WO2020018353A1 - Leadless or single conduit multi-electrode cardiac pacemakers and methods of implantation and using thereof - Google Patents

Abstract

A device and method for providing cardiac pacing of triangle of Koch and bundle of His zones by multiple individual electrodes (34-39, 54-59, 67) inserted using in a single flexible conduit (16, 32, 60, 81) are provided. The method includes providing a single conduit (16, 32, 60, 81) with multiple individual electrodes (34-39, 54-59, 67), positioning these electrodes in the target zone of a heart, selecting a subset of acceptable electrodes as active based on a predetermined criteria and providing cardiac stimulation for multiple chambers of the heart from a single location. Also disclosed are various configurations for leadless cardiac pacemakers (220, 230, 240, 250, 260, 270, 280, 290, 300, 320) with a plurality of individual electrodes scattered around the vicinity of the implantation site. The controller is operated by first evaluating individual electrodes for their suitability for sensing and pacing of atrial and ventricular chambers of the heart. A subset of individual electrodes is then selected, and a controller is operated in a therapeutic mode for delivery of cardiac pacing to multiple heart chambers from a single intra-cardiac location.

Description

LEADLESS OR SINGLE CONDUIT MULTI-ELECTRODE CARDIAC PACEMAKERS AND METHODS OF IMPLANTATION AND USING THEREOF CROSS-REFERENCE DATA

[001] This patent application is a continuation-in-part of a co-pending US Patent Application No. 16/035,653 filed 15 July 2018; US Patent Application No. 16/221,547 filed 16 December 2018; and US Patent Application No. 16/293,104 filed 05 March 2019, all of which are incorporated herein by reference in their entirety.

BACKGROUND

[002] The present invention relates generally to cardiac pacing. More particularly, the invention describes multiple embodiments of leadless multi-electrode pacemakers or a single-conduit multi-electrode pacemakers configured for stimulating the bundle of Elis and surrounding areas for pacing the entire heart and methods of implantation and using thereof.

[003] In a healthy heart, a heartbeat originates in a specialized cardiac conduction system and spreads via this system to all parts of the myocardium The structures that make up the conduction system are the sinoatrial node (SA node), the intemodal atrial pathways, the atrioventricular node (AV node), the bundle of His and its branches, and the Purkinje system. Activation spreads quickly across the atria to the AV node, which then delays the wave of excitation. The delay enables the atria to contract before the ventricles contract. After the activation is delayed by, and leaves, the AV node, it enters and excites the bundle of His. This excitation of the bundle of His spreads in a precise pattern to the ventricles through the ventricular conduction system composed of Purkinje fibers. Excitation spreading through this system activates each ventricular cell at a precise time to produce a coordinated ventricular contraction. These events are seen generally as a normal QRS signal composed of group of waveforms on electrocardiogram (ECG) representing ventricular depolarization.

[004] For various reasons, this process of normal propagation of the electrical excitation wave throughout the heart may be disrupted leading to a variety of conduction abnormalities and subsequently to abnormal heart contractility. Many such abnormalities may be seen on the ECG signal and can be detected as distorted or absent P-wave or QRS signal. Such abnormalities may be treated by using an implantable cardiac pacemaker configured to generate artificial pacing signals when natural excitation/conduction is disrupted or absent altogether.

[005] Current conventional implantable cardiac pacemakers include a housing and one or more eleetxically-eonductive leads that connect to the housing through an electro-mechanical connection. The housing is implanted outside of the heart, such as in the pectoral region of the patient and contains controller electronics (e.g. a power source, microprocessor, capacitors, etc.) that provide pacemaker functionality. The leads traverse blood vessels between the housing and heart chambers in order to position one or more electrodes carried by the leads within the heart, thereby allowing the device electronics to electrically stimulate or pace cardiac tissue and measure or sense myocardial electrical activity.

[006] To sense atrial cardiac signals and to provide a right atrial chamber stimulation therapy, the housing is conventionally coupled to an implantable right atrial lead including an atrial tip electrode that typically is implanted in the patient's right atrial appendage. The right atrial lead may also include an atrial ring electrode to allow bipolar stimulation or sensing in combination with the atrial tip electrode.

[007] Recent experience with cardiac pacing indicates that traditional pacing sites may not be ideal for a good number of patients. Particularly, this is the case for right ventricular pacing, which may result in decline in heart function in some patients due to asynchronous cardiac contraction. Therefore, new direction in pacing is needed to avoid asynchronous cardiac contraction. This was attempted by pacing directly into the natural conduction system of the heart and more specifically - stimulating the bundle of His. This area is located right in the center of the heart in close proximity to atrial and ventricular tissue - and therefore may allow stimulation of one or multiple chambers of the heart from essentially the same location. For this description, the term‘His bundle’' generally refers to a heart electrical signals conduction system traversing His bundle a.s well as further distal pails thereof including but not limited to left bundle branch and right bundle branch.

[008] Permanent His bundle pacing has a potential to be used for treatment of at least some of the conduction abnormalities such as for example intra- and infra-hisian block including a complete heart block and left bundle branch block. In patients undergoing pacemaker implantation, His bundle pacing was found to be associated with reduction in death or heart failure hospitalization during long-term follow-up compared to a more conventional right ventricular pacing. Bundle of His pacing was also associated with higher rates of lead revisions and generator change. In patients with heart failure and left bundle branch block, His bundle pacing, as an alternative means to achieve cardiac ^synchronization, has been shown to be feasible and possibly beneficial compared to biventricular pacing.

[009] Despite the recent technological progress with the design of electrophysiology (EP) mapping catheters and pacing leads, their ability to reliably reach the target area at and surrounding the bundle of His in patients with broad anatomical variations is very limited. Currently, successful placement of the pacing lead to a bundle of His is only achieved in approximately 80% of the cases. This is frequently due to the inability to attach the electrode to a successfully identified target site with a reasonable capture threshold. To this day, the area to deploy the pacing electrode is identified by traditional methods of a multipolar electrode catheter used as a rough guide in a point-by-point electrogram mapping. Additionally, determination of the bundle of His capture is not always clear or easy to determine clinically.

[0010] Conventionally, a single electrode is used for probing and searching for the best position for implantation. Such probing procedure uses a temporary attachment of the electrode to the endocardial surface of the cardiac tissue followed by successive cardiac stimulation starting at higher voltages and subsequently reducing the voltage until the response of the cardiac tissue is no longer observed on the ECG - so as to determine a threshold for the lowest effective stimulation voltage. If the desired ECG response cannot be achieved at all or can be achieved only at high voltages, the electrode is disconnected from the tissue and moved to another location where the process is repeated again. As more than one cardiac chamber stimulation is frequently desired, this process may be time consuming and may involve large number of fluoroscopy images - leading to increased radiation exposure for both the patient and the physician.

[0011] The lead placement therefore is dependent on a point-by-point mapping and pacing using a trial-and-error methodology. The need therefore exists for better pacing tools and pacing leads to achieve a more rapid and effective permanent cardiac pacing. The need also exists to resolve a guidance problem of the pacing leads and achieve a reproducible navigation to predetermined capture sites - so as to improve the operator’s confidence, expedite the process of lead implantation and reduce radiation exposure due to excessive fluoroscopy imaging.

[0012] Since a conventional pacemaker housing is placed outside of the heart the patient may be susceptible to a number of lead-related complications, such as lead decay, dislodgement, Twiddler’s syndrome, etc. Hie need exists therefore for a novel cardiac pacemaker that addresses the lead-related complications

[0013] In addition implanted leads may experience certain further complications such as incidences of venous stenosis or thrombosis, device -related endocarditis, lead perforation or disruption of the tricuspid valve and concomitant tricuspid insufficiency; and lacerations of the right atrium right ventricle, coronary sinus, superior vena cava and innominate vein or pulmonary embolization of electrode fragments during lead extraction.

[0014] A more recent innovation is the use of so-called leadless pacemakers, which are located inside the heart and therefore do not require an extended conduit traversing the distance between a subcutaneous traditional pacemaker and the heart. As used herein, the term Headless” generally refers to an absence of electrically-conduelive leads or wires that traverse vessels or other anatomy outside of the intra-cardiac space, while“intra-cardiac” means generally, located entirely within the heart and associated vessels, such as the superior vena cava (SVC), inferior vena cava (TVC), coronary sinus (CS), pulmonary arteries (PA) and the like.

[0015] An implantable device, such as an implantable cardiac rhythm management device (e.g., a pacemaker, a defibrillator, or a cardioverter - all of which are contemplated by this disclosure and referred to generally as a“pacemaker”) may be used to monitor cardiac function and provide cardiac stimulation therapy for a patient who suffers from cardiac arrhythmia. The implantable pacemaker may track cardiac signals and provide suitable cardiac pacing stimulation by using one or more leads implanted in the heart of the patient. 'The implantable pacemaker may process electrical signals received via implanted leads and then attempt to characterize the received signals as a particular cardiac event. Such cardiac events may include, for example, P waves, R waves, T waves, or arrhythmia events. By analyzing the type and timing of these cardiac events, the implantable device may determine whether therapy should be provided and, if so, the type of therapy to be provided (e.g., stimulation pulses).

[0016] Functionally, conventional or leadless pacemakers may operate as a single-chamber pacemaker with leads in the right atrium (RA) or right ventricle (R V) and would typically be programmed in AAI or VVI modes, respectively to inhibit pacing whenever intrinsic activity in that chamber is detected. A dual-chamber pacemaker with RA and RV leads or a dual- chamber lead may have the ability to sense both atrial and ventricular electrical activity. For any patient with intermittent AV node conduction, it may be preferable to inhibit ventricular pacing and allow' an intrinsic R wave to occur for a time after any P wave is detected on the RA lead. If ventricular pacing is needed, it is desirable to synchronize ventricular activity to atrial activity using an AV delay. The VDD programming mode has become common in dual-chamber pacemakers for patients with various degrees of AV block. Other common dual chamber modes include DDL) and DDDR.

[0017] A cardiac rhythm management system may also deliver resynchronization therapy, in which electrical stimulation is delivered to coordinate the electromechanical activity of the chambers of the heart. Such system may use the leads placed in the right atrium and right ventricle along with an additional lead coupled to the pacemaker housing that extends through the coronary sinus to a distal tip electrode on the outer surface of the left ventricle. There may be one or more ring electrodes in electrical contact with the left ventricle the left atrium or both. The tip electrode may reach a location in the venous vasculature of the left ventricle including any portion of the coronary sinus, great cardiac vein, left marginal vein left posterior ventricular vein, middle cardiac vein, and/or small cardiac vein, or any other cardiac vein accessible by the coronary sinus

[0018] Modern day ieadless pacemakers are typically characterized by the following features: they are devoid of leads that pass out of the heart to another component, such as a pacemaker housing outside of the heart; they include electrodes that are affixed directly to the pacemaker housing of the device: the entire device is attached to the heart; and the device is capable of pacing and sensing in the chamber of the heart where it is implanted.

[0019] Leadless pacemaker devices that have been proposed thus far offer limited functional capability. These devices can sense electrical activity in one chamber and deliver pacing pulses in that same chamber and thus offer single chamber functionality. For example, a leadless pacemaker device which is located in the right atrium would be limited to offering AA1 mode functionality. An AAI mode leadless pacemaker can only sense electrical activity in the right atriu , pace in the right atrium and inhibit pacing function when an intrinsic event is detected in the right atrium within a preset time limit.

[0020] Further it is difficult to maintain a reliable wireless communications link between Ieadless pacemaker devices. The leadless pacemaker devices utilize low-power transceivers that are located in a constantly changing electrical environment within the associated heart chamber. Tire transmission characteristics of the environment surrounding a Ieadless pacemaker device change due in pat to the continuous cyclical motion of the heart and change in blood volume. Hence, the potential exists that the communication link is broken or intermittent

[0021] A further limitation of the existing cardiac Ieadless pacemakers is their limited life span, which is typically less than about 5 years. This limitation is a result of having to use a very small battery so as to minimize the overall size of the device and facilitate its minimally invasive implantation techniques. The need exists to configure a Ieadless pacemaker in such as way as to extend its useful life, for example by providing a longer lasting battery, allowing for a battery recharge or battery replacement when it is depleted.

[0022] The need therefore exists for a single Song-lasting Ieadless pacemaker capable of sensing and pacing one or more chambers of the heart from a single location, such as triangle of Koch and His bundle and closely surrounding areas of the heart.

BRIEF SUMMARY OF THE INVENTION

[0023] Accordingly, it is an object of the present invention to overcome these and other drawbacks of the prior art by providing a novel single conduit cardiac pacemaker configured for electrical evaluation and stimulation of the bundle of His and surrounding areas including the atrium.

[0024] It is another object of the present invention to provide a single conduit cardiac pacemaker configured for reliable and deterministic implantation in a broad range of patients with a variety of anatomical variations and abnormalities in electrical conduction of the cardiac tissue.

[0025] A further object of the present invention is to provide a single conduit cardiac pacemaker and methods of using thereof allowing to rapidly identify best stimulation sites after implantation and to provide cardiac pacing without a need to implant multiple individual electrodes.

[0026] A further yet object of the present invention is to overcome various drawbacks of the prior art by providing a novel multi-electrode leadless pacemaker and methods of implantation and using thereof aimed at providing heart stimulation for one or more heart chambers from a single intra-cardiac location.

[0027] It is yet another object of the present invention to provide a multi-electrode cardiac pacemaker adapter configured to use a conventional single-electrode leadless pacemaker for producing cardiac pacing of His bundle with multiple electrodes as a therapy for pacing one or more multiple cardiac chambers at the same time.

[0028] It is a further yet object of the present invention to provide an adapter for converting a conventional cardiac pacemaker for use with an implantable multi-electrode assembly.

[0029] It is yet another object of the present invention to provide the leadless cardiac pacemaker configured for stimulation of the heart in the area of triangle of Koch and His bundle.

[0030] In embodiments, the novel single conduit multi-electrode pacemaker comprises a single elongated insulated conduit housing a plurality of electrical conductors operably connected to a plurality of respective individual electrodes at the distal end of the conduit. Individual electrodes may be configured to be retained near the center of the conduit while constrained by a surrounding sheath. Retraction of the sheath allows individual electrodes to spread out radially away from the center so as to allow simultaneous implantation into the target area of the cardiac tissue. As a result, a plurality of spaced apart electrodes may be positioned in the cardiac tissue via a single implantation procedure. A central tissue attachment spring may also be provided to secure the conduit and all the individual electrodes in place. Individual position of the electrodes may be selected to reliably cover the target area of the cardiac tissue. The target area may include a location suitable for pacing of a cardiac atrium and a location suitable for pacing of a cardiac ventricle of the heart, such as the bundle of His with at least some of the electrodes located in and around this selected target area which may include the atrial tissue. More than one of the plurality of individual electrodes may be positioned at the location suitable for pacing of the cardiac atrium or at the location suitable for pacing of the cardiac ventricle of the heart. In embodiments, the number of placed individual electrodes may exceed the number of selected electrodes used for heart pacing following the implantation procedure.

