Patent Description:
Patients suffering from heart failure or other cardiovascular related diseases can benefit from cardiac resynchronization therapy. In cardiac resynchronization therapy, electrodes are inserted into the left and right ventricles of the heart and provide stimulation to coordinate the function of the left and right ventricles. However, a subset of patients suffering from heart failure or other cardiovascular related diseases can have intact atrial-ventricular (AV) conduction to the right side of the heart, but can have a condition known as left bundle branch block (LBBB). LBBB is a cardiac condition where contraction of the left ventricle is delayed and/or non-existent, while contraction of the right ventricle is largely unaffected. LBBB can cause the left ventricle to contract later than the right ventricle or prevent the left ventricle from contracting. In certain cases, LBBB is currently treated with traditional pacemakers designed to pace the contraction of the heart.

A pacemaker is a battery-powered electronic device implanted under the skin and connected to the heart by an insulated metal lead wire with a tip electrode. Pacemakers were initially developed for and are most commonly used to treat bradycardia (slow heart rates), which can result from several conditions. More recently, advancements in pacemaker complexity, and associated sensing and pacing algorithms, have allowed progress in using pacemakers for the treatment of other conditions, notably heart failure (HF) and fast heart rhythms (tachyarrhythmia/tachycardia).

In a common application, pacemaker leads are placed through the skin into a subclavian vein or branch to access the venous side of the cardiovascular system. Such systems can be either single chamber with a lead placed in either the right atrium or right ventricle, or dual chamber systems with one lead placed in contact with the right atrial wall and a second lead placed in contact with the right ventricular wall. For the treatment of HF, through what is commonly known as cardiac resynchronization therapy, bi-ventricular pacing uses an additional (e.g., third) lead placed in contact with the left ventricle. To access the left ventricle, the third lead is typically advanced into the right atrium, through the orifice of the coronary sinus, and then maneuvered through the coronary sinus veins to a position on the epicardial aspect of the posterolateral or lateral wall of the left ventricle. In patients with LBBB, however, the leads can only be required to be placed in contact with the left ventricle.

Though now less common after several decades of improvement in designs and materials, failure of a pacemaker lead is still a significant risk to the patient-not only for the loss of pacing which can represent a life-threatening event, but also because extracting pacemaker leads after implantation involves significant risks. Additionally, the location of an existing non-functional lead, if not removable, can prevent implantation of a replacement lead. Pacemaker leads can fail due to several reasons including breakage of the insulator or conductor and loose or incompatible connectors.

<CIT> describes systems including an implantable receiver-stimulator and an implantable controller-transmitter, which are used for leadless electrical stimulation of body tissues. Cardiac pacing and arrhythmia control is accomplished with one or more implantable receiver-stimulators and an external or implantable controller-transmitter. Systems are implanted by testing external or implantable devices at different tissue sites, observing physiologic and device responses, and selecting sites with preferred performance for implanting the systems. In these systems, a controller-transmitter is activated at a remote tissue location to transmit/deliver acoustic energy through the body to a receiver-stimulator at a target tissue location. The receiver-stimulator converts the acoustic energy to electrical energy, for electrical stimulation of the body tissue. The tissue locations(s) can be optimized by moving either or both of the controller, transmitter and the receiver-stimulator to determine the best patient and device responses.

The present disclosure is generally directed to wireless stimulation systems, devices, and methods that stimulate tissue by harvesting acoustic energy transmitted into the tissue and converting the acoustic energy into electrical energy which is then delivered to the tissue. More specifically, the present disclosure includes systems and methods for electrically stimulating the left side of the heart in a patient with intact right-side conduction (e.g., in a patient with Left Bundle Branch Block (LBBB)).

