EP2370158A1

EP2370158A1 - Single-chamber pacing using a dual-chamber pacing device

Info

Publication number: EP2370158A1
Application number: EP09736768A
Authority: EP
Inventors: Qingsheng Zhu; Daniel Felipe Ortega; Julio Cesar Spinelli
Original assignee: Cardiac Pacemakers Inc
Current assignee: NEWSTIM, INC.
Priority date: 2008-10-10
Filing date: 2009-10-10
Publication date: 2011-10-05
Also published as: JP2012505054A; AU2009303324A1; JP5319776B2; AU2009303324B2

Abstract

Various embodiments of the present invention are directed to systems, methods and devices for cardiac applications including those relating to pacing devices. One such device is directed to a cardiac rhythm therapy (CRT) device designed for dual chamber pacing using two pacing signals each having a positive and negative component that has been modified for single chamber pacing. The device comprises a first output that connects to a pacing lead; a second output that connects to the pacing lead; a third output that connects to a reference point; and electrical circuitry connecting the second electrical connection to the first output, the third electrical connection to the second output, and the first and fourth electrical connections to the third output.

Description

SINGLE-CHAMBER PACING USING A DUAL-CHAMBER PACING DEVICE

CLAIM OF PRIORITY This application claims the benefit of priority of Zhu et al. U.S. Patent

Application No. 12/249,508, filed on October 10, 2008, entitled METHODS, DEVICES AND SYSTEMS FOR SINGLE-CHAMBER PACING USING A DUAL-CHAMBER PACING DEVICE, which is incorporated by reference herein.

FIELD OF THE INVENTION

This invention generally relates to systems, devices and methods relating to cardiac monitoring and treatments such as ventricular pacing. More particular aspects of this invention concern use of a cardiac -rhythm therapy arrangement for improving heart function by pacing of a patient's left and right ventricles by providing pacing signals to one or more electrodes residing in the patient's right ventricle.

BACKGROUND Pacemakers are perhaps the most well known devices that provide chronic electrical stimulus, such as cardiac rhythm management. Modern pacemakers are designed to be implanted within a patient receiving the medical therapy. Other examples of cardiac stimulators include implantable cardiac defibrillators (ICDs) and implantable devices capable of performing pacing and defibrillating functions. Such implantable devices provide electrical stimulation to selected portions of the heart in order to treat disorders of cardiac rhythm. An implantable pacemaker paces the heart with timed pacing pulses. The pacing pulses can be timed relative to other pacing pulses or to sensed (intrinsic) electrical activity. If functioning properly, the pacemaker enforces a minimum heart rate to make up for the heart's inability to pace itself at an appropriate rhythm for metabolic demand. Some pacing devices synchronize pacing pulses delivered to different areas of the heart in order to coordinate the contractions. Coordinated contractions allow the heart to pump efficiently to provide sufficient cardiac output. Clinical data has shown that cardiac resynchronization, achieved through synchronized biventricular pacing, results in a significant improvement in cardiac function. Cardiac resynchronization therapy improves cardiac function in heart failure patients. Heart failure patients have reduced autonomic balance, which is associated with LV (left- ventricular) dysfunction and increased mortality.

Commonly treated conditions relate to the heart beating too fast or too slow. When the heart beats too slow, often leading to a condition referred to as bradycardia, pacing can be used to increase the intrinsic heart rate and correct the condition. When the heart beats too fast, often due to a condition referred to as tachycardia, intrinsic electrical stimulus of the heart itself, in the presence of certain myocardial substrate modifications (i.e., infarcted or non-conducting areas), can find a circuit that allows them to re-enter into the original activation circuit and re-trigger a new activation. These re-entrant circuits can lead to very fast heart rates that are undesirable and even fatal. To correct for this condition, antitachycardia pacing at rates higher than the tachyarrhytmia rates can be used to regain control of the heart rhythm by using specialized sequences of pulses and trains of pulses. Once the system delivering the antytachycardia fast pacing takes control of the heart it gradually reduces its pacing rate in the hopes that the normal sinus rhythm will take control again, and reduce the intrinsic heart rate. Antytachycardia pacing is generally used in combination with an implantable defibrillator, because the pacing burst could accelerate the arrhythmia into ventricular fibrillation.

When pacing for bradycardia, percutaneously placed pacing electrodes are commonly positioned in the right-side chambers (right atrium or right ventricle) of the heart. Access to such chambers is readily available through the superior vena cavity, the right atrium, the tricuspid valve and then into the right ventricle. Pacing of both the right atrium and right ventricle was developed. Such dual chamber pacing resulted in better hemodynamic output than right ventricle-only pacing. In addition to treating bradycardia, dual chamber pacing maintained synchrony between the chambers.

Electrode placement in the left ventricle is normally avoided, where access is not as direct as in right ventricle placement. Moreover, emboli risk in the left ventricle is greater than in the right ventricle. Emboli which might develop in the left ventricle by reason of the electrode placement have direct access to the brain via the ascending aorta from the left ventricle. This presents a significant risk of stroke. Recent clinical evidence suggests that conventional ventricular pacing from the right ventricle creates asynchronous contraction of the left and right ventricles, thereby resulting in inefficient mechanical contraction and reduced hemodynamic performance. Long term right ventricular pacing has even been found to be associated with an increased risk of developing and/or worsening heart failure.

SUMMARY

The present invention can, in certain examples, help overcome one or more of the above-mentioned challenges or others. The present invention is exemplified in a variety of implementations and applications, many of which involve tools and methods helpful, or particularly suited, for certain cardiac conditions advantaged by ventricular pacing. Aspects of the present invention are exemplified by ventricular pacing of the right and left ventricles from a lead in the right ventricle. Embodiments may be used, among other applications, to facilitate mechanically and/or electrically synchronous contractions for resynchronization or to maintain synchrony during ventricular pacing. Specific implementations relate to such pacing for treatment of bradycardia.

According to one implementation, a patient is treated by directly stimulating the normal physiologic conduction system of the heart to elicit a conduction sequence. The conduction sequence follows the conduction sequence found in a normal heart, both spatially and temporarily. The degree to which the conduction sequence follows that of a normal heart can be effected by the state of the myocites, current composition of the extracellular matrix, magnitude, number and distribution of scar tissue due to infarcts, ischemic areas due to coronary obstructions to cardiac blood flow and the status of the myocardial substrate in general.

Aspects of the present invention build upon the discovery relating to simultaneously or nearly simultaneously (within 1-20 ms) applying two opposite polarity waveforms (pulse width between .01 to 5 ms) to two electrodes with respect to a reference, also referred to as an XSTIM waveform. It has been discovered that it is possible to, not only penetrate the root of the His Bundle and Purkinje system, but also to reach regions of the His after its bifurcation in the multiple bundles. The penetration of the multiple bundles generates a relatively normal conduction response through the right ventricle, the left ventricle and the septum. This allows for electrically activation of distal bundles at a point that allows bypassing of many conduction defects of the normal physiologic conduction system of the ventricles. One embodiment of the present invention is directed to a cardiac rhythm therapy (CRT) method, system or device for dual ventricular pacing (also known as a biventricular pacing device) using two pacing signals each having a positive and negative component that has been modified for single ventricular pacing (if the device is a dual chamber biventricular device that has the capability of atrial sensing and pacing, that aspect of the device can be left intact). A first output is provided for connecting to a pacing lead; a second output is provided for connecting to a pacing lead; and a third output is provided for connection to a reference point. The reference point can be the conductive can of the device or an electrode on any other lead connected to the device. For instance, the reference point could be the distal or proximal defibrillation coil of a defibrillation lead, where the defibrillator device has been modified to implement the XSTIM right ventricular waveform configuration. Electrical circuitry is provided for connecting the second electrical connection to the first output, the third electrical connection to the second output, and the first and fourth electrical connections to the third output. If the device has the capability to sense and pace the atrium, the atrial sensing and pacing outputs can remain connected to the atrial lead.