[0031] In other embodiments, following the positioning of the plurality of electrodes in and around the target area of the cardiac tissue, indi vidual interrogation of these electrodes may be conducted with the aim of identifying desired electrodes located directly at the target site. Those electrodes that do not provide desired ECG response during test stimulation may be abandoned. If more than one electrode is found to provide desired stimulation behavior, additional selection within this group may be conducted to identify one or more electrodes with the lowest threshold for effective cardiac stimulation. A subset of selected electrodes may be used for heart capturing and pacing afterwards using for example a pacemaker located outside the heart, using either the same pacing signal for all selected individual electrodes, a set of chamber-specific pacing signals, or supplying each individual or groups of individual electrodes with their corresponding pacing signals as the invention is not limited in this regard.

[0032] In further embodiments, a method of providing cardiac pacing includes the steps of providing a flexible single conduit housing a plurality of individual wires extending therethrough and positioned alongside each other at least in a portion of the single conduit. The individual wires may be terminated with a plurality of corresponding individual electrodes located at the distal end of the single conduit; advancing the single conduit to position a distal end thereof near a cardiac tissue target area while the plurality of individual electrodes are held in a collapsed position next to a center of the distal end of the single conduit; expanding the plurality of individual electrodes to an expanded position forming a expanded scattered pattern of the individual electrodes about and away from the center of the distal end of the single conduit; advancing the single conduit to implant the individual electrodes into the cardiac tissue target area; interrogating the plurality of individual electrodes to determine a subset of the individual electrodes meeting a predetermined acceptance criteria; and initiating cardiac capture and pacing using at least some of individual electrodes of the subset of individual electrodes meeting the predetermined acceptance criteria, these at least some individual electrode connected via the single conduit to a pacemaker located outside the heart. Permanent pacing may then be initiated with an implantable pacemaker using a subset of the plurality of electrodes that are best matched to desired cardiac pacing outcome.

[0033] The leadless cardiac pacemaker of the invention may also be used for the purposes of stimulating the His bundle to capture one or two cardiac chambers from a single location. In this case, the leadless pacemaker may generally comprise a housing configured to be implanted entirely within a single heart chamber at a predetermined target area. The target area may include a location suitable for pacing of a cardiac atrium and a location suitable for pacing of a cardiac ventricle of the heart, such as triangle of Koch, His bundle and surrounding nearby areas. The leadless pacemaker may also comprise a plurality of individual electrodes located on or extending from the housing and configured for delivering electrical stimuli to a cardiac tissue at the target area implantation site. At least some of the plurality of individual electrodes may be further configured to sense electrical activity of said cardiac tissue at the target area, such as sensing right atrial electrical activity for example.

[0034] The leadless cardiac pacemaker of the invention may further comprise a controller hermetically sealed within the housing. The controller may be configured to operate in one of the following two modes following implantation of the leadless cardiac pacemaker:

an individual electrodes evaluation mode, wherein the controller is operated to interrogate the individual electrodes individually or in groups to determine a subset thereof meeting a predetermined acceptance criteria, and

a therapeutic mode, wherein the controller is operated to deliver the electrical stimuli to the cardiac tissue at the target area.

[0035] Implantation of the plurality of individual electrodes is intended to cover the area of triangle of Koch and His bundle. At least some individual electrodes are expected to be implanted in the His bundle conduction pathways. Other individual electrodes may be located near His bundle conduction pathways but not be electrically coupled thereto. Electrical evaluation of those electrodes that are electrically coupled to His bundle may be used to identify at least one or more electrodes suitable for subsequent ventricular pacing using at least one predetermined criteria, such as for example a best capture threshold. Evaluation of those electrodes that are positioned to not be electrically coupled to His bundle may be used to identify one or more individual electrodes suitable for subsequent atrial pacing and/or sensing of atrial electrical activity. Remaining individual electrodes may be abandoned. In further embodiments, previously abandoned individual electrodes may be reactivated at a later time when a malfunction of previously active electrodes is detected or if they become more suitable for use for other reasons.

[0036] Depending on the condition of the subject, using selected subset of individual electrodes may allow providing of cardiac pacing of multiple cardiac chambers (such as direct atrial pacing and ventricular pacing via stimulation of His bundle) from a single intra-cardiac location with a single implantable cardiac pacemaker. The present invention therefore allows to avoid a need to implant multiple leadless cardiac pacemakers and coordinate their pacing activities when more than one cardiac chamber is in need of a dedicated rhythm management therapy.

[0037] The present invention further describes an adapter for delivering rhythm management electrical stimuli to one or multiple heart chambers using a conventional cardiac pacemaker. The adapter in this case may include a housing configured to be implanted entirely within a single heart chamber at a predetermined target area. The housing may be also configured to operably connect to the conventional cardiac pacemaker and retain thereof at the implantation site.

[0038] The adapter may further include a plurality of individual electrodes located on or extending from the housing and configured for delivering electrical stimuli to a cardiac tissue at target area of implantation site such as His bundle or triangle of Koch. At least some of the plurality of individual electrodes may be further configured or used to sense electrical activity of local cardiac tissue at the target area.

[0039] The adapter may further include an electronic switch hermetically sealed within the housing and configured to deliver atrium pacing stimuli generated by the conventional cardiac pacemaker to at least one of the individual electrodes selected for atrial pacing. The electronic switch may be further configured to deliver ventricular pacing stimuli from the conventional cardiac pacemaker to at least one other individual electrodes selected for ventricular pacing via stimulation of His bundle, whereby said multiple heart chambers may be paced from a single intra-cardiac location.

[0040] The electronic switch may be also configured for operating to select a subset of the individual electrodes using best capture threshold criteria, while the leadless conventional cardiac pacemaker may be configured to deliver electrical stimuli to triangle of Koch or His bundle for ventricular pacing purposes when atrial pacing or sensing of atrial electrical activi ty is not needed, such as for example in case of permanent atrial fibrillation.

[0041] The present invention also describes a method for providing cardiac rhythm management therapy comprising the following steps:

a. providing a leadless cardiac pacemaker comprising a housing configured to be implanted entirely within a single heart chamber, a plurality of individual electrodes located on or extending from the housing, and a controller located within the housing and operably connected with the individual electrodes, b. implanting the leadless cardiac pacemaker at a target area defined by triangle of Koch, His bundle and surrounding areas while positioning the individual electrodes throughout said target area

c. evaluating the plurality of individual electrodes using a predetermined acceptance criteria to select at least one individual electrode suitable for atrial pacing, and at least one other individual electrode suitable for ventricular pacing via delivering of electrical stimuli to His bundle, and

d. operating the controller to deliver atrial pacing and ventricular pacing via the respective selected individual electrodes from a single intra-cardiac location.

BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Subject matter is particularly pointed out and distinctly claimed in the concluding portion of the specification. The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with die disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

[0043] FIGURE 1 is a general cross-sectional view of a heart with implanted multiple electrodes into a target zone.

[0044] FIGURE 2 is a schematic view of a close-up portion of the heart of FIG. 1 including the triangle of Koch and bundle of His as the target zone.

[0045] FIGURES 3A, 3B, and 3C are perspective views of a tip of a conduit with multiple electrodes according to the first embodiment of the invention.

[0046] FIGURES 4A, 4B, and 4C are perspective views of a tip of a conduit with multiple electrodes according to the second embodiment of the invention.

[0047] FIGURES 5 A and 5B are perspective views of a tip of a conduit with multiple electrodes according to the third embodiment of the invention.

[0048] FIGURES 6A and 6B are perspective views of a tip of a conduit with multiple electrodes according to the fourth embodiment of the invention.

[0049] FIGURE 7 is a view of an implantable pacemaker assembly with multiple electrodes according to the fifth embodiment of the present invention.

[0050] FIGURE 8 is a schematic diagram of a cardiac pacemaker with a single conduit combining multiple electrodes therein.

[0051] FIGURE 9 is a block diagram illustrating the sequence of the steps according to one method of the invention. [0052] FIGURE 10 illustrates measurement of HV interval with intracardiac electrogram recording.

[0053] FIGURE 11 illustrates selective stimulation of the His bundle with the prototype electrode in an animal heart.

[0054] FIGURE 12 illustrates stimulation of ventricular myocardium by both selective and nonselective His bundle capture with the prototype electrode in an animal heart.

[0055] FIGURE 13 illustrates stimulation of atrial myocardium by the prototype electrode implanted into the triangle of Koch of an animal heart from the same position where the His bundle capture was obtained from different electrode pairs of the prototype.

[0056] FIGURE 14 is a cross-sectional view of a prior art leadless pacemaker positioned in die right ventricle of the heart.

[0057] FIGURE 15 is a cut-out view of various chambers of the heart.

[0058] FIGURE 16 is a schematically-drawn close-up of the triangle of Koch and His bundle.

[0059] FIGURE 17 illustrates a top view of a general location for positioning the multi -electrode leadless pacemaker of the invention in the area of triangle of Koch and His bundle.

[0060] FIGURE 18 illustrates a sagittal cross-sectional view of the same as in Fig. 17.

[0061] FIGURE 19 shows a top view of a general position of an alternative configuration of the multi-electrode leadless pacemaker in the area of triangle of Koch and His bundle.

[0062] FIGURE 20 shows a cross-sectional side view of the same as in Fig. 19.

[0063] FIGURE 21 shows a cross-sectional side view of yet another variation of the multi electrode leadless pacemaker of the present invention as in Fig. 19.

[0064] FIGURE 22 is a top perspective view of yet another configuration of the leadless pacemaker of the present invention.

[0065] FIGURE 23 is the bottom perspective view of the same as in Fig. 22.

[0066] FIGURE 24 is illustrating an intermediate stage of delivery of the leadless pacemaker shown in Figs. 22 and 23.

[0067] FIGURE 25 shows a final stage of delivery of the same as in Fig. 24.

[0068] FIGURE 26 is yet a further configuration of the leadless pacemaker of the present invention shown in an intermediate stage of deployment.

[0069] FIGURE 27 shows a final stage of deployment of the leadless pacemaker of Fig. 26.

[0070] FIGURE 28 shows a cross-sectional general view of the heart illustrating an alternative position of the leadless pacemaker of the present invention capable of reaching His bundle as well as left bundle branch and right bundle branches from a right ventricle.

[0071] FIGURE 29 is a schematic view of a close-up showing the leadless cardiac pacemaker reaching a left bundle branch.

[0072] FIGURE 30 is die same as in Fig. 29 wherein the leadless cardiac pacemaker is configured for reaching either left bundle branch, right bundle branch, or both left and right bundle branches.

[0073] FIGURE 31 shows an initial stage of minimally invasive delivery of the leadless pacemaker of the invention into the heart.

[0074] FIGURE 32 shows a more advanced stage of the same delivery process.

[0075] FIGURE 33 shows a final configuration following the delivery of the leadless cardiac pacemaker and attachment thereof to the cardiac tissue.

[0076] FIGURE 34 shows a cross-sectional view of an alternative delivery procedure for deployment of the leadless pacemaker of the present invention using a suction cup.

[0077] FIGURE 35 shows a top view of the same as in Fig. 34.

[0078] FIGURE 36 shows yet another alternative procedure of delivery of the leadless pacemaker or components thereof into position and attachment to the target heart tissue.

[0079] FIGURE 37 shows a cross-sectional side view of yet a further alternative procedure of delivery of the leadless cardiac pacemaker of the present invention.

[0080] FIGURE 38 schematically shows a top view of the same as in Fig. 37.

[0081] FIGURE 39 is a side view of yet another configuration of the leadless cardiac pacemaker of the present invention in its expanded state.

[0082] FIGURE 40 is a side view of the same wherein the cardiac pacemaker is in its compressed state.

[0083] FIGURE 41 shows the same as in Fig. 40 but with all emerging leads forming engagement hooks when deployed.

[0084] FIGURE 42 shows yet another configuration of the leadless implantable pacemaker of the present invention with movable emerging attachment screw and multiple leads shown during initial stages of implantation.

[0085] FIGURE 43 shows the same as in Fig. 42 but in a final stage of deployment.

[0086] FIGURE 44 is a side view of a further yet configuration of the invention with the leadless pacemaker featuring a plurality of electrode zones.

[0087] FIGURE 45 shows a side view of yet another embodiment of the leadless pacemaker of the present invention while in a deployment sheath.

[0088] FIGURE 46 shows die same as in Fig. 45 but with the leadless pacemaker of the invention shown in its final deployment position.

[0089] FIGURE 47 shows a block diagram of another embodiment of the present invention configured for using a conventional leadless or traditional pacemaker as a source of pacing signals for the purposes of a multi-electrode pacing of the present invention.

[0090] FIGURE 48 shows a schematic cross-section of the embodiment of the present invention equipped with a switch to change electrode configuration remotely.

[0091] FIGURE 49 shows an exemplary cross-sectional view of an embodiment of the present invention comprising the conventional single-lead pacemaker and a novel adapter for use thereof for the purposes of multi -electrode pacing.

[0092] FIGURE 50 shows a leadless cardiac pacemaker with a selector switch configured to connect thereof to the selected electrodes after implantation and evaluation of such electrodes prior to insertion thereof.

[0093] The following description sets forth various examples along with specific details to provide a thorough understanding of claimed subject matter. It will be understood by those skilled in the art, however, that claimed subject matter may be practiced without one or more of the specific details disclosed herein. Further, in some circumstances, well-known methods, procedures, systems, components and/or circuits have not been described in detail in order to avoid unnecessarily obscuring claimed subject matter. In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. Tire illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.

DETAILED DESCRIPTION OF SINGLE CONDUIT PREFERRED EMBODIMENTS

[0094] The present invention describes a single cardiac pacing conduit with a plurality of individual electrodes located at the distal end thereof. Initially, individual electrodes are located in a compressed state next to the center of the conduit - so as to facilitate easy insertion and advancement to the implantation site. While in the vicinity of the desired implantation site, individual electrodes are expanded away from die center so as to form a plurality of electrodes configured to cover the target area of the cardiac tissue. The conduit is then advanced further and all electrodes are implanted into the cardiac tissue at the desired site. Location of individual electrodes may be selected to provide adequate coverage of the target area and surrounding tissues so that at least a subset of electrodes may be useful for subsequent cardiac pacing.

