阅读说明：本技术 用于自适应心脏疗法的系统、方法和装置 (Systems, methods, and apparatus for adaptive cardiac therapy ) 是由 S·戈什 A·T·桑贝拉什威利 J·M·吉尔伯格 M·尤斯滕 S·R·法雷尔 于 2020-02-25 设计创作，主要内容包括：本文描述了用于评估、调整和递送自适应心脏疗法的系统、方法和装置。所述系统、方法和装置可以利用电异质性信息来针对多个不同心率确定和/或选择一个或多个起搏设置和起搏类型或配置。所述自适应心脏疗法可以根据当前所测得的心率以所选择的起搏设置,例如A-V间期和/或V-V间期递送心脏疗法,并且还根据所述当前所测得的心率在仅左心室心脏起搏疗法或双心室心脏起搏疗法之间切换。(Systems, methods, and devices for evaluating, adjusting, and delivering adaptive cardiac therapy are described herein. The systems, methods, and devices may utilize electrical heterogeneity information to determine and/or select one or more pacing settings and pacing types or configurations for a plurality of different heart rates. The adaptive cardiac therapy may deliver cardiac therapy at selected pacing settings, such as an a-V interval and/or a V-V interval, according to a current measured heart rate, and also switch between left ventricular only cardiac pacing therapy or bi-ventricular cardiac pacing therapy according to the current measured heart rate.)

1. A system, comprising:

an electrode apparatus including a plurality of external electrodes for monitoring electrical activity from tissue of a patient; and

a computing device comprising processing circuitry and coupled to the electrode device and configured to:

monitoring electrical activity of the patient's heart using one or more of the plurality of external electrodes during left ventricular only pacing therapy delivered at a plurality of different A-V intervals at a plurality of different heart rates and during biventricular pacing therapy delivered at a plurality of different A-V intervals and V-V intervals at a plurality of different heart rates,

generating Electrical Heterogeneity Information (EHI) from the monitored electrical activity from the electrode device, wherein the EHI represents one or both of mechanical cardiac function and electrical cardiac function,

selecting an A-V interval for left ventricular only pacing therapy for each different heart rate based on the EHIs generated by the monitored electrical activity during left ventricular only pacing therapy, and

selecting an A-V interval and a V-V interval for biventricular pacing therapy for each different heart rate based on the EHIs generated by the monitored electrical activity during biventricular pacing therapy.

The system of claim 1, wherein the computing device is further configured to:

measuring, for each different heart rate, an intrinsic a-V delay during the absence of delivered pacing therapy; and is

For each different heart rate, determining an A-V interval adjustment value to adjust the A-V interval based on intrinsic A-V delays sensed during delivery of pacing therapy, wherein the A-V interval adjustment for each different heart rate is based on the selected A-V interval and measured intrinsic A-V delays corresponding to the different heart rate.

2. The system of claim 2, wherein determining the a-V interval adjustment value for each different heart rate comprises determining a difference between the selected a-V interval and the measured intrinsic a-V delay.

3. The system of claim 2, wherein determining the a-V interval adjustment value for each different heart rate comprises determining a percentage of the selected a-V interval to the measured intrinsic a-V delay.

4. The system of claim 1, wherein the controller is further configured to select a left ventricular only pacing therapy or a biventricular pacing therapy as an initial pacing therapy modality based on the EHIs generated from the electrical activity monitored during the left ventricular only pacing therapy and the electrical activity monitored during the biventricular pacing therapy.

5. The system of claim 1, wherein the EHI comprises a measure of activation time Standard Deviation (SDAT).

6. The system of claim 1, wherein the plurality of external electrodes comprises surface electrodes positioned in an array configured to be positioned near the skin of the patient.

Disclosure of Invention

The illustrative systems and methods described herein may be configured to assist a user (e.g., a physician) in evaluating and configuring cardiac therapy (e.g., performing cardiac therapy on a patient during and/or after implantation of a cardiac therapy device). In one or more embodiments, the systems and methods may be described as non-invasive. For example, in some embodiments, the systems and methods may not require or include an implantable device (e.g., a lead, a probe, a sensor, a catheter, an implantable electrode, etc.) to monitor or acquire a plurality of cardiac signals from tissue of a patient for use in evaluating and configuring cardiac therapy being delivered to the patient. Rather, the systems and methods may use electrical measurements made non-invasively using, for example, a plurality of external electrodes attached to the patient's skin around the patient's torso.

