# Patent

## Title
Systems and methods for configuration of interventricular interval

## Abstract

Systems and methods are described herein for assisting a user in identification of interventricular (V-V) delay for cardiac therapy. The systems and methods may monitor electrical activity of a patient using external electrode apparatus to provide electrical heterogeneity information for a plurality of different V-V intervals and may identify a V-V interval based on the electrical heterogeneity information.

## Background
This application claims the benefit of U.S. Provisional Patent Application 62/037,694 entitled “Systems and Methods for Configuration of Interventricular Interval” and filed on Aug. 15, 2014, which is incorporated herein by reference in its entirety.


The disclosure herein relates to systems and methods for use in the configuration (e.g., optimization) of interventricular interval, or delay, for cardiac therapy being performed on a patient.
Cardiac therapy, such as cardiac resynchronization therapy (CRT), may correct symptoms of electrical dyssynchrony of a patient's heart by providing pacing therapy to one or both ventricles or atria, e.g., by providing pacing to encourage earlier activation of the left or right ventricles. By pacing, the ventricles may be controlled such that they contract in synchrony.
Providing cardiac therapy to a patient may involve determining effective programming of device parameters. For example, the selection of the timing of the pacing pulses delivered to the electrodes, such as atrioventricular (A-V) and interventricular (V-V) intervals, or delays, may be adjusted to deliver effective and/or optimal pacing therapy. Biventricular pacing includes the pacing (e.g., delivery of electrical stimulation) to both ventricles in a coordinated manner. V-V interval optimization may be challenging (e.g., especially in non-responder patients). Echocardiographic methods may be used for V-V interval optimization but may not be preferable.
SUMMARY
The exemplary systems, methods, and interfaces described herein may be configured to assist a user (e.g., a physician) in configuring cardiac therapy (e.g., cardiac therapy being performed on a patient during and/or after implantation of cardiac therapy apparatus). The systems, methods, and interfaces may be described as being noninvasive. For example, the systems, methods, and interfaces may not need implantable devices such as leads, probes, sensors, catheters, etc. to evaluate and configure the cardiac therapy. Instead, the systems, methods, and interfaces may use electrical measurements taken noninvasively using, e.g., a plurality of external electrodes attached to the skin of a patient about the patient's torso.
The exemplary systems and methods may monitor electrical activity using a plurality of external electrodes during the delivery of cardiac therapy using a plurality of different V-V intervals. The electrical activity may be used to generate electrical heterogeneity information (e.g., data) representative of mechanical cardiac functionality and/or electrical cardiac functionality of the patient for each of the plurality of different V-V intervals. One or more of the V-V intervals may be identified based on the electrical heterogeneity information (e.g., data) for each of the plurality of different V-V intervals.
The exemplary systems and methods may further determine which of the left ventricle or right ventricle should be pre-excited using a V-V interval based on baseline electrical heterogeneity information (e.g., data) from electrical activity monitored during delivery of cardiac therapy with an initial V-V interval (e.g., a V-V interval of 0 milliseconds).
One exemplary system for use in cardiac therapy may include electrode apparatus and computing apparatus coupled to the electrode apparatus. The electrode apparatus may include a plurality of external electrodes configured to be located proximate tissue of a patient (e.g., surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient). The computing apparatus may be configured to initiate delivery of bi-ventricular pacing therapy at a plurality of different V-V intervals (e.g., delivered by at least one implantable electrode coupled to at least one lead, bi-ventricular pacing therapy delivered at an optimized A-V interval, etc.), monitor electrical activity using the plurality of external electrodes for each of the plurality of V-V intervals during the delivery of bi-ventricular pacing therapy, and generate electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the monitored electrical activity. The computing apparatus may be further configured to identify a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.
One exemplary method for use in cardiac therapy may include initiating delivery of bi-ventricular pacing therapy at a plurality of different V-V intervals, monitoring electrical activity using a plurality of external electrodes (e.g., surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient) for each of the plurality of V-V intervals during the delivery of bi-ventricular pacing therapy (e.g., delivered by at least one implantable electrode coupled to at least one lead, bi-ventricular pacing therapy delivered at an optimized A-V interval, etc.), and generating electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the monitored electrical activity. The exemplary method may further include identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.
One exemplary system for use in cardiac therapy may include electrode means and computing means. The electrode means may include a plurality of external electrodes configured to be located proximate tissue of a patient (e.g., surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient). The computing means may be for initiating delivery of bi-ventricular pacing therapy at a plurality of different V-V intervals, monitoring electrical activity using the electrode means for each of the plurality of V-V intervals during the delivery of bi-ventricular pacing therapy (e.g., delivered by at least one implantable electrode coupled to at least one lead, bi-ventricular pacing therapy is delivered at an optimized A-V interval, etc.), and generating electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the monitored electrical activity. The computing means may further be for identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.
One exemplary system for use in cardiac therapy may include electrode apparatus and computing apparatus coupled to the electrode apparatus. The electrode apparatus may include a plurality of external electrodes configured to be located proximate tissue of a patient (e.g., surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient). The computing apparatus may be configured to monitor electrical activity using the plurality of external electrodes, initiate delivery of bi-ventricular pacing therapy at an initial V-V interval (e.g., delivered by at least one implantable electrode coupled to at least one lead, bi-ventricular pacing therapy is delivered at an optimized A-V interval, etc.), and generate initial electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for the initial V-V interval based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the initial V-V interval. The computing apparatus may be further be configured to configure a plurality of different V-V intervals to pre-excite the left ventricle or the right ventricle based on the initial electrical heterogeneity information, initiate delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals, generate electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of different V-V intervals based on the monitored electrical activity, and identify a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.
One exemplary method for use in cardiac therapy may include monitoring electrical activity using a plurality of external electrodes (e.g., surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient), initiating delivery of bi-ventricular pacing therapy at an initial V-V interval (e.g., delivered by at least one implantable electrode coupled to at least one lead, bi-ventricular pacing therapy is delivered at an optimized A-V interval, etc.), generating initial electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for the initial V-V interval based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the initial V-V interval. The exemplary method may further include configuring a plurality of different V-V intervals to pre-excite the left ventricle or the right ventricle based on the initial electrical heterogeneity information, initiating delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals, generating electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals; and identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.
One exemplary system for use in cardiac therapy may include electrode means and computing means. The electrode means may include a plurality of external electrodes configured to be located proximate tissue of a patient (e.g., surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient). The computing means may be for monitoring electrical activity using the electrode means, initiating delivery of bi-ventricular pacing therapy at an initial V-V interval (e.g., delivered by at least one implantable electrode coupled to at least one lead, bi-ventricular pacing therapy is delivered at an optimized A-V interval, etc.), and generating initial electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for the initial V-V interval based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the initial V-V interval. The computing means may be further for configuring a plurality of different V-V intervals to pre-excite the left ventricle or the right ventricle based on the initial electrical heterogeneity information, initiating delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals, generating electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals, and identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.
In one or more embodiments, the electrical heterogeneity information (e.g., data) may include a global standard deviation of surrogate electrical activation times monitored by the plurality of external electrodes, and identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information may include identifying the V-V interval from the plurality of different V-V intervals that generated the lowest global standard deviation of surrogate electrical activation times.
In one or more embodiments, the plurality of electrodes may include two or more left external electrodes configured to be located proximate the left side of the patient. In at least one embodiment, the electrical heterogeneity information may include a left standard deviation of surrogate electrical activation times monitored by the two or more left external electrodes and identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information may include identifying the V-V interval from the plurality of different V-V intervals that generated the lowest left standard deviation. In at least one embodiment, the electrical heterogeneity information may include a left average of surrogate electrical activation times monitored by the two or more left external electrodes, and identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information may include identifying the V-V interval from the plurality of different V-V intervals that generated the lowest left average.
In one or more embodiments, the plurality of different V-V intervals may be configured to pre-excite the left ventricle if the electrical heterogeneity information indicates an increase in heterogeneity in the electrical activity monitored by the plurality of external electrodes. For example, the plurality of electrodes may include two or more left external electrodes configured to be located proximate the left side of the patient and two or more posterior external electrodes configured to be located proximate the posterior side of the patient. The plurality of different V-V intervals may be configured to pre-excite the left ventricle if the monitored electrical activity indicates an increase in surrogate electrical activation times monitored by at least one of the two or more left external electrodes and the two or more posterior external electrodes. Further, for example, the plurality of electrodes may include two or more right external electrodes configured to be located proximate the right side of the patient and two or more anterior external electrodes configured to be located proximate the anterior side of the patient. The plurality of different V-V intervals may be configured to pre-excite the right ventricle if the monitored electrical activity indicates an increase in surrogate electrical activation times monitored by at least one of the two or more right external electrodes and the two or more anterior external electrodes.
In one or more embodiments, display apparatus may include, or be configured to display, a graphical user interface configured to present information for use in assisting a user in evaluating and adjusting cardiac therapy delivered to a patient. The information may include the identified V-V interval and/or a graphical representation of surrogate electrical activation times monitored by the plurality of external electrodes about a portion of human anatomy monitored for each V-V interval of the plurality of different V-V intervals (e.g., color scaling the portion of human anatomy on the graphical user interface according to the surrogate electrical activation times).
It may be described that the exemplary systems and methods may focus on optimizing ventriculo-ventricular, or interventricular, (V-V) intervals, or delays, based on electrical activation and heterogeneity patterns monitored using a ECG electrode belt or a collection of surface ECG electrodes during cardiac resynchronization therapy (CRT) pacing. Further, the exemplary methods and systems may determine which ventricle to pre-excite and provide feedback identifying an optimal V-V delay.
The exemplary systems and methods may use one or more metrics, or indices, of electrical heterogeneity derived from ECG electrodes applied on the anterior as well as on posterior surfaces of the torso. The metrics of electrical heterogeneity may include a global metric, which includes a standard deviation of activation times (SDAT) from all electrodes, and two regional left-sided metrics. The two regional left-sided metrics may include one based on a standard deviation of activation times (LVED) from the left-sided electrodes and another based on a mean activation time (LVAT) of the left-sided electrodes. The exemplary systems and methods may provide V-V optimization that helps patients respond better to CRT therapy, especially when simultaneous biventricular pacing with an optimized atrioventricular delay fails to generate an effective response to CRT therapy.
The optimization of the V-V interval, or delay, which can be done either at implant or post-implant, may be based on the heterogeneity patterns during baseline biventricular pacing with zero V-V delay and an optimized A-V delay. In one or more embodiments, electrical activation times can be displayed in terms of color-coded maps (e.g., red for early activation times, blue for late activation times, etc.). If there is increased global heterogeneity (e.g., the SDAT is greater than or equal to about 25 milliseconds (ms)) and/or increased local heterogeneity (e.g., the LVED is greater than or equal to about 25 ms, the LVAT is greater than or equal to about 60 ms, etc.), it may indicate that conduction delay is present on the left side or posterior side of the patient and LV pre-excitation would be performed.
Different pre-excitation intervals, or delays, may be used, for example, starting from 10 ms to 100 ms in steps of 10 ms. In at least one embodiment, the interval that gives the least value of one or a combination of heterogeneity metrics may be identified as the optimal V-V interval. The optimal V-V interval may be programmed into the pacing apparatus used to deliver the biventricular pacing therapy.
If conduction delay is present on the right side or anterior side of the patient during simultaneous biventricular pacing at an optimized A-V interval, then the right ventricle may be pre-excited. Again, activation times for different V-V intervals starting from 10 ms to 100 ms may be evaluated and the settings that provide the least, or smallest, heterogeneity values may be chosen for pacing therapy.
It may be described that the present disclosure provides a roadmap to V-V interval optimization that can improve response in some CRT patients. Maximizing CRT response during simultaneous biventricular pacing can help identify areas of conduction delay and may localize, or identify, which ventricle is activating later than the other and can benefit from a possible pre-excitation interval. Further, the exemplary systems and methods can also provide feedback on what V-V interval gives the optimal setting.
The above summary is not intended to describe each embodiment or every implementation of the present disclosure. A more complete understanding will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram of an exemplary system including electrode apparatus, display apparatus, and computing apparatus.
FIGS. 2-3 are diagrams of exemplary external electrode apparatus for measuring torso-surface potentials.
FIG. 4 is a block diagram of an exemplary method for V-V interval identification (e.g., optimization).
FIG. 5 depicts five sets of graphical electrical activation information and electrical heterogeneity information for five different V-V intervals.
FIGS. 6-7 are block diagrams of exemplary methods for determining pre-excitation for V-V intervals.
FIG. 8 is a diagram of an exemplary system including an exemplary implantable medical device (IMD).
FIG. 9A is a diagram of the exemplary IMD of FIG. 9.
FIG. 9B is a diagram of an enlarged view of a distal end of the electrical lead disposed in the left ventricle of FIG. 9A.
FIG. 10A is a block diagram of an exemplary IMD, e.g., the IMD of FIGS. 8-9.
FIG. 10B is another block diagram of an exemplary IMD (e.g., an implantable pulse generator) circuitry and associated leads employed in the system of FIG. 8.



DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
In the following detailed description of illustrative embodiments, reference is made to the accompanying figures of the drawing which form a part hereof, and in which are shown, by way of illustration, specific embodiments which may be practiced. It is to be understood that other embodiments may be utilized and structural changes may be made without departing from (e.g., still falling within) the scope of the disclosure presented hereby.
Exemplary systems and methods shall be described with reference to FIGS. 1-10. It will be apparent to one skilled in the art that elements or processes from one embodiment may be used in combination with elements or processes of the other embodiments, and that the possible embodiments of such methods and systems using combinations of features set forth herein is not limited to the specific embodiments shown in the Figures and/or described herein. Further, it will be recognized that the embodiments described herein may include many elements that are not necessarily shown to scale. Still further, it will be recognized that timing of the processes and the size and shape of various elements herein may be modified but still fall within the scope of the present disclosure, although certain timings, one or more shapes and/or sizes, or types of elements, may be advantageous over others.
Cardiac electrical activation times can be detected or estimated in proximity of a reference location (e.g., which can be a chosen location for a left ventricle lead during implant) using unipolar electrocardiogram (ECG) recordings. The cardiac electrical activation times may be used to generate electrical heterogeneity information that may be used by a user (e.g., physician) to optimize one or more settings, or parameters, of pacing therapy. Further, the electrical activation times may be measured and displayed, or conveyed, to a user by a system. As described herein, electrical activation times and/or electrical heterogeneity information may be used in noninvasive configuration (e.g., optimization, adjustment, etc.) of cardiac therapy.
Various exemplary systems, methods, and interfaces may be configured to use electrode apparatus including external electrodes, display apparatus, and computing apparatus to noninvasively assist a user (e.g., a physician) in the configuration (e.g., optimization) of cardiac therapy. An exemplary system 100 including electrode apparatus 110, display apparatus 130, and computing apparatus 140 is depicted in FIG. 1.
The electrode apparatus 110 as shown includes a plurality of electrodes incorporated, or included, within a band wrapped around the chest, or torso, of a patient 14. The electrode apparatus 110 is operatively coupled to the computing apparatus 140 (e.g., through one or wired electrical connections, wirelessly, etc.) to provide electrical signals from each of the electrodes to the computing apparatus 140 for analysis, evaluation, etc. Exemplary electrode apparatus may be described in U.S. patent application Ser. No. 14/227,719 entitled “Bioelectric Sensor Device and Methods” and filed Mar. 27, 2014, which is incorporated herein by reference in its entirety. Further, exemplary electrode apparatus 110 will be described in more detail in reference to FIGS. 2-3.
Although not described herein, the exemplary system 100 may further include imaging apparatus. The imaging apparatus may be any type of imaging apparatus configured to image, or provide images of, at least a portion of the patient in a noninvasive manner. For example, the imaging apparatus may not use any components or parts that may be located within the patient to provide images of the patient except noninvasive tools such as contrast solution. It is to be understood that the exemplary systems, methods, and interfaces described herein may further use imaging apparatus to provide noninvasive assistance to a user (e.g., a physician) to locate, or select, a pacing electrode or vector proximate the patient's heart in conjunction with the configuration of cardiac therapy.
For example, the exemplary systems, methods, and interfaces may provide image guided navigation that may be used to navigate leads including electrodes, leadless electrodes, wireless electrodes, catheters, etc., within the patient's body while also providing noninvasive cardiac therapy configuration including determining an effective, or optimal, V-V interval. Exemplary systems and methods that use imaging apparatus and/or electrode apparatus may be described in U.S. patent application Ser. No. 13/916,353 filed on Jun. 12, 2013 and entitled “Implantable Electrode Location Selection,” U.S. patent application Ser. No. 13/916,377 filed on Jun. 12, 2013 and entitled “Implantable Electrode Location Selection,” U.S. patent application Ser. No. 14/227,955 filed on Mar. 27, 2014 and entitled “Systems, Methods, and Interfaces for Identifying Effective Electrodes,” U.S. patent application Ser. No. 14/227,919 filed on Mar. 27, 2014 and entitled “Systems, Methods, and Interfaces for Identifying Optimal Electrical Vectors,” each of which is incorporated herein by reference in its entirety.
Exemplary imaging apparatus may be configured to capture x-ray images and/or any other alternative imaging modality. For example, the imaging apparatus may be configured to capture images, or image data, using isocentric fluoroscopy, bi-plane fluoroscopy, ultrasound, computed tomography (CT), multi-slice computed tomography (MSCT), magnetic resonance imaging (MRI), high frequency ultrasound (HIFU), optical coherence tomography (OCT), intra-vascular ultrasound (IVUS), two dimensional (2D) ultrasound, three dimensional (3D) ultrasound, four dimensional (4D) ultrasound, intraoperative CT, intraoperative MRI, etc. Further, it is to be understood that the imaging apparatus may be configured to capture a plurality of consecutive images (e.g., continuously) to provide video frame data. In other words, a plurality of images taken over time using the imaging apparatus may provide video frame, or motion picture, data. Additionally, the images may also be obtained and displayed in two, three, or four dimensions. In more advanced forms, four-dimensional surface rendering of the heart or other regions of the body may also be achieved by incorporating heart data or other soft tissue data from a map or from pre-operative image data captured by MRI, CT, or echocardiography modalities. Image datasets from hybrid modalities, such as positron emission tomography (PET) combined with CT, or single photon emission computer tomography (SPECT) combined with CT, could also provide functional image data superimposed onto anatomical data, e.g., to be used to navigate implantable apparatus to target locations within the heart or other areas of interest.
Systems and/or imaging apparatus that may be used in conjunction with the exemplary systems and methods described herein are described in U.S. Pat. App. Pub. No. 2005/0008210 to Evron et al. published on Jan. 13, 2005, U.S. Pat. App. Pub. No. 2006/0074285 to Zarkh et al. published on Apr. 6, 2006, U.S. Pat. App. Pub. No. 2011/0112398 to Zarkh et al. published on May 12, 2011, U.S. Pat. App. Pub. No. 2013/0116739 to Brada et al. published on May 9, 2013, U.S. Pat. No. 6,980,675 to Evron et al. issued on Dec. 27, 2005, U.S. Pat. No. 7,286,866 to Okerlund et al. issued on Oct. 23, 2007, U.S. Pat. No. 7,308,297 to Reddy et al. issued on Dec. 11, 2011, U.S. Pat. No. 7,308,299 to Burrell et al. issued on Dec. 11, 2011, U.S. Pat. No. 7,321,677 to Evron et al. issued on Jan. 22, 2008, U.S. Pat. No. 7,346,381 to Okerlund et al. issued on Mar. 18, 2008, U.S. Pat. No. 7,454,248 to Burrell et al. issued on Nov. 18, 2008, U.S. Pat. No. 7,499,743 to Vass et al. issued on Mar. 3, 2009, U.S. Pat. No. 7,565,190 to Okerlund et al. issued on Jul. 21, 2009, U.S. Pat. No. 7,587,074 to Zarkh et al. issued on Sep. 8, 2009, U.S. Pat. No. 7,599,730 to Hunter et al. issued on Oct. 6, 2009, U.S. Pat. No. 7,613,500 to Vass et al. issued on Nov. 3, 2009, U.S. Pat. No. 7,742,629 to Zarkh et al. issued on Jun. 22, 2010, U.S. Pat. No. 7,747,047 to Okerlund et al. issued on Jun. 29, 2010, U.S. Pat. No. 7,778,685 to Evron et al. issued on Aug. 17, 2010, U.S. Pat. No. 7,778,686 to Vass et al. issued on Aug. 17, 2010, U.S. Pat. No. 7,813,785 to Okerlund et al. issued on Oct. 12, 2010, U.S. Pat. No. 7,996,063 to Vass et al. issued on Aug. 9, 2011, U.S. Pat. No. 8,060,185 to Hunter et al. issued on Nov. 15, 2011, and U.S. Pat. No. 8,401,616 to Verard et al. issued on Mar. 19, 2013, each of which is incorporated herein by reference in its entirety.
The display apparatus 130 and the computing apparatus 140 may be configured to display and analyze data such as, e.g., electrical signals (e.g., electrocardiogram data), electrical heterogeneity information, etc. Electrical heterogeneity information, or electrical dyssynchrony information, may be representative of at least one of mechanical cardiac functionality and electrical cardiac functionality, surrogate electrical activation information or data, etc. that is generated using electrical signals gathered, monitored, or collected, using the electrode apparatus 110. In at least one embodiment, the computing apparatus 140 may be a server, a personal computer, or a tablet computer. The computing apparatus 140 may be configured to receive input from input apparatus 142 and transmit output to the display apparatus 130. Further, the computing apparatus 140 may include data storage that may allow for access to processing programs or routines and/or one or more other types of data, e.g., for driving a graphical user interface configured to noninvasively assist a user in configuring one or more pacing parameters, or settings, such as, e.g., V-V interval, A-V interval, etc.
The computing apparatus 140 may be operatively coupled to the input apparatus 142 and the display apparatus 130 to, e.g., transmit data to and from each of the input apparatus 142 and the display apparatus 130. For example, the computing apparatus 140 may be electrically coupled to each of the input apparatus 142 and the display apparatus 130 using, e.g., analog electrical connections, digital electrical connections, wireless connections, bus-based connections, network-based connections, internet-based connections, etc. As described further herein, a user may provide input to the input apparatus 142 to view and/or select one or more pieces of configuration information related to the cardiac therapy.
Although as depicted the input apparatus 142 is a keyboard, it is to be understood that the input apparatus 142 may include any apparatus capable of providing input to the computing apparatus 140 to perform the functionality, methods, and/or logic described herein. For example, the input apparatus 142 may include a mouse, a trackball, a touchscreen (e.g., capacitive touchscreen, a resistive touchscreen, a multi-touch touchscreen, etc.), etc. Likewise, the display apparatus 130 may include any apparatus capable of displaying information to a user, such as a graphical user interface 132 including one or more pacing parameters, electrical heterogeneity information, textual instructions, graphical depictions of electrical activation information, graphical depictions of anatomy of a human heart, images or graphical depictions of the patient's heart, graphical depictions of locations of one or more electrodes, graphical depictions of a human torso, images or graphical depictions of the patient's torso, graphical depictions or actual images of implanted electrodes and/or leads, etc. Further, the display apparatus 130 may include a liquid crystal display, an organic light-emitting diode screen, a touchscreen, a cathode ray tube display, etc.
The processing programs or routines stored and/or executed by the computing apparatus 140 may include programs or routines for computational mathematics, matrix mathematics, decomposition algorithms, compression algorithms (e.g., data compression algorithms), calibration algorithms, image construction algorithms, signal processing algorithms (e.g., various filtering algorithms, Fourier transforms, fast Fourier transforms, etc.), standardization algorithms, comparison algorithms, vector mathematics, or any other processing required to implement one or more exemplary methods and/or processes described herein. Data stored and/or used by the computing apparatus 140 may include, for example, electrical signal/waveform data from the electrode apparatus 110, electrical activation times from the electrode apparatus 110, graphics (e.g., graphical elements, icons, buttons, windows, dialogs, pull-down menus, graphic areas, graphic regions, 3D graphics, etc.), graphical user interfaces, results from one or more processing programs or routines employed according to the disclosure herein (e.g., electrical signals, electrical heterogeneity information, etc.), or any other data that may be necessary for carrying out the one and/or more processes or methods described herein.
In one or more embodiments, the exemplary systems, methods, and interfaces may be implemented using one or more computer programs executed on programmable computers, such as computers that include, for example, processing capabilities, data storage (e.g., volatile or non-volatile memory and/or storage elements), input devices, and output devices. Program code and/or logic described herein may be applied to input data to perform functionality described herein and generate desired output information. The output information may be applied as input to one or more other devices and/or methods as described herein or as would be applied in a known fashion.
The one or more programs used to implement the systems, methods, and/or interfaces described herein may be provided using any programmable language, e.g., a high level procedural and/or object orientated programming language that is suitable for communicating with a computer system. Any such programs may, for example, be stored on any suitable device, e.g., a storage media, that is readable by a general or special purpose program running on a computer system (e.g., including processing apparatus) for configuring and operating the computer system when the suitable device is read for performing the procedures described herein. In other words, at least in one embodiment, the exemplary systems, methods, and/or interfaces may be implemented using a computer readable storage medium, configured with a computer program, where the storage medium so configured causes the computer to operate in a specific and predefined manner to perform functions described herein. Further, in at least one embodiment, the exemplary systems, methods, and/or interfaces may be described as being implemented by logic (e.g., object code) encoded in one or more non-transitory media that includes code for execution and, when executed by a processor, is operable to perform operations such as the methods, processes, and/or functionality described herein.