[0095] Once implantation of individual electrodes is accomplished (with optional temporary or permanent tissue attachment to secure the electrodes in place), individual or group interrogation of the electrodes may commence. To evaluate individual electrodes, one electrode at a time may be activated in a unipolar or bi-polar mode with various levels of pacing voltage so as to determine whether its location and performance is adequate for desired cardiac pacing purposes. Evaluation of all electrodes may be conducted using one electrode at a time or pairing electrodes with each other. Separate evaluations may be conducted for individual electrodes positioned at die location suitable for pacing of each of the targeted cardiac chambers, such as a location suitable for pacing of a cardiac atrium and a location suitable for pacing of a cardiac ventricle for example. As a result of the evaluation procedure, a preferred subset of electrodes may be identified to include the best individual electrodes or pairs of electrodes suitable for subsequent capturing and pacing purposes of each targeted cardiac chamber, preferably those electrodes with the lowest effective capture voltage thresholds.

[0096] In embodiments, covering the bundle of His and triangle of Koch as well as surrounding areas of cardiac tissues may result if identifying electrodes suitable for atrial pacing, selective bundle of His pacing or mixed pacing as locations suitable for pacing the atrium and for pacing the ventricle may overlap or be adjacent to each other. Depending on the nature of cardiac abnormalities, a final selection of electrodes may be conducted aimed at identifying the best electrodes located at the proper target area for each individual patient.

[0097] In situations when no electrodes are found to be suitable for subsequent cardiac pacing, repositioning and re-implantation of the plurality of electrodes may be conducted so as to attempt to relocate the plurality of electrodes in another position so as to allow another attempt to find one or more electrodes suitable for permanent cardiac pacing. Remaining electrodes may be abandoned and not used for cardiac pacing following such interrogation procedure. These remaining electrodes may remain passive but can be optionally re-activated in the future if the cardiac disease progresses and a different mode of pacing is needed for the patient later in life. Another reason to leave passive electrodes in place is to allow optional activation thereof in case of lead fracture or another malfunction of the initially selected electrodes. Having other electrodes suitable for cardiac pacing may prevent immediate complications when switching to their use is done automatically by a suitable cardiac pacemaker operably connected to and programmed to perform such switch in this case. A further yet advantage of providing additional electrodes is to avoid a surgical intervention to replace the entire conduit when one of the electrodes experienced a malfunction.

[0098] Referring to FIG. 1, a human heart 1 is illustrated in a general way with implanted therein a conduit of the invention 16 having multiple electrodes 2 extending from a distal end thereof and into a target zone in the heart. Seen in the drawing are the following elements and heart structures: distal electrodes 2 are extending from the distal tip of the conduit 16 into the target zone, which includes bundle of Mis 3. Bachmann’s bundle 4 is seen as a conduction structure. Also shown are the left atrium 5, left ventricle 6, left conduction bundle (or left bundle branch) 7, descending aorta 8, inferior vena cava 9, right conduction bundle (or right bundle branch) 10, right ventricle 11, atrioventricular node 12, right atrium 13, sinoatrial node 14, and a superior vena cava 15. As with other pacing leads, a pacing conduit 16 of the invention may be minimally invasively delivered through the superior vena cava 15, aorta 17, or left pulmonary artery 18.

[0099] FIG. 2 shows a schematic view of a portion of the heart of FIG. 1 including the triangle of Koch 22 and bundle of His 3 that together and along with surrounding atrial tissues may be contemplated as the target area 21 suitable for implantation of a plurality of pacing electrodes 2. lire target area 21 may be accessed through the right atrium 13. To allow distinct pictorial identification of the proper location of die target area 21, the following heart anatomical and functional structures are depicted in FIG. 2: left bundle branch 24, right bundle branch 25, tricuspid valve 26, coronary sinus ostium 27, inferior vena cava 28, tendon of Todaro 29, and fossa ovalis 30. The penetrating bundle of His 3 is a structure consisting of specialized conducting tissue located within the membranous portion of the ventricular septum. Bundle of His is surrounded by connective tissue from the central fibrous body 23, which constitutes an insulating layer to the chord-like bundle. Referring to FIGS. 1 and 2, the compact atrioventricular node 12 located in the right atrium 13 within the triangle of Koch 22 serves as die gateway of electrical conduction to the ventricles 6 and 11. Anatomic target area 21 may be intended for stimulatory pacing electrodes making contact with (a) the penetrating Bundle of His and surrounding areas, which traverses through the membrane of septum, and (b) conduction elements of the triangle of Koch 22 and surrounding areas. This target area for electrodes implantation may be selected to allow controlled pacing of one or multiple myocardial structures.

[00100] At least some of the individual electrodes may be targeted for implantation into the atrial tissues located in the vicinity of the target area 21. Activation of these electrodes may be used for conventional atrial pacing. The approach of implanting some electrodes into the bundle of His while some other electrodes into the atrial tissues nearby may be advantageous for allowing cardiac pacing of both the atrium (using atrial electrodes) and the one or both ventricles of the heart (using electrodes in the bundle of His) - all from the same single implantation procedure and using the same conduit for activation thereof, the conduit in this case extending from a proximal end outside the heart to a distal end inside the heart.

[00101] FIGS. 3 A, 3B, and 3C show perspective views of a distal tip of the conduit of the invention with multiple electrodes according to the first embodiment thereof. Specifically, FIG 3A shows the compressed assembly of individual electrodes illustrated during the steps of delivery to the heart target area. The electrode assembly may include a tissue attachment spring/screw portion 31 designed to deliver spring/screw 33 initially hidden inside the distal end of the conduit 32, as well as a plurality of pacing electrodes 34-39 located distally of the screw 33. Individual electrodes 34-39 at the distal end may be made into a Z-shape and initially compressed and placed within the insulating outer sheath 40 with opening 41 distally. The tissue attachment screw 33 may also be configured to serve itself as an electrode. The number of individual electrodes can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 electrodes. Each individual electrode or a group of individual electrodes may be equipped with an individual wire connecting the respective electrode or a group of electrodes to the pacing device on the other end of the single conduit 32. In embodiments, effective and efficient delivery of electrical energy to the myocardium via the individual electrodes 34-39 can be achieved by incorporation of steroid-elution into the individual electrode tips 42 (electrode-tissue interface) that allows reliable heart pacing with low stimulation threshold.

[00102] Spaced proximally from the individual electrodes along the conduit 32 there may be provided a ring electrode 34a, which may be used for bipolar pacing purposes or individual electrode interrogation purposes.

[00103] After placing the conduit 32 in the vicinity of the target area, the sheath 40 may be retracted backwards to reveal the distal end of the conduit 32, as shown by an arro in FIG. 3B directed up. This allows individual electrodes 34-39 to be released to spring outwards and away from the central axis of the lead 32 and spread radially around the lead 32. At this stage, rotating the distal end of the lead 32 allows changing the position of electrode tips if desired. Once the desired orientation and position of individual electrodes is achieved, the distal end of the lead 32 may be advanced forward to allow the tips 42 of individual electrodes to penetrate into the cardiac tissue as seen in FIG. 3C. The screw 33 may be advanced forward from the inside cavity of the conduit 32 and rotated to secure the entire assembly of individual electrodes to the cardiac tissue as shown by an arrow directed down.

[00104] Those skilled in the art will recognize that screw 33 can be shorter than 5 mm and longer than 3 mm. Also, those skilled in the art will recognize that individual electrodes 34-39 can cover the suitable target area with a diameter from about 5 mm to about 30 m. In embodiments, the diameter of the circle formed by individual electrodes may be 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm or any size in between.

[00105] Following evaluation of electrical functionality of individual electrodes (described below in greater detail), the screw 33 may be retracted and die conduit 32 may be repositioned if needed until the proper function of at least some of the individual electrodes is achieved.

[00106] In embodiments, expanding individual electrodes released by retracting of the sheath 40 may form other geometrical figures in addition to a circle, for example they may form a line of dots representing individual electrodes, a spiral of dots, and other arrangements as the invention is not limited in this regard.

[00107] The material and design of the individual electrodes may follow a convention established for these devices. A biocompatible wire with suitable mechanical properties and electrical conductivity may be used to form an individual electrode capable of being stored in a compressed state inside the sheath 40 and when released spring outwards to a desired position for subsequent implantation into the cardiac tissue.

[00108] In yet further embodiments, some or all individual electrodes may be stacked along die conduit 32 along some length thereof so as to avoid crowding of all electrodes together and occupying the entire available cross-sectional area. In this case, the ends of electrodes 41 may be made longer for those electrodes which are moved away from the distal end of the conduit 32 so as to assure a uniform height of all individual electrodes upon release thereof from the sheath 40.

[00109] While in some embodiments, all individual electrodes 34-39 may be fixedly assembled within the conduit 32, in other embodiments individual electrodes may be organized together and placed within a lumen inside the conduit 32 so as to allow one or several individual electrodes to be removed after initial interrogation is complete.

[00110] FIG. 4 presents a perspective view of a distal end of a single conduit with multiple electrodes according to the second embodiment of the present invention. Specifically, FIG 4A shows the conduit assembly in a compressed state during delivery to the heart target area. The assembly includes a spring/screw tissue attachment portion 31 inside the conduit 32, spring/screw 33 in this case located distal to a plurality of multiple pacing electrodes 34-39, and outer insulating sheath 43 with opening 41 distally. The number of individual pacing electrodes can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 electrodes. After retraction of the sheath 43, the conduit 32 is revealed, as shown by an arrow in FIG. 4B directed up, which in turn allows the electrodes 34-39 to spread radially and away from the distal tip of the conduit 32. [00111] FIG. 4C shows the step when the conduit 32 is moved closer to the spring 33. After that, the spring 33, working optionally as an additional electrode or as a ground reference electrode, may be screwed into the tissue of target area and electrodes 34-39 may be advanced to penetrate the tissue of the target area as well. After the screw' 33 enters the cardiac tissue, further manipulation (push forward and rotation) with the distal portion of the electrode wires may be used to reposition electrode tips to a more desired location.

[00112] FIG. 5 presents a perspective view of a tip of a conduit 60 with multiple electrodes according to the third embodiment of the present invention. More particularly, FIG 5A show_'s the conduit assembly during the delivery to the heart target area. The assembly includes a spring/screw tissue attachment portion 31 which may be retracted and retained inside the distal portion of the conduit sheath 51, spring/screw 33 extending from the portion 31, multiple pacing electrodes 55-58, and the outer insulating retractable sheath 43. The electrodes 55-58 may be arranged along the periphery of the conduit 60; every electrode may be placed in an individual delivery slot, e.g. electrode 55 may be located inside the slot 61, electrode 58 may be positioned inside the slot 62 and so on. Each slot may contain an exit shaped to direct each respective electrode on a trajectory diagonally outwards and away from the center of the conduit, for example using an enlargement 53 configured to deflect the electrodes as they are moved along their respective slots. In embodiments, the angle of direction for advancing each electrode diagonally outwards and away from the center may be from about 25 degrees to about 70 degrees to the central axis of the single conduit. In further embodiments, the angle of electrodes direction may be adjusted by moving the enlargement 53 either closer or further awny from the expanded distal end of the sheath 51. Adjustment of the angle may be used to control the degree of spreading of individual electrodes over the target area of cardiac tissue, which may be advantageous for achieving proper sizing of the device for various patients.

[00113] After the distal end of the conduit 60 is delivered to the target area, the screw tissue attachment portion 31 may be advanced out of the conduit 60 and exposed to the cardiac tissue as shown by an arrow in FIG. 5B. Further, the screw/spring 33 may be screwed into the cardiac tissue of target area. After that, individual electrodes 54-59 may be one by one or as a group (using a slider engaging some or all individual electrodes - not shown) advanced forward and inserted into the cardiac tissue of the target area.

[00114] One advantage of individual deployment of each electrode is that it may be positioned at various desired depths so as to adapt the generally circular pattern of electrodes to fit a particular geometry of the cardiac tissue for an individual patient. Another advantage of this design is that those individual electrodes that may not be selected for final inclusion in the cardiac pacing of the patient may be withdrawn from the single conduit so as not to be present to remain in the cardiac tissue in a passive role.

[00115] Further illustrated in Fig. 5A and Fig. 5B is an optional modification of the attachment screw' 33, which in this case includes a short straight tip 33a with a sharp distal end. The length of such straight portion 33a of the spring/screw 33 may be about 1 to 3 mm. Also shown is a preliminary confirmation ring electrode 52 placed near the distal end of the sheath 51. During the deployment procedure, either one or both the ring electrode 52 and the straight portion 33a may be used for temporary engagement with the cardiac tissue to verify positioning at or near the bundle of His. More specifically, while the entire plurality of the individual electrodes is still located in the compressed state inside the sheath 51, the spring portion 33a may be moved outward and caused to engage at the potential target area inside the heart. Alternatively, the ring electrode 52 may be located at the end of the sheath 51 and caused to engage with the cardiac tissue. Following such initial engagement at the prospective target area, the preliminary confirmation ring electrode 52 and/or the spring/screw portion 33a may be used to confirm the position of the distal end of the conduit 60 at the proper location. This can be done for example by recording a ventricular electrogram together with either a small atrial electrogram for standard pacing or no atrial electrogram for distal pacing in situations of left bundle branch block. If suitable electrical signal or capture of His bundle is not obtained, the tip may be easily- repositioned. Once the proper performance is confirmed with this preliminary engagement of the spring/screw portion 33a to“pin” the cardiac tissue, a further advancement of the spring/screw 33 deeper into the cardiac tissue may be performed without misplacing the conduit from the verified location, followed by deployment of the entire plurality of individual electrodes at the target area and removal of the sheath 51.

[00116] FIG. 6 presents a perspective view of a tip of a conduit with multiple electrodes according to the fourth embodiment of the present invention. Specifically, FIG 6A show's the conduit assembly as compressed and configured for the delivery to the heart target area. The assembly may include a conduit 65, a movable portion 64 and multiple pacing electrodes 67. At least some or all individual electrodes may contain a tissue attachment spring/screw 68 at a distal tip thereof.

[00117] After delivery the lead tip to the target area for electrode implantation, the movable portion 64 may be retracted away from the sheath 65 as shown in FIG 6B. The electrodes 67 may be configured to spring outwards and away from the center of the conduit, for example with the aid of a narrow' neck 69 and enlarged conduit extension 70. Furthermore, one, several or every electrode 67 may be delivered individually and secured to the cardiac tissue of the target area by moving it up/down and rotating thereof using individual electrode wires 63 at the proximal end of the conduit of the invention.