It may be described that the illustrative systems and methods involve the use of external electrode devices or ECG strips applied to the torso of a patient to determine optimal synchronization during biventricular and left ventricular pacing. Optimal a-V timing for each pacing configuration (such as, for example, biventricular pacing and left ventricular only pacing) across multiple heart rates may be identified based on a measure of electrical dyssynchrony derived or generated from electrical activity monitored across the multiple heart rates using the external electrode device. For example, an optimal pre-excitation interval for each configuration may be determined or calculated by subtracting the optimal a-V timing from the patient's intrinsic a-V conduction, and used to adaptively update the a-V delay for delivering pacing based on periodically measuring the patient's intrinsic a-V and subtracting the optimal pre-excitation interval. If the patient's intrinsic a-V exceeds a certain absolute value (e.g., about 300 milliseconds (ms) to about 350ms) or exceeds a value above a certain threshold (e.g., about 20ms, about 30ms, about 40ms, etc.) or the heart rate is greater than 100bpm, as compared to the baseline intrinsic a-V, and the current pacing configuration is left ventricle only, the device may switch to biventricular pacing with optimal pre-excitation for the biventricular configuration. Further, it may be described that the device may be programmed to biventricular pacing or left ventricular only pacing at baseline, based on which pacing configuration provides more synchronization. Thus, illustrative systems, methods, and devices may be described as providing a way to personalize adaptive cardiac resynchronization therapy with patient-specific optimal pre-excitation intervals and pacing configurations (biventricular pacing or left ventricular only pacing).

An illustrative system may include an electrode apparatus including a plurality of external electrodes for monitoring electrical activity from tissue of a patient; and a computing device including processing circuitry and coupled to the electrode device. The computing device may be configured to monitor electrical activity of the patient's heart using one or more of the plurality of external electrodes during left ventricular only pacing therapy delivered at a plurality of different a-V intervals at a plurality of different heart rates and during biventricular pacing therapy delivered at a plurality of different a-V intervals and V-V intervals at a plurality of different heart rates, and generate Electrical Heterogeneity Information (EHI) from the monitored electrical activity from the electrode device, wherein the EHI represents one or both of mechanical heart function and electrical heart function. The computing device may be further configured to select an a-V interval for left ventricular only pacing therapy for each different heart rate based on the EHI generated by the monitored electrical activity during left ventricular only pacing therapy, and select an a-V interval and a V-V interval for biventricular pacing therapy for each different heart rate based on the EHI generated by the monitored electrical activity during biventricular pacing therapy.

An illustrative method may include monitoring electrical activity of a heart of a patient using one or more electrodes of a plurality of external electrodes during left ventricular only pacing therapy delivered at a plurality of different a-V intervals and during biventricular pacing therapy delivered at a plurality of different a-V intervals and V-V intervals at a plurality of different heart rates; and generating Electrical Heterogeneity Information (EHI) from the monitored electrical activity from the electrode device, wherein the EHI is representative of one or both of mechanical cardiac function and electrical cardiac function. The method may further include selecting an a-V interval for left ventricular only pacing therapy for each different heart rate based on the EHI generated from the electrical activity monitored during left ventricular only pacing therapy, and selecting an a-V interval and a V-V interval for biventricular pacing therapy for each different heart rate based on the EHI generated from the electrical activity monitored during biventricular pacing therapy.

An illustrative implantable medical device may include a plurality of electrodes including an atrial pacing electrode, a left ventricular pacing electrode, and a right ventricular pacing electrode; therapy delivery circuitry operably coupled to the plurality of electrodes to deliver cardiac therapy to a heart of a patient; a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of a heart of a patient; and a controller comprising processing circuitry operatively coupled to the therapy delivery circuitry and the sensing circuitry. The controller may be configured to: calibrating the left ventricular only pacing therapy for a plurality of heart rates based on Electrical Heterogeneity Information (EHI) generated from electrical activity monitored from the plurality of external electrodes during the left ventricular only pacing therapy; the method further includes calibrating the biventricular pacing therapy for a plurality of heart rates based on EHIs generated from electrical activity monitored from the plurality of external electrodes during the biventricular pacing therapy, and delivering one or both of the calibrated left ventricular-only pacing therapy and the calibrated biventricular pacing therapy.

