross-validation was employed: the dataset was randomly split into 5 folds, and iterative training / testing yielded out-of-fold predicted probabilities for each case. The area under the ROC curve (AUC) was calculated from these cross-validated predictions. Also explored were risk stratification thresholds for the continuous anatomical variables (angle and distance) by identifying cut-off values that maximized the separation in PPI risk. All tests were two-sided, and a p-value < 0.05 was considered statistically significant.

[0851] A total of 181 patients met the inclusion criteria (consecutive TTVR without prior pacemaker). The median age was 80.0 years (IQR 11.0), and 71% were female. Atrial fibrillation was present in the majority (81%) of patients. Baseline ECG revealed underlying conduction system disease in many patients: 20% had RBBB, 15% had left anterior fascicular block, 3% had left posterior fascicular block, and 3% had LBBB. Roughly a quarter of the cohort had a history of prior heart valve interventions (such as surgical aortic / mitral valve replacement or transcatheter edge-to- edge repair of the mitral valve), reflecting the complex comorbidity of this population. No patient had an existing pacemaker at baseline by study design. During the TTVR procedures, the Evoque valve, Edwards Lifesciences, was implanted; the chosen prosthesis sizes ranged from 44 mm to 56 mm in diameter. Implantation was successful in all cases, with no procedural device dislodgements or need for emergency surgery reported.

[0852] The following table shows Clinical, demographic, & cardiac-anatomic characteristics (CTA) of the study population (N = 181).

[0853] New permanent pacemaker implantation occurred in 44 of 181 patients, an incidence of 24.3%. Some of these PPI events occurred during the index hospitalization (typically within 2-5 days post TTVR), with a some late-occurring high-grade AV blocks leading to pacemaker placement shortly after discharge (all within 30 days). There were no periprocedural deaths; thus, all patients were evaluable for the PPI endpoint at 1 month. There were no significant differences in age, gender, pre-procedure ECG findings and history of valve procedures between those who required and those who avoided PPI at follow-up (see above table). Participants requiring PPI were implanted devices with slightly larger diameter (52 mm [IQR 4] v 48 mm [IQR 4]), which did not reach statistical significance (p = 0.101).

[0854] When comparing the pre-procedural CTA measurements between these two groups it is noted that patients who developed high-grade AV block requiring PPI tended to have a wider conduction system exposure angle (33.4 mm [15.0] v 31.4 mm [15.2]), which did not reach statistical significance (p = 0.077), and a shorter lateral offset distance on their pre-TTVR imaging, compared to those who did not require PPI (4.6 mm [2.7] v 5.6 mm [2.5], p = 0.018). Additionally, the tricuspid annulus perimeter-derived diameter (PDD) was slightly larger in patients who required a pacemaker (48.7 mm [2.7] v 46.5 mm [2.5] ± 4.7 mm; p = 0.044) compared to those who did not. These relationships are demonstrated in Fig. 43J (which is a set of three charts showing CTA-based predictors of PPI in a study sample in accordance with some embodiments of the invention: observed (bars) and predicted (trendlines) risk of PPI, error bars are 95% confidence intervals (Wilson method)). The univariate predictions of the latter three variables are presented in the following table:

[0855] On multivariable logistic regression analysis of pre-procedural factors, three anatomic and one electrocardiographic variable emerged as independent predictors of new pacemaker implantation (see following table which shows simple and multivariable logistic regressions for pre-procedural anatomic and electrocardiographic predictors of new permanent pacemaker implantation (PPI).). A larger conduction system exposure angle was associated with higher odds of PPI, with an adjusted OR of 1.04 per degree increase (95% CI 1.01-1.08, p=0.027). In other words, the wider (more exposed) the His bundle’s course across the annulus, the greater the risk of post-TTVR AV block. Conversely, a greater lateral offset distance was protective: each 1 mm increase in offset distance (i.e., the farther the conduction path from the septal annulus) was associated with an aOR of 0.79 (0.65-0.93, =0.008) for PPI. Apparently, patients whose conduction system stayed more distant from the annular ring had lower risk of conduction injury. The third independent factor found and optionally used was the tricuspid annulus size - annulus PDD - where each 1 mm larger annulus diameter conferred an OR of 1.09 (1.00-1.19, p=0.048) for requiring a pacemaker. A larger annulus likely necessitates a larger TTVR device, which may exert more pressure on the septal area and conduction system. These three variables together constituted a pre-procedural risk model which can be used as a predictor in some embodiments of the invention. Notably, the presence of baseline LBBB on ECG showed a strong trend toward increased PPI risk (OR =2.2), but did not reach statistical significance in the model (p = 0.392. Thus, LBBB is not included in the predictor but it may optionally be included. The planned device size (prosthesis diameter) significantly correlated with PDD (r = 0.72, p < 0.0001), was not a significant predictor of PPI in the multivariable model after accounting for annulus PDD (p = 0.767), and it did not improve the model fit. In some embodiments of the invention, it may be used as an alternative variable for PDD. No other baseline clinical characteristics (such as age, sex, or prior interventions) were significantly associated with pacemaker outcomes in this analysis.