[00118] FIG. 7 shows a schematic diagram of a leadless implantable pacemaker 71 providing multiple electrodes. The pacemaker body 72 may be designed to cover multiple individual pacing electrodes 76 with tissue attachment springs at their respective ends/tips, wireless communicating microchip 73, programmable processing microchip 74, single source of electric power (battery) for energizing multiple electrodes 75 of the leadless pacemaker 71, electrode multiplexer 78 and a signal amplifier 79. One, some or every electrode may contain a spring/screw 77 at its tip for tissue attachment. After the delivery the pacemaker to the target area, the electrodes may be activated and advanced to penetrate the tissue of the target area. In embodiments the number of electrodes may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 electrodes. In further embodiments, the leadless pacemaker 71 may have individual electrodes arranged as individually-activated zones on a surface thereof, avoiding some or all of spring/screw altogether. Tissue attachment may be provided by the external shape of the pacemaker 71 selected to provide adequate contact with the target cardiac tissue once implanted.

[00119] After implantation of the leadless pacemaker 71 to a target area of cardiac tissue as described elsewhere in the specification, multiple individual electrodes 75 may be interrogated to determine a subset thereof meeting a predetermined acceptance criteria, after which these selected active electrodes may be operated to provide electrical stimulation of multiple chambers of the heart from a single location, using a single pacemaker with a single battery to operate multiple active electrodes 75.

[00120] In addition to providing a dedicated pacemaker to activate all electrodes of the above described embodiments of the conduit of the invention, it is contemplated that a multiplexer can be used to allow using a conventional pacemaker with the conduit of the invention. FIG. 8 shows a schematic diagram of a pacemaker of the present invention having a single lead with multiple electrodes at the distal end thereof. Idle pacemaker may comprise multiple electrodes 80 configured for implantation into cardiac tissue of the target area, a single conduit 81 for individual electrical connections with multiple electrodes 80, and a multiplexer 82 for communicating the multiple electrode connections to the standard electrical inlet/outlet connections 83 of currently available pacemakers. The multiplexer may be configured to allow connecting suitable electrodes to the pacemaker connections 83 at an appropriate time during the cardiac cycle. In one example, connectors 83 may be connected by the multiplexer 82 to the individual electrodes 80 selected for atrial pacing during the first part of the cardiac cycle. This may be used to provide a suitable P-wave stimulation to the atria of the heart. At a later portion of the cardiac cycle, the multiplexer 82 may be configured to connect other individual electrodes 80 to the connections 83, this time activating those individual electrodes 80 that are selected during the implantation procedure for stimulating the His bundle and cardiac ventricles with an electrical impulse generating a QRS complex.

[00121] In use, the single conduit of the present invention may be advanced through the blood vessels or subcutaneously towards the heart as in a conventional pacemaker implantation procedure. Once the distal end of the conduit is located in the vicinity of the target area, the outer sheath may be retracted over the conduit (or another deployment mechanism may be activated) so as to reveal multiple individual electrodes. The electrodes may be then urged to spread av ay from the center of the distal end of the conduit to assume a predetermined expanded scattered pattern.

[00122] After final positioning of the plurality of electrodes in the expanded scattered pattern over the target cardiac tissue area, the conduit may be further advanced forward and individual electrodes may be caused to be implanted into the cardiac tissue. Using the conduit of the present invention, all individual electrodes may be implanted at the same time or closely following each other - a key advantage in time savings and reduction in radiation exposure to the patient and the physician.

[00123] Individual electrodes at the proximal end of the conduit may then be connected to a pacemaker programming device - individually, in groups, or via a multiplexer. Following this implantation and electrical connection procedure, individual interrogation of each electrode or groups of electrodes may be commenced.

[00124] In embodiments, individual electrodes may be evaluated one by one or in groups following a similar approach used for evaluating single electrodes in a traditional pacemaker implantation procedure. In one example, each individual electrode may be fully characterized by applying cardiac pacing impulses at various voltages (typically in a descending pattern) in a unipolar or bipolar mode so as to determine a response from the heart. The heart response may be determined using for example an ECG signal collected internally close to the heart and/or externally using skin electrodes.

[00125] If positioned properly, an expanded scattered pattern of electrodes may cover the target area including the triangle of Koch and the bundle of His as well as surrounding atrial tissues. Collecting response signals from interrogation of each individual electrodes may produce three families of responses - that of (i) pure atrial pacing, (ii) mixed signal pacing, and (iii) pure ventricular pacing resulting from stimulation of the bundle of His. Based on collected results, all individual electrodes may be separated into those producing one of these three signal patterns and others that may or may not be useful for pacing purposes. Within these groups of individual electrodes divided into groups based on their respective recorded responses, further separation may be attempted, for example individual electrodes may be ranked based on the level of minimally effective threshold - lower threshold electrodes may be preferred for activation on a continuous basis so as to conserve the electrical energy of the pacemaker and to extend the useful life of the pacemaker battery.

[00126] Acceptance of individual electrodes for cardiac atrium pacing may be determined using a first predetermined acceptance criteria, for example appearance of a paced P-wave on the ECG tracing at the lowest stimulating voltage. Presence or absence of a paced P-wave may be determined by a person skilled in the art of reading an ECG signal. Alternatively to observing an ECG using skin electrodes, a recording of electrical activity inside the heart from one or more individual electrodes under evaluation may be used to detect whether electrical stimulation using thereof is effective, such as by recording evoked electrode potentials from the individual electrode under study. Similarly, acceptance of an individual electrode as suitable for cardiac ventricle pacing may be determined using a second predetermined acceptance criteria, for example appearance of a QRS complex on the ECG tracing at the lowest stimulating voltage or appearance of an evoked potential following the electrical stimulus on the recording form the intracardiac electrodes.

[00127] For the purposes of His bundle pacing, a QRS complex may be expected to appear on the ECG tracing following an electrical stimulus after a suitable delay due to conduction propagation time through His bundle and its branches. In addition to this delay, another expected difference of the ECG tracing with His bundle pacing as compared to a straight ventricular pacing is a different shape of the QRS complex. While ventricular paced QRS complex may appear wider and overall different from a natural QRS complex, His bundle paced QRS complex may appear much closer in shape and resemblance to a natural one. Additionally, aforementioned delay from the electrical stimulus to the QRS characteristic for His bundle capture is much shorter with ventricular-only pacing.

[00128] In embodiments, a further additional or an alternative acceptance criteria may be a confirmed selective or non-seleetive capture of the bundle of His as may be preferred for specific pacing needs of a particular patient.

[00129] Depending on the nature of cardiac arrhythmia for a particular patient defining a specific pacing need therefor, a final selection of the most useful electrodes may be conducted so as to assure a reliable stimulation arrangement for a particular patient. [00130] As an alternative to a unipolar interrogation of each individual electrode, a bipolar interrogation using an optional ring electrode or a central screw electrode may be conducted if that offers any advantage for a particular patient.

[00131] In further embodiments, individual electrodes may be paired so as to conduct interrogation of certain pairs of electrodes. In this case, if the total number of electrodes is not excessively high, all combinations of pairs of electrodes may be evaluated. If however, there is a high number of electrodes present and conducting evaluation of each possible combination of electrodes is time consuming, additional selection methods may be deployed. In one example, a subset of acceptable individual electrodes may be stratified further by each electrode first undergoing a determination of die lowest voltage threshold for its stimulating efficacy, followed by selecting of the top few electrodes that exhibit the best stimulating pattern at the lowest voltage. Following such initial selection, these top selected electrodes may be evaluated in pairs to determine their best combination suitable for stimulating purposes for a particular patient.

[00132] In case none or only a few electrodes are exhibiting satisfactory performance, the conduit may be disconnected from the cardiac tissue and moved to another location so as to implant the plurality of individual electrodes at a better site in cardiac tissue. Following a repositioning of the electrodes, another round of testing as described above may be commenced to proceed until a suitable number and combination of individual electrodes may be found to satisfy pacing needs for a patient.

[00133] In further embodiments, as opposed to fully evaluating each individual electrode by supplying a series of characterizing stimulating impulses thereto and then moving to the next individual electrode, all electrodes may be evaluated with the same initial characterizing impulse supplied to individual electrodes one at a time. Following detection of response from each individual electrode to the same initial impulse, a second impulse can be used to interrogate all electrodes followed by die third impulse, fourth impulse etc. One advantage of this technique is that the first impulse may be selected to be at a low voltage, the second impulse may be at a higher voltage, and subsequent impulses may be of yet higher predetermined voltage levels. This approach may be advantageous when increasing the voltage of the circulating impulse so as to determine when at least one or a subset of the individual electrodes start to exhibit desired stimulating efficacy and a suitable response from the heart. Once that is achieved, further interrogation may be stopped - so as to conduct evaluation of all available electrodes in a shorter period of time.

[00134] FIG. 9 shows a block diagram illustrating an exemplary sequence of steps of the method of using the cardiac pacemaker of the invention. The method may include the steps of inserting multiple pacing electrodes of the single conduit into target heart zone (triangle of Koch and bundle of His), individually testing heart pacing effectiveness of every individual electrode inserted into the target heart zone using a predetermined acceptance criteria, selecting acceptable electrodes for further use as active electrodes, abandoning and optionally removing (at least in some embodiments) rejected pacing electrodes from the heart tissue, optimizing pacing parameters such as intrinsic delays/phase shifts for ail accepted pacing electrodes, and adjusting the lead length, position and slack before connection to multiplexer of a pacemaker.

Example:

[00135] The proof of concept was achieved in the animal experiment using an open chest porcine model The prototype of a single conduit terminating with a plurality of individual electrodes was created using 6 Fr pacemaker electrode with an extendable-retractable helix spring/screw tip and 4 additional individual electrodes centered around the distal end of the conduit and electrically insulated from each other. The prototype was implanted in 4 adult animals on a beating heart through a small incision in the right atrium and then secured by a purse-string suture to minimize blood loss. The prototype single conduit was manipulated inside the heart, guided manually and assisted by straight and shaped stylets positioned in the inner lumen. Placement was further assisted by intracardiac electrogram recording. The prototype was placed into the area of the triangle of Koch and successfully secured to the endocardium via an extendable spring/screw at the tip thereof. Electrograms were recorded from all recording configurations. The presence of a ventricular electrogram was confirmed in all configurations, the presence of a bundle of His electrogram was confirmed in some configurations, and the presence of an atrial and His electrogram was also seen in some but not all of the recording configurations.

[00136] Subsequent testing demonstrated selective and nonselective His bundle capture when pacing between one of the two individual electrodes (used as a negative electrode) and the distal tip of the conduit (used as a positive electrode). Atrial capture was demonstrated between one of the four individual electrodes and the distal tip of the conduit. Furthermore, atrial capture at low output (1 V) with His bundle capture at higher output (6V) was seen between one individual electrode and the distal tip.

[00137] Additional pacing configurations in between the individual electrodes and between the individual electrodes and the ring electrode demonstrated an ability to capture different areas of die heart and variable capture thresholds. In further experiments, in addition to these observations both selective and nonselective His bundle capture was observed when pacing from different individual electrodes. [00138] Examples of a bundle of His signal recording and pacing with different chambers/tissues being captured from the same prototype electrode location are shown in Figures 10, 11, 12 and 13. After the animal sacrifice the prototype electrode fixation was confirmed by visual inspection and manual tug. The extendable-retractable spring/screw was shown to be implanted in the triangle of Koch, which effectively positioned the individual electrodes around it in an area of approximately 1 cm in diameter.

[00139] FIGURE 10 illustrates exemplary measurement of an HV interval in an animal heart. Generally, the HV interval defines the conduction time from the bundle of His to the first identifiable onset of ventricular activation. The HV interval may be measured at 34 ms, as seen in measurement 110 on the second QRS complex. Shown on tracings 100, 101, 102, 103, 104 and 105 are some of the recorded EGG leads signals, line 106 reflects intracardiac recording from an electrode that is positioned near the bundle of His. Individual positions 107 (atrial electrogram), 108 (His bundle electrogram) and 109 (ventricular electrogram) are shown with arrows.

[00140] FIGURE 11 illustrates selective exemplary stimulation of the bundle of His using individual electrodes like those shown in FIG. 5 in an animal heart. Stimulation between the individual electrodes B3-B4 was attempted. Tracing illustrates selective His bundle capture when pacing in this configuration. After stimulation was discontinued on Ai electrode, the sinus rhythm tracing shows serial activation of the atria (corresponding to a P wave on the EGG tracing) followed by ventricles (corresponding to a QRS complex on the EGG tracing). Shown as tracings Ti l, 112, 113, 114, 115, and 116 are some exemplary recordings of the EGG leads signals, tracing 117 reflects intracardiac recording between the electrodes B3-B4 that have been implanted into the triangle of Koch. Stimulus to QRS time 121 identical to the HV interval of 34 ms (see 110 in FIG.10) and narrow QRS may be used to confirm successful selective His bundle capture using the individual electrodes as described above. Retrograde conduction to the atria is seen after the complexes with His bundle capture - as indicated by arrows 118, 119 and 120. This excludes direct capture of the atria by the pacing stimulus.

[00141] FIGURE 12 illustrates activation of the ventricular myocardium by both selective and nonselective His bundle capture in the animal heart. Stimulation was conducted between the individual electrodes B2-B4. Tracings 122, 123, 124, 125, 126 and 127 are some of the EGG lead signals, while tracing 128 reflects intracardiac recording from the prototype electrode that has been implanted into the triangle of Koch (between individual electrodes B2 and B4). Both selective (first 3 QRS complexes) and nonselective His bundle capture (last 3 QRS complexes) are seen as the pacing output is decreased from 7 V to 5 V. Nonselective His bundle capture reflects some capture of the adjacent ventricular myocardium as indicated by slight slurring of the initial QRS complex shown by arrow 129. Stimulus to QRS time during the selective His capture is equal to HV interval shown in FIG. 10 - confirming His bundle capture. Retrograde conduction to the atria is seen in tracing 128 as indicated by arrow 130 (same as in Fig.11). This excludes direct capture of the atria by the pacing stimulus.

[00142] Finally, FIGURE 13 illustrates pacing of the atria by the prototype electrode implanted into the triangle of Koch of an animal heart. Prototype electrode is still fixed in the same position. Pacing is attempted between the individual electrodes B 1 and B2. Atrial capture is seen in the first 2 complexes as indicated by a much longer stimulus-to-QRS time - 137. Atrial capture by the pacing stimulus is further confirmed by the appearance of captured P waves in the first 2 complexes on tracings 130, 131, 132, 133, 134 and 135. First 2 PQRS complexes are paced, whereas the last 3 PQRS complexes are not and show native conduction. Shown on tracings 130, 131, 132, 133, 134 and 135 are the ECG leads signals, whereas tracing 136 reflects intracardiac recording between the individual electrodes B1-B2 from the prototype that has been implanted into the triangle of Koch in the same position where His bundle capture was demonstrated from other electrode pairs (FIGURES 11-12).

