Patent Description:
Cardiac pacing by an artificial pacemaker provides an electrical stimulation of the heart when its own natural pacemaker and/or conduction system fails to provide synchronized atrial and ventricular contractions at rates and intervals sufficient for a patient's health. Such antibradycardial pacing provides relief from symptoms and even life support for hundreds of thousands of patients. Cardiac pacing may also provide electrical overdrive stimulation to suppress or convert tachyarrhythmias, again supplying relief from symptoms and preventing or terminating arrhythmias that could lead to sudden cardiac death.

Cardiac pacing by currently available or conventional pacemakers is usually performed by a pulse generator implanted subcutaneously or sub-muscularly in or near a patient's pectoral region. The pulse generator usually connects to the proximal end of one or more implanted leads through a feedthrough assembly, which creates an isolated electrical pass-through into a hermetic case for pulse/sense transmissions to a target tissue. The feedthrough assembly can be used in low voltage or high voltage applications. A distal end of the implanted leads, which typically have lengths of <NUM> to <NUM> centimeters, contains one or more electrodes for positioning adjacent to the inside or outside wall of a cardiac chamber. The leads have an insulated electrical conductor or conductors for connecting the pulse generator to the electrodes in the heart. Accordingly, the pulse generator can deliver a pacing pulse from within a hermetically sealed housing through the feedthrough assembly, the lead, and the electrode to the target tissue.

Conventional pacemakers have several drawbacks, including a risk of lead or feedthrough assembly breakage, complex connections between the leads and the feedthrough assembly, and a risk of infection and morbidity due to the separate leads and pulse generator components. Many of the issues associated with conventional pacemakers are resolved by the development of a self-contained and self-sustainable biostimulator, or so-called leadless biostimulator. The leadless biostimulator can be attached to tissue within a dynamic environment, e.g., within a chamber of a beating heart, to deliver pacing pulses directly to the tissue without the use of leads.

<CIT> discloses an implantable medical device with a housing. A first ID tag is secured relative to the housing at a first position and defines a first radiopaque manufacturer code section that visually identifies a manufacturer of the implantable medical device. A second ID tag is secured relative to the housing at a second position that is offset from the first position in at least one dimension. The second ID tag defines a second radiopaque manufacturer code section that also visually identifies the manufacturer of the implantable medical device.

<CIT> discloses a biostimulator, such as a leadless cardiac pacemaker, including coaxial fixation elements to engage or electrically stimulate tissue. The coaxial fixation elements include an outer fixation element extending along a longitudinal axis and an inner fixation element radially inward from the outer fixation element. One or more of the fixation elements are helical fixation elements that can be screwed into tissue. The outer fixation element has a distal tip that is distal to a distal tip of the inner fixation element, and an axial stiffness of the outer fixation element is lower than an axial stiffness of the inner fixation element. The relative stiffnesses are based on one or more of material or geometric characteristics of the respective fixation elements.

<CIT> discloses a biostimulator, such as a leadless cardiac pacemaker, including an electrical feedthrough assembly mounted on a housing. An electronics compartment of the housing can contain an electronics assembly to generate a pacing impulse, and the electrical feedthrough assembly can include an electrode tip to deliver the pacing impulse to a target tissue. A monolithically formed electrode body can have a pin integrated with a cup. The pin can be electrically connected to the electronics assembly, and the cup can be electrically connected to the electrode tip. Accordingly, the biostimulator can transmit the pacing impulse through the monolithic pin and cup to the target tissue. The cup can hold a filler having a therapeutic agent for delivery to the target tissue and may include retention elements for maintaining the filler at a predetermined location within the cup.

Existing leadless biostimulators have a hermetically sealed device package containing internal components to generate and receive electrical pulses through an electrode of a header assembly. The electrode can include an enclosed cup containing a therapeutic agent. The cup may be capped, and the therapeutic agent can elute through a hole in the cap of the cup toward a target tissue when the leadless biostimulator is implanted. The capped cup provides a relatively large surface area that may inconsistently contact the target tissue, and thus, may provide inconsistent impedance and electrical pulse control. Furthermore, the small hole in the cap may restrict transport of fluid into the cup or become clogged, and thus, may restrict the elution of therapeutic agent-laden fluid out of the cup. Accordingly, there is a need for a header assembly having greater control over electrode impedance and therapeutic agent release.

The present invention provides a header assembly for a leadless biostimulator as defined in claim <NUM> and a method of manufacturing a leadless biostimulator as defined in claim <NUM>. The dependent claims define embodiments of the present invention.

The present disclosure relates to a leadless biostimulator including a header assembly for controlled delivery of therapeutic agent around an electrode to a target tissue. Methods of manufacturing the header assembly are also described. The header assembly includes a flange having a flange channel extending along a longitudinal axis. An insulator can be disposed in the flange channel, and can include an insulator cavity. The header assembly can include an electrode that extends longitudinally through the insulator cavity. A space can be formed between the insulator and the electrode. A monolithic controlled release device (MCRD) is disposed in the insulator cavity such that therapeutic agent elutes from the MCRD into the space when the leadless biostimulator is implanted in blood. The header assembly can include a helical fixation element to affix the biostimulator to a target tissue site. Accordingly, the therapeutic agent can be delivered to the target tissue site upon implantation.