In some embodiments, a stimulation system includes a controller-transmitter configured to emit acoustic energy, and a receiver-stimulator configured to (i) receive the emitted acoustic energy, (ii) convert the acoustic energy to electrical energy, and (iii) deliver the electrical energy to adjacent tissue (e.g., to the left ventricle of a patient with LBBB). The controller-transmitter can include one or more sensors configured to detect real-time electrical activity of the heart. As the sensors detect certain aspects of the heart-beat, the controller-transmitter can emit acoustic energy that activates the receiver-stimulator, which then electrically stimulates the left side of the heart. If the electrical stimulation is applied to the left ventricle within a range of time immediately following the onset of right ventricular electrical conduction (e.g., QRS onset), the left ventricular pacing will synchronize with the right sided natural conduction to create a synchronized contraction of both ventricles.

In one aspect of the present disclosure, the stimulation system is configured to operate without wired leads and without a co-implanted conventional pacemaker system. In contrast, many conventional systems include a co-implanted device, such as a pacemaker device, that drives the pacing function. Accordingly, the present technology can include a stand-alone system that uses a controller-transmitter to drive the pacing in certain patients.

<FIG> is a schematic illustration of an electrocardiogram (ECG) trace of a patient having LBBB. As shown in <FIG>, a patient having LBBB will have a P-wave representing atrial depolarization that results in atrial contraction. Subsequently, the onset of the QRS segment is marked by a rapid deflection of the ECG trace and indicates the electrical signal for ventricular contraction. In the illustrated embodiment, the QRS segment has a duration t<NUM>. Patients with LBBB will have a duration t<NUM> that is longer than the duration of the QRS segment in a healthy patient. For example, the duration t<NUM> for a patient with LBBB can be greater than about <NUM> milliseconds.

<FIG> is a schematic illustration of another ECG trace of a patient having LBBB. Dashed-line <NUM> in <FIG> illustrates the beginning of the QRS segment when the electrical signal initially depolarizes (e.g., to contract) the ventricles. However, the actual mechanical contraction of the ventricle happens sometime after the onset of the electrical signal to depolarize, as the electrical signal does not instantaneously cause the ventricles to contract. Thus, there is a range of time t<NUM> beginning at the onset of the QRS segment (e.g., at dashed-line <NUM>) and terminating at dashed-line <NUM> in which electrical stimulation could be applied to the left ventricle to improve synchronization of the left ventricle and the right ventricle in patients with LBBB.

In some embodiments, the time t<NUM> can be between about <NUM> millisecond and <NUM> milliseconds. For example, the time t<NUM> can be about <NUM> millisecond, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, about <NUM> milliseconds, or about <NUM> milliseconds. If electrical stimulation is provided to the left ventricle within the time t<NUM>, the left and right ventricles can have improved synchronization. In one aspect of the present technology, such stimulation of the left ventricle can shorten the overall duration of the QRS segment (indicated by t<NUM> in <FIG>) and/or improve the morphology of patients with LBBB.

Accordingly, the present disclosure includes systems and devices configured to stimulate the left ventricle within the duration t<NUM> to synchronize the contraction of the right and left ventricles. Furthermore, the systems and devices can be configured to detect the initiation of the QRS segment and, in response, determine when to initiate stimulation to ensure stimulation of the left ventricle within the duration t<NUM>. For example, the system can initiate stimulation of the left ventricle immediately upon sensing initiation of the QRS segment. In other embodiments, the system can slightly delay initiating stimulation of the left ventricle after sensing initiation of the QRS segment. In other embodiments, the system can be configured to detect other cardiac conduction segments (e.g., the P-wave) and pace the stimulation of the left ventricle based off such segments. Because the systems and devices can both sense the electrical conduction of the heart and stimulate the heart in response to specific electrical signals (e.g., the initiation of the QRS segment), the present technology does not require a co-implanted pacemaker or external ECG leads to pace stimulation. Instead, the present technology provides systems and devices configured to effectively treat LBBB without co-implantation of another device.