DETAILED DESCRIPTION OF LEADLESS PACEMAKER PREFERRED EMBODIMENTS

[00143] Shown in Fig. 14 is a prior art leadless pacemaker 210 implanted in the apex of the right ventricle using a helix screw 211, which also serves as an electrode. One or more other electrodes 212 may be used for sensing electrical activity in the right ventricle, wherein electrode 211 is used for pacing in the right ventricle or inhibiting pacing function when an intrinsic event is detected in the right ventricle within a preset time limit. To gain widespread acceptance by clinicians, it would be highly desirable for leadless pacemaker devices to have dual chamber pacing/sensing capability (VDD or DDD mode) along with other features, such as rate adaptive pacing.

[00144] The leadless pacemaker of the invention is described starting with a general cut-out view of Fig. 15 and a close-up shown in Fig. 16, showing compact AY node 201 in the right atrium (RA) converges into a transitional zone 202 broadly including the triangle of Koch 205 before continuing as the His bundle 203 at the apex 206 of the triangle of Koch 205. The His bundle 203 penetrates the membranous septum and continues as left 204 and right 204’ bundle branches on the summit of the muscular septum. Also shown are inferior vena cava 207, foramen ovale 208, superior vena cava 209, tricuspid valve annulus 219 and leaflet 215, tendon of Todaro 216, central fibrous body 217, and coronary sinus 218. [00145] According to the present invention, one general location for the leadless pacemaker 220 may be anchored in the target area of the apex of the triangle of Koch transitioning to His bundle - as seen in Fig. 17 and Fig. 18. Multiple electrically separated individual electrodes 221 may be located throughout this location and closely surrounding areas. At least two, at least three, at least four, at least five or more of individual electrodes 221 may be provided. In embodiments, any number of individual electrodes between 2 and 16 may be provided. The number of individual electrodes can be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 electrodes. Individual electrodes 221 may or may not be arranged in a linear fashion upon their placement. In embodiments, individual electrodes 221 may or may not be located along one or a few implantable leads so as a single lead contains more than one individual electrode 221 as the invention is not limited in this regard. The device of the invention may be configured to allow individual electrodes to be placed to cover at least a large two-dimensional portion or the entire 2D surface of the target area as described herein. At least some or all of the electrodes 221 may be individually positioned at desired locations at the target area independently of other individual electrodes 221.

[00146] This target area is advantageous for locating the leadless pacemaker 220 because among other reasons it allows probing, evaluation, sensing and corresponding pacing of one or more chambers of the heart from a single intra-cardiac location.

[00147] A general design for the leadless pacemaker 220 comprises electronic pacemaker controller that is substantially enclosed in a hermetic housing suitable for placement on or attachment to the inside or outside of a single cardiac chamber. The pacemaker may have a plurality of individual electrodes located on or near the housing, for delivering pacing pulses or other electrical stimuli to the muscle of the cardiac chamber and optionally for sensing electrical activity of the heart. The housing may contain a primary battery and suitable electronic circuitry to provide power and control for pacing, sensing, and communication according to programmed instructions, for example bidirectional communication (in particular by using an antenna or a telemetry coil) with at least one other device within or outside the body, such as an external programmer. The housing may optionally contain controller circuits for sensing cardiac activity from the electrodes. The housing may further optionally contain controller circuits for monitoring its own status and operational parameters. The housing may also contain circuits for controlling these operations in a predetermined manner.

[00148] Some exemplary embodiments of the controller may be configured to provide communication between the implanted leadless pacemaker pulse generator and a device internal or external to the body, with power requirements similar to those for cardiac pacing to enable optimization of battery performance. In an illustrative embodiment, an outgoing telemetry can be adapted to use no additional energy other than the energy contained in the pacing pulse, although the invention is not limited in this regard.

[00149] A power supply may be hermetically contained within the housing of the leadless pacemaker 220 and coupled to the internal pulse generator of the device controller. The power supply may supply all energy for operations and electrical pulse generation as a source internal to the housing. In the illustrative embodiment, the power supply may include a primary battery with an energy density of at least 2 watt-hours/cubic centimeter (W-h/cc).

[00150] In various embodiments, the electrodes 221 may be formed on the housing, integrally to the housing of the pacemaker 220 or may extend from the housing and coupled there while separated by a distance, for example up to 2 cm, from the housing as is typical for a screw-in electrode.

[00151] The controller may be configured to communicate with a device external to the leadless pacemaker 220, for example typically an external programmer or another implanted device, by using communication signals transmitted wirelessly. Communication is typically bidirectional although some implementations may include only one-way communication, either to or from the leadless pacemaker 220. Implantable systems of the invention may be configured to communicate to an outside device via long distance radio frequency (RF) schemes, for example, Medical Implant Communication Service (MICS) transceivers, and other RF or inductive telemetry schemes. The controller may control electrical stimuli delivery based on one or more programmable parameters and can be programmed by wirelessly transmitted communication signals.

[00152] The illustrative power supply may also be a primary battery including a beta-voltaic converter that obtains electrical energy from radioactivity. In some embodiments, the power supply can be selected as a primary battery that has a volume less than approximately 1 cubic centimeter. Yet, in further embodiments, the power supply may be a rechargeable battery, in which case an additional energy conversion element may be provided within the housing of the pacemaker to facilitate power transmission and conversion of energy in order to recharge the main battery of the device. One example of such power conversion is a device configured to convert high intensity focused ultrasound (HIFU) waves which may be supplied from an external single or a plurality of ultrasound transducers and focused on a location of the leadless pacemaker of the invention - in which case the incoming ultrasound energy may be converted by a piezoelectric transducer into electrical power suitable for recharging of a device batter_}? from time to time, such as explained for example in the US Patent No 8,649,875 incorporated herein in its entirety by reference.

[00153] In an illustrative embodiment, the primary battery may be selected to source no more than 70 microwatts instantaneously since a higher consumption may cause the voltage across the battery terminals to collapse. Accordingly, in one illustrative embodiment, the circuits of the leadless pacemaker may be designed to consume no more than a total of about 65 microwatts. The design may in some instances avoid usage of a large filtering capacitor for the power supply or other accumulators such as a supercapacitor or rechargeable secondary cell to supply peak power exceeding the maximum instantaneous power capability of the battery, components that would add volume and cost.

[00154] In various embodiments, the system can manage power consumption to draw limited power from the battery, thereby reducing device volume. Each circuit in the system can be designed to avoid large peak currents. For example, cardiac pacing can be achieved by discharging a tank capacitor (not shown) across the pacing individual electrodes 21. Recharging of the tank capacitor is typically controlled by a charge pump circuit. In a particular embodiment, the charge pump circuit may be throttled to recharge the tank capacitor at constant power from the battery.

[00155] Specific placement and subsequent usage of individual electrodes 221 may be arranged based the description provided above.

[00156] In a broad sense, a leadless cardiac pacemaker may comprise:

• a housing configured to be implanted entirely within a single heart chamber at a predetermined target area,

• a plurality of individual electrodes located on or extending from the housing, these individual electrodes may be configured for delivering electrical stimuli to a cardiac tissue at the target area, at least some of the plurality of individual electrodes may be further configured to sense electrical activity of the cardiac tissue at the target area,

• a controller hermetically sealed within the housing and which may be configured to operate in one of the following two modes of operation following implantation of the leadless cardiac pacemaker:

o an individual electrodes evaluation mode, wherein the controller may be operated to interrogate the individual electrodes to determine a subset of selected individual electrodes meeting a predetermined criteria, and

o a therapeutic mode, wherein the controller may be operated to deliver the electrical stimuli to the cardiac tissue at the target area.

[00157] As also described above, the target area of cardiac tissue may be containing triangle of Koch, bundle of His and surrounding areas, and may include a location suitable for pacing of a cardiac atrium and a location suitable for pacing of a cardiac ventricle of the heart. More than one of the plurality of individual electrodes may be positioned at the location suitable for pacing of the cardiac atrium or at the location suitable for pacing of the cardiac ventricle of the heart.

[00158] The controller of the leadless pacemaker 220 may be configured for operating in the individual electrode evaluation mode to select at least one or more individual electrodes suitable for atrial pacing and, at the same time, select at least one or more other individual electrodes suitable for ventricular pacing via delivering of electrical stimuli to His bundle.

[00159] In embodiments, to evaluate individual electrodes 221, one electrode at a time may be activated in a unipolar or bi-polar mode with various levels of pacing voltage so as to determine whether its particular location and performance is adequate for desired cardiac pacing purposes. Evaluation of all individual electrodes 221 may be conducted using one electrode at a time or pairing electrodes with each other.

[00160] Individual electrodes 221 may then be ranked as to their suitability based on one or more predetermined criteria. Examples of the predetermined criteria for selecting a subset of individual electrodes may include (i) appearance of an acceptable paced P-wave on an ECG tracing when the cardiac pacing is desired to correct an atrial arrhythmia, (ii) selective capture of the bundle of His and/or triangle of Koch, (iii) non-selective capture of the bundle of His and/or triangle of Koch, (iv) appearance of an acceptable QRS complex on an ECG tracing when the cardiac pacing is desired to correct a ventricular arrhythmia. Once the initial selection is made, an addition sub-selection of the most suitable subset of selected individual electrodes 221 may be conducted so as to determine the best individual electrodes or pairs of individual electrodes 221 suitable for subsequent pacing purposes with the lowest effective voltage thresholds.

[00161] Subject-specific cardiac stimulation may then commence using the subset of individual electrodes 221 selected based on their highest ranking. The controller may be switched to operate in the therapeutic mode, in which the controller may function to deliver electrical stimuli suitable for atrial pacing using one or a group of selected individual electrodes 221 and, at the same time, deliver other electrical stimuli suitable for ventricular pacing via stimulation of His bundle using another one or several individual electrodes 221. At least one, at least two, at least three or more individual electrodes 221 may be used for active cardiac pacing after the selection process is complete. Non-selected one or more individual electrodes 221 may be abandoned or used for sensing or other supplemental purposes. The entire electrode selection process may be repeated from time to time if the subject condition changes or for other reasons, whereby previously dormant electrodes may be re-activated and used for cardiac pacing purposes if their suitability ranking increases and exceeds other individual electrodes 221. The present invention therefore provides for a uniquely advantageous opportunity to deliver suitable individualized atrial and ventricular cardiac pacing via respective individual electrodes 221 (after their initial evaluation) from a single intra-cardiac location using a single implantable device.

[00162] In embodiments, individual electrodes 221 may be secured in place and achieve close electrical coupling to the cardiac tissue using a variety of known securement methods, including being held in close contact with the surface of the cardiac tissue, being implanted under the surface of the cardiac tissue, being fused with the cardiac tissue, or by other known methods. In embodiments, one or more electrodes may be equipped with a helical cork-screw - type distal end and configured to be turned so as to bury themselves into the layers of cardiac tissue underneath thereof. As described later, all, some, or one-at-a-time placement of individual electrodes 221 may be used prior to, during, or after the implantation of the leadless pacemaker 220 so as to achieve their placement into the target area of the heart.

[00163] In one exemplary embodiment seen in Figs. 17 and 18, the leadless pacemaker 220 may be implanted and secured in position by a fixation screw electrode 223 to connect thereof electrically to His bundle 203. For the purposes of this invention, the term“fixation screw” is used to include other similar fixation approaches such as one or more self-activated spring-loaded or shape-memory staple, claw, hook and others that generally act by clamping onto or embedding themselves into nearby cardiac tissue once released from their captive straight position.

[00164] Since the His bundle is a structure located deep within the myocardium, the positioning of the individual electrodes 221 may be optimized in three dimensions. Typically, the His bundle is reached from the atrium by mapping in the area of the triangle of Koch. Tire correct region at which the endocardium should be penetrated with the individual electrodes 221 to reach the His bundle may be identified at least on a preliminary basis by finding the spot where the largest His bundle potential is measured. The fixation screw may then be placed in this spot.

[00165] Previously published studies have revealed that both the capture threshold and the sense thresholds as well as the ability to distinguish the signal from the His bundle with the implantable electrodes may be dependent on the depth of the individual electrode in the tissue, see, for example, Deshrnukh et ah, Circulation 2000: 101; 869-877 and Laske et al., PACE 2006; 29; 397-405. With a conventional fixation screw, which has a length of the helix of approximately 1.5-2 0 mm, the helix may in some cases never reach the optimal depth. In order to reach the desired spot in close proximity to the bundle of His, a longer fixation screw may be required. This has been studied in Karpawich et. al., PACE, Part II, 1992; 15; 2011- 2015, where a helix screw having a length of 4.5 mm was used to pace His bundle. Useful examples of suitable fixation screws are found in U.S. Pat. No. 7,177,704, which describes a helically shaped electrode partially masked with an insulative material, leaving an intermediate area unmasked and electrically conductive to allow' for pacing at specific depths within the heart tissue. Another suitable fixation approach configured for operating at the His bundle location is found in U.S. Pat App. No. 20100318147.

[00166] Other individual electrodes 221 may be positioned throughout surrounding areas of triangle of Koch and may penetrate at same or different depths into the myocardium 214 at least in some locations. In embodiments, electrodes 221 may be made using electrically conductive single- or multi- strand wires or other electrical conduits. Some or all electrodes 221 may be made to have electrical insulation along a part or their entire depth. In further embodiments, some or all electrodes 221 may be made to be flexible, ranging in stiffness from flaccid to more rigid, such as for example pre-shaped and spring-like, whereby their location and shape as related to the housing of the leadless pacemaker 220 may be predetermined.

[00167] While the details of implantation techniques and methods with regard to individual embodiments will be described in greater detail below, the following is a description of a general implantation approach suitable for many of the leadless pacemaker embodiments of the present invention. Broadly speaking, the leadless pacemaker of the invention may be implanted using a surgical implantation approach or a minimally invasive implantation approach, wdiich is, of course, a preferred implantation approach to minimize trauma to the subject. Surgical approach may still be used in certain circumstances, such as when the subject’s vasculature is compromised and is not suitable for traversing therethrough of the leadless pacemaker delivery system. Another opportunity for surgical implantation may be when a heart surgery results in a need for a cardiac pacemaker at the end thereof. Surgical approach may also be used in animal experiments so as to speed up the implantation technique and assure accurate placement of the individual electrodes under direct vision guidance. When a surgical implantation technique is used, simple direct suturing or stapling of the leadless pacemaker to the exposed target cardiac tissue may be used to secure the device in place. As an alternative to suturing, a gluing operation or another fusing between the pacemaker and the cardiac tissue may be accomplished as the invention is not limited in this regard. In further embodiments, the positioning of the pacemaker under a tissue flap which may be optionally closed with a suture or a staple may also be used to secure the device in place.