The MCRD can have an annular body. For example, the annular body can be tubular, and can be disposed within the insulator cavity such that a central lumen of the tubular body is aligned with the longitudinal axis of the flange. Accordingly, an electrode pin of the electrode can extend longitudinally through the central lumen. An electrode tip is mounted on a distal end of the electrode pin. Alternatively, an electrode helix may be mounted on the distal end of the electrode pin. The electrode tip and/or electrode helix can be disposed within a helix mount channel of a helix mount that supports the helical fixation element. Furthermore, the electrode tip and/or electrode helix can deliver pacing impulses from the electrode to the target tissue. Accordingly, the therapeutic agent can elute from the MCRD and be delivered between the helix mount and the distal end of the electrode pin to the target tissue at the pacing site.

A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings.

The present disclosure relates to a leadless biostimulator, e.g., a leadless cardiac pacemaker, having a header assembly that includes a monolithic controlled release device (MCRD) to elute therapeutic agent around an electrode. The leadless biostimulator may be used to pace cardiac tissue, e.g., in the ventricles or the atria of a heart. The leadless biostimulator may be used in other applications, however, such as deep brain stimulation. Thus, reference to the leadless biostimulator as being a cardiac pacemaker is not limiting.

The use of relative terms throughout the description may denote a relative position or direction. For example, "distal" may indicate a first direction along a longitudinal axis of a leadless biostimulator. Similarly, "proximal" may indicate a second direction opposite to the first direction. Such terms are provided to establish relative frames of reference, however, and are not intended to limit the use or orientation of a leadless biostimulator to a specific configuration described in the various examples below.

In an aspect, a leadless biostimulator includes a header assembly having an electrode extending longitudinally through an insulator cavity of an insulator. A MCRD containing a therapeutic agent can be located within the insulator cavity. For example, the MCRD can be retained within the insulator cavity by a distal tip of the electrode or via a press fit between the MCRD and an electrode helix of the electrode. The retained MCRD can therefore elute the therapeutic agent into the insulator cavity toward a target tissue when the leadless biostimulator is implanted in blood. For example, the therapeutic agent can elute through a space between the insulator and the electrode, and around the electrode through a channel of a helix mount to a surrounding environment. The channel of the helix mount can have sufficient cross-sectional area, e.g., an annular cross-sectional area, to permit blood and therapeutic agent to be exchanged between the MCRD and the surrounding environment. Accordingly, the header assembly described below can provide controlled therapeutic agent release.

In an aspect, the electrode of the header assembly includes an electrode pin to carry pacing pulses distally toward the target tissue. Furthermore, the electrode can have a distal tip that includes a small distal surface area that can securely engage the target tissue. For example, the distal tip can be a cap mounted on a distal end of the electrode pin, or an electrode helix that can be screwed into the target tissue. The electrode can therefore provide consistent and stable surface area contact between the electrode and the target tissue. Accordingly, the header assembly described below can provide controlled impedance and pacing.

Referring to <FIG>, a perspective view of a leadless biostimulator. A biostimulator <NUM> can be a leadless biostimulator, e.g., a leadless cardiac pacemaker used to deliver pacing impulses to the atria or ventricles of a heart. The biostimulator <NUM> can include a housing <NUM> having electrodes. For example, the biostimulator <NUM> includes each of a distal electrode <NUM> and a proximal electrode <NUM> disposed on or integrated into the housing <NUM>. The distal electrode <NUM> and the proximal electrode <NUM> can be used to sense and pace the heart. The electrodes <NUM>, <NUM> can be integral to the housing <NUM> or connected to the housing <NUM>, e.g., at a distance of less than several centimeters from the housing.

In an example, the housing <NUM> contains an energy source (not shown) to provide power to the pacing electrodes <NUM>, <NUM>. For example, the energy source can create a potential difference between a cathode, e.g., the distal electrode <NUM>, and an anode, e.g., the proximal electrode <NUM>, of the device. The energy source can be, for example, a battery, such as a lithium carbon monofluoride (CFx) cell, or a hybrid battery, such as a combined CFx and silver vanadium oxide (SVO/CFx) mixed-chemistry cell. Similarly, the energy source can be an ultracapacitor. In one implementation, the energy source can be an energy harvesting device, such as a piezoelectric device that converts mechanical strain into electrical current or voltage. The energy source can also be an ultrasound transmitter that uses ultrasound technology to transfer energy from an ultrasound subcutaneous pulse generator to a receiver-electrode implanted on an endocardial wall.

The housing <NUM> can have a longitudinal axis <NUM>, which may be an axis of symmetry along which several other biostimulator components are disposed. For example, a header assembly <NUM> can be mounted on a distal end of the housing <NUM> along the longitudinal axis <NUM>. The header assembly <NUM> can include an electrical feedthrough assembly, incorporating a flange <NUM>, a helix mount <NUM>, and a helical fixation element <NUM> mounted on the helix mount <NUM>. The assembled components of the header assembly <NUM>, which are described further below, can provide a distal region of the biostimulator <NUM> that attaches to the target tissue, e.g., via engagement of the fixation element <NUM> with the target tissue. The distal region can deliver a pacing impulse to the target tissue, e.g., via the distal electrode <NUM> that is held against the target tissue, when the leadless biostimulator <NUM> is implanted in a surrounding environment <NUM>, e.g., blood within an atrium or ventricle.