[0856] In some embodiments of the invention, only the significant predictors were retained in the final risk stratification model / predictor. Fig. 43K is a chart showing sensitivity and specificity of a predictor created using data in accordance with some embodiments of the invention, which shows receiver-operating characteristic (ROC) curve and predictor structure for the final model predicting new pacemaker implantation after TTVR, using the pre-procedural anatomic and ECG variables.

[0857] The combined pre-procedural PPI risk model demonstrated modest discriminative ability, with an AUC of 0.73 (95% CI: 0.64-0.82), sensitivity of 0.73 (95% CI: 0.57-0.86) and specificity of 0.76 (95% CI: 0.67-0.86) at the optimal cutoff maximizing Youden’s index. The 5-fold cross validation of 10 repeats produced a mean AUC of 0.70 (95% CI: 0.53-0.87).

[0858] Fig. 43L shows a confusion matrix for the predictor of the chart of Fig. 43J, using exemplary (but not mandatory) practical cut-off values in the anatomical predictors to stratify patients into higher- and lower-risk categories. In this cohort, a conduction exposure angle of 42° and a lateral offset distance of 5.5 mm served as useful threshold values delineating higher risk geometry. For instance, patients with a lateral offset <5.5 mm had a markedly higher incidence of PPI (32% required PPI) compared to those with offset >5.5 mm (only 16% required PPI; p = 0.0147). Eikewise, patients with a conduction exposure angle >42° had a higher PPI rate (40%) versus those with a shallower angle of <42° (21%; p = 0.032). When considering both factors together, those with a steep conduction angle and a close annular proximity (angle >42° and offset <5.5 mm) represented a high- risk subgroup - 62% of such patients required a pacemaker. In contrast, patients with a shallow angle and a distant conduction course (angle <42° and offset >5.5 mm) had the lowest risk, with PPI needed in only 21% in that group (p = 0.0032). These observations suggest that a combined consideration of the conduction path’s occupied angle (exposure) and the...

Claims

WHAT IS CLAIMED IS:

1. A method of planning an implantation procedure of a prosthetic tricuspid valve implant in a heart of a patient, comprising:(a) receiving at least one relative geometry of a conduction system and (i) a native tricuspid valve annulus; and / or (ii) one or more parts of a prosthetic valve which move during deployment; and(b) estimating a risk of conduction system damage due to implantation of said prosthetic valve based on said received relative geometry.

2. The method according to claim 1, wherein said estimating comprises taking into account one or more of the following damage mechanisms: stretching or compression of a conduction system section due to expansion of a body of the prosthetic valve; pressure by an anchor section of the prosthetic valve; pinching between an anchor and a body of said prosthetic valve; pressure or shearing during a movement of an anchor of said prosthetic valve during deployment; and timing and force of contact between the valve and a central fibrous body near the conduction system.

3. The method according to claim 1 or claim 2, wherein said estimating is based on a simulation of a deployment and mechanical interaction thereat.

4. The method according to any of claims 1-3, wherein said estimating is based on a fixed danger zone defined by such motion.

5. The method according to any of claims 1-4, wherein said estimating is based on at least one distance between said conduction system and a native valve annulus.

6. The method according to claim 5, wherein said at least one distance comprises a minimal distance, a maximal distance and / or an average distance.

7. The method according to claim 5 or claim 6, wherein said at least one distance is a distance calculated by projection onto a plane.

8. The method according to any of claims 5-7, wherein said at least one distance comprises at least two or at least three distances.

9. The method according to any of claims 5-8, wherein said at least one distance comprises a minimum lateral distance.

10. The method according to any of claims 5-9, wherein said at least one distance comprises a vertical distance.

11. The method according to any of claims 5-10, wherein said at least one distance comprises an Euclidian distance.

12. The method according to claim 7, wherein said plane is defined using three points along a tricuspid annulus.

13. The method according to any of claims 1-12, wherein said estimating is based on an exposure of said conduction system near said annulus to manipulation by said implant.

14. The method according to any claim 13, wherein said estimating is based on a slope of a conduction system near and relative to said annulus.

15. The method according to any claim 13, wherein said estimating is based on an exposure angle of said conduction system near said annulus.