<FIG> is a partially-schematic view of a wireless tissue stimulation system <NUM> configured to electrically stimulate a human heart <NUM> in accordance with embodiments of the present disclosure. In the illustrated embodiment, the wireless tissue stimulation system <NUM> includes an implantable or external controller-transmitter <NUM> and one or more receiver-stimulators <NUM> configured to be implanted in and/or positioned proximate to the heart <NUM>. The controller-transmitter <NUM> generates acoustic energy <NUM> (e.g., an acoustic waveform, acoustic signal, etc.) of sufficient amplitude and frequency to allow the receiver-stimulators <NUM> to generate electrical energy for tissue stimulation. The receiver-stimulators <NUM> are configured to (i) harvest a portion of the acoustic energy <NUM>, (ii) convert the harvested acoustic energy <NUM> into electrical energy, and (iii) deliver the electrical energy to electrically stimulate tissue of the heart <NUM>. In some embodiments, the wireless tissue stimulation system <NUM> can include features similar or identical to those of the leadless tissue stimulation systems described in detail in, for example: (i) <CIT>; and (ii) <CIT>.

The acoustic signal <NUM> generated and emitted by the controller-transmitter <NUM> can be defined through several characteristics. For example, the acoustic signal <NUM> can operate at a frequency between about <NUM> and <NUM>, between about <NUM> and <NUM>, or between about <NUM> and <NUM>. The acoustic signal <NUM> generated by the controller-transmitter <NUM> can further comprise pulse width and pulse amplitude information that can be used by the receiver-stimulators <NUM> to construct a corresponding electrical output. In some embodiments, the acoustic energy <NUM> can be emitted as a single burst or as multiple bursts.

The acoustic energy <NUM> propagates via an acoustic field whose acoustic intensity is defined as the amount of acoustic power passing through a cross-sectional area and can be expressed as Watts per square meter. The effective cross-sectional area of the receiver-stimulators <NUM> is defined as the area available for harvesting acoustic energy. In some embodiments, the receiver-stimulators <NUM> include an acoustic transducer assembly for converting acoustic energy into electrical energy. In some embodiments, the effective cross-sectional area of each of the receiver-stimulators <NUM> can be generally equal to the cross-sectional area of the acoustic transducer assembly. In practice, the effective area can be less than that, due to inefficiencies in harvesting and energy conversion. In one embodiment, the receiver-stimulators <NUM> further include a tissue attachment mechanism and a catheter delivery interface. Due to the tissue attachment mechanism, catheter delivery interface, and other components of the receiver-stimulators <NUM>, the effective area can be substantially less than the cross-sectional area of the receiver-stimulators <NUM>. In some embodiments, the receiver-stimulators <NUM> can have a cross-sectional area of about <NUM> and an estimated effective area of <NUM><NUM>=<NUM>·<NUM>-<NUM> m<NUM>. In some embodiments, to stimulate the heart <NUM>, the effective area of the receiver-stimulators <NUM> can result in a minimum acoustic field intensity of around: <MAT> For example, the electrical energy sufficient to stimulate the heart <NUM> can be about <NUM>µJ for a <NUM> millisecond electrical pulse. This means that about <NUM> mW of power is delivered to the tissue during the <NUM> millisecond pacing pulse for sufficient stimulation of the heart <NUM>.

In some embodiments, a single receiver-stimulator <NUM> can be implanted for single site pacing. In other embodiments, multiple of the receiver-stimulators <NUM> can be implanted. The receiver-stimulators <NUM> can be configured to stimulate (i) simultaneously by receiving the same transmitted acoustic energy, (ii) sequentially through fixed or programmable delays after receiving the same transmitted acoustic energy, (iii) or independently by responding only to signal information of the transmitted acoustic energy of a specific character (e.g., of a certain frequency, amplitude, or by other modulation or encoding of the acoustic waveform <NUM>) intended to energize only that specific device or spatial focusing of the ultrasound beam.