The computing apparatus 140 may be, for example, any fixed or mobile computer system (e.g., a controller, a microcontroller, a personal computer, mini computer, tablet computer, etc.). The exact configuration of the computing apparatus 140 is not limiting, and essentially any device capable of providing suitable computing capabilities and control capabilities (e.g., graphics processing, etc.) may be used. As described herein, a digital file may be any medium (e.g., volatile or non-volatile memory, a CD-ROM, a punch card, magnetic recordable tape, etc.) containing digital bits (e.g., encoded in binary, trinary, etc.) that may be readable and/or writeable by computing apparatus 140 described herein. Also, as described herein, a file in user-readable format may be any representation of data (e.g., ASCII text, binary numbers, hexadecimal numbers, decimal numbers, graphically, etc.) presentable on any medium (e.g., paper, a display, etc.) readable and/or understandable by a user.
In view of the above, it will be readily apparent that the functionality as described in one or more embodiments according to the present disclosure may be implemented in any manner as would be known to one skilled in the art. As such, the computer language, the computer system, or any other software/hardware which is to be used to implement the processes described herein shall not be limiting on the scope of the systems, processes or programs (e.g., the functionality provided by such systems, processes or programs) described herein.
Electrical activation times of the patient's heart may be useful to evaluate cardiac therapy being delivered to a patient. Surrogate electrical activation information or data of one or more regions of a patient's heart may be monitored using electrode apparatus 110 as shown in FIG. 1 and in FIGS. 2-3. The exemplary electrode apparatus 110 may be configured to measure body-surface potentials of a patient 14 and, more particularly, torso-surface potentials of a patient 14. As shown in FIG. 2, the exemplary electrode apparatus 110 may include a set, or array, of electrodes 112, a strap 113, and interface/amplifier circuitry 116. The electrodes 112 may be attached, or coupled, to the strap 113 and the strap 113 may be configured to be wrapped around the torso of a patient 14 such that the electrodes 112 surround the patient's heart. As further illustrated, the electrodes 112 may be positioned around the circumference of a patient 14, including the posterior, lateral, posterolateral, anterolateral, and anterior locations of the torso of a patient 14.
Further, the electrodes 112 may be electrically connected to interface/amplifier circuitry 116 via wired connection 118. The interface/amplifier circuitry 116 may be configured to amplify the signals from the electrodes 112 and provide the signals to the computing apparatus 140. Other exemplary systems may use a wireless connection to transmit the signals sensed by electrodes 112 to the interface/amplifier circuitry 116 and, in turn, the computing apparatus 140, e.g., as channels of data. For example, the interface/amplifier circuitry 116 may be electrically coupled to each of the computing apparatus 140 and the display apparatus 130 using, e.g., analog electrical connections, digital electrical connections, wireless connections, bus-based connections, network-based connections, internet-based connections, etc.
Although in the example of FIG. 2 the electrode apparatus 110 includes a strap 113, in other examples any of a variety of mechanisms, e.g., tape or adhesives, may be employed to aid in the spacing and placement of electrodes 112. In some examples, the strap 113 may include an elastic band, strip of tape, or cloth. In other examples, the electrodes 112 may be placed individually on the torso of a patient 14. Further, in other examples, electrodes 112 (e.g., arranged in an array) may be part of, or located within, patches, vests, and/or other manners of securing the electrodes 112 to the torso of the patient 14. Still further, in other examples, the electrodes 112 may be part of, or located within, two sections of material or two “patches.” One of the two sections or patches may be located on the anterior side of the torso of the patient 14 (to, e.g., monitor electrical signals representative of the anterior side of the patient's heart, measure surrogate cardiac electrical activation times representative of the anterior side of the patient's heart, etc.) and the other section or patch may be located on the posterior side of the torso of the patient 14 (to, e.g., monitor electrical signals representative of the posterior side of the patient's heart, measure surrogate cardiac electrical activation times representative of the posterior side of the patient's heart, etc.).
The electrodes 112 may be configured to surround the heart of the patient 14 and record, or monitor, the electrical signals associated with the depolarization and repolarization of the heart after the signals have propagated through the torso of a patient 14. Each of the electrodes 112 may be used in a unipolar configuration to sense the torso-surface potentials that reflect the cardiac signals. The interface/amplifier circuitry 116 may also be coupled to a return or indifferent electrode (not shown) that may be used in combination with each electrode 112 for unipolar sensing. In some examples, there may be about 12 to about 50 electrodes 112 spatially distributed around the torso of patient. Other configurations may have more or fewer electrodes 112.
The computing apparatus 140 may record and analyze the torso-surface potential signals sensed by electrodes 112 and amplified/conditioned by the interface/amplifier circuitry 116. The computing apparatus 140 may be configured to analyze the signals from the electrodes 112 to provide surrogate electrical activation information or data such as surrogate cardiac electrical activation times, e.g., representative of actual, or local, electrical activation times of one or more regions of the patient's heart as will be further described herein. For example, electrical signals measured at the left anterior surface location of a patient's torso may be representative, or surrogates, of electrical signals of the left anterior left ventricle region of the patient's heart, electrical signals measured at the left lateral surface location of a patient's torso may be representative, or surrogates, of electrical signals of the left lateral left ventricle region of the patient's heart, electrical signals measured at the left posterolateral surface location of a patient's torso may be representative, or surrogates, of electrical signals of the posterolateral left ventricle region of the patient's heart, and electrical signals measured at the posterior surface location of a patient's torso may be representative, or surrogates, of electrical signals of the posterior left ventricle region of the patient's heart. In one or more embodiments, measurement of activation times can be performed by measuring the period of time between an onset of cardiac depolarization (e.g., onset of QRS complex) and the next onset of cardiac depolarization. In one or more embodiments, measurement of activation times can be performed by picking an appropriate fiducial point (e.g., peak values, minimum values, minimum slopes, maximum slopes, zero crossings, threshold crossings, etc. of a near or far-field EGM) and measuring time between fiducial points (e.g., within the electrical activity).
Additionally, the computing apparatus 140 may be configured to provide graphical user interfaces depicting the surrogate electrical activation times obtained using the electrode apparatus 110. Exemplary systems, methods, and/or interfaces may noninvasively use the electrical information collected using the electrode apparatus 110 to evaluate and configure cardiac therapy being delivered to the patient.
FIG. 3 illustrates another exemplary electrode apparatus 110 that includes a plurality of electrodes 112 configured to surround the heart of the patient 14 and record, or monitor, the electrical signals associated with the depolarization and repolarization of the heart after the signals have propagated through the torso of the patient 14. The electrode apparatus 110 may include a vest 114 upon which the plurality of electrodes 112 may be attached, or to which the electrodes 112 may be coupled. In at least one embodiment, the plurality, or array, of electrodes 112 may be used to collect electrical information such as, e.g., surrogate electrical activation times. Similar to the electrode apparatus 110 of FIG. 2, the electrode apparatus 110 of FIG. 3 may include interface/amplifier circuitry 116 electrically coupled to each of the electrodes 112 through a wired connection 118 and be configured to transmit signals from the electrodes 112 to computing apparatus 140. As illustrated, the electrodes 112 may be distributed over the torso of a patient 14, including, for example, the posterior, lateral, posterolateral, anterolateral, and anterior locations of the torso of a patient 14.
The vest 114 may be formed of fabric with the electrodes 112 attached to the fabric. The vest 114 may be configured to maintain the position and spacing of electrodes 112 on the torso of the patient 14. Further, the vest 114 may be marked to assist in determining the location of the electrodes 112 on the surface of the torso of the patient 14. In some examples, there may be about 25 to about 256 electrodes 112 distributed around the torso of the patient 14, though other configurations may have more or fewer electrodes 112.
As described herein, the electrode apparatus 110 may be configured to measure electrical information (e.g., electrical signals) representing different regions of a patient's heart. For example, activation times of different regions of a patient's heart can be approximated from surface electrocardiogram (ECG) activation times measured using surface electrodes in proximity to surface areas corresponding to the different regions of the patient's heart.
The exemplary systems and methods may be used to provide noninvasive assistance to a user in the evaluation and configuration of cardiac therapy (e.g., cardiac therapy being presently-delivered to a patient during implantation or after implantation). For example, the exemplary systems and methods may be used to assist a user in the configuration and/or adjustment of one or more cardiac therapy settings for the cardiac therapy being delivered to a patient. Specifically, the exemplary systems and methods may provide optimization of the V-V interval, or delay, of biventricular pacing therapy.
Exemplary method 200 depicted in FIG. 4 may be used to provide this functionality. The exemplary method 200 may be generally described to be used in the noninvasive evaluation and configuration (e.g., optimization) of cardiac therapy. The exemplary method 200 may be described as being noninvasive because the method does not use invasive apparatus to perform the evaluation and configuration of the cardiac therapy. The cardiac therapy being delivered, however, may be described as being invasive such as, e.g., one or more pacing electrodes implanted proximate a patient's heart. The exemplary method 200 may be used to evaluate and configure the invasive cardiac therapy. Further, the exemplary method 200 may be generally performed, or executed, after optimizing the A-V interval for the pacing therapy being performed. In other words, the exemplary method 200 may be used to adjust and/or optimize the V-V interval after the A-V interval has already been adjusted and/or optimized. Exemplary systems, methods, and apparatus for optimizing A-V interval may be described in U.S. Pat. No. 7,215,998 issued on May 8, 2007 to Wesselink et al., U.S. Pat. No. 7,848,807 issued on Dec. 7, 2010 to Li Wang, U.S. Pat. No. 6,507,756 issued on Jan. 14, 2003 to Heynen et al., and U.S. Pat. No. 8,214,041 issued to Gelder, et al. on Jul. 3, 2012, each of which is incorporated by reference in its entirety.
The exemplary method 200 may include monitoring, or measuring, electrical activity using a plurality of external electrodes 202. The plurality of external electrodes may be similar to the external electrodes provided by the electrode apparatus 110 as described herein with respect to FIGS. 1-3. For example, the plurality of external electrodes may be part, or incorporated into, a vest or band that is located about a patient's torso. More specifically, the plurality of electrodes may be described as being surface electrodes positioned in an array configured to be located proximate the skin of the torso of a patient. The electrical activity monitored during process 202 prior to the delivery of cardiac therapy may be referred to as “baseline” electrical activity because no therapy is delivered to the patient such that the patient's heart is in its natural, or intrinsic, rhythm.
During, or simultaneous with, the monitoring, or collecting, of electrical activity 202, the exemplary method 200 may initiate the delivery of cardiac therapy 204 such as, e.g., biventricular pacing therapy. The cardiac therapy 204 may be delivered by at least one electrode configured to electrically stimulate (e.g., depolarize, pace, etc.) the patient's left ventricle and at least one electrode configured to electrically stimulate (e.g., depolarize, pace, etc.) the patient's right ventricle in a coordinated manner. The cardiac therapy may be delivered to both ventricles using an initial V-V interval or delay. In at least one embodiment, the initial V-V interval may be 0 milliseconds (ms) or zero delay.
In at least one embodiment, each of the electrodes may be coupled to one or more leads implanted in, or proximate to, the patient's heart. Further, in at least one embodiment, the cardiac therapy 204 may be delivered by one or more leadless electrodes. Exemplary cardiac therapy using an implantable electrode and lead may be further described herein with reference to FIGS. 8-10. As described herein, although the cardiac therapy delivery may be described as being invasive, the exemplary methods and systems may be described as being noninvasive because the exemplary methods and systems may only initiate the delivery of and configure the cardiac therapy, and the exemplary methods and systems may further use electrical signals that are monitored, or taken, from the patient noninvasively.