Aspects of the present invention are directed to a pacing system having a signal generator that provides a first pacing signal and a second pacing signal, each pacing signal having positive and negative signal components. A pacing lead paces a heart from a single chamber of the heart, the pacing lead having a first electrode and a second electrode. Circuitry routes at least some of the signal components of the two pacing signals to the pacing lead by connecting a positive component of a first pacing signal and a negative component of a second pacing signal to a common reference and by connecting the negative component of the first pacing signal to the first electrode and the positive component of the second pacing signal to the second electrode. Aspects of the present invention can be used in connection with a biventricular cardiac resynchronization therapy (CRT) device that provides biventricular pacing using a first pacing signal and a second pacing signal, each pacing signal having a positive and a negative signal component. Second and third outputs are connected to a reference point. First and fourth outputs are connected to respective inputs of the pacing lead. The positive component of a first pacing signal is provided to the first output and the negative component of the first pacing signal is provided to the second output and the positive component of the second pacing signal is provided to the third output and the negative component of the second pacing signal is provided to the fourth output. According to an example embodiment of the present invention, a cardiac resynchronization therapy (CRT) device is improved upon. The unimproved CRT device provides biventricular pacing using a first pacing signal for one chamber of a heart and a second pacing signal for another chamber of the heart. The CRT device is improved by adding circuitry for referencing each pacing signal to a common reference component; and a pacing lead for using the CRT device to provide single chamber pacing using a negative component from one pacing signal and a positive component from the other pacing signal to pace the single chamber, wherein the pacing signal includes a negative pulse and a positive pulse, each referenced to the common reference component. Aspects of the present invention are directed toward a circuit for use with a cardiac resynchronization therapy (CRT) device designed for biventricular pacing using a first pacing signal having a positive component provided to a first electrical connection and negative component provided to a second electrical connection and a second pacing signal with a positive component provided to a third electrical connection and negative component provided to a fourth electrical connection. The circuit includes a first output for connecting to a pacing lead, a second output for connecting to the pacing lead; a third output for connection to a reference point, and electrical circuitry connecting the second electrical connection to the first output, the third electrical connection to the second output, and the first and fourth electrical connections to the third output.

Another embodiment of the present invention relates to a device for connecting a pacing lead to a cardiac rhythm therapy (CRT) apparatus designed for dual chamber pacing using two pacing signals each having positive and negative signal components, the positive component of a first pacing signal being provided to a first output and the negative component of the first pacing signal being provided to a second output and the positive component of the second pacing signal being provided to a third output and the negative component of the second pacing signal being provided to a fourth output wherein, for dual chamber pacing, the first and second outputs are for use with a first pacing lead and the third and fourth outputs are for use by a second pacing lead. The interface includes a connector housing for physically mating with two interfaces of the CRT apparatus. The first interface provides the first and second signal components and the second interface provides the third and fourth signal components, each interface arranged for physically mating with a pacing lead. The housing also mates with a single pacing lead. The device includes electrical connections from the second and third outputs to a reference point and from the first and fourth outputs to respective inputs of the single pacing lead, thereby allowing single chamber pacing using the single pacing lead.

Aspects of the present invention are directed toward a method of creating a pacing system from a cardiac rhythm therapy (CRT) device having a signal generator that provides a first pacing signal and a second pacing signal, each pacing signal having respective positive and negative signal components. A pacing lead is provided for delivering pacing to a chamber of a heart, the pacing lead having a first electrode and a second electrode. The signal components of the two pacing signals are connected to the pacing lead by connecting a positive component of a first pacing signal and a negative component of a second pacing signal to a common reference and by connecting the negative component of the first pacing signal to the first electrode and the positive component of the second pacing signal to the second electrode.

An embodiment of the present invention is directed to a method of manufacturing a pacing system. A signal generator is produced that provides a first pacing signal and a second pacing signal, each pacing signal having respective positive and negative signal components. A pacing lead is produced for delivering pacing to a chamber of a heart, the pacing lead having a first electrode and a second electrode. Circuitry is produced for routing the signal components of the two pacing signals to the pacing lead by connecting a positive component of a first pacing signal and a negative component of a second pacing signal to a common reference and by connecting the negative component of the first pacing signal to the first electrode and the positive component of the second pacing signal to the second electrode. Aspects of the present invention are directed toward a signal routing matrix for connecting a pacing lead to a cardiac rhythm therapy (CRT) device designed for dual chamber pacing using two pacing signals each having positive and negative signal components, the positive component of a first pacing signal being provided to a first output and the negative component of the first pacing signal being provided to a second output and the positive component of the second pacing signal being provided to a third output and the negative component of the second pacing signal being provided to a fourth output wherein for dual chamber pacing the first and second outputs are for use with a first pacing lead and the third and fourth outputs are for use by a second pacing lead. The signal routing matrix includes electrical connections from the second and third outputs to a reference point and from the first and fourth outputs to respective inputs of a single pacing lead, thereby allowing single chamber pacing using the single pacing lead.

Example 1 can include a pacing system for use with a lead including a first electrode and a second electrode for pacing a heart from a single chamber of the heart. The pacing system can comprise a signal generator, configured to provide first and second pacing signals, each having positive and negative signal components. A configurable routing circuit, can be capable of being configured for routing a positive component of the first pacing signal and a negative component of the second pacing signal to a common signal reference and routing a negative component of the first pacing signal to the first electrode and a positive component of the second pacing signal to the second electrode. In Example 2, the subject matter of Example 1 can optionally include a first capacitive component for providing the first pacing signal and a second capacitive component for providing the second pacing signal.

In Example 3, the subject matter of any one of Examples 1-2 can optionally include the lead including the first electrode and the second electrode for pacing the heart from the single chamber of the heart.

In Example 4, the subject matter of any one of Examples 1-3 can optionally include an interface for electrically connecting to first and second outputs of the signal generator, each of the first and second outputs providing a respective one of the first and second pacing signals, to the lead.

In Example 5, the subject matter of any one of Examples 1-4 can optionally further include a third output configured for providing a pacing signal.

In Example 6, the subject matter of any one of Examples 1-5 can optionally include a sense input for detecting an electrical signal of the heart. In Example 7, the subject matter of any one of Examples 1-6 can optionally include pacing control circuitry for modifying the first and second pacing signals.

In Example 8, the subject matter of any one of Examples 1-7 can optionally include a lead configured for sensing atrial activity. In Example 9, the subject matter can include, or can optionally be combined with the subject matter of any one of Examples 1-8 to include, for use with a biventricular cardiac resynchronization therapy (CRT) device that is configured to provide biventricular pacing using first and second pacing signals, each having a positive and a negative signal component, a method comprising connecting second and third outputs to a signal reference; and connecting first and fourth outputs to respective inputs of a lead, wherein the positive component of a first pacing signal is provided to the first output and the negative component of the first pacing signal is provided to the second output and the positive component of the second pacing signal is provided to the third output and the negative component of the second pacing signal is provided to the fourth output.

In Example 10, the subject matter of any one of Examples 1-9 can optionally include placing the lead in association with a left ventricle of a heart, and providing electrical signals, carried on the first and fourth outputs, to the left ventricle of the heart.

In Example 11, the subject matter of any one of Examples 1-10 can optionally include: placing the lead in association with a left ventricle of a heart; providing, to the left ventricle of the heart, electrical signals carried on the first and fourth outputs; monitoring heart function that is responsive to the provided electrical signals; assessing effectiveness as a function of the monitored heart function; and adjusting a placement of the lead or a characteristic of one or more of the electrical signals in response to the assessment. In Example 12, the subject matter of any one of Examples 1-11 can optionally include iteratively repeating the steps of providing, monitoring and adjusting; and responsive to the multiple assessments, selecting a placement of the lead or a characteristic of one or more of the electrical signals to use for chronic pacing. In Example 13, the subject matter of any one of Examples 1-12 can optionally include sensing an atrial activation; and, responsive to sensing the atrial activation and an atrioventricular (AV) delay, providing, to the left ventricle of the heart, electrical signals carried on the first and fourth outputs. In Example 14, the subject matter of any one of Examples 1-13 can optionally include modifying the AV delay as a function of heart response to the provided electrical signals.

Example 15 can include, or can optionally be combined with the subject matter of any one of Examples 1-14 to include, a cardiac resynchronization therapy (CRT) device that, when providing biventricular pacing, uses a first pacing signal for one chamber of a heart and a second pacing signal for another chamber of the heart, wherein the CRT device comprises: circuitry for referencing each of the first and second pacing signals to a common reference component; and a pacing output, configured to be coupled to a lead, for using the CRT device to provide single chamber pacing using a negative component from one pacing signal and a positive component from the other pacing signal to pace the single chamber, wherein the pacing signal includes a negative pulse and a positive pulse, each referenced to the common reference component. In Example 16, the subject matter of any one of Examples 1-15 can optionally include pacing control circuitry for modifying a characteristic of at least one of the first and second pacing signals.

In Example 17, the subject matter of any one of Examples 1-16 can optionally include a sensing circuit for generating a signal indicative of synchronicity of a contraction of the heart.

In Example 18, the subject matter of any one of Examples 1-17 can optionally include circuitry for providing a third pacing signal.

In Example 19, the subject matter of any one of Examples 1-18 can optionally include sense circuitry for detecting atrial activation signals of the heart.