[00168] Minimally invasive or percutaneous deliver_}' of the leadless pacemaker of the invention may be accomplished using conventional leadless pacemaker delivery approaches, with some modifications for specific embodiments as described later. In general, a minimally invasive or a percutaneous entry to a major blood vessel may be first established and a suitably sized catheter may be threaded towards the right atrium of the heart. While in most cases, a femoral vein approach may be used so the delivery catheter reaches the right atrium from the lower vena cava 207, upper vasculature may also be used, in this case the delivery catheter may be inserted through a left subclavian vein for example and reach the right atrium from the superior vena cava 209.

[00169] In embodiments, the distal end of the delivery catheter may be positioned over the target area as described above, followed by the deployment of the leadless pacemaker of the invention along with its individual electrodes and securement thereof in place using for example at least one securement screw, which in some cases may also be used as one of the individual electrodes of the leadless pacemaker. As an alternative to a fixation screw, some or all of the embodiments may also feature one or more shape-memory hook or claw configured to form a loop and grasp onto nearby cardiac tissue when released from their captive initially- straight configuration.

[00170] Pacemaker implantation procedure may be aided by using one or more visualization modalities such as ultrasound, X-Ray, fluoroscopy, CT, MRI, TEE or others, such as known in the field as the invention is not limited in this regard.

[00171] Evaluation of individual electrodes may be conducted following the implantation of the leadless pacemaker as described above, which in turn may be followed by selecting of the most suitable electrodes and activating the rhythm management functionality of the pacemaker.

[00172] Following initial implantation, the leadless pacemaker and its individual electrodes are expected to be encapsulated at their location over time. To facilitate retrieval and replacement, at least some embodiments of the invention may feature engagement elements such as loops extending from the main housing of the device. Once access to the device is established, these engagement features may be used to rotate the fixation screw in the direchon opposite the one used during device placement so as to retrieve the fixation screw from cardiac tissue. A retrieval system may be further used in this case to gain a minimally invasive access and secure connection to the device. Once such a connection is established, the pacemaker may be dislodged from its location and retrieved if needed.

[00173] To summarize the above description, the invention broadly describes a method for providing cardiac rhythm management therapy comprising the following steps:

a. providing a leadless cardiac pacemaker comprising a housing configured to be implanted entirely within a single heart chamber, a plurality of individual electrodes located on or extending from the housing, and a controller located within the housing and operably connected with the individual electrodes,

b. implanting the leadless cardiac pacemaker at a target area defined by triangle of Koch, His bundle and surrounding areas while positioning the individual electrodes throughout the target area,

c. evaluating each of the plurality of individual electrodes using a predetermined criteria to select at least one individual electrode suitable for atrial pacing, and at least one other individual electrode suitable for ventricular pacing via delivering of electrical stimuli to His bundle, whereby selecting a subset of the electrodes which may be smaller than the initial number of the plurality of individual electrodes, and

d. operating the controller to deliver atrial pacing and ventricular pacing via the respective subset of selected individual electrodes from a single intra-cardiac location.

Subject-specific configurations of the leadless pacemaker

[00174] Figs. 19 and 20 illustrate a further embodiment of the invention in which individual electrodes 232 and the main pacemaker housing 231 may be embedded in an elastic flexible member 230. Individual electrodes 232 may be encapsulated in the flexible member 230 in such a way that when the flexible member 230 is placed at the target implantation zone, the electrodes 232 are in close contact with the cardiac tissue, whereby assuring electrical conductance thereto from the main housing 231, see Figs. 22 and 23. Individual electrodes 232 may be positioned along the periphery or throughout the surface of the flexible member exposed to the cardiac tissue.

[00175] The flexible member 230 may be made in a general shape of a thin disk using an elastic biocompatible and biostable material such as a polyurethane, a silicone, or a mix thereof. One or more standard sizes and shapes of the flexible member 230 may be provided such as for example between 1 and 6 sizes, such as 1 size, 2 sizes, 3 sizes, 4 sizes, 5 sizes, 6 sizes or even more if necessary as the invention is not limited in this regard. Each size and shape may be selected based on a predetermined range of lengths, widths and 3D shapes of the target area for implantation of the device as described above - as recorded for a large enough number of subjects to be representative of the general population. Accurate cardiac imaging techniques may be used for this purpose as mentioned elsewhere in this specification, primarily cardiac MRI or CT imaging.

[00176] In embodiments, the flexible member 230 may have a round disk shape, an oval disk shape, a pear-shaped disk, a generally triangular shaped disk repeating the geometry of triangle of Koch and extending into His bundle, or any other suitable shape. A general length dimension may be selected to be about 20 to 40 mm long, such as 20, 25, 30, 35, 40 mm or any length in between. A general width dimension may be selected to be about 15-35 mm, such as 15, 20, 25, 30, 35 mm or any width in between. In embodiments, an exemplary shape of the flexible member 30 may be a 25x35 mm oval with a thickness ranging from about 0.5 mm to 6 mm. such as 0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm. 6 mm or any thickness in between.

[00177] Individual electrodes 232 may include flexible leads made for example from a small diameter single wire or a multi-strand wire, such wires may be encapsulated in or attached to the body of the flexible member 230, see Fig. 22. Locations of distal tips of individual electrodes 32 may be selected to assure adequate coverage of the target area of the heart despite possible small deviations of positioning the leadless pacemaker of the invention from the intended location.

[00178] One advantage of this embodiment is in the ease of implantation of the device with all individual electrodes having a predetermined and fixed position with regard to the main housing 231. Since the flexible member 230 may bend easily, a delivery system may take advantage of the folding of the periphery or“wings” of the flexible member 230 around the main housing 231 so as to position the device in its folded state inside the delivery catheter configured for minimally invasive implantation. After positioning the flexible member 230 at the target area in the heart, it may be secured to remain at the site by using a fixation screw 233 or by other suitable means, see Fig. 20.

[00179] A further advantage of this configuration is that the shape of the flexible member 230 may be adj usted and trimmed to the size and shape most suitable for an individual subject. In embodiments, the original shape of the flexible member 230 and locations of individual electrodes 232 may be selected to assure that subject- specific trimming of the outer portions of the flexible member 230 would not disturb or damage any of the individual electrodes 232. In other embodiments, however, at least some of the individual electrodes 232 may be deliberately located in areas of the flexible member 230 which may be trimmed off prior to implantation so as to allow the physician to have flexibility as to the location of remaining electrodes on the trimmed flexible member 230. This configuration may be advantageous for example in situations where cardiac rhythm management is done via excitation of groups of electrodes rather than each individual electrode one at a time.

[00180] A further yet advantage of this embodiment is that the ability to trim the device to an individual size and shape may help in reducing the number of device sizes that may be required to treat a broad range of subjects, with subsequent advantages in device procurement, logistics and stocking for a hospital.

[00181] In other embodiments, the flexible member 230 may also be made to size to match the target area geometry by (i) obtaining a detailed 3D image of the target area using any suitable imaging techniques such as MRI, CT, fluoroscopy, transesophageal echo (TEE), other ultrasound imaging, etc. and (ii) producing a custom-shaped flexible member 30 by using a custom mold or by using 3D printing techniques. In embodiments, a subject-specific flexible member 230 may be produced to incorporate some or all individual electrodes 232 and have provisions to either retain or connect to the main housing 231.

[00182] Figs. 21 and 23 show a sagittal view and a top view of a further advantageous variation of the embodiment shown in Figs 19 and 20. In this case, at least some or all of the individual electrodes 232 may be equipped with extension wires 235, extending away from the flexible member 230 towards the underlying cardiac tissue and configured to penetrate therein. Fixation screws or staples may also be used instead of some or all extension wires as seen in Fig. 23. The intent of such extension wires 235 is two-fold: (i) to improve long-term fixation of the device in place and (ii) to provide an improved electrical coupling between the leadless pacemaker of the invention and heart tissue at locations closer to the triangle of Koch and His bundle conduction pathways. In embodiments, all extensions 235 may be made of the same length, while in other embodiments, the length of individual extensions may be made different and optionally trimmable - depending on the expected location of the target conduction pathways. In embodiments, individual extension wires and/or fixation screws may be configured to penetrate the cardiac tissue to sufficient individualized depth to provide electrical connections to the controller suitable for delivering electrical stimuli to the cardiac tissue in a therapeutic mode of operation of the controller. [00183] In further embodiments, the flexible member 230 may be made both flexible as well as malleable to an extent (as defined for example by the malleable leads of individual electrodes 232 embedded therein). The malleability of the flexible member or another method to provide the flexible member 230 in a predetermined or at least preferred shape may be advantageous in assuring that all electrodes 232 are placed in good and intimate contact with the underlying cardiac tissue.

[00184] At the same time, providing the flexible member in a predefined shape may be done without jeopardizing the ability of the flexible member to wrap in a tight fashion in order to be deployed through a delivery catheter. This may be achieved for example by using flexible shape memory materials such as Nitinol wires to be encapsulated in the flexible member 230 (not shown in the drawings) and configured to define its predetermined shape. Such Nitinol wires may be provided inside the body of the flexible member 230 as a standalone plurality of wires, as a wire framework. In further embodiments, Nitinol wires may also be used as electrical conductors to the individual electrodes 232, while in alternative embodiments at least some or all of the individual electrodes may be comprising dedicated electrical conductors selected to be made in a way to only conduct electrical signals and not impact the shape of the flexible member 230.

[00185] Embodiments of the invention described starting in Fig. 19 may be delivered and deployed in place either as a single self-contained unit as mentioned before or can be modified to facilitate deployment in stages. To that end, one, some or all individual electrodes 232 may be terminated with a small electrically conductive ring or a loop 236 configured to be slidingly engaged with a corresponding individual lead 237, which in turn may be equipped with a fixation screw 238 on a distal end thereof. The lead 237 may be made to have an outer electrical insulation along most of its length other than that close to its distal end.

[00186] To implant die leadless pacemaker of the invention, a plurality of individual leads 237 may be first implanted individually through a deployment catheter 239 (or in case of an open- heart surgery, directly engaged with the cardiac tissue one by one) so as to position individual fixation screws 238 at the expected locations of the target area of the cardiac tissue. Once positioned, the other remaining component of the system, namely the flexible member 230 incorporating the main pacemaker housing 231 and individual electrodes 232 may be advanced over the remaining section of the individual leads 237 - see Fig. 24.

[00187] Fig. 25 shows a final step in the deployment of the leadless pacemaker of the invention, in which individual electrodes 237 are engaged both mechanically and electrically with corresponding individual electrodes 232 while providing a reliable fixation and electrical coupling with the target area of the cardiac tissue. Once the flexible member 230 is positioned in place, the remaining portion of the individual leads 237 may be trimmed and tied together to assure that the flexible member 230 remains in place.

[00188] A further variation of these embodiments and the steps of its deployment are shown in Figs. 26 and 27. In this case, the main rigid housing 231 is equipped with flexible electrodes 232, each terminating in an electrically conductive ring 236. There is no flexible member 230 in this configuration, although individual leads 237 are present.

[00189] In the first several steps of the implantation procedure (Fig. 26), individual leads 237 may be deployed one at a time using conventional methods - such as through the delivery sheath 239. Distal ends of the individual leads 237 may again be equipped with fixation screws 238 so as to position thereof with sufficient attachment to the cardiac tissue at the target area. Once individual leads are deployed, the main housing 231 and individual electrodes 232 may be moved into position by rings 236 sliding along the corresponding individual leads 237 - see Fig. 27. Once the main housing 231 is in position, the leads 237 may be trimmed or otherwise truncated and optionally collected together in a single spot over the main housing 231 - so as to assure its secure placement in the heart.

[00190] The main advantage of this approach is the lack of flexible member 230 making it less bulky in size and facilitating a less invasive implantation. Another advantage is that the location of each individual fixation screw 238 does not have to match precisely to the corresponding location on the flexible member 230 - so that the implantation procedure requires less precision to accomplish.

Left bundle branch configurations of the leadless pacemaker

[00191] As seen previously in Fig. 16, His bundle 203 bifurcates into a left 204 and right 204’ bundle branch as it leaves die area of the right atrium and penetrates the atrio-ventricular septum. It may be desirable for certain subjects to implant the leadless pacemaker of the invention 240 in a way to access only the left bundle branch 204, only the right bundle branch 204’ or both left and right bundle branches 204 and 204’, but not the His bundle directly. This need may arise for example in situations of a left bundle branch block, which may be accompanied by a low ejection fraction and/or ventricular dyssynchrony, possibly leading to low cardiac output.

[00192] In order to reach the bundle branches in that case, the leadless pacemaker of the invention 240 may be implanted in an alternative location, namely at the top of the right ventricle under one of the leaflets of the tricuspid valve 215 - see Fig. 28. Care needs to be taken so as to not have the pacemaker 240 interfere with the leaflets of the tricuspid valve, as can be appreciated by those knowledgeable in the art. As shown in a close-up in Fig. 29, the pacemaker 240 may be equipped with a fixation screw 243, which may be long enough and configured to reach the left bundle branch 204. Other individual electrodes are not shown in this view but may be configured to reach other areas of the conductive pathways of the triangle of Koch and His bundle and may be used for sensing and pacing operations.

[00193] A further embodiment of the invention is seen in Fig. 30. In this case, two fixation screws 243 and 244 may be provided in order to reach the corresponding left 204 and the right 204’ bundle branches if needed for clinical reasons. In alternate embodiments, a single fixation scre 243 in a left bundle branch 4 may be supplemented with one or more individual electrodes configured to reach the right bundle branch 204’ (not shown in the drawings).

Implantation approaches for die leadless pacemaker of the invention

[00194] Figs. 31 through 33 depict further details of die minimally invasive implantation approach for the leadless pacemaker 250 of the present invention. As described above, a delivery catheter 255 may be first inserted via a percutaneous or local tissue cutdown procedure into a major blood vessel and advanced to die area of the right atrium of die heart via an in ferior or a superior vena cava. The distal end of the delivery catheter 255 may then be positioned in the vicinity of the target area of the heart 257 located at the triangle of Koch or His bundle and surrounding areas. A fixation screw 253 may be first advanced to reach the target area 257. As the main housing of the leadless pacemaker 250 may be made to have an elongated shape in order to fit into a small diameter delivery catheter 255, initially the long axis of the pacemaker 250 may be aligned with the long axis of the fixation screw - see Fig. 31. This may be achieved in a variety of ways, such as:

a. the fixation screw 253 and its activation wire 252 may be placed in parallel and not interfere with the leadless pacemaker 250 while in the delivery catheter 255 and its corresponding pusher tube 251 ;

b. the fixation screw 253 may reside inside an opening in the leadless pacemaker 250 which in turn may reside inside the delivery catheter 255, in which case the pusher tube 251 may contain a lumen housing the activation wire 252 of the fixation screw 253;

c. the housing of the leadless pacemaker 250 may contain a passage sized to allow only the activation wire 252 to reside therein but not a larger diameter fixation screw 253, in which case the fixation screw 253 may be located distally in front of the leadless pacemaker 250 while inside the delivery catheter 255, or any other suitable configurations as may be understood by those skilled in the art, as the present invention is not limited in this regard.