The wireless tissue stimulation system <NUM> can further include a power source <NUM>. The power source <NUM> can comprise a battery (e.g., a rechargeable battery) and/or a transmit power supply (e.g., a DC-DC converter or AC-DC converter). In some embodiments, the power source <NUM> can be external to the controller-transmitter <NUM> while, in other embodiments, the power source <NUM> can be adjacent to or attached to the controller-transmitter <NUM>. As can be appreciated by one of skill in the art, several different power sources could be utilized in the present disclosure and are included within the scope of the present disclosure.

The controller-transmitter <NUM> and/or the power source <NUM> can also include one or more sensors <NUM> (e.g., sensing electrodes). The sensors <NUM> are configured to detect electrical conduction of the heart <NUM> in at least substantially real-time (e.g., in real-time or with a delay of less than about <NUM> milliseconds, less than about <NUM> milliseconds, less than about <NUM> milliseconds, less than about <NUM> milliseconds, or less than about <NUM> millisecond). For example, the sensors <NUM> can be configured to detect the beginning of the period in which the controller-transmitter <NUM> needs to emit acoustic energy <NUM> to initiate electrical stimulation of the heart <NUM> by the receiver-stimulators <NUM> (e.g., the sensors <NUM> can be configured to detect the onset of the QRS segment). Thus, in some embodiments, the sensors <NUM> are capable of detecting when the acoustic energy <NUM> should be emitted to ensure electrical stimulation is provided that will facilitate improved synchronization of the left and right ventricles of the heart <NUM>. In some embodiments, the controller-transmitter <NUM> can include one, two, three, four, five, six, or seven or more of the sensors <NUM>.

<FIG> is a block diagram of the wireless tissue stimulation system <NUM> of <FIG> illustrating further details of the wireless tissue stimulation system <NUM> in accordance with embodiments of the present disclosure. In the illustrated embodiment, the controller-transmitter <NUM> includes control circuitry <NUM> (e.g., a controller) and an output transducer assembly <NUM> for generating the acoustic energy <NUM> for transmission to the receiver-stimulators <NUM> (only a single one of the receiver-stimulators <NUM> is shown in <FIG> for the sake of clarity). The control circuitry <NUM> can include an amplifier configured to apply electrical energy to the transducer assembly <NUM>, which in turn produces the acoustic energy <NUM> having selected characteristics/properties. The transducer assembly <NUM> can be a single transducer or can comprise multiple phased array transducers for steering and focusing the acoustic energy <NUM> on the receiver-stimulators <NUM>. The control circuitry <NUM> can be connected to the sensors <NUM>. As described above, the sensors <NUM> can be configured to detect electrical conduction of the heart and therefore drive the pacing of the controller-transmitter <NUM> and the receiver-stimulators <NUM>.

The sensors <NUM> can be attached to or positioned within different aspects of the controller-transmitter <NUM> and/or the power source <NUM>. For example, in some embodiments, the sensors <NUM> can be fully or partially disposed on an outer casing of the controller-transmitter <NUM>. In some embodiments, the sensors <NUM> can be spaced apart from the controller-transmitter <NUM> and can be wirelessly connected to the controller-transmitter <NUM>. In other embodiments, the sensors <NUM> can be connected to the controller-transmitter <NUM> via cables. In some embodiments, the sensors <NUM> can be disposed within a combination of the positions discussed herein. For example, when the wireless tissue stimulation system <NUM> includes two of the sensors <NUM>, a first one of the sensors <NUM> can be attached to the power source <NUM> (e.g., to a battery) and a second one of the sensors <NUM> can be attached to the transducer assembly <NUM> of the controller-transmitter <NUM>. When the wireless tissue stimulation system <NUM> includes four of the sensors <NUM>, for example, three of the sensors <NUM> can be attached to the housing of the controller-transmitter <NUM> and the other one of the sensors <NUM> can be attached to the power source <NUM>. As one skilled in the art will appreciate, a variety of sensor configurations based on the descriptions herein can be capable of sensing the electrical conduction of the heart in real-time and are within the scope of the present disclosure.