The housing <NUM> can have an electronics compartment <NUM> (shown by hidden lines). More particularly, the electronics compartment <NUM> can be a cavity laterally surrounded by a housing wall, e.g., a cylindrical wall, extending around the longitudinal axis <NUM>. The housing wall can include a conductive, biocompatible, inert, and anodically safe material such as titanium, <NUM> stainless steel, or other similar materials, to laterally enclose the electronics compartment <NUM>. More particularly, the electronics compartment <NUM> can be enclosed between the energy source of the biostimulator <NUM> (that is within a proximal portion of the housing <NUM>) and the header assembly <NUM> (that is at the distal portion of the biostimulator <NUM>). The energy source container can proximally enclose the electronics compartment <NUM> and the header assembly <NUM> can distally enclose the electronics compartment <NUM>. The header assembly <NUM>, the housing wall, and the energy source container can surround a volume of the electronics compartment <NUM>.

In one implementation, the electronics compartment <NUM> contains an electronics assembly <NUM> (shown by hidden lines). The electronics assembly <NUM> can be mounted in the electronics compartment <NUM>. For example, the electronics assembly <NUM> can include, without limitation, a flexible circuit or a printed circuit board having electrical connectors that connect to electrical pins of the header assembly <NUM> and the energy source. As described below, the header assembly <NUM> can include an electrode that connects to an electrical connector (e.g., a socket connector) of the electronics assembly <NUM> within the electronics compartment <NUM> to transmit pacing and sensing signals to and from the target tissue. The electronics assembly <NUM> has one or more electronic components mounted on a substrate. For example, the electronics assembly <NUM> can include one or more processors, capacitors, etc., interconnected by electrical traces, vias, or other electrical connectors. The electronics components can be configured to perform sensing and pacing of the target tissue.

The biostimulator components, e.g., the energy source container, the electronics compartment <NUM> containing the electronics assembly <NUM>, and the header assembly <NUM>, can be arranged on the longitudinal axis <NUM>. Accordingly, each component can extend along the longitudinal axis <NUM> and have a respective axial location relative to another component along the longitudinal axis <NUM>. For example, the energy source container can be offset from the electronics compartment <NUM> in a proximal direction <NUM> and the header assembly <NUM> can be offset from the electronics compartment <NUM> in a distal direction <NUM>.

Referring to <FIG>, a perspective view of a header assembly having controlled therapeutic agent release is shown. The header assembly <NUM> can perform several functions. First, the header assembly <NUM> provides for fixation of the leadless biostimulator <NUM> to the target tissue via the helical fixation element <NUM> mounted on the helix mount <NUM>. The fixation element can be screwed into the target tissue to retain the leadless biostimulator <NUM> with the distal electrode <NUM> in contact with the target tissue. Second, the header assembly <NUM> provides the electrical feedthrough from the electronics compartment <NUM> to the surrounding environment <NUM> to allow for sensing and pacing of the target tissue. More particularly, the electrical feedthrough assembly of the header assembly <NUM> can transmit electrical pulses through the distal electrode <NUM> to the target tissue. Third, the header assembly <NUM> contains a therapeutic agent between the helix mount <NUM> and the flange <NUM> that can elute outward to the target tissue when the leadless biostimulator <NUM> is implanted in the surrounding environment <NUM>. More particularly, fluid, e.g., blood, from the surrounding environment <NUM> can flow inward through a gap <NUM> between the distal electrode <NUM> and the helix mount <NUM> to a space contained axially between the helix mount <NUM> and the flange <NUM>, and agent-laden fluid can then flow outward through the gap <NUM> toward the target tissue.

Referring to <FIG>, a sectional view of a header assembly having a monolithic controlled release device (MCRD) between an insulator and electrode is shown. In certain implementations, each of the components of the header assembly <NUM> may be symmetrically formed about the longitudinal axis <NUM>. For example, the cross-sectional area of the flange <NUM> illustrated in <FIG> can be swept about the longitudinal axis <NUM> such that the outer surface has a profile as shown in <FIG>. In other implementations, the profiles of the components of the header assembly <NUM> may be non-cylindrical. For example, a cross-section of the flange <NUM> taken about a transverse plane extending orthogonal to the longitudinal axis <NUM> may reveal an outer surface of the flange <NUM> that is square, pentagonal, elliptical, etc., or any other suitable shape. Accordingly, the particular shapes illustrated in the figures are provided by way of example only and not necessarily by way of limitation.

The flange <NUM> can be mounted on the housing <NUM> (<FIG>). For example, a proximal flange end <NUM>, e.g., a lip, may be mounted on a distal end of the housing wall that surrounds the electronics compartment <NUM>. The flange <NUM> can be connected to the housing <NUM> by a hermetic seal, e.g., a weld or any other similar hermetically sealed connection. For example, the hermetic weld can be formed circumferentially around a seam between the proximal flange end <NUM> and the distal end of the housing wall.

In an example, the flange <NUM> includes a shoulder <NUM>. The flange <NUM> can have a flange wall extending distally from the proximal flange end <NUM> to the shoulder <NUM>. The shoulder <NUM> can be a transition region between the flange wall that extends substantially longitudinally, from the proximal flange end <NUM>, to the flange wall that extends substantially transversely. In an example, the shoulder <NUM> has a distal shoulder surface that extends substantially transversely, and thus, the distal shoulder surface can extend transverse to the longitudinal axis <NUM>. Accordingly, the distal shoulder surface can face the distal direction <NUM>. The distal shoulder surface extends radially inward toward a flange connector <NUM>. The flange connector <NUM> can extend distally from the distal shoulder surface, and may receive the helix mount <NUM>. For example, the flange connector <NUM> can have an external thread that couples to an internal thread of the helix mount <NUM>.