16. The method according to any of claims 1-15, wherein said estimating is based on a perimeter or other indication of a size of said annulus.

17. The method according to any of claims 1-12, wherein said estimating is based on a pre-existing damage to the conduction system.

18. The method according to any of claims 1-12, wherein said estimating is based on a procedural parameter or indication thereof.

19. The method according to claim 18, wherein said procedural parameter comprises a valve design and / or size.

20. The method according to claim 18 or claim 19, wherein said procedural parameter comprises a lateral offset of implantation in an annulus plane.

21. The method according to any of claims 18-20, wherein said procedural parameter comprises an angulation of implantation relative to an annulus plane.

22. The method according to any of claims 18-21, wherein said procedural parameter comprises a rotational position of implantation in said annulus plane.

23. The method according to any of claims 18-21, wherein said procedural parameter comprises a height of implantation relative to said annulus plane.

24. The method according to any of claims 18-21, wherein said procedural parameter comprises a CFB height of implantation relative to said annulus plane.

25. The method according to any of claims 1-24, comprising displaying said risk to a user.

26. The method according to claim 25, wherein said risk is shown as binary or ternary.

27. The method according to claim 25 or claim 26, comprising displaying to a user the option to modify one or more valve or procedure parameter and show a risk for the updated parameter.

28. The method according to any of claims 1-27, comprising selecting a patient for therapy based on said risk.

29. The method according to any of claims 1-28, planning a pacemaker implantation based on said risk.

30. The method according to any of claims 1-29, changing a valve selection or recommendation based on said risk.

31. The method according to any of claims 1-30, generating procedure guidance and / or overlay markings based on said risk.

32. The method according to any of claims 1-31, wherein the valve comprises a plurality of anchors that bend back during deployment.

33. The method of claim 32, comprising selecting a valve orientation and / or lateral off- axial positioning and / or tilt according to said risk and / or said relative geometry.

34. The method of claim 32 or claim 33, comprising selecting an inter-anchor gap geometry according to said risk and / or said relative geometry.

35. The method of any of claims 32-34, comprising selecting an anchor geometry and / or body geometry according to said risk and / or said relative geometry.

36. The method of any of claims 1-35 being computer implemented, for at least providing an automatic recommendation.

37. A preplanning and / or intra-operative computer system configured to support and / or carry out the methods of any of claims 1-36.

38. A computing device, comprising: a processor operatively coupled to a data storage device storing code, the code comprising instructions for executing a model that generates a prediction of risk for pacemaker implantation in response to an input of tricuspid valve and adjacent conduction system geometry.

39. The computing device of claim 38, wherein the model is a machine learning model trained on a training dataset comprising patient tricuspid valve and conduction system geometries labeled with need for pacemaker.

40. A method of training a machine learning model for predicting pacemaker implantation after tricuspid valve implantation, comprising: generating a training dataset of a plurality of records, wherein a record comprises:an indication of an exposure of a conduction system to forces applied during and / or after valve implantation and a ground truth label of need for a pacemaker after implantation; and training the machine learning model on the training dataset for predicting a need for a pacemaker in response to an input of the indication of exposure.

41. A processor coupled to a memory having thereon a model trained by the method of claim 40.

42. A method for predicting the need for a pacemaker after a tricuspid valve implantation, comprising: feeding data comprising of an indication of an exposure of a conduction system to forces applied during and / or after valve implantation into a model; and executing the model to obtain a prediction of conduction system damage which may require implanting a pacemaker.

43. A method for planning a cardiac procedure, comprising:(a) modeling at least a portion of the heart mechanically;(b) simulating said procedure on said modeled heart portion; and(c) identifying, in a result of said simulation, a potential interaction between said heart or said procedure and a conduction system of the heart.

44. A method according to claim 43, wherein said simulating comprises using a finite element and / or a finite volume simulation.

45. A method according to claim 43 or claim 44, wherein said modeling comprises modeling a CFB (central fibrous body) of the heart with at least one mechanical parameter differently from that used for other modeled tissue.

46. A method according to any of claims 43-45, wherein said simulating comprises simulating multiple points along the procedure.

47. A method according to any of claims 43-45, wherein said simulating comprises simulating a static state.

48. A method according to any of claims 43-47, comprising repeating said method for multiple procedural parameter values.

49. A method according to claim 48, wherein said parameter comprises one or more of implant design, implant size, implant location and implant expansion timing.

50. A method according to any of claims 43-49, comprising generating instructions to an operator based on said simulating and said identifying.

51. A method according to any of claims 43-50, wherein said procedure comprises a TTVR (Transcatheter Tricuspid Valve Replacement) procedure.