Example 20 can include, or can optionally be combined with the subject matter of any one of Examples 1-19 to include, for use with a cardiac resynchronization therapy (CRT) device designed for biventricular pacing using a first pacing signal having a positive component provided to a first electrical connection and negative component provided to a second electrical connection and a second pacing signal with a positive component provided to a third electrical connection and negative component provided to a fourth electrical connection, a circuit comprising: a first output, configured to connect to a pacing lead; a second output, configured to connect to the pacing lead; a third output, configured to connect to a reference point; and electrical circuitry, configured to connect the second electrical connection to the first output, the third electrical connection to the second output, and the first and fourth electrical connections to the third output. In Example 21, the subject matter of any one of Examples 1-20 can optionally include the electrical circuitry being programmable such that the first and second outputs can be connected to any of the first, second, third, or fourth electrical connections.

In Example 22, the subject matter of any one of Examples 1-21 can optionally include the first and second pacing signals being generated using an independently referenced signal source.

In Example 23, the subject matter of any one of Examples 1-22 can optionally include first and second capacitive sources, each including respective positive and negative terminals, the positive and negative terminals of the first capacitive source corresponding to the first and second electrical connections, respectively, and the positive and negative terminals of the second capacitive source corresponding to the third and fourth electrical connections, respectively, wherein each of the first and second pacing signals is provided by one of the first and second capacitive sources that is independently referenced from the other of the first and second capacitive sources.

Example 24 can include, or can optionally be combined with the subject matter of any one of Examples 1-23 to include a device for connecting a single lead to a cardiac rhythm therapy (CRT) apparatus designed for dual chamber pacing using two leads for respectively providing first and second pacing signals, each having positive and negative signal components, the positive component of the first pacing signal being provided to a first output and the negative component of the first pacing signal being provided to a second output and the positive component of the second pacing signal being provided to a third output and the negative component of the second pacing signal being provided to a fourth output wherein, for dual chamber pacing, the first and second outputs are for use with a first lead and the third and fourth outputs are for use by a second lead, the device comprising: a connector configured for physically mating with two interfaces of the CRT apparatus, the first interface providing the first and second outputs and the second interface providing the third and fourth outputs, each interface arranged for physically mating with a respective lead; and electrical connections from the second and third outputs to a signal reference and from the first and fourth outputs to respective inputs of the single lead, thereby allowing single chamber pacing using the single lead.

In Example 25, the subject matter of any one of Examples 1-24 can optionally include a device configured for physically mating with a third interface of the CRT apparatus.

In Example 26, the subject matter of any one of Examples 1-25 can optionally include a device wherein the electrical connections further include a connection between a sense signal of the third interface and the single lead. In Example 27, the subject matter of any one of Examples 1-26 can optionally include a device, wherein the electrical connections further include connections between fifth and sixth outputs and a second lead.

Example 28 can include, or can optionally be combined with the subject matter of any one of Examples 1-27 to include a method of creating a pacing system from a cardiac rhythm therapy (CRT) device having a signal generator that provides a first pacing signal and a second pacing signal, each of the first and second pacing signals having respective positive and negative signal components, the method comprising: using a lead for delivering pacing to a chamber of a heart, the lead including a first electrode and a second electrode; and connecting the signal components of the first and second pacing signals to the lead by connecting a positive component of a first pacing signal and a negative component of a second pacing signal to a common reference, and by connecting the negative component of the first pacing signal to the first electrode and the positive component of the second pacing signal to the second electrode.

In Example 29, the subject matter of any one of Examples 1-28 can optionally include attaching an electrical interface to the CRT device, the electrical interface providing said connection of the signal components.

In Example 30, the subject matter of any one of Examples 1-29 can optionally include configuring a programmable connection array of the CRT device, the configuration resulting in said connection of the signal components.

In Example 31, the subject matter of any one of Examples 1-30 can optionally include connecting a sensing signal component to the lead.

Example 32 can include, or can optionally be combined with the subject matter of any one of Examples 1-31 to include, a method of manufacturing a pacing system, the method comprising: producing a signal generator that provides a first pacing signal and a second pacing signal, each of the first and second pacing signals including respective positive and negative signal components; and producing circuitry for routing the signal components of the first and second pacing signals to a single lead comprising first and second electrodes by connecting a positive component of a first pacing signal and a negative component of a second pacing signal to a common reference and by connecting the negative component of the first pacing signal to the first electrode and the positive component of the second pacing signal to the second electrode. Example 33 can include, or can optionally be combined with the subject matter of any one of Examples 1-32 to include or use a signal routing matrix for connecting a lead to a cardiac rhythm therapy (CRT) device designed for dual chamber pacing using first and second leads for respectively using two pacing signals each having positive and negative signal components, the positive component of a first pacing signal being provided to a first output and the negative component of the first pacing signal being provided to a second output and the positive component of the second pacing signal being provided to a third output and the negative component of the second pacing signal being provided to a fourth output wherein for dual chamber pacing the first and second outputs are for use with the first lead and the third and fourth outputs are for use by the second lead, the signal routing matrix comprising: electrical connections from the second and third outputs to a signal reference and from the first and fourth outputs to respective inputs of the lead, thereby allowing single chamber pacing using the lead.

In Example 34, the subject matter of any one of Examples 1-33 can optionally include or use a matrix comprising electrical connections from an output of the lead to a sensing input of the CRT device.

In Example 35, the subject matter of any one of Examples 1-34 can optionally include or use a matrix comprising electrical connections for fifth and sixth outputs to respective inputs of a second lead.

As previously indicated, the above-discussed aspects and examples are not to be treated as limiting the scope or teachings of the disclosure herein. The skilled artisan would appreciate that, partly based on the various discoveries identified herein, the present invention can be embodied in many ways including but not limited to the above-discussed aspects and examples.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention may be more completely understood in consideration of a detailed discussion of various example embodiments, described in accordance with the present invention, as presented hereinafter in connection with the following figures, each of which is consistent with the present invention:

FIG. IA shows an illustration of a modified CRT device, consistent with an example embodiment of the present invention; FIG. IB shows an illustration of a CRT device, such as those modified in

FIGs. 1A-8, placed within the heart, consistent with an example embodiment of the present invention.

FIG. 2 shows an interface and circuit for providing a pacing signal, consistent with the present invention; FIG. 3 shows an interface and circuit for providing pacing signals, consistent with embodiments of the present invention;

FIG. 4 shows an illustration of a modified dual chamber pacemaker (DDD) device, consistent with an example embodiment of the present invention;

FIG. 5 shows an illustration of a modified dual chamber pacemaker (DDD) device, consistent with an example embodiment of the present invention;

FIG. 6 shows an illustration of a modified DDD device, consistent with an example embodiment of the present invention;

FIG. 7 shows an illustration of a modified DDD device, consistent with an example embodiment of the present invention; and FIG. 8 shows an illustration a Biventricular DDD CRT device, consistent with an example embodiment of the present invention.

While the invention is amenable to various modifications and alternative forms, various embodiments have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the scope of the invention. DETAILED DESCRIPTION

The present invention is believed to be applicable to a variety of different types of devices and approaches, and the invention has been found to be particularly suited for maintaining and re-establishing a normal conduction of the activation sequence of the ventricles, both its spatial and time distributions from a lead in the right ventricle that has electrodes positioned behind the root of the septal leaflet of the tricuspid valve. The exact spot depends on the location of the block that needs to be bypassed. This spot can be dependent upon the location of the bundle fibers that are interrupting the conduction circuit and creating the abnormality. In many patients this location is close to the septal leaflet of the tricuspid valve and the fibrous atrio-ventricular and interventricular septum. While the present invention is not necessarily limited to such applications, various aspects of the invention may be appreciated through a discussion of various examples using this context. It has been discovered that various aspects of the invention, including methods and devices, facilitate the deep penetration into the His root and distal Bundles. This penetration can include the left bundle and its bifurcations, the right bundle and its bifurcations and the septal bundle. This can be particularly useful for electrically bypassing various types of bundle branch blocks (e.g., right bundle branch block RBBB, proximal and distal; left bundle branch block LBBB, proximal and distal; left anterior hemiblock LAHB, proximal and distal, left posterior hemiblock LPHB, proximal and distal, intraventricular conduction defects IVCD, RBBB with left axis deviations and many other kinds of complex conduction defects). One such aspect of the invention is directed to the ability and use of waveforms, such as XSTIM, to penetrate deeply into the conduction system near the His Bundle. For example, the use of an XSTIM waveform creates a larger virtual electrode than with other waveforms and can be useful to overcome capacitance of the body.