The flange <NUM> includes a flange channel <NUM> extending along the longitudinal axis <NUM> from the proximal flange end <NUM> to a distal flange end. More particularly, the flange channel <NUM> can be a through-hole extending entirely through the flange <NUM> in the longitudinal direction. The shoulder <NUM> of the flange <NUM> can extend around and circumferentially surround a proximal region of the flange channel <NUM>. Similarly, the flange connector <NUM> can extend around and circumferentially surround a distal region of the flange channel <NUM>. Accordingly, the shoulder <NUM> and the flange connector <NUM> can define the flange channel <NUM>. The proximal region of the flange channel <NUM> can define a distal region of the electronics compartment <NUM> that contains the electronics assembly <NUM> when the flange <NUM> is mounted on the housing <NUM>.

The header assembly <NUM> includes an insulator <NUM> in the flange channel <NUM>. In an example, the insulator <NUM> includes an insulator wall <NUM> extending around an insulator cavity <NUM>. The insulator wall <NUM> can extend longitudinally from a proximal end of the insulator <NUM> to a distal end of the insulator <NUM>. For example, the insulator wall <NUM> can be a cylindrical, annular wall having an outer insulator surface facing radially outward, and an inner insulator surface <NUM> facing radially inward and partially defining the insulator cavity <NUM>. The insulator <NUM> can also include an insulator base <NUM> extending laterally at a location between the distal end and the proximal end of the insulator <NUM>. The insulator base <NUM> can be a transverse wall extending across the interior of the insulator <NUM>, orthogonal to the longitudinal axis <NUM>. The insulator base <NUM> can have an upper wall surface facing distally and partially defining the insulator cavity <NUM> of the insulator <NUM>. Accordingly, the insulator <NUM> can be mounted within the flange channel <NUM> to insulate the insulator cavity <NUM> from the metallic flange connector <NUM>, and to provide a receptacle for a therapeutic agent, as described below.

In an example, the header assembly <NUM> includes the electrode <NUM> mounted within the insulator <NUM> and the flange <NUM>. More particularly, the electrode <NUM> extends longitudinally through the insulator cavity <NUM> along the longitudinal axis <NUM>. The electrode <NUM> can include several components. For example, the electrode <NUM> can include an electrode pin <NUM> extending along the longitudinal axis <NUM> from the electronics compartment <NUM> through the insulator cavity <NUM> to a distal end <NUM>. The distal end <NUM> may be located distal to the distal end of the insulator <NUM>. In an example, the electrode <NUM> includes an electrode tip <NUM> at the distal end <NUM>. The electrode tip <NUM> can be a cap that is mounted on, and bonded to, the distal end <NUM>. For example, the electrode tip <NUM> can include an electrode cap having a counterbore or a through-hole to receive, and be welded to, the distal, tissue-facing end of the electrode pin <NUM>. Alternatively, the electrode tip <NUM> can be a portion of the electrode that is formed to have a different dimension than the electrode pin <NUM>. For example, the electrode tip <NUM> can having an outer dimensions that is greater than an outer dimension of the electrode pin <NUM>. The electrode tip <NUM> may therefore have a proximal surface that faces the insulator cavity <NUM> to restrict the elution of therapeutic agent distally from the insulator cavity <NUM>.

The electrode tip <NUM> can act as the active, tissue-touching electrode to sense and deliver electrical impulses to the target tissue. In an example, a distal surface area of the electrode tip <NUM> is sized to provide predetermined impedance parameters. The electrode <NUM>, e.g., the pin and the cap, can be formed from platinum iridium or another biocompatible conductor. Based on the electrical properties of the electrode material, the distal surface area can be sized to provide a predetermined impedance at the contact area between the target tissue and the electrode. Generally, the smaller the distal surface area, the larger the impedance. Given that the electrode tip <NUM> can be formed to be quite small, and because the tip will reliably engage the target tissue over the surface area, the impedance of the electrode can be controllable and suitably high for reliable pacing. It will be appreciated that the electrical feedthrough assembly can be a filtered or unfiltered assembly, as is known in the art. More particularly, the electrical feedthrough assembly can incorporate an integral EMI filter capacitor in electrical communication with the electrode <NUM> (filtered feedthrough assembly) or not (unfiltered feedthrough assembly).

In an example, the flange <NUM>, the insulator <NUM>, and the electrode <NUM> are joined. For example, a joint <NUM> can be formed between the flange <NUM>, the insulator <NUM>, and the electrode <NUM> to fasten the components together and to provide a hermetic seal between the flange channel region proximal to the insulator <NUM> (e.g., the electronic compartment) and the flange channel region distal to the insulator <NUM>. In an example, the joint <NUM> is a brazed joint, e.g., a gold brazed joint, which radially surrounds a portion of the components to fill gaps between the components and form the hermetic joint. The electrode <NUM> can pass through the joint <NUM>, and through a hole in the insulator base <NUM>, to transfer electrical signals between the target tissue and the internal circuitry of the leadless biostimulator <NUM>.

In an example, the header assembly <NUM> includes a MCRD <NUM>. The MCRD <NUM> can be an agent-containing filler that is located in the insulator cavity <NUM>. For example, the MCRD <NUM> can include a therapeutic agent loaded into a matrix or solid composition. In at least one implementation, the therapeutic agent can include a corticosteroid, such as dexamethasone sodium phosphate, dexamethasone acetate, etc. When the therapeutic agent is consistently released into the target tissue at a controlled dose, the agent can reduce inflammation associated with the device implantation.