The monitored electrical activity may be used to generate electrical heterogeneity information 206. The electrical heterogeneity information may be described as information, or data, representative of at least one of mechanical cardiac functionality and electrical cardiac functionality. Electrical heterogeneity information and other cardiac therapy information may be described in U.S. Provisional Patent Application No. 61/834,133 entitled “METRICS OF ELECTRICAL DYSSYNCHRONY AND ELECTRICAL ACTIVATION PATTERNS FROM SURFACE ECG ELECTRODES” and filed on Jun. 12, 2013, which is hereby incorporated by reference it its entirety.
Electrical heterogeneity information may be defined as information indicative of at least one of mechanical synchrony or dyssynchrony of the heart and/or electrical synchrony or dyssynchrony of the heart. In other words, electrical heterogeneity information may represent a surrogate of actual mechanical and/or electrical functionality of a patient's heart. In at least one embodiment, relative changes in electrical heterogeneity information (e.g., changes relative to baseline electrical heterogeneity) may be used to determine a surrogate value representative of acute hemodynamic response as measured by changes in the left ventricle pressure gradients. The left ventricular pressure may be typically monitored invasively with a pressure sensor located in the left ventricular of a patient's heart. As such, the use of electrical heterogeneity information to determine a surrogate value representative of the left ventricular pressure may avoid invasive monitoring using a left ventricular pressure sensor.
In at least one embodiment, the electrical heterogeneity information may include a standard deviation of ventricular activation times measured using some or all of the external electrodes, e.g., of the electrode apparatus 110. Further, local, or regional, electrical heterogeneity information may include standard deviations and/or averages of activation times measured using electrodes located in certain anatomic areas of the torso. For example, external electrodes on the left side of the torso of a patient may be used to compute local, or regional, left electrical heterogeneity information.
The electrical heterogeneity information may be generated using one or more various systems and/or methods. For example, electrical heterogeneity information may be generated using an array, or a plurality, of surface electrodes and/or imaging systems as described in U.S. Pat. App. Pub. No. 2012/0283587 A1 published Nov. 8, 2012 and entitled “ASSESSING INRA-CARDIAC ACTIVATION PATTERNS AND ELECTRICAL DYSSYNCHRONY,” U.S. Pat. App. Pub. No. 2012/0284003 A1 published Nov. 8, 2012 and entitled “ASSESSING INTRA-CARDIAC ACTIVATION PATTERNS”, and U.S. Pat. No. 8,180,428 B2 issued May 15, 2012 and entitled “METHODS AND SYSTEMS FOR USE IN SELECTING CARDIAC PACING SITES,” each of which is incorporated herein by reference in its entirety.
Electrical heterogeneity information may include one or more metrics or indices. For example, one of the metrics, or indices, of electrical heterogeneity may be a standard deviation of activation times (SDAT) measured using some or all of the electrodes on the surface of the torso of a patient. In some examples, the SDAT may be calculated using the estimated cardiac activation times over the surface of a model heart.
Another metric, or index, of electrical heterogeneity may be a left standard deviation of surrogate electrical activation times (LVED) monitored by external electrodes located proximate the left side of a patient. Further, another metric, or index, of electrical heterogeneity may include an average of surrogate electrical activation times (LVAT) monitored by external electrodes located proximate the left side of a patient. The LVED and LVAT may be determined (e.g., calculated, computed, etc.) from electrical activity measured only by electrodes proximate the left side of the patient, which may be referred to as “left” electrodes. The left electrodes may be defined as any surface electrodes located proximate the left ventricle, which includes region to left of the patient's sternum and spine. In one embodiment, the left electrodes may include all anterior electrodes on the left of the sternum and all posterior electrodes to the left of the spine. In another embodiment, the left electrodes may include all anterior electrodes on the left of the sternum and all posterior electrodes. In yet another embodiment, the left electrodes may be designated based on the contour of the left and right sides of the heart as determined using imaging apparatus (e.g., x-ray, fluoroscopy, etc.).
Another exemplary metric, or index, of dyssynchrony may be a range of activation times (RAT) that may be computed as the difference between the maximum and the minimum torso-surface or cardiac activation times, e.g., overall, or for a region. The RAT reflects the span of activation times while the SDAT gives an estimate of the dispersion of the activation times from a mean. The SDAT also provides an estimate of the heterogeneity of the activation times, because if activation times are spatially heterogeneous, the individual activation times will be further away from the mean activation time, indicating that one or more regions of heart have been delayed in activation. In some examples, the RAT may be calculated using the estimated cardiac activation times over the surface of a model heart.
Another exemplary metric, or index, of electrical heterogeneity information may include estimates of a percentage of surface electrodes located within a particular region of interest for the torso or heart whose associated activation times are greater than a certain percentile, such as, for example the 70th percentile, of measured QRS complex duration or the determined activation times for surface electrodes. The region of interest may, e.g., be a posterior, left anterior, and/or left-ventricular region. The exemplary metric, or index, may be referred to as a percentage of late activation (PLAT). The PLAT may be described as providing an estimate of percentage of the region of interest, e.g., posterior and left-anterior area associated with the left ventricular area of heart, which activates late. A large value for PLAT may imply delayed activation of a substantial portion of the region, e.g., the left ventricle, and the potential benefit of electrical resynchronization through CRT by pre-exciting the late region, e.g., of left ventricle. In other examples, the PLAT may be determined for other subsets of electrodes in other regions, such as a right anterior region to evaluate delayed activation in the right ventricle. Furthermore, in some examples, the PLAT may be calculated using the estimated cardiac activation times over the surface of a model heart for either the whole heart or for a particular region, e.g., left or right ventricle, of the heart.
In one or more embodiments, the electrical heterogeneity information may include indicators of favorable changes in global cardiac electrical activation such as, e.g., described in Sweeney et al., “Analysis of Ventricular Activation Using Surface Electrocardiography to Predict Left Ventricular Reverse Volumetric Remodeling During Cardiac Resynchronization Therapy,” Circulation, 2010 Feb. 9, 121(5): 626-34 and/or Van Deursen, et al., “Vectorcardiography as a Tool for Easy Optimization of Cardiac Resynchronization Therapy in Canine LBBB Hearts,” Circulation Arrhythmia and Electrophysiology, 2012 Jun. 1, 5(3): 544-52, each of which is incorporated herein by reference in its entirety. Electrical heterogeneity information may also include measurements of improved cardiac mechanical function measured by imaging or other systems to track motion of implanted leads within the heart as, e.g., described in Ryu et al., “Simultaneous Electrical and Mechanical Mapping Using 3D Cardiac Mapping System: Novel Approach for Optimal Cardiac Resynchronization Therapy,” Journal of Cardiovascular Electrophysiology, 2010 February, 21(2): 219-22, Sperzel et al., “Intraoperative Characterization of Interventricular Mechanical Dyssynchrony Using Electroanatomic Mapping System—A Feasibility Study,” Journal of Interventional Cardiac Electrophysiology, 2012 November, 35(2): 189-96, and/or U.S. Pat. App. Pub. No. 2009/0099619 A1 entitled “METHOD FOR OPTIMIZAING CRT THERAPY” and published on Apr. 16, 2009, each of which is incorporated herein by reference in its entirety.
The electrical heterogeneity information may be generated 206 for electrical activity monitored without, or before the delivery of, cardiac therapy, which may be referred to as baseline electrical heterogeneity information. The electrical heterogeneity information may be further generated 206 for electrical activity monitored during pacing therapy delivered at an initial, or first, V-V interval, which may be referred to as initial electrical heterogeneity information, and for electrical activity monitored during pacing therapy delivered at one or more V-V intervals that are adjusted following the initial, or first, V-V interval, which may be described as being subsequent, or following, electrical heterogeneity information.
After the initial, or first, V-V interval, the exemplary method 200 may further configure the following, or subsequent, V-V intervals of the biventricular pacing therapy 204 to pre-excite one of the left ventricle or right ventricle based on the monitored electrical activity and/or generated electrical heterogeneity information 208. Pre-excitation may refer to the ventricle that is paced, or stimulated, using the biventricular pacing therapy first, or before the other ventricle. For example, if the left ventricle is to be pre-excited with a V-V delay of 50 ms, the left ventricle would be paced 50 ms before the right ventricle (in other words, the right ventricle would be paced 50 ms after the left ventricle). Likewise, if the right ventricle is to be pre-excited with a V-V delay of 50 ms, the right ventricle would be paced 50 ms before the left ventricle (in other words, the left ventricle would be paced 50 ms after the right ventricle). Exemplary methods of determining ventricular pre-excitation are shown in FIGS. 6-7. As shown, process step 208 is drawn using broken, or dotted, lines because determining ventricular pre-excitation may only occur after the initial V-V interval. In other words, after the ventricle to be pre-excited has been determined, it may not be determined again.
An exemplary method 230 of determining whether to pre-excite the patient's left ventricle is depicted in FIG. 6. As shown, if the electrical heterogeneity information indicates an increase in heterogeneity 232, the exemplary method 230 may determine and/or indicate that the left ventricle should be pre-excited 236. An increase in heterogeneity 232 may be determined by comparing one or more indices or metrics of electrical heterogeneity information to one or more threshold values. For example, a SDAT that is greater than or equal to 25 ms may indicate an increase in heterogeneity 232, and thus, the exemplary method 230 may determine that the left ventricle should be pre-excited 236.
Further, if the electrical heterogeneity information indicates an increase in surrogate electrical activation times monitored by one or more left external electrodes (e.g., external electrodes located proximate the left side of the patient's torso) or one or more posterior external electrodes (e.g., external electrodes located proximate the posterior side of the patient's torso) 234, the exemplary method 230 may determine and/or indicate that the left ventricle should be pre-excited 236. An increase in left or posterior surrogate activation times may be determined by comparing one or more indices or metrics of electrical heterogeneity information to one or more threshold values. For example, a LVED that is greater than or equal to 25 ms may indicate an increase in left-sided activation times 234, and thus, the exemplary method 230 may determine that the left ventricle should be pre-excited 236. Further, for example, a LVAT that is greater than or equal to 70 ms may indicate an increase in left-sided activation times 234, and thus, the exemplary method 230 may determine that the left ventricle should be pre-excited 236. Still further, for example, if the LVAT of the left external electrodes exceeds the LVAT of the right external electrodes, the exemplary method 230 may determine that the left ventricle should be pre-excited 236.
An exemplary method 240 of determining whether to pre-excite the patient's right ventricle is depicted in FIG. 7. As shown, if the electrical heterogeneity information indicates an increase in surrogate electrical activation times monitored by one or more right external electrodes (e.g., external electrodes located proximate the right side of the patient's torso) 242, the exemplary method 240 may determine and/or indicate that the right ventricle should be pre-excited 244. For example, if the LVAT of the right external electrodes exceeds the LVAT of the left external electrodes, the exemplary method 240 may determine that the right ventricle should be pre-excited 242.
The determination of whether to pre-excite one ventricle versus the other during biventricular pacing therapy may be based upon determination that cardiac resynchronization therapy delivered with simultaneous biventricular pacing at an optimal atrio-ventricular delay results in no change or increase in electrical heterogeneity metrics compared to the baseline. Then, the extent of electrical delay during biventricular pacing with zero V-V delay may be determined for both the anterior and posterior side. If the average activation time of the posterior electrodes exceeds the average activation time of the anterior electrodes, the left ventricle should be pre-excited. If the average activation time of the anterior electrodes exceed the average activation time of the posterior electrodes, the right ventricle should be pre-excited.
In another embodiment, the proportions of anterior and posterior electrodes activating late (e.g., later than 50% of the latest activation time or later than 50% of QRS duration) during biventricular pacing with zero V-V delay may be determined. If the proportion of posterior electrodes activating late exceeds the proportion of anterior electrodes activating late, the left ventricle may be pre-excited. Further, if the proportion of anterior electrodes activating late exceeds the proportion of posterior electrodes activating late, the right ventricle may be pre-excited.