The conduction system near the His Bundle can be thought of as a group of multiple electrical conductors each surrounded by electrical isolators. Thus, pacing signals introduced to the conduction system can be effected by capacitance between the electrical conductors. The electrical conductors are able to conduct the electrical impulse longitudinally from cell to cell, but there is very little conductivity, within the bundles, in the transversal direction. However, it is believed that strategically located bridges between cells allow the electrical stimulus to jump from one bundle to the other. This mechanism is believed to provide some redundancy in case a particular bundle stops working, for instance due to an infarct or micro-infarct. The bundles branch into sets of multiple conduction fibers as they progress towards their destination at the Purkinje fibers. The sets of fibers are electrically isolated from the rest of the myocardium by specialized tissue to prevent electrical depolarization of the surrounding distributed capacitor network, with, in its transversal cut, the bundle of His being in the myocites from electrical pulses passing through the specialized conduction system. It is believed that this combination of electrical conductors and isolators effectively creates a middle of at least two serial capacitors. Because the cell membranes of the His bundle cells are also isolators, the intracellular fluid inside the His bundle cells are placed inside still another capacitor.

The XSTIM waveform provides a relatively large virtual electrode, whose asymmetrical dog bone shape will be affected by the polarity of the waveform, henceforth allowing the penetration of the waveform to be adjusted by modifying the relative polarities applied to the two electrodes. The XSTIM waveform also provides a high frequency stimulation energy that is able to bypass the capacitors. Thus, it is believed that the XSTIM waveform is able to deeply penetrate the His bundle. Even when the two opposite polarity pulses are separated by a few milliseconds (0 to 20 ms), the waveform is seen to penetrate and reach the bundles, even distal bundles, previously thought to be unreachable. Furthermore, it has been discovered through experimental data that there is not a single capture threshold for the myocardium and for the His bundle. Indeed the response in many patients varies as the pacing voltage is increased. When the XSTIM amplitude is gradually increased from subthreshold values a first capture (previous art) threshold is found that triggers a depolarization sequence that activates the ventricles. In many patients this is followed by a second threshold that triggers the capture of some fibers of the His bundle. In patients with ventricular conductions defects, a continuous change in the electrocardiogram (ECG), QRS width, level of fractionation and vector of the 12 lead ECG is observed when the XSTIM amplitude is increased further. At some point a saturation point is reached and little or no further improvement is seen. It is believed that through careful positioning and selection of amplitude level, the pacing stimulus is able to reach the furthest blocked fibers of the conduction system, thus improving the coordination of the contraction to near normal levels.

The ability to achieve a normal conduction response may depend on the health of the substrate including, but not limited to, number of infarcts, myocites degeneration, availability of mitochondria, blood supply, presence of interstitial fibrosis, degradation of the metallo-proteinase matrix, etc. The implication of these and other findings is that a similar effect can be achieved with a variety of wave-shapes and electrode configurations designed to traverse the capacitive networks (e.g., due to high frequency signal components). The effective capacitance is lower for higher frequency components, including frequency components that are sufficient to trigger an action potential (.01 to 20 ms). While some waveforms may be less efficient and use more energy to achieve similar results, the invention is not limited to applications of the most efficient waveforms.

Aspects of the present invention relate to the discovery that the distal blocks of the bundle of His can be bypassed using proximal stimulation of the bundles. For instances, such blocks can be bypassed by applying the appropriate electrical energy (pacing pulse) to a region of the His bundle. This region is located proximal to the tricuspid annulus and passes directly behind the septal leaflet of the tricuspid valve on the right ventricular side. This same region can be reached from the right atrium on the atrial side of the tricuspid valve by the root of the septal leaflet of the tricuspid valve.

Other aspects of the invention relate to the use of a high-amplitude (20- 36 Volts) unipolar or bipolar pulse applied to the region. For instance, a unipolar pulse can be applied between the two electrodes located in the region of His and also allows for penetration that is deep enough to activate many fibers of the conduction system. Generally, the voltage required is much higher on the average than the energy required for an XSTIM pacing signal. Furthermore, results of human studies suggest that these high voltage pulses are felt by the patients and in certain cases they can cause undesired muscle contractions. Aspects of the present invention are directed to modification of existing devices (e.g., those used for Bradyarrhythmia (pacemakers), Tachyarrhythmia (defibrillators -ICD) and Heart Failure (Cardiac Resynchronizers that deliver Cardiac Resynchronization Therapy -CRT)) into devices that can implement the XSTIM waveform and Electrical Bypass Therapy, either alone or in combination with CRT or ICD or CRT+ICD.

Normally the activation sequence of the ventricles starts in the atrial side of the atrio-ventricular node and propagates to the root of the His Bundle, where it bifurcates into a multitude of small bundles that are grouped into the right and left bundles. The fibers within each bundle are generally insulated from one another; however, there are locations exhibiting lesser insulation at intervals along the bundle. These bundles are electrically isolated from the surrounding tissue and terminate into the Purkinje cells that are in charge of communicating the electrical activation to the myocites. A normal heart conducts an electrical signal from the His Bundle throughout the ventricles in around 60-70 ms. Conduction abnormalities, such as those due to infarct or micro-infarcts, can impede or block the conduction of the electrical activation impulse through the specialized His fibers. Such blocks result in Purkinje cells that do not receive the electrical activation impulse over the conduction fibers. The myocites that are normally stimulated by these Purkinje cells are therefore not stimulated in the normal fashion. Instead, these myocites are stimulated from electrical signals propagating through myocites that did receive the electrical activation pulse from the conduction fibers. The conduction velocity between myocites is significantly slower than the conduction velocity of the conduction fibers. For example, the conduction fibers have a conduction velocity of around 2 m/s whereas the cell to cell conduction velocity of myocites is around 0.5 m/s. Accordingly, these blocks can significantly distort both the spatial and time distributions of the electrical activation of the ventricles. These temporal and spatial activation sequence distortions introduce mechanical asynchronies that can adversely affect the hemodynamics of the heart. Such mechanical asynchronies can lead to a set of progressive mal-adaptive compensatory processes, among them dilatation, in the late activated regions: fibroblast proliferation, local proto-oncogene activations, compensatory regional hypertrophy, sympathetic/parasympathetic balance increases, among others. These processes can lead to heart failure that may have been delayed or prevented had the conduction abnormalities not being there to start with. Therefore, according to aspects of the present invention, both maintaining (when ventricular pacing is required due to bradycardia) or re-establishing a normal conduction sequence (or as normal as possible if the substrate is already degraded due to infarcts, micro-infarcts, amyloidosis, Chagas disease, advanced dilatation and degradation of the metalloproteinase support matrix of the myocites, myocites degradation, etc.) can have significant advantages for delaying, stopping or even reversing the progression towards Heart Failure.

For other forms of resynchronization therapy the activation sequence is started from two sites in the right and left ventricles to directly stimulate the myocites rather than use the normal the conduction system. This leads to abnormal activation sequences. In one implementation, physicians are directed to place at least one lead in the epicardium of the left ventricle (e.g., by placing this lead in the coronary vein system of the left ventricle). This placement creates a further type of asynchrony as the activation sequence will not only be slow but also inverted with respect to a normal/healthy sequence. Despite these problems of such treatment, this type of the cell to cell (without the activation of the conduction system) activation sequence is better than the other applications of CRT. The success rate of CRT using biventricular pacing is limited to only about 60 to 70% of patients where the untreated activation sequence is "worse" than the new artificial sequence created by biventricular pacing.

Therefore, aspects of the present invention are useful for providing a modality of resynchronizing the ventricles and can be easily implemented. For example, embodiments of the present invention relate to a method that does not require the step of placing a lead in the LV through the coronary sinus into the LV cardiac veins something that could only be achieved by highly specialized physicians in only high complexity institutions and after long, expensive and sophisticated training. Moreover, embodiments of the present invention can safely (e.g., one less lead that can fail or cause problems) provide pacing benefits to patients that would not otherwise have viable treatment options. In certain implementations, the invention is used to facilitate mechanically and/or electrically synchronous contractions for resynchronization (possibly due to conduction abnormalities such as Left Bundle Branch Block (LBBB)) where, responsive to aspects of the invention, the left ventricle has regained its ability to rapidly contract and/or to synchronize contractions of cardiac muscle of the septum and respective free wall(s). While the present invention is not necessarily limited to such applications, various aspects of the invention may be appreciated through a discussion of various examples using this context. Consistent with specific embodiments and various discoveries realized in connection with the present invention, heart function can be improved by pace- mapping and/or by delivering pulses to a cardiac site. The heart function is indicated or measured using a variety of techniques. Representative examples include, but are not limited to, measuring/detecting: a narrowing of the QRS width, decreased level of QRS fractionation in the 12 lead ECG, normalization or improvement of the vector angle of the 12 lead ECG, decrease in the late LV activation timing, improvement in the mechanical synchronicity of free wall and septal wall, improvement in the rate of increase of left ventricular pressure, improvements in hemodynamics indirectly assessed from right ventricular pressure measurements, a decrease in the left ventricular end diastolic pressure, improvements in the effective pressure, improvements in the heart sounds, disappearance of the S3 component of the heart sounds, improvement in the acceleration profile of the heart as evaluated with an accelerometer, improvement in efficiency of the contraction (amount of energy spent per 100 ml of blood ejected), improvement in the respiratory profile of the patient or his/her minute ventilation as assessed with impedance or other techniques, an increased parasympathetic/sympathetic balance, improvements in the heart rate variability profile, improvements in the percentage of time the patient is active, improvements in the level of lung edema as assessed by the impedance technique, and/or by any combination thereof. In specific implementations, the pacing can be implemented using XSTIM waveform at a target pacing region.