The MCRD <NUM> can be placed or located in the insulator cavity <NUM> radially inward from the insulator wall <NUM> and distal to the insulator base <NUM>. Elution of the therapeutic agent from the MCRD <NUM> can be controlled by a geometry of the MCRD <NUM>, as well as by the ingress and egress of fluid, e.g., blood, from the surrounding environment <NUM> into the insulator cavity <NUM>. Accordingly, the header assembly <NUM> can be configured to allow for fluid transport between the MCRD <NUM> and the surrounding environment <NUM> through the insulator cavity <NUM>. A specified dose of the therapeutic agent may therefore flow, or weep, from the MCRD <NUM> through the insulator cavity <NUM> and the helix mount <NUM> to the target tissue at an implantation site of the biostimulator <NUM> within a patient.

In an example, the MCRD <NUM> is in fluid communication with a space <NUM> between the insulator <NUM> and the electrode <NUM> to elute the therapeutic agent into the space <NUM> when the leadless biostimulator <NUM> is implanted in blood. The space <NUM> can be between the inner insulator surface <NUM> and an outer electrode surface <NUM> of the electrode <NUM>. More particularly, the space <NUM> can be defined radially between the inner insulator surface <NUM> and the outer electrode surface <NUM>. Furthermore, the space <NUM> can be defined longitudinally between the insulator base <NUM> and a distal end of the insulator <NUM>. Accordingly, the space <NUM> is an annular region of the insulator cavity <NUM> defined between the electrode <NUM> and the insulator <NUM>.

In an example, the MCRD <NUM> can be received within the space <NUM>. For example, the MCRD <NUM> can have an annular body <NUM> that is located between the electrode <NUM> and the insulator <NUM> within the insulator cavity <NUM>, and thus, may be positioned within the space <NUM>. The annular body <NUM> can include an outer surface and an inner surface that are generally cylindrical and extend between proximal and distal ends <NUM> of the MCRD <NUM>. The inner surface of the MCRD <NUM> can define a central lumen <NUM> that extends longitudinally through the MCRD <NUM>. In an example, the central lumen <NUM> receives the electrode <NUM>. For example, the electrode pin <NUM> can extend longitudinally through the central lumen <NUM> to the distal end <NUM> that is distal to the distal end of the MCRD <NUM>. Therapeutic agent eluted from the MCRD <NUM> is therefore initially in the space <NUM> between the electrode pin <NUM> and the inner surface of the insulator <NUM>. The therapeutic agent, after elution, can be carried outward by blood transfer to the surrounding environment <NUM>.

The header assembly <NUM> can include the helix mount <NUM>. The helix mount <NUM> may be formed from an insulating material, such as a ceramic material (e.g., alumina, ruby, glass, or another ceramic insulating material) and/or a non-ceramic material (e.g., polyetheretherketone (PEEK)). The helix mount <NUM> can be mounted on the flange <NUM>. For example, the helix mount <NUM> can have an inner surface that is threaded to engage external threads of the flange connector <NUM>. The helix mount <NUM> may also include an external threaded feature. More particularly, the helix mount <NUM> can include a mount flange <NUM>, which may be a helical ledge extending around an outer surface of the helix mount <NUM>. The mount flange <NUM> can receive the helical fixation element <NUM>. More particularly, the helical fixation element <NUM> can be mounted on the helix mount <NUM> by screwing the fixation element onto the helical ledge until a distal tip of the fixation element is properly located for tissue engagement.

In an example, the helix mount <NUM> includes a helix mount channel <NUM> through which therapeutic agent can be eluted when the leadless biostimulator <NUM> is implanted in blood. The helix mount channel <NUM> can be a hole extending through a distal wall of the helix mount <NUM>. The hole can be centrally located, e.g., along the longitudinal axis <NUM>, such that the helix mount channel <NUM> is concentric with the electrode pin <NUM> and/or the electrode tip <NUM>. Furthermore, the helix mount channel <NUM> can have a hole dimension that is larger than the electrode pin <NUM> and the electrode tip <NUM> such that the annular gap <NUM> is formed between the helix mount <NUM> and the electrode <NUM>. More particularly, the annular gap <NUM> can be a gap formed around the electrode <NUM> and extending from the insulator cavity <NUM> to the surrounding environment <NUM> to provide an elution path for the therapeutic agent to be transferred through. Accordingly, when the leadless biostimulator <NUM> is implanted, blood can enter the insulator cavity <NUM> through the annular gap <NUM> to dissolve the therapeutic agent and transfer the drug-laden agent through the space <NUM> and the helix mount channel <NUM> to the surrounding environment <NUM>. Advantageously, the annular gap <NUM> may be less likely to clog than a single small hole, and thus, may promote consistent and continuous elution of the therapeutic agent into the target tissue.