52. A computer implemented method of in-procedure annotation of an ultrasound image, comprising:(a) identify, on a structural image, elements of a cardiac valve;(b) in an acquired ultrasound image, identify matching elements of the valve; and(c) map one or more annotation from a space of the structural image to a coordinate system of the ultrasound image; and(d) annotate the ultrasound image with markings corresponding to the one or more annotations.

53. The method of claim 52, wherein (a) comprises identifying elements of a conduction system adjacent said cardiac valve.

54. The method of claim 52 or claim 53, wherein (c) comprises identifying a slice of said ultrasound image aligned with an annulus of said valve.

55. The method of any of claims 52-54, wherein said elements of the cardiac valve comprise one or more of CFB (central fibrous body) portions, one or more commissures and / or an annulus section.

56. The method of any of claims 52-55, wherein said cardiac valve comprise a tricuspid valve.

57. A method of supporting navigation and / or guidance of an implantation procedure of a prosthetic tricuspid valve implant in a heart of a patient, comprising:(a) determining at least one relative geometry of a conduction system portion of the patient, relative to the patient’s heart; and(b) showing, on an ultrasound image acquired during the procedure, markings corresponding to the conduction system of the patient.

58. A method according to claim 57, wherein said determining comprises determining from a CT image of said heart.

59. A method according to claim 58 or claim 59 wherein said markings comprise one or more templates of a part of the conduction system.

60. A method according to any of claims 57-59, wherein said showing is in real-time, better than 5 frames per second.

61. A method according to any of claims 57-60, wherein said showing comprises showing a relative location of said conduction system portion and a tricuspid annulus.

62. A method according to any of claims 57-61, wherein said showing comprises showing a distance between said conduction system portion and a tricuspid annulus.

63. A method according to any of claims 57-62, wherein said showing comprises showing an angle of exposure.

64. A method according to any of claims 57-63, wherein said showing comprises showing at least an indication of an angle of a nonbranching bundle and / or a bundle of His relative to a tricuspid annulus.

65. Apparatus for supporting navigation and / or guidance of an implantation procedure of a prosthetic tricuspid valve implant in a heart of a patient, comprising:(a) a conduction system input which receives at least one relative geometry of a conduction system portion of the patient, relative to the patient’s heart;(b) an ultrasound input which receives a stream of ultrasound data; and(c) an overlayer configured to overlay markings corresponding to at least a portion of the conduction system of the patient on said ultrasound data, at a rate of at least 5 frames per second.

66. Apparatus according to claim 65, comprising an image display configured to display an ultrasound image based on said data and said overlay.

67. A computer- implemented method of generating a display for supporting implanting a prosthetic tricuspid valve in a heart of a patient, comprising:(a) estimating a relative location of at least a portion of a conduction system of the patient and a tricuspid valve region; and(b) displaying an indication of the at least a portion of a conduction system of the patient, a planning indication and / or a risk indication when implanting a prosthetic tricuspid valve in said region.

68. A system for supporting implantation of a prosthetic tricuspid valve in a heart of a patient, comprising:(a) a conduction system identifier which receives an anatomical image of the heart and generates an estimate of a conduction system location;(b) a processor programmed to generate at least one indication related to a portion of the conduction system adjacent a tricuspid annulus; and(c) an overlayer which overlays said indication on a 2D or 3D representation of the heart.

69. A prosthetic tricuspid valve, comprising: a body; and one or more anchoring elements, wherein said anchoring elements are arranged around said body and define a gap of between 20 and 60 degrees where they do not apply radial pressure in a direction away from said body on cardiac tissue, when implanted.

70. A computer-implemented method of selecting a valve and / or valve implant location for a prosthetic tricuspid valve, comprising:(a) receiving a location of a conduction system adjacent an annulus of a tricuspid valve in a patient;(b) selecting one or more of a valve geometry, valve size, valve rotation, valve orientation and / or valve elevation which reduces a risk of damage to said conduction system when said valve is implanted according to said selection.

71. A computer- implemented method of operation of circuitry for supporting implantation of a prosthetic tricuspid valve in a heart of a patient, comprising:(a) receiving an anatomical image of the heart;(b) generating an estimate of a conduction system location based on said image;(c) generating at least one indication related to a portion of the conduction system adjacent a tricuspid annulus; and(d) overlaying said indication on a 2D or 3D representation of the heart.

72. A method of machine-assisted setting up of a procedure for tricuspid valve implantation in a patient with a heart, comprising:(a) identifying a conduction system location on an image data set of said heart, said image acquired using data collection from outside the heart; and(b) providing machine-assisted guidance of a tricuspid valve implantation and / or selection based on a risk to the conduction system from valve implantation.

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