A variety of sensing devices can be used to assess the efficacy of the pacing signal and location. Examples of suitable sensors include, but are not limited to sensors that can be used to: assess the dP/dt max (maximum rate of increase of left intraventricular pressure, directly measured or indirectly derived from echo-techniques or right ventricular pressure measurements), cardiac output, electrocardiographs can be used to quantify the narrowing of the QRS width, decreased level of QRS fractionation in the 12 lead ECG. Other examples include, but are not limited to, the following devices or sensed heart- functionality: vectocardiographs or body surface mapping equipment can be used to assess the normalization or improvement of the vector angle of the 12 lead ECG, decrease in the late LV activation timing, improvement in the mechanical synchronicity of free wall and septal wall, many methods and equipment exist to assess the improvement in the rate of increase of left ventricular pressure both directly or indirectly, implantable or external sensors can be used to assess the improvements in hemodynamics indirectly from right ventricular pressure, and/or a decrease in the left ventricular end diastolic pressure, and/or improvements in the effective pressure, microphones and heart sounds quantification equipment can be used to assess the improvements in the heart sounds, disappearance of the S3 component of the heart sounds, an accelerometer either implanted, inside the patient (i.e., in the tip of a lead) or on the surface of the body can be used to assess the improvement in the acceleration profile of the heart, intracardiac temperature can be used among other techniques to assess the improvement in efficiency of the contraction (amount of energy spent per 100 ml of blood ejected), transthoracic impedance measurements or intracardiac lead impedance measurements can be used to assess the improvement of the respiratory profile of the patient or his/her minute ventilation, Heart Rate variability analysis can be used to assess an increased arasympathetic/sympathetic balance and/or general improvements in the heart rate variability profile, an implantable accelerometer can be used to assess the improvements in the percentage of time the patient is active, transthoracic or lead impedance can be used to assess improvements in the level of lung edema, and/or any combination thereof. These and other aspects can be directly measured or using indirect non-invasive measurements like cuff based estimations of the systolic and diastolic arterial pressure, with an increase in the systolic pressure or a decrease of the diastolic pressure and with no change of the systolic being the goal. Another indirect method of estimating includes extrapolation of relevant hemodynamic information from right ventricular pressures.

Aspects of the invention are directed to locating and/or pacing at a target pacing region. In one implementation, the target pacing region is at or near the His Bundle. In specific implementations, locating the target pacing region can be assisted by determining a likely location of the blocked fibers. This can be accomplished using anatomical knowledge and extrapolation to 2-dimensional fluoroscopy. A pacing catheter can be placed near the determined location for delivery of the pacing signals. A sensor, such as a 12 lead ECG detecting improved/normal QRS and activation vector possible for the patient, is used to locate the optimum application site.

According to one embodiment of the present invention, a pre-shaped sheath or a steerable or a deflectable sheath with a pair of electrodes on its tip is used for pace-mapping. Once the optimal application site is determined, the permanent pacing catheter is introduced to the site identified by the sheath, without moving its tip, and the catheter is then fixed to the location, e.g., by screwing into the septal wall. The parameters of the device, such as atrioventricular delay (the time from the sensed atrial event till the issuance of a pacing stimulus in the optimum site), the pacing {e.g., XSTIM) amplitude, the interpulse distance (from -20ms for the first pulse to the second opposite polarity pulse to +20ms), the polarity of the pulses (either - to tip or + to tip), the order of the polarities if the interpulse distance is more than zero (- first or + first) can be optimized in one embodiment using indirectly derived electrocardiograms obtained from the electrodes present in the implanted leads (see above for other sensors that can also be used for site optimization). For background information on such implanting procedures, reference can be made to U.S. Patent No. 7,299,086 to McCabe et ah, Wireless ECG in implantable devices and issued on November 20, 2007, which is fully incorporated herein by reference. In certain implementations, the optimization can be performed by implanting a right ventricular pressure sensor to sense direct right ventricular pressure measurements. Such a sensor can detect right ventricular systolic pressure. This detection can be used to extrapolate left ventricular responses, such as left ventricular systolic pressure or preferably dP/dtmax or left ventricular end-diastolic pressure (LVEDP). To ensure hemodynamic stability, these measurements can be performed during periods when the patient is at rest. The atrial rate can be monitored and when it is discovered that a period of low and stable rate occurs other sensors can be used (i.e. an accelerometer to determine that the patient is still or doing minimal movements). These measurements taken during a stable rate are then used to adjust the parameters of the pulse generator and/or placement. The parameter adjustment can be automatically implemented by the device after the implant has been completed, for instance it can be accomplished in a standard dicotomic way, where the starting point is the previous point and the parameter is adjusted up by 10-30%. If no different effect is seen the parameter is adjusted 10-30% down. If a beneficial effect is seen, the parameter is then adjusted further down by 10-30% until a detrimental effect is seen, at that point the last adjustment is cut in half and the parameter adjusted up by 5-15% and measurements taken again. If the effect is still detrimental, the parameter is adjusted up by 2.5-7.5% until a beneficial effect is seen. The adjustment will then naturally converge to the optimum parameters.

According to another embodiment, in patients with dilated hearts, the physician may choose to give preference to the heart as an organ, rather than to the rest of the body, to facilitate healing and reverse remodeling of the heart. For that purpose, the preload of the left ventricle can be reduced while keeping the heart synchronous using pacing, such as XSTIM, at the optimum site. This differs from some of the methods discussed herein where the parameters were adjusted to find optimal left ventricular function so as to find the point of functioning where the heart was providing a high level of cardiac output to the body. This type of optimization, however, can be less than optimal with respect to the effect on the heart. Aspects of the present invention allow the maintenance of ventricular synchrony for a variety of different AV delays. For example, the ability of XSTIM CRT to maintain synchrony at various AV delays allows for the use of AV delays that are beneficial for the dilated heart, even where the AV delays are suboptimal for preload of the left ventricle. Therefore, for patients with extremely dilated hearts, the AV delay can be set to a very short delay. The AV delay can be determined by reducing the AV delay until the left atrial contraction starts occurring after the closure of the mitral valve. This event represents the shortest possible AV delay that will not compromise lung function by increasing pulmonary capillary wedge pressure. At the same time this AV delay will allow the heart to function with the lowest possible end diastolic pressure and preload. These measurements can be easily done using current art Doppler echocardiography. Optimizing the AV delay in the manner taught in this disclosure can allow the heart to work with a low preload to increase the likelihood of reverse remodeling. After the heart shows improvement/reverse- remodels, the AV delay can be increased to a setting that is set according to the previously mentioned techniques (e.g., ECG, RV pressure, LV dP/dt, ECG measurements, LVEDP, etc.).

In an embodiment of the present invention, the AV delay setting is started at a very low AV delay determined by the implanting physician, using an estimate, patient symptoms or Doppler echocardiography as described above. After a predetermined amount of time (ranging from weeks to months, programmable by the physician), the device can be set to automatically switch the AV delay of the implantable device to improve global hemodynamic function. Alternatively, less complex devices could be programmed with an initial, short delay. The device also is programmed with a long AV delay target, which is obtained by slowly increasing the AV delay from the short value to the long value determined by the physician in the time period established by the physician using clinical judgment.

Certain methods and specific aspects consistent with these and other embodiments of the present invention concern directing a catheter-type device for delivering pulses to a cardiac site where the improved heart function involves: determining a pacing (voltage) threshold, beyond the capture threshold, to improve heart function; delivering pulses of opposite polarity to achieve such heart- function improvement; delivering pulses of opposite polarity at a site near the His bundle; electrode-based His-pacing, without necessarily penetrating into the His bundle; generating and/or delivering multiple pacing profiles, e.g., by iterating through different pacing profiles, including a pacing profile that delivers pulses of opposite polarity and another pacing profile; delivering a pacing profile to generate a synchronous contraction of the septal wall and free wall of the LV from a RV (right- ventricle) pacing location; and treating one or more of distal BBB (bundle branch blocks) and/or diffuse BBB by pacing at a site near the root of the His bundle. Various embodiments of the present invention include stimulation catheters, systems and methods that employ two or three electrodes. In specific embodiments of the present invention, the most distal two electrodes are located at the tip of the catheter. According to a specific implementation, the distal two electrodes are separated by 4 mm and the electrodes are implemented as a 2mm thick ring in a 4 French catheter and a 4mm radius half sphere in the tip of the catheter. An optional third electrode can be located in a number of places, such as on the lead body some distance from the first pair or even located between the pairs. An intravenous location for the reference electrode can be used where the time separating the two opposite polarity pulses is not zero. This can be useful to reduce the likelihood of pocket stimulation.