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 readily appreciated by reference to the following detailed description and claims when taken in conjunction with the accompanying drawings.

Drawings

FIG. 1 is a diagram of an illustrative system containing an electrode device, a display device, and a computing device.

Fig. 2-3 are diagrams of illustrative external electrode devices for measuring torso-surface potentials.

Fig. 4 is a block diagram of an illustrative method of evaluating and configuring cardiac therapy.

Fig. 5 is a block diagram of an illustrative method of performing or delivering adaptive cardiac therapy.

Fig. 6 is a diagram of an illustrative system including an illustrative Implantable Medical Device (IMD).

Fig. 7A is a diagram of the illustrative IMD of fig. 6.

Fig. 7B is a diagram of an enlarged view of the distal end of an electrical lead disposed in the left ventricle of fig. 7A.

Fig. 8A is a block diagram of an illustrative IMD, such as the system of fig. 6-7.

Fig. 8B is another block diagram of illustrative IMD (e.g., implantable pulse generator) circuitry and associated leads employed in the systems of fig. 6-7.

Detailed Description

In the following detailed description of illustrative embodiments, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration specific embodiments that 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 present disclosure as hereby presented.

Illustrative systems, methods, and apparatus will be described with reference to fig. 1-8. It will be apparent to those skilled in the art that elements or processes from one embodiment may be used in combination with elements or processes of other embodiments, and that possible embodiments of such systems, methods, and apparatuses using combinations of features set forth herein are not limited to the specific embodiments shown in the drawings and/or described herein. Further, it will be appreciated that embodiments described herein may incorporate many elements that are not necessarily shown to scale. Still further, it will be recognized that the timing of the processes herein and the size and shape of the various elements may be modified and still fall within the scope of the present disclosure, but that certain timings, one or more shapes and/or sizes, or element types may be preferred over other timings, one or more shapes and/or sizes, or element types.

A plurality of Electrocardiogram (ECG) signals (e.g., torso-surface potentials) may be measured or monitored using a plurality of external electrodes positioned about the surface or skin of the patient. The ECG signals may be used to evaluate and configure cardiac therapy, such as, for example, cardiac therapy provided by an implantable medical device performing Cardiac Resynchronization Therapy (CRT). As described herein, ECG signals may be acquired or obtained non-invasively, as, for example, implanted electrodes may not be used to measure ECG signals. Further, the ECG signal may be used to determine cardiac electrical activation times, which may be used to generate various metrics (e.g., electrical heterogeneity information) that may be used by a user (e.g., a physician) to optimize one or more settings or parameters of cardiac therapy (e.g., pacing therapy), such as CRT.

Various illustrative systems, methods, and graphical user interfaces may be configured to non-invasively assist a user (e.g., a physician) in assessing the configuration (e.g., optimization) of cardiac health and/or cardiac therapy using an electrode device including external electrodes, a display device, and a computing device. An illustrative system 100 including an electrode apparatus 110, a computing apparatus 140, and a remote computing device 160 is depicted in fig. 1.

The electrode apparatus 110 as shown includes a plurality of electrodes incorporated or contained within a strap wrapped around the chest or torso of the patient 14. The electrode device 110 is operatively coupled to the computing device 140 (e.g., by one or wired electrical connections, wirelessly, etc.) to provide electrical signals from each of the electrodes to the computing device 140 for analysis, evaluation, etc. An illustrative electrode apparatus may be described in U.S. patent No. 9,320,446 entitled "Bioelectric Sensor Device and Methods" filed 3/27 2014 and published 26/2016 3/26. Further, the illustrative electrode apparatus 110 will be described in more detail with reference to fig. 2-3.

Although not described herein, the illustrative system 100 may further comprise an imaging device. The imaging device may be any type of imaging device configured to image or provide an image of at least a portion of a patient in a non-invasive manner. For example, the imaging device may provide an image of the patient without the use of any components or parts that may be located within the patient, other than non-invasive tools such as contrast solutions. It should be appreciated that the illustrative systems, methods, and interfaces described herein may further use an imaging device to provide non-invasive assistance to a user (e.g., physician) to position or place one or more pacing electrodes near a patient's heart in conjunction with the configuration of cardiac therapy.