The flange <NUM> may be a portion of the proximal electrode <NUM>, and thus, the electrical feedthrough assembly of the header assembly <NUM> may also include the proximal electrode <NUM>. In such case, the electrodes (the electrode tip <NUM> and the flange <NUM>) may be in close proximity, separated by an electrode gap extending radially between the flange connector <NUM> and the electrode <NUM>. If blood were allowed to fill the electrode gap between the flange <NUM> and the electrode <NUM>, the electrodes <NUM>, <NUM> could be electrically shorted and pacing impulses may not properly pace the cardiac tissue. Accordingly, a barrier can be included in the biostimulator <NUM> to prevent blood from filling the electrode gap and/or to block an electrical path between the flange <NUM> and the electrode <NUM>. In an example, the barrier includes a gasket <NUM>. The gasket <NUM> can be an annular seal that is pressed between a distal end of the flange connector <NUM> and the insulator <NUM>, and a proximal inner surface of the helix mount <NUM>. The gasket <NUM> bridges the gap between the insulative helix mount <NUM> and insulator <NUM>, and thus, blood that enters the insulator cavity <NUM> to facilitate therapeutic agent release does not contact the flange <NUM>.

In an example, the MCRD <NUM> is retained in part by the electrode <NUM>. For example, the electrode tip <NUM> can have an outer dimension that is greater than a dimension of the MCRD <NUM> central lumen <NUM>. Accordingly, the MCRD <NUM> may be restrained from sliding off of the electrode <NUM> into the surrounding environment <NUM>. Furthermore, an inner dimension of the helix mount channel <NUM> may be less than a dimension of the central lumen <NUM> of the MCRD <NUM>. Accordingly, the MCRD <NUM> may be restrained from sliding out of the insulator cavity <NUM> by the helix mount <NUM>.

Instead of or in addition to the retention features described above, the MCRD <NUM> may be partly retained via a press fit against one or more of the insulator <NUM> or the electrode <NUM>. More particularly, the outer surface of the MCRD <NUM> may press against the inner insulator surface <NUM> of the insulator <NUM> and/or the inner surface of the MCRD <NUM> may press against the outer electrode surface <NUM>. Accordingly, friction caused by a press fit between the MCRD <NUM> and one or more of the insulator <NUM> or the electrode <NUM> can retain the MCRD <NUM> within the insulator cavity <NUM>. In an example, at least one of the side surfaces of the MCRD <NUM> has a clearance with an opposing surface of the insulator <NUM> or the electrode <NUM>. For example, when the MCRD <NUM> is press fit against the insulator <NUM>, the MCRD <NUM> may have a clearance fit with the electrode <NUM> (<FIG>). The clearance can maximize the MCRD surface area exposed to blood after implantation to promote elution of the therapeutic agent into the space <NUM>.

Optionally, the MCRD <NUM> can include a time-release coating. The time-release coating may be applied, e.g., by spray or dip coating, to an exterior surface of the MCRD <NUM>. The time release coating can be an absorbable coating, such as a hydrophilic coating, that absorbs within minutes to an hour of being in contact with blood. Accordingly, the exterior surface can contact blood when the biostimulator <NUM> is implanted, and the release of therapeutic agent can be delayed while the coating dissolves. After the coating dissolves, the therapeutic agent can elute from the MCRD <NUM> and follow an elution path through the space <NUM> and the helix mount channel <NUM> toward the surrounding environment <NUM>.

Referring to <FIG>, a sectional view of a header assembly having a MCRD in an insulator cavity of a ceramic helix mount is shown. The header assembly <NUM> can include a helix mount <NUM> that combines features of the insulator <NUM> and the helix mount <NUM> described above with respect to <FIG>. More particularly, the insulator <NUM> and the helix mount <NUM> are monolithically formed from ceramic. The fully-ceramic helix mount <NUM> can connect to the flange <NUM> via a threaded or threadless connector that attaches the flange connector <NUM> to the helix mount <NUM>. For example, the helix mount <NUM> can be screwed onto the flange connector <NUM> to secure the flange <NUM> to the helix mount <NUM>. Similarly, the fixation element can be screwed onto the mount flange <NUM>.

In an example, the helix mount <NUM> can have a hole extending from a proximal end of the helix mount <NUM> to a distal end of the helix mount <NUM>. The electrode <NUM> can be inserted into the hole, and secured by the joint <NUM>, as described above. More particularly, the joint <NUM> can be a brazed joint securing and sealing the electrode <NUM> to the helix mount <NUM>. Accordingly, the header assembly <NUM> can include the flange <NUM>, the helix mount <NUM> (which incorporates the insulator <NUM>), and the electrode <NUM> securely fastened to each other and hermetically sealed to prevent ingress of blood from the surrounding environment <NUM> into the electronics compartment <NUM>.

The insulator cavity <NUM> can be formed directly into the helix mount <NUM>. More particularly, a counterbore can be formed in a distal end of the fully-ceramic helix mount <NUM> such that the counterbore includes the inner insulator surface <NUM>. When the electrode <NUM> is secured relative to the helix mount <NUM>, the inner insulator surface <NUM> faces the outer electrode surface <NUM>, providing the space <NUM> between the insulator <NUM> and the electrode <NUM>. The MCRD <NUM> can be loaded into the space <NUM>, and thus, can elute therapeutic agent into the space <NUM> when the biostimulator <NUM> is implanted in blood.

The electrode <NUM> may include a through-post configuration. The through-post configuration includes an electrode tip <NUM> having a through-hole to receive the electrode pin <NUM>. More particularly, when the electrode pin <NUM> is inserted into the through-hole of the electrode tip <NUM>, the distal end <NUM> of the electrode pin <NUM> can be exposed to the surrounding environment <NUM>.