As a specific example of an unexpected result, it has been discovered that His bundle pacing and/or para-Hisian pacing can be used to treat patients exhibiting a variety of cardiac abnormalities previously thought to be unsuitable for His bundle pacing (e.g., large QRS complexes due to distal left bundle blocks or diffuse left bundle blocks). It has also been discovered that implantation complexities (e.g., duration and/or invasiveness) can be beneficially affected by the use of specific devices, systems and placement methods.

According to an example embodiment of the present invention, a specialized stimulation profile is used to capture a synchronous contraction of the left and right ventricles. The stimulation profile is provided to a lead in the right ventricle. The lead placement and stimulation profile are selected in response to sensed heart function during the pacing. In particular, the lead placement and stimulation profile are determined based upon more than whether the placement/profile results in capture (e.g., QRS width or late activation site timing). In certain instances, this can result in pacing voltages/profiles not otherwise believed to be desirable (e.g., voltages derived from criteria other than the capture threshold and/or His bundle pacing without penetrating the surrounding (fibrous) tissue with a pacing lead). The understanding of various implementations of the present invention can be facilitated with a discussion of existing pacing, implantation and related procedures and devices. While a substantial number of differences exist between various embodiments of the present invention and such existing pacing, the present invention does not exclude implementations that include aspects of existing pacing. Quite to the contrary, aspects of the present invention are particularly useful for implementing in conjunction with existing pacing methods and devices. Accordingly, a number of embodiments of the present invention provide the flexibility to be useful when combined with existing implementations.

Aspects of the present invention facilitate the use of existing CRT device architecture as produced by a number of manufacturers to function for use with the newly discovered inventions of the underlying patent documents. These inventions include, but are not limited to, the use of XSTIM waveforms (two opposite polarity pulses used to capture a single contraction of the heart) to provide resynchronization therapy from a lead located in the right ventricle.

Current art Biventricular CRT (cardiac resynchronization therapy) devices have two independent ventricular channels, one for the RV and the other for the LV. Such CRT devices are often arranged to provide two negative- polarity pulses with programmable amplitude, pulse width and relative time delay. Aspects of the present invention facilitate the output of two opposite polarity pulses with programmable amplitude, pulse width and relative time delay (including no delay).

According to one embodiment of the present invention, modifications are made to Biventricular CRT devices that have flexible analog/digital chip design architecture allowing on-chip reconnections between different output terminals to the output circuitry. For example, XSTIM-capable devices can be produced through reprogramming switches/multiplexers used to define the electrical connections to one or more pacing leads. FIG. IA shows an illustration of one such modified CRT device, consistent with an example embodiment of the present invention. FIG. IA shows two pacing capacitors Cl and C2 that provide pacing output signals for the ventricular channels. Pace Control 102 and 104 provide various functions for pacing delivery including, but not limited to, timing control, amplitude settings, and pulse duration. The connection grid 100 provides selectable connection between the pacing capacitors Cl, C2 and the various outputs 120. The solid boxes of connection grid 100 represent connections between the capacitors Cl, C2 and the output directly above. Thus, the positive signal component of C 1 and the negative component of C2 are both connected to a reference, such as the can of the CRT device. The negative signal component of C 1 is connected to one portion of the right ventricle (RV) lead and the positive signal component of C2 is connected to another portion of the right ventricle lead. In this configuration the right ventricle lead would be used to provide the pacing signal. It should be noted that a similar configuration could be implemented for what is conventionally thought of as the left ventricle lead, although the pacing would still preferably be applied to the right ventricle of the patient. Accordingly, aspects of the invention involve a Biventricular CRT device configured to connect a first electrical connection (Cl-) to a first output (RV-), a second electrical connection (C2+) to a second output (RV+), and the third (Cl+) and fourth (C2-) electrical connections to a third output/reference.

FIG. IA shows the connection grid 100 being configurable in response to a connection control circuit. The connection grid 100 shown in FIG. IA is a relatively simple connection grid that allows each terminal to select between the five different outputs. More complex or simple connection grids can also be implemented, including a connection grid that allows for selection applying the pacing control to either or both terminals of the capacitors Cl and C2. The specific circuit shown in FIG. IA is merely representative of any number of configurable circuits that can be implemented in accordance with the present invention. For example, the power source for the pacing signals need not be capacitive per se and could be provided by various power providing circuits and electrical elements. Although not shown, an atrial channel could also be included as part of the device; however, it could remain essentially identical between the Biventricular CRT device and the modified implementation discussed herein. FIG. IB shows an illustration of a CRT device, such as those modified in FIGs. 1A-8, placed within the heart, consistent with an example embodiment of the present invention. A heart H is shown in a cross-section showing a right ventricle RV and a left ventricle LV divided by a septum S. A catheter is provided in the right ventricle RV with a distal electrode 12 secured to the septum and a proximal electrode 14 in the right ventricle. The right-hand side of the figure shows the catheter 10 enlarged and energized by pacemaker 1 to create two monopolar pulsewaves between electrodes 12, 14 and the pacemaker 1. The pulsewaves can be modified in as discussed herein including, but not limited to, phase, duration, amplitude and polarity configuration.

As discussed in U.S. Patent Application Serial No. 11/300,242, aspects of the present invention relate to a method of application and a way to facilitate the implantation and to avoid the connection and disconnection of the catheter 10. Sense circuit 2 can be used to check the proper placement and pulsewave configuration. In a specific embodiment a deflectable sheath with an electrode on its edge can be used. This allows stimulation to be applied in order to check the proper placement of the catheter (e.g., responsive to signals received by sense circuit 2) and for affixing (e.g., screwing into the heart) of the catheter into the proper place. The sheath, if used, can then be removed and is eventually disposable.

As discussed herein, the sense circuit 2 can be implemented according to any number of different sensing signals that represent heart function due to pacing signals delivered by a pacing generator.

According to a specific embodiment of the present invention, a pacemaker and a method of application are implemented as follows:

• A pulse generator, single-chambered or dual-chambered has ventricular output including at least two superimposed monopolar pulsewaves of reversed polarity between each other, with programmable configuration, in respect to a neutral reference point. The neutral reference point can be, for example, the pacemaker's metallic box or a third electrode implemented as a tripolar catheter.

• An active- fixation ventricular catheter. • A deflectable and/or pre-shaped sheath with a distal tip having an electrode.

• Determining a stimulation place in the right interventricular septum (or otherwise near the His Bundle) using the sheath. • Where the determined stimulation place is such that pacing therefrom allows for a greater interventricular synchrony making the stimulation of the left ventricle easier, such as by the application of an electric alternative circuit principle or Electrical Bypass that reestablishes the physiological conduction of a damaged (e.g., conduction abnormality) heart.

The general aspects of FIG. IB can be implemented in combination with one or more of the various embodiments disclosed herein including, but not limited to, aspects discussed in connection with each of the figures.

FIG. 2 shows an interface and circuit for providing a pacing signal, consistent with the present invention. Header/connecter 200 is a circuit and interface for connecting the outputs of CRT device 202 to a single pacing lead 204 (again an atrial channel could also be included). The connection lines between the outputs of CRT device 202 (RV+/- and LV+/-) and the header 200 show the connection functionality provided by the circuit of connector 200. Thus, the positive component of one of the RV and LV signals is connected to the pacing lead 204 and the negative component of the other of the RV and LV signals is also connected to the pacing lead 204.

The reference electrode 206 as placed on pacing lead 204 is an optional component. Another option is to use the can of the CRT device as a reference (alone or in combination with one or more reference points/electrodes). One or both of the other signal components (e.g., LV- or RV+) are connected to a reference component, such as the can of CRT device 202 and/or to a reference electrode 206 of the pacing lead 204. In this specific embodiment, the CRT is configured to provide RV signal as a unipolar pacing signal (since the RV(+) is not connected to the CAN/or electrode 206) and the LV signal as a bipolar pacing signal. Unipolar pacing signals use a single signal component, which can be referenced to the can of the device, to be delivered to the pacing site, whereas bipolar pacing signals use a signal component referenced to the other nearby electrode to be delivered to the pacing sites. In unipolar mode, the devices internal logic connects the (+) side of the signal to the can and the negative to the active electrode at the tip or ring (in case of LV leads) of the intracardiac leads.