For example, the illustrative systems and methods may provide image-guided navigation that may be used to navigate a lead containing electrodes, leadless electrodes, wireless electrodes, catheters, etc. within a patient while also providing a non-invasive cardiac therapy configuration, including determining valid or optimal pre-excitation intervals, such as a-V intervals and V-V intervals, etc. Illustrative systems and methods of using imaging devices and/or electrode devices may be described in U.S. patent application publication No. 2014/0371832 to Ghosh published at 18.12.2014, U.S. patent application publication No. 2014/0371833 to Ghosh et al published at 18.12.2014, U.S. patent application publication No. 2014/0323892 to Ghosh et al published at 30.10.2014, and U.S. patent application publication No. 2014/0323882 to Ghosh et al published at 20.10.2014.

The illustrative imaging device may be configured to capture x-ray images and/or any other alternative imaging modality. For example, the imaging device may be configured to capture images or image data using isocentric fluoroscopy, biplane fluoroscopy, ultrasound, Computed Tomography (CT), multi-slice computed tomography (MSCT), Magnetic Resonance Imaging (MRI), high frequency ultrasound (HIFU), Optical Coherence Tomography (OCT), intravascular ultrasound (IVUS), two-dimensional (2D) ultrasound, three-dimensional (3D) ultrasound, four-dimensional (4D) ultrasound, intraoperative CT, intraoperative MRI, and so forth. Further, it should be understood that the imaging device may be configured to capture a plurality of consecutive images (e.g., consecutively) to provide video frame data. In other words, a plurality of images taken over time using the imaging device can provide video frames or moving images, data. In addition, images may also be acquired and displayed in two, three, or four dimensions. In a more advanced form, four-dimensional surface rendering of the heart or other regions of the body may also be achieved by incorporating cardiac data or other soft tissue data from maps 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 Computed Tomography (SPECT) combined with CT, may also provide functional image data superimposed on anatomical data, for example, for navigating an implantable device to a target location within the heart or other region of interest.

Systems and/or imaging devices that may be used in conjunction with the illustrative systems and methods described herein are described in U.S. patent application publication No. 2005/0008210 issued to Evron et al at 1/13 2005, U.S. patent application publication No. 2006/0074285 issued to Zarkh et al at 6.4/2006, U.S. patent No. 8,731,642 issued to Zarkh et al at 20.5/2014, U.S. patent No. 8,861,830 issued to Brada et al at 14.10/2014, U.S. patent No. 6,980,675 issued to Evron et al at 27/2005, U.S. patent No. 7,286,866 issued to oxrun et al at 23/2007, U.S. patent No. 7,308,297 issued to Reddy et al at 11/2011, U.S. patent No. 7,308,299 issued to Burrell et al at 12/2011, U.S. patent No. 3684 issued to Evron et al at 22/2008, U.S. patent No. 2008 No. 7,321,677 issued to oxrun et al at 7,346,381, U.S. patent No. 7,454,248 issued on 11/18 2008 of Burrell et al, U.S. patent No. 7,499,743 issued on 3/3 2009 of Vass et al, U.S. patent No. 7,565,190 issued on 21/7 2009 of Okerlund et al, U.S. patent No. 7,587,074 issued on 8/9 2009 of Zarkh et al, U.S. patent No. 7,599,730 issued on 6/10 2009 of Hunter et al, U.S. patent No. 7,613,500 issued on 3/11/2009 of Vass et al, U.S. patent No. 7,742,629 issued on 22/2010 of Zarkh et al, U.S. patent No. 7,747,047 issued on 6/29 2010 of Okerlund et al, U.S. patent No. 7,778,685 issued on 17/8/17 of ev2010 of 2010 ron et al, U.S. patent No. 5635 issued on 17/2010 of Vass et al, U.S. patent No. 48335 issued on 201110/2011 of Okerlund et al, U.S. patent No. 468/10 issued on 10/4838/10 of okerlang et al, U.S. patent No. published on 2 of okarkhaki et al, U.S. patent No. 7 of vachell et al, U.S. patent No. 7 of vachellr et al, U.S. patent No. published on 15, Hunter et al, U.S. patent No. 8,060,185 issued on day 11/15 2011 and Verard et al, U.S. patent No. 8,401,616 issued on day 3/19 2013.