In an example, the electrode pin <NUM> includes a stop <NUM> to provide a positional reference to the electrode tip <NUM>. The stop <NUM> can include a protuberance or a ledge extending radially from the longitudinal pin of the electrode <NUM>. An outer dimension of the stop <NUM> may be greater than an inner dimension of the electrode tip through-hole, and thus, when the electrode tip <NUM> is inserted over the distal end <NUM> of the electrode pin <NUM>, the electrode tip <NUM> can rest on the stop <NUM>. The electrode tip <NUM> may then be welded or otherwise attached to the electrode pin <NUM> to form the electrode <NUM>.

As described above, the MCRD <NUM> can be located within the insulator cavity <NUM> between the electrode <NUM> and the insulator <NUM>. For example, an inner dimension of the MCRD <NUM> extending around the central lumen <NUM> may be less than an outer dimension of the electrode tip <NUM>. Thus, the electrode tip <NUM> can retain the MCRD <NUM> within the space <NUM> of the insulator cavity <NUM>. Also as described above, the MCRD <NUM> can elute therapeutic agent through the space <NUM> and through the annular gap <NUM> to the surrounding environment <NUM> when the biostimulator <NUM> is implanted in blood.

Combining the insulator <NUM> and the helix mount <NUM> in a fully-ceramic helix mount <NUM>, as described above, can reduce an overall height of the header assembly <NUM>. As illustrated, with the fully ceramic helix mount <NUM>, the height of the flange connector <NUM> and the height of the helix mount <NUM> can be reduced, which shortens the header assembly <NUM>. Advantageously, by shortening the header assembly <NUM>, the device length may instead be devoted to extending a length of the energy source. Accordingly, an energy capacity and operational longevity can be extended as compared to biostimulators <NUM> having non-integrated helix mount <NUM> and insulator <NUM> components.

Referring to <FIG>, a perspective view of a header assembly having controlled therapeutic agent release is shown. The header assembly <NUM> can include a fully-ceramic helix mount <NUM>, as described above. In an example, the electrode <NUM> of the header assembly <NUM> includes an electrode helix <NUM>. The electrode helix <NUM> can provide a distal portion of the electrode <NUM>. More particularly, the electrode helix <NUM> can be a portion of the electrode <NUM> that engages tissue during implantation. For example, the electrode helix <NUM> can be coaxial with the helical fixation element <NUM> and, during implantation, both the helical fixation element <NUM> and the electrode helix <NUM> can be screwed into the target tissue.

An electrode helix <NUM>, like the electrode tip <NUM> described above, can provide controlled impedance for reliable pacing. In the case of the electrode helix <NUM>, the electrode <NUM> can be securely and predictably engaged with the target tissue by virtue of the electrode anchoring within the tissue. The anchored electrode can provide consistent tissue contact from case to case, and may therefore provide for more predictable impedance between the electrode and the tissue. Accordingly, the helical electrode can provide more consistent impedance and pacing.

Referring to <FIG>, a sectional view of a header assembly having a MCRD within an electrode helix is shown. Several features of the embodiment shown in <FIG> are similar to those described above with respect to <FIG> and <FIG>, and thus, are not described again in the interest of brevity.

The electrode pin <NUM> can extend longitudinally through the insulator cavity <NUM>. In an example, the electrode helix <NUM> is mounted on the electrode pin <NUM>. For example, the electrode helix <NUM> can be slipped over and mounted on the distal end <NUM> of the electrode pin <NUM>. The electrode pin <NUM> may include the stop <NUM>, and thus, the electrode helix <NUM> can rest on the stop <NUM>. The electrode helix <NUM> may therefore be welded to the electrode pin <NUM> in a consistent manner. More particularly, the stop <NUM> can provide a positional reference to ensure that the electrode helix <NUM> is properly located relative to the fixation element. The electrode pin <NUM> and the electrode helix <NUM> may therefore be joined to form the electrode <NUM> that carries electrical signals between the electronics compartment <NUM> and the target tissue that the electrode helix <NUM> is screwed into.

In an example, the MCRD <NUM> has a cylindrical shape. More particularly, the MCRD <NUM> can be a cylindrical plug, having no central channel, and may be inserted into the inner lumen of the electrode helix <NUM>. Alternatively, the MCRD <NUM> can have the annular or ring-shaped structure described above, and may be loaded into the electrode helix <NUM>. The plug can be press fit within the electrode helix <NUM>. Accordingly, the press fit between the electrode helix <NUM> and the MCRD <NUM> can retain the MCRD and prevent dislodgement of the MCRD from the insulator cavity <NUM>.

It will be appreciated that, although the MCRD <NUM> is radially inward from the electrode helix <NUM> (rather than being radially outward from the electrode pin <NUM> as shown in <FIG>), the MCRD <NUM> can still elute therapeutic agent along an elution path that passes through the space <NUM> between the insulator <NUM> and the electrode <NUM>. More particularly, when blood enters the insulator cavity <NUM>, the therapeutic agent can be dissolved and flow radially outward from the inner lumen of the helix through the helical turns into the space <NUM> between the outer electrode surface <NUM> of the helical turns and the inner insulator surface <NUM> of the helix mount <NUM>. From the space <NUM>, the therapeutic agent can travel distally outward from the insulator cavity <NUM> into the surrounding environment <NUM> through the annular gap <NUM>. Advantageously, elution through the space <NUM> can allow for the therapeutic agent to be released controllably through the annular gap <NUM> that is larger and less likely to be clogged than a single hole in an electrode cup, for example.