Baseline, initial, and subsequent electrical heterogeneity information 250 for an exemplary patient is depicted in FIG. 5. As shown, the baseline electrical heterogeneity information 252 was generated from electrical activity monitored without the delivery of cardiac therapy (e.g., the patient was in intrinsic rhythm) and indicated a SDAT of 35 ms, a LVED of 38 ms, and a LVAT of 67 ms. The initial electrical heterogeneity information 254 was generated from electrical activity monitored during the delivery of biventricular pacing therapy at a V-V interval of 0 ms and indicated a SDAT of 34 ms, a LVED of 34 ms, and a LVAT of 57 ms. As shown by comparing the baseline electrical heterogeneity information 252 and the initial electrical heterogeneity information 254, the patient's overall heterogeneity did not improve with biventricular pacing therapy at a V-V interval of 0 ms (e.g., with an optimized A-V interval). Further, the extent of delay on posterior side was more than in the anterior side, which indicates that the V-V interval should be configured for left ventricular pre-excitation.
After selecting the left ventricle for pre-excitation 208, the exemplary method 200 may adjust the V-V interval 210 from the previous V-V interval value, which if the V-V interval is the initial V-V interval, may be 0 ms. For example, the V-V interval may be selected to be a pre-determined value, or value within a range of values, that is different than the previous V-V interval. In at least one embodiment, the predetermined V-V interval may be about 80 milliseconds (ms). The predetermined V-V interval may be greater than or equal to about 50 ms, greater than or equal to about 60 ms, greater than or equal to about 70 ms, greater than or equal to about 80 ms, greater than or equal to about 90 ms, greater than or equal to about 100 ms, etc. Further, the predetermined V-V interval may be less than or equal to about 125 ms, less than or equal to about 115 ms, less than or equal to about 105 ms, less than or equal to about 95 ms, less than or equal to about 85 ms, less than or equal to about 75 ms, etc.
The exemplary method 200 may then deliver bi-ventricular pacing therapy 204, monitor electrical activity 202, and generate electrical heterogeneity information 206 for the predetermined V-V interval 210. It may be described that the V-V interval is “swept” from the predetermined, long V-V interval until the V-V interval is back to 0. Thus, the method 200 may continue repeating the same cycle for a different V-V interval until, e.g., a plurality of V-V different intervals have been utilized and/or the V-V interval is adjusted to zero.
For example, the V-V interval may be decreased by a step size, or decrement, until the V-V interval is zero. In at least one embodiment, the step size, or increment, may be about 20 ms. The step size, or increment, may be greater than or about 5 ms, greater than or equal to about 10 ms, greater than or equal to about 15 ms, greater than or equal to about 20 ms, greater than or equal to about 25 ms, greater than or equal to about 30 ms, etc. Further, the step size, or decrement, may be less than or equal to about 50 ms, less than or equal to about 40 ms, less than or equal to about 35 ms, less than or equal to about 30 ms, less than or equal to about 25 ms, etc.
In other words, the exemplary methods and systems initiate delivery of bi-ventricular pacing therapy at a plurality of different V-V intervals 204 (e.g., a different V-V interval for each cycle) and monitor the electrical activity 202 for each of the plurality of V-V intervals. Further, electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality may be generated 206 for each of the plurality of V-V intervals.
In FIG. 5, the left ventricle was determined to be pre-excited and the V-V interval (i.e., left ventricle-to-right ventricle delay) was adjusted, or set, to 80 ms after the initial V-V interval (e.g., 0 ms). The V-V interval was then decremented by 20 ms for each cycle. As shown, the subsequent heterogeneity information 256 was generated from electrical activity monitored during the delivery of biventricular pacing therapy at a V-V interval of 80 ms and indicated a SDAT of 28 ms, a LVED of 20 ms, and a LVAT of 23 ms. The subsequent electrical heterogeneity information 256 indicates an improvement from the initial electrical heterogeneity information 254 that resulted from a V-V interval of 0 ms.
The V-V interval was then decremented by 20 ms to 60 ms and subsequent heterogeneity information 258 was generated from electrical activity monitored during the delivery of biventricular pacing therapy at a V-V interval of 60 ms. The subsequent heterogeneity information 258 indicated a SDAT of 25 ms, a LVED of 17 ms, and a LVAT of 31 ms.
The V-V interval was then further decremented by 20 ms to 40 ms and subsequent heterogeneity information 260 was generated from electrical activity monitored during the delivery of biventricular pacing therapy at a V-V interval of 40 ms. The subsequent heterogeneity information 260 indicated a SDAT of 29 ms, a LVED of 13 ms, and a LVAT of 24 ms.
After monitoring the electrical activity 202 for a plurality of different V-V intervals and generating electrical heterogeneity information 206 based on the monitored electrical activity for each of the plurality of different V-V intervals, the exemplary method 200 may identify one or more (e.g., one, two, etc.) V-V intervals of the plurality of different V-V intervals 212 based on the electrical heterogeneity information that may benefit the patient's cardiac therapy.
To identify one or more V-V intervals from the plurality of different V-V intervals 212, the exemplary method 200 may use one or more metrics or indices of electrical heterogeneity, alone or together. For example, the V-V interval that generated the lowest global standard deviation of surrogate electrical activation times (SDAT), the lowest left standard deviation (LVED) and/or the lowest left average (LVAT) may be identified (e.g., identified as the optimal V-V interval).
When it is described that V-V intervals are identified, it is to be understood that the exemplary methods and systems may identify the V-V intervals in various different ways. For example, the identified V-V intervals may be displayed on a graphical user interface along with heterogeneity information. The heterogeneity information may be graphical and/or textual, and may include graphical maps of electrical activation times about one or more regions of the patient's torso and/or heart. In at least one embodiment, the heterogeneity information 250 of FIG. 5 may be depicted on a graphical user interface such that, e.g., a user may view the results from each of the different V-V intervals.
Additionally, the exemplary methods and systems may be further configured to select the identified V-V interval and program, or set, the cardiac therapy apparatus to use the identified V-V interval. In other embodiments, a user may use the exemplary systems and methods to program, or configure the cardiac therapy apparatus using the identified V-V interval as well as other parameters and settings.
In at least one embodiment, an exemplary graphical user interface may include, among other things, a graphical representation 270 of measured surrogate electrical activation times and electrical heterogeneity information 272. The graphical representation 270 of measured surrogate cardiac electrical activation times may be depicted in a variety of fashions. As shown, the surrogate electrical activation times may be depicted as a color-coded, or color-scaled, segment (as shown, the color-coding is depicted in gray-scale). More specifically, anterior and posterior side color-coded segments graphically depicting surrogate electrical activation times measured, e.g., using the electrical apparatus described herein with reference to FIGS. 1-3, are depicted in FIG. 5. Further, the graphical representation 270 of measured surrogate cardiac electrical activation times for the anterior side may be measured using electrodes located on, or proximate to, the anterior side of the patient's torso, and likewise, the graphical representation 270 of measured surrogate cardiac electrical activation times for the posterior side may be measured using electrodes located on, or proximate to, the posterior side of the patient's torso. In other words, the graphical representation 270 of measured surrogate cardiac electrical activation times for the anterior side correlates to actual electrical signals measured using electrodes configured to measure electrical signals on the anterior side of the patient's torso, and the graphical representation 270 of measured surrogate cardiac electrical activation times for the posterior side of the human torso correlates to actual electrical signals measured using electrodes configured to measure electrical signals on the posterior side of the patient's torso.
Additional exemplary graphical representations of surrogate electrical activation times may be described in U.S. Patent Application Publication No. 2012/0284003 A1 published on Nov. 8, 2012 and entitled “Assessing Intra-Cardiac Activation Patterns” and U.S. Patent Application Publication No. 2012/0283587 A1 published on Nov. 8, 2012 and entitled “Assessing Intra-Cardiac Activation Patterns and Electrical Dyssynchrony,” each of which is hereby incorporated by reference in its entirety.
The exemplary systems, methods, and graphical user interfaces described herein may be used with respect to the implantation and configuration of an implantable medical device (IMD) and/or one or more leads configured to be located proximate one or more portions of a patient's heart. For example, the exemplary systems, methods, and interfaces may be used in conjunction with an exemplary therapy system 10 described herein with reference to FIGS. 8-10.
FIG. 8 is a conceptual diagram illustrating an exemplary therapy system 10 that may be used to deliver pacing therapy to a patient 14. Patient 14 may, but not necessarily, be a human. The therapy system 10 may include an implantable medical device 16 (IMD), which may be coupled to leads 18, 20, 22. The IMD 16 may be, e.g., an implantable pacemaker, cardioverter, and/or defibrillator, that delivers, or provides, electrical signals to and/or measures, or monitors electrical signals from the heart 12 of the patient 14 via electrodes coupled to one or more of the leads 18, 20, 22.
The leads 18, 20, 22 extend into the heart 12 of the patient 14 to sense electrical activity of the heart 12 and/or to deliver electrical stimulation to the heart 12. In the example shown in FIG. 8, the right ventricular (RV) lead 18 extends through one or more veins (not shown), the superior vena cava (not shown), and the right atrium 26, and into the right ventricle 28. The left ventricular (LV) coronary sinus lead 20 extends through one or more veins, the vena cava, the right atrium 26, and into the coronary sinus 30 to a region adjacent to the free wall of the left ventricle 32 of the heart 12. The right atrial (RA) lead 22 extends through one or more veins and the vena cava, and into the right atrium 26 of the heart 12.
The IMD 16 may sense, among other things, electrical signals attendant to the depolarization and repolarization of the heart 12 via electrodes coupled to at least one of the leads 18, 20, 22. In some examples, the IMD 16 provides pacing therapy (e.g., pacing pulses) to the heart 12 based on the electrical signals sensed within the heart 12. The IMD 16 may be operable to adjust one or more parameters associated with the pacing therapy such as, e.g., V-V delay, A-V delay and other various timings, pulse wide, amplitude, voltage, burst length, etc. Further, the IMD 16 may be operable to use various electrode configurations to deliver pacing therapy, which may be unipolar, bipolar, quadripoloar, or further multipolar. For example, a multipolar lead may include several electrodes that can be used for delivering pacing therapy. Hence, a multipolar lead system may provide, or offer, multiple electrical vectors to pace from. A pacing vector may include at least one cathode, which may be at least one electrode located on at least one lead, and at least one anode, which may be at least one electrode located on at least one lead (e.g., the same lead, or a different lead) and/or on the casing, or can, of the IMD. While improvement in cardiac function as a result of the pacing therapy may primarily depend on the cathode, the electrical parameters like impedance, pacing threshold voltage, current drain, longevity, etc. may be more dependent on the pacing vector, which includes both the cathode and the anode. The IMD 16 may also provide defibrillation therapy and/or cardioversion therapy via electrodes located on at least one of the leads 18, 20, 22. Further, the IMD 16 may detect arrhythmia of the heart 12, such as fibrillation of the ventricles 28, 32, and deliver defibrillation therapy to the heart 12 in the form of electrical pulses. In some examples, IMD 16 may be programmed to deliver a progression of therapies, e.g., pulses with increasing energy levels, until a fibrillation of heart 12 is stopped.
FIGS. 9A-9B are conceptual diagrams illustrating the IMD 16 and the leads 18, 20, 22 of therapy system 10 of FIG. 8 in more detail. The leads 18, 20, 22 may be electrically coupled to a therapy delivery module (e.g., for delivery of pacing therapy), a sensing module (e.g., for sensing one or more signals from one or more electrodes), and/or any other modules of the IMD 16 via a connector block 34. In some examples, the proximal ends of the leads 18, 20, 22 may include electrical contacts that electrically couple to respective electrical contacts within the connector block 34 of the IMD 16. In addition, in some examples, the leads 18, 20, 22 may be mechanically coupled to the connector block 34 with the aid of set screws, connection pins, or another suitable mechanical coupling mechanism.
Each of the leads 18, 20, 22 includes an elongated insulative lead body, which may carry a number of conductors (e.g., concentric coiled conductors, straight conductors, etc.) separated from one another by insulation (e.g., tubular insulative sheaths). In the illustrated example, bipolar electrodes 40, 42 are located proximate to a distal end of the lead 18. In addition, bipolar electrodes 44, 45, 46, 47 are located proximate to a distal end of the lead 20 and bipolar electrodes 48, 50 are located proximate to a distal end of the lead 22.
The electrodes 40, 44, 45, 46, 47, 48 may take the form of ring electrodes, and the electrodes 42, 50 may take the form of extendable helix tip electrodes mounted retractably within the insulative electrode heads 52, 54, 56, respectively. Each of the electrodes 40, 42, 44, 45, 46, 47, 48, 50 may be electrically coupled to a respective one of the conductors (e.g., coiled and/or straight) within the lead body of its associated lead 18, 20, 22, and thereby coupled to a respective one of the electrical contacts on the proximal end of the leads 18, 20, 22.