Computing device 140 and remote computing device 160 may each include a display device 130, 160, respectively, that may be configured to display and analyze data, such as, for example, electrical signals (e.g., electrocardiographic data), electrical activation times, electrical heterogeneity information, and the like. For example, one cardiac cycle or one heartbeat of a plurality of cardiac cycles or heartbeats represented by electrical signals collected or monitored by electrode device 110 may be analyzed and evaluated for one or more metrics including activation time and electrical heterogeneity information that may be related to a therapeutic property related to one or more parameters of cardiac therapy, such as, for example, pacing parameters, lead location, etc. More specifically, for example, QRS complexes of a single cardiac cycle may be evaluated for one or more metrics, such as, for example, QRS onset, QRS shift, QRS peak, Electrical Heterogeneity Information (EHI), electrical activation time, left ventricular or thoracic standard deviation of electrical activation time (LVED), Standard Deviation of Activation Time (SDAT), average left ventricular or thoracic surrogate electrical activation time with reference to earliest activation time (LVAT), QRS duration (e.g., interval between QRS onset to QRS shift), difference between average left surrogate activation time and average right surrogate activation time, relative or absolute QRS morphology, difference between upper and lower percentiles of activation time (upper percentile may be 90%, 80%, 75%, 70%, etc., and lower percentile may be 10%, 15%, 20%, 25%, and 30%, etc.), central trend (e.g., median or mode), dispersion (e.g., mean deviation, standard deviation, variance, inter-quartile deviation, range), and the like. Further, each of the one or more metrics may be location specific. For example, some metrics may be calculated from signals recorded or monitored from electrodes positioned around a selected region of the patient (e.g., the left side of the patient, the right side of the patient, etc.).

In at least one embodiment, one or both of the computing apparatus 140 and the remote computing device 160 can be a server, a personal computer, or a tablet computer. The computing device 140 may be configured to receive input from an input device 142 (e.g., a keyboard) and transmit output to the display device 130, and the remote computing apparatus 160 may be configured to receive input from an input device 162 (e.g., a touchscreen) and transmit output to the display device 170. One or both of computing device 140 and remote computing device 160 may contain data storage that may allow access to a handler or routine and/or one or more other types of data, e.g., for analyzing a plurality of electrical signals captured by electrode device 110, for determining a QRS onset, a QRS shift, a median, a mode, a mean, a peak or maximum, a trough or minimum, for determining an electrical activation time, for driving a graphical user interface configured to non-invasively assist a user in configuring one or more pacing parameters or settings, such as, for example, a pacing rate, a ventricular pacing rate, an a-V interval, a V-V interval, a pacing pulse width, a pacing vector, a multi-point vector (e.g., left ventricular vector quadrupole lead), a pacing voltage, a pacing configuration (e.g., biventricular pacing, etc.) Right ventricular only pacing, left ventricular only pacing, etc.) as well as arrhythmia detection and treatment, rate adaptation settings and performance, etc.

The computing device 140 may be operatively coupled to the input device 142 and the display device 130, for example, to transfer data to and from each of the input device 142 and the display device 130, and the remote computing apparatus 160 may be operatively coupled to the input device 162 and the display device 170, for example, to transfer data to and from each of the input device 162 and the display device 170. For example, the computing device 140 and the remote computing device 160 may be electrically coupled to the input devices 142, 162 and the display devices 130, 170 using, for example, analog electrical connections, digital electrical connections, wireless connections, bus-based connections, network-based connections, internet-based connections, and the like. As further described herein, a user may provide input to the input device 142, 162 to view and/or select one or more pieces of configuration information related to cardiac therapy delivered by a cardiac therapy device, such as, for example, an implantable medical device.