Referring to <FIG>, a flowchart of a method of manufacturing a leadless biostimulator is shown. As a preliminary operation, the insulator <NUM> can be loaded into the flange channel <NUM> such that the insulator cavity <NUM> and the flange channel <NUM> are concentric. The insulator <NUM> may have a thin, metallic coating deposited on its outer surface to allow for a brazing process to be performed on it, as described below. The electrode <NUM> can be loaded into the concentrically arranged flange channel <NUM> and insulator cavity <NUM>. More particularly, the electrode pin <NUM> can be inserted into the hole in the insulator base <NUM> such that the electrode <NUM> extends longitudinally through the insulator cavity <NUM>. The electrode pin <NUM> can be cut to a length (before or after loading the electrode into the assembly) such that the electrode pin <NUM> extends to a predetermined length distal to and proximal to the insulator base <NUM>. The distal portion of the electrode pin <NUM> can have a length to align the distal end <NUM> of the pin with the helix mount channel <NUM>. The proximal region of the electrode pin <NUM> can have a length to extend to a proximal end of the pin that will engage the electronics assembly <NUM> in the electronics compartment <NUM>.

At operation <NUM>, the flange <NUM>, the insulator <NUM>, and the electrode <NUM> are joined together. The concentrically arranged components can be secured by the joint <NUM>. In an example, gold is flowed into the junctions between the components in a brazing process. The molten gold can be cooled to braze the components together to provide a hermetic seal through which the electrode <NUM> can pass electrical signals.

At operation <NUM>, the MCRD <NUM> is mounted within the insulator cavity <NUM>. In an example, the MCRD <NUM> can be loaded over the electrode <NUM>, e.g., by inserting the electrode pin <NUM> through the central channel of the annular MCRD <NUM>. Alternatively, the MCRD <NUM> can be loaded into the electrode <NUM>, e.g., by sliding the MCRD <NUM> into an interior lumen of the electrode helix <NUM>.

After loading the MCRD <NUM> into the insulator cavity <NUM>, the MCRD <NUM> can be retained to a degree. For example, the MCRD <NUM> can form a press fit to one or more of the insulator wall <NUM>, the electrode pin <NUM>, or the electrode helix <NUM>, depending upon the header assembly configuration being manufactured. At operation <NUM>, the MCRD <NUM> may be further retained. More particularly, the electrode tip <NUM> or the electrode helix <NUM> can be mounted on the distal end <NUM> of the electrode pin <NUM> to retain the MCRD <NUM> within the insulator cavity <NUM>. In the case of the electrode tip <NUM>, the electrode <NUM> can include a cap that has a larger outer dimension than the central lumen <NUM> of the MCRD <NUM>, and thus, the cap can resist distal movement of the MCRD <NUM> from the electrode pin <NUM>. In the case of the electrode helix <NUM>, the MCRD <NUM> can be press fit within the interior of the helix. The electrode helix <NUM> can be connected, e.g., welded, to a distal end <NUM> of the electrode pin <NUM>, and thus, the electrode helix <NUM> can resist distal movement of the MCRD <NUM> relative to the electrode pin <NUM>. In either case, the electrode features can both retain the MCRD <NUM> within the insulator cavity <NUM> and provide electrical conduction of pacing signals to the target tissue.

The operations of the method may be performed in an alternative order. For example, for the header assembly configuration shown in <FIG>, the operation of mounting (and optionally welding) the electrode helix <NUM> on the electrode pin <NUM> at operation <NUM> may precede the operation of loading the MCRD <NUM> into the electrode helix <NUM> (and the insulator cavity <NUM>) at operation <NUM>. Accordingly, it will be appreciated that the operations may be reordered, omitted, or modified as needed to manufacture the header assembly configurations described above.

At operation <NUM>, the helix mount <NUM> is mounted on the flange <NUM>. The helix mount <NUM> can be fastened to the flange connector <NUM>, e.g., by engaging mating threads of the components. Alternatively, other fasteners can secure the helix mount <NUM> to the flange <NUM>. When the helix mount <NUM> is attached to the flange <NUM>, the helix mount channel <NUM> can be positioned to receive the electrode <NUM>, e.g., the electrode tip <NUM>, such that the gap <NUM> provides an elution pathway between the insulator cavity <NUM> within the header assembly <NUM> and the surrounding environment <NUM>. The gap <NUM> can be sized to achieve good fluid exchange between the interior and the exterior of the header assembly <NUM>.

At operation <NUM>, the helical fixation element <NUM> is mounted on the helix mount <NUM>. The helical fixation element <NUM> can be screwed onto the mount flange <NUM>. Optionally, the fixation element can be adhered to the mount flange <NUM> by a thermal or adhesive weld. Accordingly, the fixation element can be secured to the helix mount <NUM> to retain the header assembly <NUM> against the target tissue when the fixation element is screwed into the target tissue during device implantation.

Claim 1:
A header assembly (<NUM>) for a leadless biostimulator (<NUM>), comprising:
a flange (<NUM>) including a flange channel (<NUM>) extending along a longitudinal axis (<NUM>);
an insulator (<NUM>) in the flange channel (<NUM>) and including an insulator cavity (<NUM>);
an electrode (<NUM>) extending longitudinally through the insulator cavity (<NUM>); and
a monolithic controlled release device (MCRD) (<NUM>) in the insulator cavity (<NUM>), characterized in that the MCRD (<NUM>) is within a space (<NUM>) radially between the insulator (<NUM>) in the flange channel (<NUM>) and the electrode (<NUM>) to elute therapeutic agent into the space (<NUM>) when the leadless biostimulator (<NUM>) is implanted.