[00195] Depending on the specific configuration of the delivery system and the interaction of the fixation screw 253 with the leadless pacemaker 250, after positioning of the distal end of the delivery catheter 255 adjacent to die target area 257, the fixation screw 253 may be first advanced towards the cardiac tissue 257 and turned to engage therewith using the activation wire 252.

[00196] Once the connection between the fixation screw 253 and the cardiac tissue is established, the leadless pacemaker 250 may be advanced distally to be positioned next to the fixation screw 253 - see Fig. 32. This may involve in some cases a quarter-turn rotation of the leadless pacemaker 250 to position its middle portion next to the fixation screw 253. Either one or both the leadless pacemaker 250 and/or the fixation screw 253 may have engagement elements to establish a secure connection therebetween once both are in their respective final positions - see Fig. 33. After achieving a proper position of both components 250 and 253, the activation wire 252, the pusher tube 251, and the delivery catheter 255 may be withdrawn.

[00197] Figs. 34 and 35 show another yet embodiment of the delivery approach, in which the delivery catheter 265 is equipped with a distal suction cup 266 configured to allow a temporary engagement of the distal end of the delivery catheter 265 with the target area tissue. In embodiments, the suction cup 266 may be made to be sufficiently flexible to allow it to be collapsed and fitted (folded or otherwise compressed) into the percutaneous access sheath at the entry point of the delivery catheter 265 into the vasculature of the subject. The edge of the suction cup 266 may be made supple enough to assure vacuum-tight engagement with the cardiac tissue, while at the same time optionally containing an expansion member to assure its opening when allowed by surrounding space. One example of a suitable expansion member may be a ring made of a shape memory wire or a shape memory polymer material (not shown in the drawings). Once the distal end of the delivery catheter 265 has passed through a smaller blood vessel and entered the vicinity of the right atrium, for example via an inferior vena cava as seen in Fig. 35, the suction cup 266 may be allowed to expand so as to position thereof over the target area for implantation of the leadless pacemaker 260.

[00198] Suction may then be applied to the interior space of the deliver_}' catheter 265, while allowing the leadless pacemaker 260 and the fixation screw 263 to be advanced forward via the pusher tube 261 or by other suitable means. Application of suction to the interior space of the delivery catheter 265 and the interior space of the suction cup 266 allow advantageously to first removably engage the delivery system with the heart tissue so as to confirm the location thereof - prior to the permanent deployment of the leadless pacemaker 260. In case the location of the delivery catheter 265 is determined to be inaccurate, the suction can be discontinued and the suction cup 266 may be repositioned until a proper location for further implantation of the device is confirmed.

[00199] A further advantage of the use of the suction cup 266 is in pulling in and retaining the target area cardiac tissue in close vicinity and in front of the fixation screw 263, which facilitates its reliable engagement with therewith. As can be appreciated by those skilled in the art, the walls of the delivery catheter 265 need to be made with a sufficient hoop strength to resist collapse upon applying a suitable level of vacuum to the interior thereof. This may be accomplished by either one or a combination of (i) incorporating a wire reinforced braided structure within the wall of the delivery catheter 65, (ii) providing ribs or other interior features to avoid collapse of the interior space, (iii) using internal members to prevent such collapse, for example, the pusher tube 261, or by other suitable design choices.

[00200] Another yet delivery approach is shown schematically in Figs. 36-38. In order to achieve the same temporary engagement of the delivery system with the target area in the heart and to verify the placement location before a permanent placement of the leadless pacemaker 270, a preliminary step of positioning a first fixation screw' 273 or a stiff straight or curved distal end 273’ may be taken. In embodiments, this reversible placement of a first fixation screw' 273 or distal end 273’ may be made in one of the following two approaches:

a. the first removable fixation screw 273 or distal end 273’ may be used as a temporary guide towards the target area and may be removed after implantation of the leadless pacemaker 270 is complete, in which case it may be positioned in ventricular tissues or elsewhere in the vicinity but yet outside the target area (not at the His bundle for example) so as not to interfere with the subsequent placement of the second and permanent fixation screw 271 for securing the leadless pacemaker 270 in place (see Figs. 36 and 37). A reversibly placed first fixation screw 273 may be delivered via a dedicated first delivery catheter of a smaller diameter - once in place, the first delivery catheter may be removed and the second delivery catheter 275 containing the leadless pacemaker 270 may be inserted using a guiding wire 277 to reach the vicinity of the first fixation screw 273; or

b. the first fixation screw is intended to remain in place and become a part of the leadless pacemaker 270 individual electrodes group, in which case it may be placed to reach His bundle or other desirable locations in the target area (see Fig. 38). Tissue engagement elements of the leadless pacemaker of the present invention

[00201] In addition to external tissue engagement components such as fixation screws and staples as described above, the present invention also contemplates incorporation of tissue fixation elements inside of the housing of the leadless pacemaker itself. This general approach may be advantageous since the tissue engagement elements may be configured for operation in two positions: (i) a collapsed position, in which none of the tissue engagement elements are protruding beyond the bounds of the housing of the leadless pacemaker; and (ii) as expanded position in which tissue engagement elements are caused to emerge from the housing of the leadless pacemaker and engage with the adjacent cardiac tissue upon moving the first housing portion closer to the second housing portion. In this case, the tissue engagement elements may be first placed in a collapsed position so that the leadless pacemaker may be advanced through the vasculature in a small diameter delivery catheter. Once in the vicinity of the target area, the tissue engagement elements may be activated to secure the device in place and provide electrical coupling to the target area of the heart.

[00202] In embodiments, conventional shape memory hooks and claws may be incorporated with the housing of the leadless pacemaker as was described above. The release of the device from the tightly surrounding tube of the delivery catheter may be used to free up these elements and allow them to expand and engage with the cardiac tissue.

[00203] Further embodiments of the tissue engagement elements are illustrated in Figs. 39-41, where the housing of the leadless pacemaker 280 may be split into a hermetically sealed first housing portion 281 and a hermetically sealed second housing portion 282. The first housing portion 281, in turn, includes a first plurality of individual electrodes 284 permanently affixed thereto and slidably residing in a second plurality of corresponding channels 285 of the second housing portion 282. In a similar fashion, the second housing portion 282 may include a second plurality of individual electrodes 287 permanently attached thereto and slidably residing in a first plurality of corresponding channels 288 of the first housing portion 281.

[00204] In further embodiments, only one of the first housing portion 281 or the second housing portion 282 may include a corresponding plurality of the individual electrodes 284 or 287 as the invention is not limited in this regard.

[00205] The leadless pacemaker 280 may have a first longitudinally expanded state (see Fig. 39) and a second compressed state (see Figs. 40 or 41). In the first state, the two housing portions 281 and 282 are extended away from each other so as to cause all of the individual electrodes 284 and 287 to reside within the bounds of the leadless pacemaker 280 and not extend beyond thereof. [00206] The first and/or the second plurality of channels 285 and 288 may be made curved so as to direct the distal sections of the individual electrodes 284 and 287 towards one side of the leadless pacemaker 280. The first housing portion 281 may also be connected to the second housing portion 282 by a flexible umbilical cable (not shown) in order to (i) provide electrical communication between both portions of the pacemaker 280 and (ii) limit the extent of travel of one housing portion relative to the other. In further embodiments, all electronic components of the leadless pacemaker 280 may be located in either the first housing portion 281 or the second housing portion 282 so there is no need for any electrical connections between thereof. In other embodiments, the length of each housing portion may be about equal to the other housing portion while in further embodiments, one of the housing portions may be made longer and contain a greater number of electronic components than the other as the invention is not limited in this regard.

[00207] Also contemplated within the scope of this invention is a removable spacer (not shown) positioned between the first and second housing portions, which may be used to prevent premature movement of the housing portions closer to each other.

[00208] Delivery of the pacemaker 280 is envisioned to start when both housing portions 281 and 282 in their extended position so as to contain all individual electrodes 284 and 287 within the internal space thereof, such as within channels 285 and 288. Tire diameter of the housing portions 281 and 282 may be made to be suitable for minimally invasive delivery via a delivery catheter as described above. The leadless pacemaker 280 is envisioned to then emerge from the distal end of the delivery catheter and located next to a target area within a heart optionally guided by any one or more of the known imaging techniques mentioned elsewhere in this description.

[00209] Once the pacemaker 280 is placed at the intended location, one or both housing portions 281 and 282 may be activated to move towards one another so as to bring the device to its collapsed position as indicated by arrows in Fig. 39. As both housing portions are advanced to be closer to each other, the individual electrodes 284 may emerge one at a time or altogether from their corresponding channels 285. As the position of the leadless pacemaker 280 may be selected to orient the openings of the second plurality of channels 285 to face the nearby cardiac tissue, emerging first plurality of electrodes may be directed by the second plurality of channels 285 to penetrate into the cardiac tissue at the target area of the heart. Similarly, the second plurality of individual electrodes 287 may be directed by their respective first plurality of channels 288 to emerge from within the first housing portion 281 and penetrate into the adjacent area of the cardiac tissue. [00210] The geometry and length of the individual electrodes 284 and 287 and their respective channels 285 and 288 may be selected to position the ends of individual electrodes within the desired depth into the target area of the heart so as to facilitate cardiac sensing and stimulation operations as described above.

[00211] To further secure the leadless pacemaker 280 at the implantation site, one, some (Fig. 40) or all (Fig. 41) distal ends of the individual electrodes 284 may be configured to form hooks or claws at the same or different depths once released from the channels 285 and 288 - in order to firmly engage with the underlying cardiac tissue.

[00212] Another yet design configured for convenient implantation and reliable attachment to die adjacent cardiac tissue is shown in Figs. 42 and 43. The leadless pacemaker 290, in this case, is made to contain a first inner channel 291 with a curved end 293 having an opening in a middle portion of the leadless pacemaker 290. An optional mechanical stop 294 may be provided near the opening of the curved end 293. A fixation screw 295 may be positioned within the first channel 291 such as to not extend beyond its bounds in the initial deployment position. The position and rotation of the fixation screw may be controlled via a releasably attached first pusher 296, configured to reside within the delivery catheter and have a sufficient length to have its external end to be outside the body of the subject during device implantation.

[00213] Also featured within the housing 290 is the second channel 298 with a similarly curved distal end containing a movable plurality of individual electrodes 297, initially residing entirely within the bounds of the housing 290. Advancement of the electrodes 297 within the second channel 298 may be controlled by a second pusher 299, which may be similarly releasably attached to the plurality of electrodes 297. The other end of the second pusher may traverse the delivery catheter in parallel with the first pusher 296 and emerge outside the body of the subject to facilitate remote activation of the individual electrodes 297. As can be appreciated by those skilled in the art, individual electrodes 297 are operably connected with the circuitry of the leadless pacemaker 290 (not shown in the drawings) so as to preserve the rhythm management functionality thereof after implantation.

[00214] Upon positioning of the leadless pacemaker 290 adjacent to the cardiac tissue in the target area such as for example at the His bundle 203, the first pusher may be activated and used to advance the fixation screw 295 around the curve 293 of the channel 291 - so as to cause the fixation screw 295 to emerge from within the pacemaker 290 and engage with the cardiac tissue 203. Advancement of the fixation screw 295 may be conducted until it is prevented from further movement by the mechanical stop 294.

[00215] In a similar fashion, the plurality of individual electrodes 297 may be advanced along the channel 298 by the second pusher 299 - so as to cause the distal ends of the individual electrodes 297 to emerge from within the pacemaker 290 and penetrate into the cardiac tissue 203 underneath thereof. The length and individual directions of the individual electrodes 297 may be selected to assure thereof reaching desired depths and width of distribution within the target area in the heart.

[00216] Once both the fixation screw 295 and the individual electrodes 297 are positioned to engage with the adjacent cardiac tissue, the first pusher 296 and the second pusher 299 may be disengaged and removed.

[00217] Another yet design of the leadless pacemaker of the present invention featuring a number of individual electrodes is shown in Fig. 44. In this case, the leadless pacemaker 300 may be secured to the underlying cardiac tissue 303 with a fixation screw 302 so as to position the pacemaker in close contact with the heart. The housing of the pacemaker 300 may be divided into individual electrically active zones 303-310, each zone may be activated individually by the electronic circuitry of the device so as to serve as an individual electrode. Such individual zones may be electrically isolated from one another so as to not cause electrical interference therebetween. One advantage of this design is that the exact location and spacing between individual zones is known in advance to sensing and pacing signals may be generated using this geometrical knowledge, which may not be well defined in at least some of the other embodiments of the present invention.

[00218] Another yet embodiment of the leadless pacemaker is seen in Fig. 45 (during deployment) and Fig. 46 (after implantation is complete). The housing 320 of the pacemaker may, in this case, be made to be elongated and capable of folding in its central portion. For example, the housing 320 may be made using a flexible biocompatible polymer such as silicone or polyurethane with embedded electronic components such as a battery, central processor chip etc. which may be connected to flexible circuits. The housing 320 may also feature sharp protrusions 324 configured for penetrating under the surface of the cardiac tissue upon implantation thereof.

[00219] During deployment, the leadless pacemaker 320 may be first folded and placed inside the delivery catheter 326, see Fig. 45. A pusher 328 may be used to advance the pacemaker 320 forward and activate the fixation screw 322. Once the pacemaker 320 emerges from the distal end of the delivery catheter 326, the housing 320 is allowed to extend into a straight configuration and the fixation screw 322 may be used to secure it in place at the target area. The pacemaker 320 may also be made with a malleable housing which can be pre-shaped into a preferred shape configuration based on anatomical features specific to a particular subject. Adapter for using a conventional pacemaker

[00220] In yet more embodiments of the invention, the novel leadless pacemaker may be configured to utilize an existing pacemaker, which may be already in use by the subject as a source of stimulation signals, while providing additional components to conduct this stimulation at the target area of the heart. Generally speaking, the invention describes an adapter for delivering rhythm management electrical stimuli to multiple heart chambers from a conventional cardiac pacemaker, the adapter comprising:

• a housing configured to be implanted entirely within a single heart chamber at a predetermined target area, the housing configured to operably connect to the conventional or leadless cardiac pacemaker,

• a plurality of individual electrodes located on or extending from the housing and configured for delivering electrical stimuli to a cardiac tissue at the target area, at least some of the plurality of individual electrodes may be further configured to sense electrical activity of the cardiac tissue at the target area,

• an electronic switch hermetically sealed within the housing and configured to deliver atrium pacing stimuli from the conventional cardiac pacemaker to at least one of the individual electrodes selected for atrial pacing, the electronic switch may be further configured to deliver ventricular pacing stimuli from the conventional cardiac pacemaker to at least one other of the individual electrodes selected for ventricular pacing via stimulation of His bundle, whereby the adapter is configured for delivering rhythm management therapy to multiple heart chambers from a single intra-cardiac location.