Although input device 142 is depicted as a keyboard and input device 162 is a touch screen, it should be understood that input devices 142, 162 may comprise any device capable of providing input to computing device 140 and computing apparatus 160 to perform the functions, methods, and/or logic described herein. For example, the input devices 142, 162 may include a keyboard, mouse, trackball, touch screen (e.g., capacitive touch screen, resistive touch screen, multi-touch screen, etc.), and the like. Likewise, the display devices 130, 170 may comprise any device capable of displaying information to a user, such as a graphical user interface 132, 172, including electrode state information, a graphical map of electrical activation, a plurality of signals of external electrodes on one or more heartbeats, a QRS complex, various cardiac therapy protocol selection regions, various ordering of cardiac therapy protocols, various pacing parameters, Electrical Heterogeneity Information (EHI), textual instructions, a graphical depiction of the anatomy of a human heart, an image or graphical depiction of the heart of a patient, a graphical depiction of the location of one or more electrodes, a graphical depiction of the torso of a human body, an image or graphical depiction of the torso of a patient, a graphical depiction or actual image of implanted electrodes and/or leads, and the like. Further, the display devices 130, 170 may include liquid crystal displays, organic light emitting diode screens, touch screens, cathode ray tube displays, and the like.

The processing programs or routines stored and/or executed by the computing apparatus 140 and the remote computing device 160 may include programs or routines for computing 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.), normalization algorithms, comparison algorithms, vector mathematics, or any other processing for implementing one or more of the illustrative methods and/or processes described herein. Data stored and/or used by computing device 140 and remote computing apparatus 160 may include, for example, electrical signal/waveform data from electrode device 110 (e.g., QRS complexes), electrical activation times from electrode device 110, heart sounds/signals/waveform data from acoustic sensors, graphics (e.g., graphical elements, icons, buttons, windows, dialog boxes, drop-down menus, graphical regions, 3D graphics, etc.), graphical user interfaces, results from one or more processing programs or routines employed in accordance with the disclosure herein (e.g., electrical signals, electrical heterogeneity information, etc.), or any other data that may be used to perform one or more processes or methods described herein.

In one or more embodiments, the illustrative systems, methods, and interfaces may be implemented using one or more computer programs executing on a programmable computer such as a computer including, for example, processing power, data storage devices (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 the functions 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 to be applied in a known manner.

Any programming language can be used to provide one or more programs for implementing the systems, methods, and/or interfaces described herein, such as a high level procedural and/or object oriented programming language suitable for communication with a computer system. For example, any such program may be stored on any suitable device, e.g., storage medium, readable by a general or special purpose program running on a computer system (e.g., comprising a processing device) for configuring and operating the computer system when read by the suitable device to perform the procedures described herein. In other words, the illustrative systems, methods, and interfaces may be implemented, at least in one embodiment, using a computer-readable storage medium configured with a computer program, where the storage medium so configured causes a computer to operate in a specific and predefined manner to perform the functions described herein. Further, in at least one embodiment, the illustrative systems, methods, and 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 that is operable, when executed by a processor or processing circuitry, to perform operations of the methods, processes, and/or functions as described herein.

The computing apparatus 140 and the remote computing device 160 may be, for example, any fixed or mobile computer system (e.g., a controller, a microcontroller, a personal computer, a microcomputer, a tablet computer, etc.). The precise configuration of computing apparatus 140 and remote computing device 160 is not limiting and essentially any device capable of providing suitable computing and control capabilities (e.g., signal analysis, mathematical functions such as median, mode, average, maximum determination, minimum determination, slope determination, minimum slope determination, maximum slope determination, graphics processing, etc.) may be used. As described herein, a digital file can be any medium (e.g., volatile or non-volatile memory, CD-ROM, punch card, magnetic recordable tape, etc.) containing digital bits (e.g., encoded in binary, ternary, etc.) that can be read by and/or written to by the computing apparatus 140 and remote computing device 160 described herein. Moreover, as described herein, a file in a user-readable format may be any representation of data (e.g., ASCII text, binary numbers, hexadecimal numbers, decimal numbers, graphics, etc.) that may be presented on any medium (e.g., paper, display, etc.) that may be read and/or understood by a user.

In view of the above, it will be readily apparent that the functionality as described in one or more embodiments in accordance with the present disclosure may be implemented in any manner known to those skilled in the art. As such, the computer language, computer system, or any other software/hardware to be used to implement the processes described herein should not be limited to the scope of the systems, processes, or programs described herein (e.g., the functionality provided by such systems, processes, or programs).