Additionally, electrodes 44, 45, 46 and 47 may have an electrode surface area of about 5.3 mm2 to about 5.8 mm2. Electrodes 44, 45, 46, and 47 may also be referred to as LV1, LV2, LV3, and LV4, respectively. The LV electrodes (i.e., left ventricle electrode 1 (LV1) 44, left ventricle electrode 2 (LV2) 45, left ventricle electrode 3 (LV3) 46, and left ventricle 4 (LV4) 47 etc.) on the lead 20 can be spaced apart at variable distances. For example, electrode 44 may be a distance of, e.g., about 21 millimeters (mm), away from electrode 45, electrodes 45 and 46 may be spaced a distance of, e.g., about 1.3 mm to about 1.5 mm, away from each other, and electrodes 46 and 47 may be spaced a distance of, e.g. 20 mm to about 21 mm, away from each other.
The electrodes 40, 42, 44, 45, 46, 47, 48, 50 may further be used to sense electrical signals (e.g., morphological waveforms within electrograms (EGM)) attendant to the depolarization and repolarization of the heart 12. The sensed electrical signals may be used to adjust one or more pacing parameters such as, e.g., A-V interval, V-V interval, etc. to provide optimal and/or effective cardiac functionality. The electrical signals are conducted to the IMD 16 via the respective leads 18, 20, 22. In some examples, the IMD 16 may also deliver pacing pulses via the electrodes 40, 42, 44, 45, 46, 47, 48, 50 to cause depolarization of cardiac tissue of the patient's heart 12. In some examples, as illustrated in FIG. 9A, the IMD 16 includes one or more housing electrodes, such as housing electrode 58, which may be formed integrally with an outer surface of a housing 60 (e.g., hermetically-sealed housing) of the IMD 16 or otherwise coupled to the housing 60. Any of the electrodes 40, 42, 44, 45, 46, 47, 48, 50 may be used for unipolar sensing or pacing in combination with the housing electrode 58. In other words, any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58 may be used in combination to form a sensing vector, e.g., a sensing vector that may be used to evaluate and/or analyze the effectiveness of pacing therapy. It is to be understood by those skilled in the art that other electrodes can also be selected to define, or be used for, pacing and sensing vectors. Further, any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, when not being used to deliver pacing therapy, may be used to sense electrical activity during pacing therapy.
As described in further detail with reference to FIG. 9A, the housing 60 may enclose a therapy delivery module that may include a stimulation generator for generating cardiac pacing pulses and defibrillation or cardioversion shocks, as well as a sensing module for monitoring electrical signals of the patient's heart (e.g., the patient's heart rhythm). The leads 18, 20, 22 may also include elongated electrodes 62, 64, 66, respectively, which may take the form of a coil. The IMD 16 may deliver defibrillation shocks to the heart 12 via any combination of the elongated electrodes 62, 64, 66 and the housing electrode 58. The electrodes 58, 62, 64, 66 may also be used to deliver cardioversion pulses to the heart 12. Further, the electrodes 62, 64, 66 may be fabricated from any suitable electrically conductive material, such as, but not limited to, platinum, platinum alloy, and/or other materials known to be usable in implantable defibrillation electrodes. Since electrodes 62, 64, 66 are not generally configured to deliver pacing therapy, any of electrodes 62, 64, 66 may be used to sense electrical activity (e.g., for use in determining electrode effectiveness, for use in analyzing pacing therapy effectiveness, etc.) and may be used in combination with any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58. In at least one embodiment, the RV elongated electrode 62 may be used to sense electrical activity of a patient's heart during the delivery of pacing therapy (e.g., in combination with the housing electrode 58, or defibrillation electrode-to-housing electrode vector).
The configuration of the exemplary therapy system 10 illustrated in FIGS. 9-11 is merely one example. In other examples, the therapy system may include epicardial leads and/or patch electrodes instead of or in addition to the transvenous leads 18, 20, 22 illustrated in FIG. 8. Additionally, in other examples, the therapy system 10 may be implanted in/around the cardiac space without transvenous leads (e.g., leadless/wireless pacing systems) or with leads implanted (e.g., implanted transvenously or using approaches) into the left chambers of the heart (in addition to or replacing the transvenous leads placed into the right chambers of the heart as illustrated in FIG. 8). Further, in one or more embodiments, the IMD 16 need not be implanted within the patient 14. For example, the IMD 16 may deliver various cardiac therapies to the heart 12 via percutaneous leads that extend through the skin of the patient 14 to a variety of positions within or outside of the heart 12. In one or more embodiments, the system 10 may utilize wireless pacing (e.g., using energy transmission to the intracardiac pacing component(s) via ultrasound, inductive coupling, RF, etc.) and sensing cardiac activation using electrodes on the can/housing and/or on subcutaneous leads.
In other examples of therapy systems that provide electrical stimulation therapy to the heart 12, such therapy systems may include any suitable number of leads coupled to the IMD 16, and each of the leads may extend to any location within or proximate to the heart 12. For example, other examples of therapy systems may include three transvenous leads located as illustrated in FIGS. 9-11. Still further, other therapy systems may include a single lead that extends from the IMD 16 into the right atrium 26 or the right ventricle 28, or two leads that extend into a respective one of the right atrium 26 and the right ventricle 28.
FIG. 10A is a functional block diagram of one exemplary configuration of the IMD 16. As shown, the IMD 16 may include a control module 81, a therapy delivery module 84 (e.g., which may include a stimulation generator), a sensing module 86, and a power source 90.
The control module 81 may include a processor 80, memory 82, and a telemetry module 88. The memory 82 may include computer-readable instructions that, when executed, e.g., by the processor 80, cause the IMD 16 and/or the control module 81 to perform various functions attributed to the IMD 16 and/or the control module 81 described herein. Further, the memory 82 may include any volatile, non-volatile, magnetic, optical, and/or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, and/or any other digital media. An exemplary capture management module may be the left ventricular capture management (LVCM) module described in U.S. Pat. No. 7,684,863 entitled “LV THRESHOLD MEASUREMENT AND CAPTURE MANAGEMENT” and issued Mar. 23, 2010, which is incorporated herein by reference in its entirety.
The processor 80 of the control module 81 may include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), and/or equivalent discrete or integrated logic circuitry. In some examples, the processor 80 may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, and/or one or more FPGAs, as well as other discrete or integrated logic circuitry. The functions attributed to the processor 80 herein may be embodied as software, firmware, hardware, or any combination thereof.
The control module 81 may control the therapy delivery module 84 to deliver therapy (e.g., electrical stimulation therapy such as pacing) to the heart 12 according to a selected one or more therapy programs, which may be stored in the memory 82. More, specifically, the control module 81 (e.g., the processor 80) may control various parameters of the electrical stimulus delivered by the therapy delivery module 84 such as, e.g., A-V delays, V-V delays, pacing pulses with the amplitudes, pulse widths, frequency, or electrode polarities, etc., which may be specified by one or more selected therapy programs (e.g., A-V and/or V-V delay adjustment programs, pacing therapy programs, pacing recovery programs, capture management programs, etc.). As shown, the therapy delivery module 84 is electrically coupled to electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, e.g., via conductors of the respective lead 18, 20, 22, or, in the case of housing electrode 58, via an electrical conductor disposed within housing 60 of IMD 16. Therapy delivery module 84 may be configured to generate and deliver electrical stimulation therapy such as pacing therapy to the heart 12 using one or more of the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66.
For example, therapy delivery module 84 may deliver pacing stimulus (e.g., pacing pulses) via ring electrodes 40, 44, 45, 46, 47, 48 coupled to leads 18, 20, 22 and/or helical tip electrodes 42, 50 of leads 18, 22. Further, for example, therapy delivery module 84 may deliver defibrillation shocks to heart 12 via at least two of electrodes 58, 62, 64, 66. In some examples, therapy delivery module 84 may be configured to deliver pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, therapy delivery module 84 may be configured deliver one or more of these types of stimulation in the form of other signals, such as sine waves, square waves, and/or other substantially continuous time signals.
The IMD 16 may further include a switch module 85 and the control module 81 (e.g., the processor 80) may use the switch module 85 to select, e.g., via a data/address bus, which of the available electrodes are used to deliver therapy such as pacing pulses for pacing therapy, or which of the available electrodes are used for sensing. The switch module 85 may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable to selectively couple the sensing module 86 and/or the therapy delivery module 84 to one or more selected electrodes. More specifically, the therapy delivery module 84 may include a plurality of pacing output circuits. Each pacing output circuit of the plurality of pacing output circuits may be selectively coupled, e.g., using the switch module 85, to one or more of the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pair of electrodes for delivery of therapy using a bipolar or multipolar pacing vector). In other words, each electrode can be selectively coupled to one of the pacing output circuits of the therapy delivery module using the switching module 85.
The sensing module 86 is coupled (e.g., electrically coupled) to sensing apparatus, which may include, among additional sensing apparatus, the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitor electrical activity of the heart 12, e.g., electrocardiogram (ECG)/electrogram (EGM) signals, etc. The ECG/EGM signals may be used to measure or monitor activation times (e.g., ventricular activations times, etc.), heart rate (HR), heart rate variability (HRV), heart rate turbulence (HRT), deceleration/acceleration capacity, deceleration sequence incidence, T-wave alternans (TWA), P-wave to P-wave intervals (also referred to as the P-P intervals or A-A intervals), R-wave to R-wave intervals (also referred to as the R-R intervals or V-V intervals), P-wave to QRS complex intervals (also referred to as the P-R intervals, A-V intervals, or P-Q intervals), QRS-complex morphology, ST segment (i.e., the segment that connects the QRS complex and the T-wave), T-wave changes, QT intervals, electrical vectors, etc.
The switch module 85 may also be used with the sensing module 86 to select which of the available electrodes are used, or enabled, to, e.g., sense electrical activity of the patient's heart (e.g., one or more electrical vectors of the patient's heart using any combination of the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66). Likewise, the switch module 85 may also be used with the sensing module 86 to select which of the available electrodes are not to be used (e.g., disabled) to, e.g., sense electrical activity of the patient's heart (e.g., one or more electrical vectors of the patient's heart using any combination of the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66), etc. In some examples, the control module 81 may select the electrodes that function as sensing electrodes via the switch module within the sensing module 86, e.g., by providing signals via a data/address bus.
In some examples, sensing module 86 includes a channel that includes an amplifier with a relatively wider pass band than the R-wave or P-wave amplifiers. Signals from the selected sensing electrodes may be provided to a multiplexer, and thereafter converted to multi-bit digital signals by an analog-to-digital converter for storage in memory 82, e.g., as an electrogram (EGM). In some examples, the storage of such EGMs in memory 82 may be under the control of a direct memory access circuit.
In some examples, the control module 81 may operate as an interrupt driven device, and may be responsive to interrupts from pacer timing and control module, where the interrupts may correspond to the occurrences of sensed P-waves and R-waves and the generation of cardiac pacing pulses. Any necessary mathematical calculations may be performed by the processor 80 and any updating of the values or intervals controlled by the pacer timing and control module may take place following such interrupts. A portion of memory 82 may be configured as a plurality of recirculating buffers, capable of holding one or more series of measured intervals (e.g., intrinsic A-V conduction times, intrinsic V-V conduction times, etc.), which may be analyzed by, e.g., the processor 80 in response to the occurrence of a pace or sense interrupt to determine whether the patient's heart 12 is presently exhibiting atrial or ventricular tachyarrhythmia.
The telemetry module 88 of the control module 81 may include any suitable hardware, firmware, software, or any combination thereof for communicating with another device, such as a programmer. For example, under the control of the processor 80, the telemetry module 88 may receive downlink telemetry from and send uplink telemetry to a programmer with the aid of an antenna, which may be internal and/or external. The processor 80 may provide the data to be uplinked to a programmer and the control signals for the telemetry circuit within the telemetry module 88, e.g., via an address/data bus. In some examples, the telemetry module 88 may provide received data to the processor 80 via a multiplexer.
The various components of the IMD 16 are further coupled to a power source 90, which may include a rechargeable or non-rechargeable battery. A non-rechargeable battery may be selected to last for several years, while a rechargeable battery may be inductively charged from an external device, e.g., on a daily or weekly basis.