According to another embodiment (not shown), the RV and LV leads can be reversed in their connections. The RV lead is then configured for bipolar pulse and the LV lead is configured for a unipolar pulse.

As shown by the signal waveforms, the pacing lead 204 can thus be configured to deliver two opposite polarity pulses, which can be simultaneously delivered or delivered with an offset between the pulses. This offset can be accomplished using the programmable interventricular delay of the device. FIG. 3 shows an interface and circuit for providing pacing signals, consistent with embodiments of the present invention. Connector/interface 302 includes a circuit for routing signal components from CRT device 312. Optionally, atrial component 304 can be implemented. For example, atrial component 304 can be used to connect to an electrode 308, which can be located on pacing lead 306 or on a separate pacing lead, to atrial port A. This electrode can be used to sense heart function, such as atrial activation. RV+ and LV- are shown as connecting to respective leads for delivery of pacing signals. The polarities of the RV and LV signal components are merely exemplary and could be reversed. RV- and LV+ are shown as connecting to a reference, such as electrode 310. Optionally, the reference could be the can of CRT device 312, a remote reference point, or both. As discussed in connection with FIG. 2, CRT device 312 can be configured with one of the RV or LV signals providing a unipolar signal. For such an implementation, the reference component (e.g. , LV+) could be left unconnected.

Fig. 3 also shows that the interface device can include a connector housing that is constructed to physically interface with two or more lead outputs of the CRT device 312. Specifically, the RV and LV outputs of CRT device 312 are designed to interface with respective leads. The connector/interface 302, however, can connect to multiple lead outputs of the CRT device and provide a single lead output, which can include connections to multiple outputs of the CRT device 312. Thus, the CRT device 312, although designed for interfacing with two or three pacing leads, can be used as a single pacing lead with little or no modifications. Similarly, the pacing lead can be implemented using a standard connection type, if so desired.

Although not shown, the polarities of ring and tip could be reversed. This can be useful for changing the shape of the virtual electrode around the physical electrodes. For example, the larger head of the dog-bone virtual electrode could be inverted to be directed towards the blocked regions of the His bundle. This can be particularly useful for correcting for small differences between the optimum site identified by the sheath and the actual placement of the implantable electrode. A rotation of the dog bone virtual electrode can be achieved by the relative timing and polarity of the two pulses (negative first, positive first, ring positive, tip positive and/or inter-pulse timing).

Although not explicitly shown, the connector/interface 302 can also be implemented for interfacing with additional outputs, including additional pacing outputs, such as those described in connection with FIG. 8. FIG. 4 shows an illustration of a modified dual chamber pacemaker

(DDD) device, consistent with an example embodiment of the present invention. FIG. 4 shows two pacing capacitors Cl and C2 that traditionally provide pacing output signals for the atrial and ventricular channels respectively. Pace Control 402 and 404 provide various functions for pacing delivery including, but not limited to, timing control, amplitude settings, and pulse duration. The connection grid 400 provides selectable connection between the pacing capacitors Cl, C2 and the various outputs 420. The solid boxes of connection grid 400 represent connections between the capacitors Cl, C2 and the output directly above. Thus, the positive signal component of C 1 and the negative component of C2 are both connected to a reference, such as the can of the DDD device. The negative signal component of C 1 is connected to one portion of the right ventricle (RV) lead and the positive signal component of C2 is connected to another portion of the right ventricle lead. In such a configuration the right ventricle lead could be used to provide the pacing signal and the atrial lead could be left disconnected. It should be noted that a similar configuration could be implemented for what is conventionally thought of as the right atrial lead, although the pacing would still preferably be applied to the right ventricle of the patient. Accordingly, aspects of the invention involve a DDD device configured to connect a first electrical connection (Cl-) to a first output (RV-), a second electrical connection (C2+) to a second output (RV+), and the third (Cl+) and fourth (C2-) electrical connections to a third output/reference. FIG. 4 shows the connection grid 400 being configurable in response to a connection control circuit. The connection grid 400 shown in FIG. 4 is a relatively simple connection grid that allows each terminal to select between the five different outputs. More complex or simple connection grids can also be implemented, including a connection grid that allows for selection applying the pacing control to either or both terminals of the capacitors Cl and C2.

The specific circuit shown in FIG. 4 is merely representative of any number of configurable circuits that can be implemented in accordance with the present invention. For example, the power source for the pacing signals need not be capacitive per se and could be provided by various power providing circuits and electrical elements.

FIG. 5 is similar to FIG. 4, however, the reference electrode(s) are connected to the negative of capacitor Cl and positive of capacitor C2, while the positive of Cl and negative of C2 are connected to the RV leads.

FIG. 6 shows an illustration of a modified DDD device, consistent with an example embodiment of the present invention. FIG. 6 shows two pacing capacitors Cl and C2 that provide pacing output signals for the ventricular channels and sense amplifier 605. For simplicity, the sense amplifiers of the ventricular channel are not shown, however, should the sense amplifiers be implemented, they can be attached to the RV channel-between RV(-) and RV(+) for bipolar sensing and between RV(-) and Can for unipolar sensing. Pace

Control 602 and 604 provide various functions for pacing delivery including, but not limited to, timing control, amplitude settings, and pulse duration. The connection grid 600 provides selectable connection between the pacing capacitors Cl, C2 and the various outputs 620. The solid boxes of connection grid 600 represent connections between the capacitors Cl, C2 and the output directly above. Thus, the negative signal component of Cl and the positive component of C2 are both connected to a reference, such as the can of the DDD device. The positive signal component of Cl is connected to one portion of the right ventricle (RV) lead and the negative signal component of C2 is connected to another portion of the right ventricle lead. In this configuration the right ventricle lead would be used to provide the pacing signal.

Accordingly, aspects of the invention involve a DDD device configured to connect a first electrical connection (Cl+) to a first output (RV+), a second electrical connection (C2-) to a second output (RV-), and the third (Cl-) and fourth (C2+) electrical connections to a third output/reference.

FIG. 6 shows the connection grid 600 being configurable in response to a connection control circuit. The connection grid 600 shown in FIG. 6 is a relatively simple connection grid that allows each terminal to select between the five different outputs. More complex or simple connection grids can also be implemented, including a connection grid that allows for selection applying the pacing control to either or both terminals of the capacitors Cl and C2.

The specific circuit shown in FIG. 6 is merely representative of any number of configurable circuits that can be implemented in accordance with the present invention. For example, the power source for the pacing signals need not be capacitive per se and could be provided by various power providing circuits and electrical elements.

Although not shown, the ventricular sense channel could be implemented using the connections that would remain essentially identical between a conventional DDD device and the embodiments of FIG. 6.

FIG. 7 is similar to FIG. 6, however, the signal polarities have been inverted such that the positive of capacitor Cl and negative of capacitor C2 have been connected to the reference (CAN), while the negative of capacitor C 1 is connected to RV(-) and the positive of C2 is connected to RV(+).

Although not shown, the RV sense channel could be implemented in a manner that is similar to those connections in a DDD device.

FIG. 8 shows an illustration a Biventricular DDD CRT device, consistent with an example embodiment of the present invention. FIG. 8 shows three pacing capacitors Cl, C2 and C3 that provide pacing output signals for the ventricular channels and the atrial channel respectively. Pace Control 802, 804 and 806 provide various functions for pacing delivery including, but not limited to, timing control, amplitude settings, and pulse duration. The connection grid 800 provides selectable connection between the pacing capacitors Cl, C2, C3 and the various outputs 820. The solid boxes of connection grid 800 represent connections between the capacitors Cl, C2, C3, and the output directly above. Thus, the negative signal component of Cl and the positive component of C3 are both connected to a reference, such as the can of the CRT device. The positive signal component of Cl is connected to one portion of the right ventricle (RV) lead and the negative signal component of C3 is connected to another portion of the right ventricle lead. In this configuration the right ventricle lead would be used to provide the pacing signal. Accordingly, aspects of the invention involve a Biventricular CRT device configured to connect a first electrical connection (Cl+) to a first output (RV+), a second electrical connection (C3-) to a second output (RV-), and the third (Cl- ) and fourth (C3+) electrical connections to a third output/reference.