In some embodiments, the controller-transmitter <NUM> can further include a communication module <NUM>. The communication module <NUM> can be configured to provide a data path (e.g., a radiofrequency (RF) communication path) to and/or from an external programmer unit to allow a physician to set device parameters and to acquire diagnostic information about the patient and/or the wireless tissue stimulation system <NUM>.

The receiver-stimulators <NUM> can include a receiving transducer assembly <NUM> (e.g., a piezoelectric transducer assembly) configured to receive the acoustic energy <NUM> and convert the received acoustic energy into electrical energy. Optionally, the receiver-stimulators <NUM> can include a rectifier component (not shown). The optional rectifier component is used to convert the electrical energy to an electrical output which can be configured to effectively stimulate the tissue of the heart <NUM> (e.g., convert AC electrical energy into a DC output; but other output waveforms are also effective). In some embodiments, the electrical output of optional rectifier components is used to directly stimulate tissue. In an alternative embodiment, the receiver-stimulators <NUM> further include processing circuitry that manipulates the electrical output converted by the rectifiers to produce an electrical signal that stimulates tissue. The processing circuitry manipulates the electrical output such that it is suitable for the stimulation application, such as cardiac pacing. Such manipulation can involve summing or conditioning the electrical signals from the individual rectifiers to produce the biologically stimulating electrical output.

The receiver-stimulators <NUM> also include a tissue-contacting electrode assembly <NUM> configured to deliver an output voltage to stimulate the tissue. The electrode assembly <NUM> can include any number of stimulation electrodes (e.g., one, two, three, four, five, or more stimulation electrodes). In one embodiment, the electrode assembly <NUM> comprises at least two stimulation electrodes in electrical contact with the tissue. Either or both of the stimulation electrodes can be mounted directly on the receiver-stimulators <NUM> and form a portion of the receiver-stimulators <NUM> casing. In other embodiments, the stimulation electrodes can extend from the receiver-stimulators <NUM>. In some embodiments, the electrode assembly <NUM> can include features generally similar or identical to those of the electrode assemblies described in <CIT>.

The receiver-stimulators <NUM> can optionally include a voltage limiter <NUM> configured to limit the output voltage delivered to tissue by the electrode assembly <NUM>. In one embodiment, the voltage limiter <NUM> is placed within the electrode assembly <NUM>, such as between the stimulation electrodes. Alternatively, the voltage limiter <NUM> can be placed on the receiving transducer assembly <NUM>, or anywhere between the receiving transducer assembly <NUM> and the electrode assembly <NUM>, such that the voltage limiter <NUM> is able to limit the electrical voltage delivered to the tissue.

Referring to <FIG> and <FIG> together, in one aspect of the present disclosure, in patients with right-side conduction intact, the wireless tissue stimulation system <NUM> can be utilized without a co-implant or leads because the sensors <NUM> are configured to detect the electrical conduction of the heart <NUM> in real-time. Accordingly, pacing of the controller-transmitter <NUM> and the receiver-stimulators <NUM> can be based off the electrical conduction of the heart <NUM> rather than signals received from a co-implant or from additional leads. This can be beneficial because, for example, it eliminates the need for implanting leads associated with traditional pacemaker systems.

The present disclosure also includes methods for synchronizing ventricular contraction in patients having LBBB. <FIG>, for example, is a flowchart of a process or method <NUM> for stimulating the left ventricle of a heart of a patient having LBBB in accordance with embodiments of the present disclosure. Some aspects of the method <NUM> are described with reference to the wireless tissue stimulation system <NUM> of <FIG> and <FIG>, although other suitable systems can be used to carry out the method <NUM>.

In the illustrated embodiment, the method <NUM> begins at block <NUM> by sensing the initiation of the electrical signal to contract the right ventricle of a patient's heart. The initiation of the electrical signal to contract the right ventricle corresponds with the onset of the QRS segment of the ECG reading. For example, the controller-transmitter <NUM> can detect the electrical conduction of the heart <NUM> in real-time using one or more of the sensors <NUM>.