FIG. 10B is another embodiment of a functional block diagram for IMD 16. FIG. 10B depicts bipolar RA lead 22, bipolar RV lead 18, and bipolar LV CS lead 20 without the LA CS pace/sense electrodes and coupled with an implantable pulse generator (IPG) circuit 31 having programmable modes and parameters of a bi-ventricular DDD/R type known in the pacing art. In turn, the sensor signal processing circuit 91 indirectly couples to the timing circuit 43 and via data and control bus to microcomputer circuitry 33. The IPG circuit 31 is illustrated in a functional block diagram divided generally into a microcomputer circuit 33 and a pacing circuit 21. The pacing circuit 21 includes the digital controller/timer circuit 43, the output amplifiers circuit 51, the sense amplifiers circuit 55, the RF telemetry transceiver 41, the activity sensor circuit 35 as well as a number of other circuits and components described below.
Crystal oscillator circuit 89 provides the basic timing clock for the pacing circuit 21 while battery 29 provides power. Power-on-reset circuit 87 responds to initial connection of the circuit to the battery for defining an initial operating condition and similarly, resets the operative state of the device in response to detection of a low battery condition. Reference mode circuit 37 generates stable voltage reference and currents for the analog circuits within the pacing circuit 21. Analog-to-digital converter (ADC) and multiplexer circuit 39 digitize analog signals and voltage to provide, e.g., real time telemetry of cardiac signals from sense amplifiers 55 for uplink transmission via RF transmitter and receiver circuit 41. Voltage reference and bias circuit 37, ADC and multiplexer 39, power-on-reset circuit 87, and crystal oscillator circuit 89 may correspond to any of those used in exemplary implantable cardiac pacemakers.
If the IPG is programmed to a rate responsive mode, the signals output by one or more physiologic sensors are employed as a rate control parameter (RCP) to derive a physiologic escape interval. For example, the escape interval is adjusted proportionally to the patient's activity level developed in the patient activity sensor (PAS) circuit 35 in the depicted, exemplary IPG circuit 31. The patient activity sensor 27 is coupled to the IPG housing and may take the form of a piezoelectric crystal transducer. The output signal of the patient activity sensor 27 may be processed and used as a RCP. Sensor 27 generates electrical signals in response to sensed physical activity that are processed by activity circuit 35 and provided to digital controller/timer circuit 43. Activity circuit 35 and associated sensor 27 may correspond to the circuitry disclosed in U.S. Pat. No. 5,052,388 entitled “METHOD AND APPARATUS FOR IMPLEMENTING ACTIVITY SENSING IN A PULSE GENERATOR” and issued on Oct. 1, 1991 and U.S. Pat. No. 4,428,378 entitled “RATE ADAPTIVE PACER” and issued on Jan. 31, 1984, each of which is incorporated herein by reference in its entirety. Similarly, the exemplary systems, apparatus, and methods described herein may be practiced in conjunction with alternate types of sensors such as oxygenation sensors, pressure sensors, pH sensors, and respiration sensors for use in providing rate responsive pacing capabilities. Alternately, QT time may be used as the rate indicating parameter, in which case no extra sensor is required. Similarly, the exemplary embodiments described herein may also be practiced in non-rate responsive pacemakers.
Data transmission to and from the external programmer is accomplished by way of the telemetry antenna 57 and an associated RF transceiver 41, which serves both to demodulate received downlink telemetry and to transmit uplink telemetry. Uplink telemetry capabilities may include the ability to transmit stored digital information, e.g., operating modes and parameters, EGM histograms, and other events, as well as real time EGMs of atrial and/or ventricular electrical activity and marker channel pulses indicating the occurrence of sensed and paced depolarizations in the atrium and ventricle.
Microcomputer 33 contains a microprocessor 80 and associated system clock and on-processor RAM and ROM chips 82A and 82B, respectively. In addition, microcomputer circuit 33 includes a separate RAM/ROM chip 82C to provide additional memory capacity. Microprocessor 80 normally operates in a reduced power consumption mode and is interrupt driven. Microprocessor 80 is awakened in response to defined interrupt events, which may include A-TRIG, RV-TRIG, LV-TRIG signals generated by timers in digital timer/controller circuit 43 and A-EVENT, RV-EVENT, and LV-EVENT signals generated by sense amplifiers circuit 55, among others. The specific values of the intervals and delays timed out by digital controller/timer circuit 43 are controlled by the microcomputer circuit 33 by way of data and control bus from programmed-in parameter values and operating modes. In addition, if programmed to operate as a rate responsive pacemaker, a timed interrupt, e.g., every cycle or every two seconds, may be provided in order to allow the microprocessor to analyze the activity sensor data and update the basic A-A, V-A, or V-V escape interval, as applicable. In addition, the microprocessor 80 may also serve to define variable, operative V-V delay intervals, A-V delay intervals, etc. and the energy delivered to each ventricle and/or atrium.
In one embodiment, microprocessor 80 is a custom microprocessor adapted to fetch and execute instructions stored in RAM/ROM unit 82 in a conventional manner. It is contemplated, however, that other implementations may be suitable to practice the present invention. For example, an off-the-shelf, commercially available microprocessor or microcontroller, or custom application-specific, hardwired logic, or state-machine type circuit may perform the functions of microprocessor 80.
Digital controller/timer circuit 43 operates under the general control of the microcomputer 33 to control timing and other functions within the pacing circuit 321 and includes a set of timing and associated logic circuits of which certain ones pertinent to the present invention are depicted. The depicted timing circuits include URI/LRI timers 83A, V-V delay timer 83B, intrinsic interval timers 83C for timing elapsed V-EVENT to V-EVENT intervals or V-EVENT to A-EVENT intervals or the V-V conduction interval, escape interval timers 83D for timing A-A, V-A, and/or V-V pacing escape intervals, an A-V delay interval timer 83E for timing the A-LVp delay (or A-RVp delay) from a preceding A-EVENT or A-TRIG, a post-ventricular timer 83F for timing post-ventricular time periods, and a date/time clock 83G.
The A-V delay interval timer 83E is loaded with an appropriate delay interval for one ventricular chamber (e.g., either an A-RVp delay or an A-LVp delay) to time-out starting from a preceding A-PACE or A-EVENT. The interval timer 83E triggers pacing stimulus delivery, and can be based on one or more prior cardiac cycles (or from a data set empirically derived for a given patient).
The post-event timer 83F times out the post-ventricular time period following an RV-EVENT or LV-EVENT or a RV-TRIG or LV-TRIG and post-atrial time periods following an A-EVENT or A-TRIG. The durations of the post-event time periods may also be selected as programmable parameters stored in the microcomputer 33. The post-ventricular time periods include the PVARP, a post-atrial ventricular blanking period (PAVBP), a ventricular blanking period (VBP), a post-ventricular atrial blanking period (PVARP) and a ventricular refractory period (VRP) although other periods can be suitably defined depending, at least in part, on the operative circuitry employed in the pacing engine. The post-atrial time periods include an atrial refractory period (ARP) during which an A-EVENT is ignored for the purpose of resetting any A-V delay, and an atrial blanking period (ABP) during which atrial sensing is disabled. It should be noted that the starting of the post-atrial time periods and the A-V delays can be commenced substantially simultaneously with the start or end of each A-EVENT or A-TRIG or, in the latter case, upon the end of the A-PACE which may follow the A-TRIG. Similarly, the starting of the post-ventricular time periods and the V-A escape interval can be commenced substantially simultaneously with the start or end of the V-EVENT or V-TRIG or, in the latter case, upon the end of the V-PACE which may follow the V-TRIG. The microprocessor 80 also optionally calculates A-V delays, V-V delays, post-ventricular time periods, and post-atrial time periods that vary with the sensor based escape interval established in response to the RCP(s) and/or with the intrinsic atrial rate and/or intrinsic ventricular rate.
The output amplifiers circuit 51 contains a RA pace pulse generator (and a LA pace pulse generator if LA pacing is provided), a RV pace pulse generator, a LV pace pulse generator, and/or any other pulse generator configured to provide atrial and ventricular pacing. In order to trigger generation of an RV-PACE or LV-PACE pulse, digital controller/timer circuit 43 generates the RV-TRIG signal at the time-out of the A-RVp delay (in the case of RV pre-excitation) or the LV-TRIG at the time-out of the A-LVp delay (in the case of LV pre-excitation) provided by AV delay interval timer 83E (or the V-V delay timer 83B). Similarly, digital controller/timer circuit 43 generates an RA-TRIG signal that triggers output of an RA-PACE pulse (or an LA-TRIG signal that triggers output of an LA-PACE pulse, if provided) at the end of the V-A escape interval timed by escape interval timers 83D.
The output amplifiers circuit 51 includes switching circuits for coupling selected pace electrode pairs from among the lead conductors and the IND-CAN electrode 20 to the RA pace pulse generator (and LA pace pulse generator if provided), RV pace pulse generator and LV pace pulse generator. Pace/sense electrode pair selection and control circuit 53 selects lead conductors and associated pace electrode pairs to be coupled with the atrial and ventricular output amplifiers within output amplifiers circuit 51 for accomplishing RA, LA, RV and LV pacing.
The sense amplifiers circuit 55 contains sense amplifiers for atrial and ventricular pacing and sensing. High impedance P-wave and R-wave sense amplifiers may be used to amplify a voltage difference signal that is generated across the sense electrode pairs by the passage of cardiac depolarization wavefronts. The high impedance sense amplifiers use high gain to amplify the low amplitude signals and rely on pass band filters, time domain filtering and amplitude threshold comparison to discriminate a P-wave or R-wave from background electrical noise. Digital controller/timer circuit 43 controls sensitivity settings of the atrial and ventricular sense amplifiers 55.
The sense amplifiers may be uncoupled from the sense electrodes during the blanking periods before, during, and after delivery of a pace pulse to any of the pace electrodes of the pacing system to avoid saturation of the sense amplifiers. The sense amplifiers circuit 55 includes blanking circuits for uncoupling the selected pairs of the lead conductors and the IND-CAN electrode 20 from the inputs of the RA sense amplifier (and LA sense amplifier if provided), RV sense amplifier and LV sense amplifier during the ABP, PVABP and VBP. The sense amplifiers circuit 55 also includes switching circuits for coupling selected sense electrode lead conductors and the IND-CAN electrode 20 to the RA sense amplifier (and LA sense amplifier if provided), RV sense amplifier and LV sense amplifier. Again, sense electrode selection and control circuit 53 selects conductors and associated sense electrode pairs to be coupled with the atrial and ventricular sense amplifiers within the output amplifiers circuit 51 and sense amplifiers circuit 55 for accomplishing RA, LA, RV, and LV sensing along desired unipolar and bipolar sensing vectors.
Right atrial depolarizations or P-waves in the RA-SENSE signal that are sensed by the RA sense amplifier result in a RA-EVENT signal that is communicated to the digital controller/timer circuit 43. Similarly, left atrial depolarizations or P-waves in the LA-SENSE signal that are sensed by the LA sense amplifier, if provided, result in a LA-EVENT signal that is communicated to the digital controller/timer circuit 43. Ventricular depolarizations or R-waves in the RV-SENSE signal are sensed by a ventricular sense amplifier result in an RV-EVENT signal that is communicated to the digital controller/timer circuit 43. Similarly, ventricular depolarizations or R-waves in the LV-SENSE signal are sensed by a ventricular sense amplifier result in an LV-EVENT signal that is communicated to the digital controller/timer circuit 43. The RV-EVENT, LV-EVENT, and RA-EVENT, LA-SENSE signals may be refractory or non-refractory, and can inadvertently be triggered by electrical noise signals or aberrantly conducted depolarization waves rather than true R-waves or P-waves.
The techniques described in this disclosure, including those attributed to the IMD 16, the computing apparatus 140, and/or various constituent components, may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, embodied in programmers, such as physician or patient programmers, stimulators, image processing devices, or other devices. The term “module,” “processor,” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry.
Such hardware, software, and/or firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, modules, or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components.
When implemented in software, the functionality ascribed to the systems, devices and techniques described in this disclosure may be embodied as instructions on a computer-readable medium such as RAM, ROM, NVRAM, EEPROM, FLASH memory, magnetic data storage media, optical data storage media, or the like. The instructions may be executed by one or more processors to support one or more aspects of the functionality described in this disclosure.
This disclosure has been provided with reference to illustrative embodiments and is not meant to be construed in a limiting sense. As described previously, one skilled in the art will recognize that other various illustrative applications may use the techniques as described herein to take advantage of the beneficial characteristics of the apparatus and methods described herein. Various modifications of the illustrative embodiments, as well as additional embodiments of the disclosure, will be apparent upon reference to this description.