FIG. 8 shows the connection grid 800 being configurable in response to a connection control circuit. The connection grid 800 shown in FIG. 8 is a relatively simple connection grid that allows each terminal to select between the five different outputs. More complex or simple connection grids can also be implemented, including a connection grid that allows for selection applying the pacing control to either or both terminals of the capacitors Cl and C2. The specific circuit shown in FIG. 8 is merely representative of any number of configurable circuits that can be implemented in accordance with the present invention. For example, the power source for the pacing signals need not be capacitive per se and could be provided by various power providing circuits and electrical elements. The circuits shown in FIG. 8 used the extra (capacitive) pacing source, previously used for atrial pacing, to configure the RV channel to provide XSTIM dual pulse therapy. This device combines simultaneously biventricular CRT and XSTIM CRT. This can be particularly useful for patients with dilated hearts where the substrate lesion is too large (i.e., due to a major infarct that destroyed the His fibers that activated a region of the LV) for XSTIM to bypass it. Thus, a second LV may be required to synchronize a late activated region in the LV.

Cardiac applications represent a specific embodiment of the invention; however, the present invention is also applicable to other therapies, such as those where high current density spot(s) away from the electrodes are beneficial for stimulating the target including, but not limited to, nerves, muscle, gastric and intestine system, and cortex. For example, U.S. Pat. No. 5,299,569 to Wernicke et al. issued April 5, 1994 (and incorporated herein by reference) describes pacing the vagus nerve to treat a wide variety of disorders. Pacing electrodes are applied directly to the vagus nerve in, for example, the neck. Application of an electrode directly to the vagus nerve creates risk of mechanical injury {e.g., pressure necrosis) to the nerve. Electrodes are placed subcutaneously near (transcutaneously or transvenously coupled) but not on the vagus nerve (VN) in the neck. A reference electrode is placed subcutaneously (transcutaneously or transvenously coupled) on an opposite side of the nerve VN. The electrodes and reference electrode are connected to a pulse generator IPG. With signals as described above, the resulting electrical field captures the vagus nerve. The signals may be selected to have amplitude, frequency and other parameters as more fully described in the '569 patent. It will be appreciated that other alternative examples of using the present invention to pace an organ or the nerve will occur to one of ordinary skill in the art with the benefit of the teachings of the present invention.

The skilled artisan will recognize that the various aspects discussed in connection with the present invention can be implemented in a variety of combinations and manners. Moreover, aspects discussed in connection with the various references disclosed and incorporated herein, including those references indicated at the beginning of this document, can be used in combination with aspects of the present invention. In particular to the extent that the references indicated at the beginning of this document include a number of similar figures and related discussions, the skilled artisan would appreciate the interoperability of aspects disclosed therein even for figures not common between documents. The teachings throughout these documents relate to aspects that can be used in combination with embodiments of the present invention. Accordingly, the documents are incorporated by reference in their entirety. For instance, the U.S. Provisional Patent Application identified by Serial No. 61/020,511 includes an appendix with figures depicting various pacing electrodes and associated circuitry, and such embodiment(s) can be used in combination with aspects of the present invention.

The various embodiments described above are provided by way of illustration only and should not be construed to limit the invention. Based on the above discussion and illustrations, those skilled in the art will readily recognize that various modifications and changes may be made without strictly following the exemplary embodiments and applications illustrated and described herein. Such modifications and changes do not depart from the true spirit and scope of the present invention.

Claims

What is claimed is:

1. A cardiac resynchronization therapy (CRT) device that, when providing biventricular pacing, uses a first pacing signal for one chamber of a heart and a second pacing signal for another chamber of the heart, wherein the CRT device comprises: circuitry for referencing each of the first and second pacing signals to a common reference component; and a pacing output, configured to be coupled to a lead, for using the CRT device to provide single chamber pacing using a negative component from one pacing signal and a positive component from the other pacing signal to pace the single chamber, wherein the pacing signal includes a negative pulse and a positive pulse, each referenced to the common reference component.

2. The device of claim 1, further including pacing control circuitry for modifying a characteristic of at least one of the first and second pacing signals.

3. The device of any one of claims 1 or 2, further including a sensing circuit for generating a signal indicative of synchronicity of a contraction of the heart.

4. The device of any one of claims 1-3, further including circuitry for providing a third pacing signal.

5. The device of any one of claims 1-4, further including sense circuitry for detecting atrial activation signals of the heart.

6. The device of any one of claims 1-5, comprising a circuit, for use with a cardiac resynchronization therapy (CRT) device designed for biventricular pacing using a first pacing signal having a positive component provided to a first electrical connection and negative component provided to a second electrical connection and a second pacing signal with a positive component provided to a third electrical connection and negative component provided to a fourth electrical connection, the circuit comprising: a first output, configured to connect to a pacing lead; a second output, configured to connect to the pacing lead; a third output, configured to connect to a reference point; and electrical circuitry, configured to connect the second electrical connection to the first output, the third electrical connection to the second output, and the first and fourth electrical connections to the third output.

7. The device of claim 6, wherein the electrical circuitry is programmable such that the first and second outputs can be connected to any of the first, second, third, or fourth electrical connections.

8. The device of any one of claims 6-7, wherein each of the first and second pacing signals is generated using an independently referenced signal source.

9. The device of any one of claims 6-8, further including first and second capacitive sources, each including respective positive and negative terminals, the positive and negative terminals of the first capacitive source corresponding to the first and second electrical connections, respectively, and the positive and negative terminals of the second capacitive source corresponding to the third and fourth electrical connections, respectively, wherein each of the first and second pacing signals is provided by one of the first and second capacitive sources that is independently referenced from the other of the first and second capacitive sources.

10. A device for connecting a single lead to a cardiac rhythm therapy (CRT) apparatus designed for dual chamber pacing using two leads for respectively providing first and second pacing signals, each having positive and negative signal components, the positive component of the first pacing signal being provided to a first output and the negative component of the first pacing signal being provided to a second output and the positive component of the second pacing signal being provided to a third output and the negative component of the second pacing signal being provided to a fourth output wherein, for dual chamber pacing, the first and second outputs are for use with a first lead and the third and fourth outputs are for use by a second lead, the device comprising: a connector configured for physically mating with two interfaces of the CRT apparatus, the first interface providing the first and second outputs and the second interface providing the third and fourth outputs, each interface arranged for physically mating with a respective lead; and electrical connections from the second and third outputs to a signal reference and from the first and fourth outputs to respective inputs of the single lead, thereby allowing single chamber pacing using the single lead.

11. The device of claim 10, wherein the connector housing is further configured for physically mating with a third interface of the CRT apparatus.

12. The device of any one of claims 10-11, wherein the electrical connections further include a connection between a sense signal of the third interface and the single lead.

13. The device of any one of claims 10-12, wherein the electrical connections further include connections between fifth and sixth outputs and a second lead.

14. A signal routing matrix for connecting a lead to a cardiac rhythm therapy (CRT) device designed for dual chamber pacing using first and second leads for respectively using two pacing signals each having positive and negative signal components, the positive component of a first pacing signal being provided to a first output and the negative component of the first pacing signal being provided to a second output and the positive component of the second pacing signal being provided to a third output and the negative component of the second pacing signal being provided to a fourth output wherein for dual chamber pacing the first and second outputs are for use with the first lead and the third and fourth outputs are for use by the second lead, the signal routing matrix comprising: electrical connections from the second and third outputs to a signal reference and from the first and fourth outputs to respective inputs of the lead, thereby allowing single chamber pacing using the lead.

15. The matrix of claim 14, further comprising electrical connections from an output of the lead to a sensing input of the CRT device.

16. The matrix of claim 15, further comprising electrical connections for fifth and sixth outputs to respective inputs of a second lead.

17. A pacing system for use with a lead including a first electrode and a second electrode for pacing a heart from a single chamber of the heart, the pacing system comprising: a signal generator, configured to provide first and second pacing signals, each having positive and negative signal components; and a configurable routing circuit, capable of being configured for routing a positive component of the first pacing signal and a negative component of the second pacing signal to a common signal reference and routing a negative component of the first pacing signal to the first electrode and a positive component of the second pacing signal to the second electrode.

18. The pacing system of claim 17, further including a first capacitive component for providing the first pacing signal and a second capacitive component for providing the second pacing signal.

19. The pacing system of any one of claims 17-18, further including the lead including the first electrode and the second electrode for pacing the heart from the single chamber of the heart.

20. The pacing system of any one of claims 17-19, further including an interface for electrically connecting to first and second outputs of the signal generator, each of the first and second outputs providing a respective one of the first and second pacing signals, to the lead.

21. The pacing system of any one of claims 17-20, wherein the signal generator further includes a third output configured for providing a pacing signal.

22. The pacing system of any one of claims 17-21, further including a sense input for detecting an electrical signal of the heart.

23. The pacing system of any one of claims 17-22, further including pacing control circuitry for modifying the first and second pacing signals.

24. The pacing system of any one of claims 17-23, further including a lead configured for sensing atrial activity.