[00221] In a broad sense, an existing new or already used before pacemaker (conventional or leadless) in combination with novel components described below may form a new rhythm management system of the invention. Schematically shown in Fig. 47, this arrangement may include a conventional pacemaker 355 operably connected wirelessly or via a conduit 356 to a comprehensive electronic switch 350, which in turn may be operably connected to a plurality of individual electrodes 352, located at the target area in the heart such as triangle of Koch and His bundle.

[00222] The electronic switch 350 may be located near individual electrodes 352 and may itself be enclosed in a housing similar to that described above for other embodiments of the invention. Hie electronic switch may include its own dedicated power supply such as a primary battery, remotely controlled operational circuitry and other components of the previously described system, with the exception of the circuitry to sense heart activity or to generate pacing stimulus signals, which in this case may be provided by a conventional pacemaker 355. In certain embodiments, the electronic switch 350 may be contained in a housing which itself is configured to accept the pacemaker 355 docked inside thereof as can be seen in certain drawings described below in more detail. Tire housing of the switch 350 and the pacemaker 355 may, in this case, be implanted at the target area in the heart to provide direct leadless stimulation at the triangle of Koch, His bundle and surrounding areas via its selected multiple individual electrodes 352.

[00223] Following implantation of the system and positioning of the individual electrodes 352 throughout the target area in the heart, the electronic switch may be activated and together with die pacemaker 355 operated to evaluate individual electrodes 352 for their suitability as sensing and/or pacing leads for a particular subject. Once the most suitable electrodes are identified, the electronic switch 350 may be remotely operated to connect the selected individual electrodes 352 to the pacemaker 355 for subsequent operation as set by the operator. The electronic switch 350 may also be operated again from time to time to adjust the selection of the most suitable individual electrodes 352 if the circumstances change and such adjustment is needed.

[00224] The advantage of this hybrid configuration is in use of conventional and time-proven cardiac pacemaker technology, which in this case does not have to be proven out via large, long term clinical studies. While the functionality of the electronic switch 350 is a novel element requiring proper verification, the overall technical risk and expense associated with its development may be lower than when developing a brand new cardiac rhythm management system. Therefore, this configuration may be in some cases more attractive as an initial configuration to prove out the concepts behind this invention.

[00225] Another advantageous configuration of this embodiment is when the electronic switch 350 is located outside the body of the subject and is connected to individual electrodes 352 by an extended flexible conduit. This is preferred for example when conducting animal tests so that a conventional pacemaker 355 may be easily switched to sense and/or deliver pacing pulses to a variety of individual electrodes during the course of such experiment.

[00226] The approach of repurposing the conventional pacemaker into the pacemaker of the present invention is even more advantageous when used with conventional leadless pacemakers. In this case, the entire system including a conventional pacemaker together with a miniaturized electronic switch may be implanted in the vicinity of the target area to provide the subject with a leadless rhythm management therapy which may not be achieved with a conventional leadless pacemaker alone. This concept of repurposing a conventional pacemaker may also allow providing more physiologic stimulation of the His bundle in subjects with atrial fibrillation who do not require atrial pacing and sensing but will benefit hemodynamically from His pacing rather than RV apical pacing. This allows making the existing leadless pacemaker instantaneously more physiologic. Furthermore, the same approach may also be used to pace the Left Bundle Branch (LBB) in subjects with atrial fibrillation, LBB block and cardiomyopathy who also do not require atrial pacing. The existing leadless pacemaker may, in this case, be implanted with the adapter of the invention into LBB and provide cardiac resynchronization therapy.

[00227] Fig. 48 shows a schematic diagram of such arrangement in which the housing 360 may be configured to retain therein or mechanically attach to a conventional leadless pacemaker 362, which may be configured to operably connect to the electronic switch 364, powered by its own dedicated power supply 366 so that together with the pacemaker 362 they can produce a system of sensing and stimulation signals that can be passed through circuitry 368 onto corresponding selected electrodes 369.

[00228] In an exemplary embodiment shown in Fig. 49, a generally cylindrical housing 360 may feature a retaining notch 361 configured to snugly fit over the conventional leadless pacemaker 362 and retain thereof inside the housing 360. The notch 361 in certain embodiments may also provide an electrical connection between the pacemaker 362 and the housing 360. The active electrode 363 of the pacemaker 362 may be retained and operatively connected to the receptacle 365 so that both anode and cathode electrodes of the leadless pacemaker 362 are placed in operable connection with the circuitry 368, which in turn is operably connected to the plurality of individual electrodes 369.

[00229] In embodiments, the arrangement described above may have sufficient power reserve for both the pacemaker 362 and separately for the electronic switch 368 to provide cardiac rhythm management therapy for sufficient period of time. At the same time, this arrangement may be advantageously used to replace at least some components of the system in case of a power failure or some other malfunction. To achieve this, the pacemaker 362 may be equipped with the engagement and retrieval loop 367, which can be used to disconnect the pacemaker 362 from the housing 360 and replace it with a new pacemaker 362.

[00230] Finally, as an alternative to an electronic switch of the previous embodiments, a mechanical selector may be used to select the configuration of individual electrodes for use in a cardiac rhythm management therapy. This embodiment is seen in Fig. 50. In this case, the adapter 376 with a multitude of individual electrodes may be first implanted at the target area of the heart. Wired or optionally wireless communication may be used to interrogate individual electrodes of the adapter 376 and select the preferred group of electrodes for use in the delivery of the rhythm management therapy. The leadless pacemaker 370 may have a selector switch 374 that can rotate about its housing so as to configure the pacemaker 370 for operating selected electrodes of the adapter 376. Turning the selector ring 374 to the right position may be followed by implantation of the pacemaker 370 and operatively docking it with the adapter 376 by- inserting it into the opening 378 such that the key 372 fits inside the groove 379 - to assure the proper orientation of the pacemaker 370 inside the adapter 376.

[00231] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method of the invention, and vice versa. It will be also understood that particular embodiments described herein are shown by way of illustration and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims.

[00232] All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[00233] The use of the word“a” or“an” when used in conjunction with the term“comprising” in the claims and/or the specification may mean“one,” but it is also consistent with the meaning of“one or more,”“at least one,” and“one or more than one.” The use of the term“or” in the claims is used to mean“and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and“and/or.” Throughout this application, the term“about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.

[00234] As used in this specification and claim(s), the words“comprising” (and any form of comprising, such as“comprise” and“comprises”),“having” (and any form of having, such as “have” and“has”),“including” (and any form of including, such as“includes” and“include”) or “containing” (and any form of containing, such as“contains” and“contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. In embodiments of any of the compositions and methods provided herein,“comprising” may be replaced with “consisting essentially of’ or“consisting of’. As used herein, the phrase“consisting essentially of’ requires the specified integer(s) or steps as well as those that do not materially affect the character or function of the claimed invention. As used herein, the term“consisting” is used to indicate the presence of the recited integer (e.g., a feature, an element, a characteristic, a property, a method/process step or a limitation) or group of integers (e.g., feature(s), element(s), characteristic(s), propertie(s), method/process steps or limitation(s)) only.

[00235] The term“or combinations thereof’ as used herein refers to all permutations and combinations of the listed items preceding the term. For example,“A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CAB ABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.

[00236] As used herein, words of approximation such as, without limitation, “about”, "substantial" or "substantially" refers to a condition that when so modified is understood to not necessarily be absolute or perfect but would be considered close enough to those of ordinary skill in the art to warrant designating the condition as being present. The extent to which the description may vary will depend on how great a change can be instituted and still have one of ordinary skilled in the art recognize the modified feature as still having the required characteristics and capabilities of the unmodified feature. In general, but subject to the preceding discussion, a numerical value herein that is modified by a word of approximation such as “about” may vary from the stated value by at least ±1, 2, 3, 4, 5, 6, 7, 10, 12, 15, 20 or 25%.

[00237] All of the devices and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the devices and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the devices and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A method of cardiac pacing of multiple chambers of a heart from a single location, the improvement in said method comprising the steps of:

a. deploying a plurality of individual electrodes (34-39, 54-59, 67) in an expanded

scattered pattern to a target area of cardiac tissue containing triangle of Koch, bundle of His and surrounding areas, said target area including a location suitable for pacing of a cardiac atrium and a location suitable for pacing of a cardiac ventricle of the heart, more than one of said plurality of individual electrodes (34- 39, 54-59, 67) to be positioned at said location suitable for pacing of the cardiac atrium or at said location suitable for pacing of the cardiac ventricle of the heart, said plurality of individual electrodes (34-39, 54-59, 67) are located at a distal end of a single conduit (16, 32, 60, 81) extending outside the heart, said plurality of individual electrodes (34-39, 54-59, 67) are connected to respective individual wires (63) contained within and positioned alongside each other at least in a portion of said single conduit (16, 32, 60, 81),

b.evaluating each individual electrode (34-39, 54-59, 67) positioned at said location for pacing of the cardiac atrium to select at least one electrode (34-39, 54-59, 67) capable of capturing and pacing of a said cardiac atrium,

c. evaluating each individual electrode (34-39, 54-59, 67) positioned at said location for pacing of the cardiac ventricle to select at least one electrode (34-39, 54-59, 67) capable of capturing and pacing of said cardiac ventricle via stimulation of said bundle of His,

d.connecting via said single conduit (16, 32, 60, 81) a selected subset of said plurality of individual electrodes (34-39, 54-59, 67) including said at least one electrode suitable for pacing of said cardiac atrium and said at least one electrode suitable for pacing of said cardiac ventricle to a pacemaker loca ed outside the heart, and

e. initiate cardiac capture and pacing of multiple chambers of the heart by operating said pacemaker to deliver pacing stimuli via said selected subset of individual electrodes.

2. The method as in claim 2, wherein said selecting in step (b) of said at least one electrode (34-39, 54-59, 67) suitable for pacing of the cardiac atrium is conducted using a first predetermined acceptance criteria or said selecting in step (c) of said at least one electrode (34-39, 54-59, 67) suitable for pacing of the cardiac ventricle is conducted using a second predetermined acceptance criteria, wherein said first predetermined acceptance criteria or said second predetermined acceptance criteria is a confirmed selective or nonselective capture of the bundle of His.

3. The method as in claim 1, wherein said step (a) further including providing said single conduit (16, 32, 60, 81) extending from a proximal end outside the heart to a distal end inside the heart, said plurality of said individual electrodes (34-39, 54-59, 67) located at the distal end of said single conduit (16, 32, 60, 81) prior to deployment step (a) in a collapsed position next to a center of said distal end and following step (a) in an expanded position forming said expanded scattered pattern of said individual electrodes (34-39, 54-

59, 67) about and away from said center of said distal end of said single conduit (16, 32,

60, 81).

4. The method as in claim 1, wherein said single conduit (16, 32, 60, 81) in said step (a) further comprising an outer sheath (40, 43) slidably positioned about said single conduit (16, 32, 60, 81), wherein each of said individual electrodes (34-39, 54-59, 67) at a distal end is formed as a Z-shaped wire configured to compress from an open position to a compressed spring-loaded collapsed position when surrounded by said outer sheath (40, 43), said open position is characterized by said individual electrodes (34-39, 54-59, 67) forming said expanded scattered pattern along with other individual electrodes (34-39, 54- 59, 67), said collapsed position is characterized by said electrodes (34-39, 54-59, 67) being in a collapsed position near the center of the distal end of said single conduit (16, 32, 60, 81).

5. Hie method as in claim 1, wherein said single conduit (16, 32, 60, 81) in said step (a) further comprising a tissue attachment spring/screw (33) configured to secure the distal end of said conduit (16, 32, 60, 81) along with said plurality of individual electrodes (34-39, 54- 59, 67) after implantation into said cardiac tissue.

6. The method as in claim 1, wherein said single conduit (16, 32, 60, 81) in said step (a) further comprising a ring electrode (34a) located on the distal end thereof and spaced apart from said plurality of individual electrodes (34-39, 54-59, 67), said ring electrode (34a) configured for use as a positive electrode with any of the individual electrodes of said plurality of individual electrodes (34-39, 54-59, 67).

7. The method as in claim 1, wherein a distal end of at least some of said individual electrodes (34-39, 54-59, 67) of said single conduit (16, 32, 60, 81) in said step (a) contains a tissue attachment spring/screw (68, 77), said corresponding individual electrode is configured for individual rotation using said individual wire attached thereto, whereby rotation of said individual wire causing said individual electrode to be secured in said cardiac tissue.

8. The method as in claim 1, wherein in said step (a) each of said individual electrical wire of said single conduit is slidably located in a corresponding slot (61, 62) provided inside said single conduit (16, 32, 60, 81), said slot (61, 62) contains an exit at the distal end of said single conduit (16, 32, 60, 81) shaped to direct said individual electrode (34-39, 54-59, 67) diagonally outward and away from a center of said distal end, whereby advancement of said individual electrodes (34-39, 54-59, 67) using said corresponding individual wires causes expansion of said individual electrodes away from said center and forming said expanded scattered pattern.

9. The method as in claim 8, wherein in said step (a) said shaped exit of said individual slot is formed using an enlargement in said single conduit (16, 32, 60, 81) positioned distally from said individual electrodes (34-39, 54-59, 67) prior to deployment in step (a) and shaped to deflect thereof along a predetermined trajectory diagonally outward and away from said center during said deployment in step (a).

10. The method as in claim 2, wherein said step of selecting in step (b) or selecting in step (c) of said subset of individual electrodes (34-39, 54-59, 67) is further stratified based on a lowest voltage while performing step (b) or step (c).

11. The method as in claim 1, wherein remaining non-selected individual electrodes of said plurality of individual electrodes (34-39, 54-59, 67) in step (d) are left in a passive state after being implanted in said cardiac tissue.

12. The method as in claim 11 further comprising a step of re-activation of said remaining non- selected individual electrodes when a malfunction of the previously selected electrodes is detected, whereby avoiding a need to implant further individual electrodes.