## Claims

1. A system for use in cardiac therapy comprising:
electrode apparatus comprising a plurality of external electrodes configured to be located proximate tissue of a patient; and
computing apparatus coupled to the electrode apparatus and configured to:
initiate delivery of bi-ventricular pacing therapy at a plurality of different V-V intervals,
monitor electrical activity using the plurality of external electrodes for each of the plurality of V-V intervals during the delivery of bi-ventricular pacing therapy,
generate electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the monitored electrical activity, and
identify a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.

2. The system of claim 1, wherein the electrical heterogeneity information comprises a global standard deviation of surrogate electrical activation times monitored by the plurality of external electrodes, wherein identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information comprises identifying the V-V interval from the plurality of different V-V intervals that generated the lowest global standard deviation of surrogate electrical activation times.

3. The system of claim 1, wherein the plurality of electrodes comprises two or more left external electrodes configured to be located proximate the left side of the patient, wherein the electrical heterogeneity information comprises a left standard deviation of surrogate electrical activation times monitored by the two or more left external electrodes, wherein identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information comprises identifying the V-V interval from the plurality of different V-V intervals that generated the lowest left standard deviation.

4. The system of claim 1, wherein the plurality of electrodes comprises two or more left external electrodes configured to be located proximate the left side of the patient, wherein the electrical heterogeneity information comprises a left average of surrogate electrical activation times monitored by the two or more left external electrodes, wherein identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information comprises identifying the V-V interval from the plurality of different V-V intervals that generated the lowest left average.

5. The system of claim 1, wherein the computing apparatus configures the plurality of different V-V intervals of the bi-ventricular pacing therapy to pre-excite the left ventricle if the electrical heterogeneity information indicates an increase in heterogeneity in the electrical activity monitored by the plurality of external electrodes.

6. The system of claim 1, wherein the plurality of electrodes comprises two or more left external electrodes configured to be located proximate the left side of the patient, wherein the plurality of electrodes comprises two or more posterior external electrodes configured to be located proximate the posterior side of the patient,
wherein the computing apparatus configures the plurality of different V-V intervals of the bi-ventricular pacing therapy to pre-excite the left ventricle if the monitored electrical activity indicates an increase in surrogate electrical activation times monitored by at least one of the two or more left external electrodes and the two or more posterior external electrodes.

7. The system of claim 1, wherein the plurality of electrodes comprises two or more right external electrodes configured to be located proximate the right side of the patient, wherein the plurality of electrodes comprises two or more anterior external electrodes configured to be located proximate the anterior side of the patient,
wherein the computing apparatus configures the plurality of different V-V intervals of the bi-ventricular pacing therapy to pre-excite the right ventricle if the monitored electrical activity indicates an increase in surrogate electrical activation times monitored by at least one of the two or more right external electrodes and the two or more anterior external electrodes.

8. The system of claim 1, wherein the plurality of external electrodes comprises surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient.

9. The system of claim 1, wherein the system further comprises:
display apparatus, wherein the display apparatus comprises a graphical user interface configured to present information for use in assisting a user in evaluating and adjusting cardiac therapy delivered to a patient,
wherein the computing apparatus is further configured to display at least the identified V-V interval on the graphical user interface.

10. The system of claim 9, wherein the computing apparatus is further configured to display a graphical representation of surrogate electrical activation times monitored by the plurality of external electrodes about a portion of human anatomy monitored for each V-V interval of the plurality of different V-V intervals.

11. The system of claim 10, wherein displaying the graphical representation of the surrogate cardiac electrical activation times about a portion of human anatomy comprises color scaling the portion of human anatomy on the graphical user interface according to the surrogate electrical activation times.

12. The system of claim 1, wherein the pacing therapy is delivered by at least one implantable electrode coupled to at least one lead.

13. The system of claim 1, wherein the bi-ventricular pacing therapy is delivered at an optimized A-V interval.

14. A system for use in cardiac therapy comprising:
electrode apparatus comprising a plurality of external electrodes configured to be located proximate tissue of a patient; and
computing apparatus coupled to the electrode apparatus and configured to:
monitor electrical activity using the plurality of external electrodes,
initiate delivery of bi-ventricular pacing therapy at an initial V-V interval,
generate initial electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for the initial V-V interval based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the initial V-V interval,
configure a plurality of different V-V intervals to pre-excite the left ventricle or the right ventricle based on the initial electrical heterogeneity information,
initiate delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals,
generate electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of different V-V intervals based on the monitored electrical activity, and
identify a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.

15. A method for use in cardiac therapy comprising:
initiating delivery of bi-ventricular pacing therapy at a plurality of different V-V intervals;
monitoring electrical activity using a plurality of external electrodes for each of the plurality of V-V intervals during the delivery of bi-ventricular pacing therapy;
generating electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the monitored electrical activity; and
identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.

16. The method of claim 15, wherein the electrical heterogeneity information comprises a global standard deviation of surrogate electrical activation times monitored by the plurality of external electrodes, wherein identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information comprises identifying the V-V interval from the plurality of different V-V intervals that generated the lowest global standard deviation of surrogate electrical activation times.

17. The method of claim 15, wherein the plurality of electrodes comprises two or more left external electrodes configured to be located proximate the left side of the patient, wherein the electrical heterogeneity information comprises a left standard deviation of surrogate electrical activation times monitored by the two or more left external electrodes, wherein identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information comprises identifying the V-V interval from the plurality of different V-V intervals that generated the lowest left standard deviation.

18. The method of claim 15, wherein the plurality of electrodes comprises two or more left external electrodes configured to be located proximate the left side of the patient, wherein the electrical heterogeneity information comprises a left average of surrogate electrical activation times monitored by the two or more left external electrodes, wherein identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information comprises identifying the V-V interval from the plurality of different V-V intervals that generated the lowest left average.

19. The method of claim 15, wherein the method further comprises configuring the plurality of different V-V intervals of the bi-ventricular pacing therapy to pre-excite the left ventricle if the electrical heterogeneity information indicates an increase in heterogeneity in the electrical activity monitored by the plurality of external electrodes.

20. The method of claim 15, wherein the plurality of electrodes comprises two or more left external electrodes configured to be located proximate the left side of the patient, wherein the plurality of electrodes comprises two or more posterior external electrodes configured to be located proximate the posterior side of the patient,
wherein the method further comprises configuring the plurality of different V-V intervals of the bi-ventricular pacing therapy to pre-excite the left ventricle if the monitored electrical activity indicates an increase in surrogate electrical activation times monitored by at least one of the two or more left external electrodes and the two or more posterior external electrodes.

21. The method of claim 15, wherein the plurality of electrodes comprises two or more right external electrodes configured to be located proximate the right side of the patient, wherein the plurality of electrodes comprises two or more anterior external electrodes configured to be located proximate the anterior side of the patient,
wherein the method further comprises configuring the plurality of different V-V intervals of the bi-ventricular pacing therapy to pre-excite the right ventricle if the monitored electrical activity indicates an increase in surrogate electrical activation times monitored by at least one of the two or more right external electrodes and the two or more anterior external electrodes.

22. The method of claim 15, wherein the plurality of external electrodes comprises surface electrodes positioned in an array configured to be located proximate the skin of the torso of the patient.

23. The method of claim 15, wherein the method further comprises displaying at least the identified V-V interval on a graphical user interface configured to present information for use in assisting a user in evaluating and adjusting cardiac therapy delivered to a patient.

24. The method of claim 23, wherein the method further comprises displaying, on the graphical user interface, a graphical representation of surrogate electrical activation times monitored by the plurality of external electrodes about a portion of human anatomy monitored for each V-V interval of the plurality of different V-V intervals.

25. A method for use in cardiac therapy comprising:
monitoring electrical activity using a plurality of external electrodes;
initiating delivery of bi-ventricular pacing therapy at an initial V-V interval;
generating initial electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for the initial V-V interval based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the initial V-V interval;
configuring a plurality of different V-V intervals to pre-excite the left ventricle or the right ventricle based on the initial electrical heterogeneity information;
initiating delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals;
generating electrical heterogeneity information representative of at least one of mechanical cardiac functionality and electrical cardiac functionality for each of the plurality of V-V intervals based on the electrical activity monitored during the delivery of bi-ventricular pacing therapy at the plurality of different V-V intervals; and
identifying a V-V interval from the plurality of different V-V intervals based on the electrical heterogeneity information.