The method <NUM> continues at block <NUM> by emitting acoustic energy in response to the sensed initiation of the electrical signal to contract the right ventricle. The acoustic energy can be emitted, for example, by the transducer assembly <NUM> of the controller-transmitter <NUM>. The controller-transmitter <NUM> can determine when to emit the acoustic energy in response to the sensed initiation of the electrical signal (e.g., immediately or with a slight delay) to facilitate synchronization.

Next, the method <NUM> includes (i) receiving the emitted acoustic energy at a receiver-stimulator (block <NUM>) and (ii) converting the received acoustic energy into electrical energy (block <NUM>). For example, the one or more of the receiver-stimulators <NUM> can receive the acoustic energy <NUM> and convert the acoustic energy to electrical energy via the receiving transducer assemblies <NUM>.

At block <NUM>, the method <NUM> continues by stimulating the left ventricle of the patient's heart with the electrical energy. The stimulation can initiate contraction of the left ventricle and improve the contraction synchronization of the left ventricle and the right ventricle. Accordingly, the stimulation can be provided within a specified duration wherein stimulation of the left ventricle will synchronize the contraction of the left and right ventricles. As described in detail above with reference to <FIG>, the duration can be between about <NUM> millisecond to <NUM> milliseconds after the initiation of the QRS complex.

The method <NUM> can return to block <NUM> and be repeated any number of times to provide continuous stimulation and synchronization of the heart.

The above disclosure is not intended to be exhaustive or to limit the present technology to the precise forms disclosed herein, since the scope of protection is defined by the appended claims. Although specific embodiments are disclosed herein for illustrative purposes, various equivalent modifications are possible as those of ordinary skill in the art will recognize. In some cases, well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the present disclosure. Similarly, certain aspects of the present disclosure disclosed in the context of particular embodiments can be combined or eliminated in other embodiments, limited only by the form of the appended claims. Furthermore, while advantages associated with certain embodiments of the present disclosure can have been disclosed in the context of those embodiments, other embodiments of the present disclosure can have been disclosed in the context of those embodiments, other embodiments can also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages or other advantages disclosed herein to fall within the scope of the appended claims. Accordingly, the disclosure can encompass other embodiments not expressly shown or described herein, and protection is limited only by the appended claims.

Claim 1:
A wireless system (<NUM>) for stimulating the left ventricle of a heart (<NUM>) of a human subject having left bundle branch block, LBBB, the system comprising:
a controller-transmitter (<NUM>) configured to be implanted in the human subject, the controller-transmitter including:
one or more sensors (<NUM>) configured to receive an indication of electrical conduction of the heart (<NUM>),
a controller (<NUM>) operably coupled to the one or more sensors (<NUM>) and configured to determine, in substantially real-time, an occurrence of an onset of a QRS segment in the electrical conduction of the heart (<NUM>), and
a first transducer (<NUM>) operably coupled to the controller (<NUM>) and configured to emit an acoustic signal (<NUM>) in response to the controller (<NUM>) determining the occurrence of the onset of the QRS segment in electrical conduction of the heart (<NUM>); and
a receiver-stimulator (<NUM>) configured to be implanted adjacent to the left ventricle of the human subject, the receiver-stimulator (<NUM>) including:
a second transducer (<NUM>) configured to (a) receive the acoustic signal (<NUM>) emitted from the first transducer (<NUM>) and (b) convert the received acoustic signal (<NUM>) into electrical energy, and
one or more stimulation electrodes (<NUM>) coupled to the second transducer (<NUM>) and configured to deliver the electrical energy to the left ventricle of the heart (<NUM>) as electrical stimulation;
wherein the system (<NUM>) is configured to synchronize contraction of the left ventricle and a right ventricle of the heart (<NUM>) by delivering the electrical stimulation to the left ventricle within a predefined duration beginning at the onset of the QRS segment in the electrical conduction of the heart (<NUM>).