The illustrative electrode device 110 may be configured to measure body surface potentials of the patient 14 and more specifically torso surface potentials of the patient 14. As shown in fig. 2, the illustrative electrode device 110 may contain an external electrode 112, a set or array of strips 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 wrap around the torso of the patient 14 such that the electrodes 112 surround the heart of the patient. As further illustrated, the electrodes 112 may be positioned around the circumference of the patient 14, including a posterior position, a lateral position, a posterolateral position, an anterolateral position, and an anterior position of the torso of the patient 14.

The illustrative electrode device 110 may be further configured to measure or monitor sound from at least one or both of the patients 14. As shown in fig. 2, illustrative electrode device 110 may contain a set or array of acoustic sensors 120 attached or coupled to a strip 113. The strap 113 may be configured to wrap around the torso of the patient 14 such that the acoustic sensor 120 surrounds the heart of the patient. As further illustrated, the acoustic sensors 120 may be positioned around the circumference of the patient 14, including a posterior position, a lateral position, a posterolateral position, an anterolateral position, and an anterior position of the torso of the patient 14.

Further, the electrodes 112 and acoustic sensors 120 may be electrically connected to the interface/amplifier circuitry 116 by wired connections 118. Interface/amplifier circuitry 116 may be configured to amplify signals from electrodes 112 and acoustic sensor 120 and provide signals to one or both of computing device 140 and remote computing device 160. Other illustrative systems may use, for example, a wireless connection as a data channel to transmit signals sensed by the electrodes 112 and acoustic sensor 120 to the interface/amplifier circuitry 116 and, in turn, to one or both of the computing apparatus 140 and the remote computing device 160. In one or more embodiments, the interface/amplifier circuitry 116 can be electrically coupled to the computing device 140 using, for example, an analog electrical connection, a digital electrical connection, a wireless connection, a bus-based connection, a network-based connection, an internet-based connection, and/or the like.

Although in the example of fig. 2, electrode device 110 includes strips 113, in other examples, any of a variety of mechanisms, such as tape or adhesive, may be employed to aid in the spacing and placement of electrodes 112 and acoustic sensors 120. In some examples, the strap 113 may comprise an elastic strap, a strip of adhesive tape, or both. Further, in some examples, the strap 113 may be part of or integrated with an article of clothing (e.g., a T-shirt). In other examples, the electrodes 112 and acoustic sensors 120 may be placed separately on the torso of the patient 14. Further, in other examples, one or both of the electrodes 112 (e.g., arranged in an array) and the acoustic sensors 120 (e.g., also arranged in an array) may be part of or located within a patch, vest, and/or other manner of securing the electrodes 112 and acoustic sensors 120 to the torso of the patient 14. Still further, in other examples, one or both of the electrodes 112 and the acoustic sensors 120 may be two portions of material or a portion of or within two patches. One of the two patches may be located on an anterior side of the torso of the patient 14 (e.g., to monitor electrical signals representative of the anterior side of the heart of the patient, to measure surrogate cardiac electrical activation times representative of the anterior side of the heart of the patient, to monitor or measure sounds of the anterior side of the patient, etc.), and the other patch may be located on a posterior side of the torso of the patient 14 (e.g., to monitor electrical signals representative of the posterior side of the heart of the patient, to measure surrogate cardiac electrical activation times representative of the posterior side of the heart of the patient, to monitor or measure sounds of the posterior side of the patient, etc.). And still further, in other examples, one or both of the electrodes 112 and acoustic sensors 120 may be arranged to extend from the anterior side of the patient 14 across the left side of the patient 14 into the top and bottom rows of the anterior side of the patient 14. Still further, in other examples, one or both of the electrodes 112 and acoustic sensors 120 may be arranged in a curve around the armpit area and may have a lesser density of electrodes/sensors on the right chest than the other remaining areas.

The electrodes 112 may be configured to surround the heart of the patient 14 and record or monitor electrical signals associated with depolarization and repolarization of the heart after the signals have propagated through the torso of the patient 14. Each of the electrodes 112 may be used in a monopolar configuration to sense torso-surface potentials reflecting cardiac signals. Interface/amplifier circuitry 116 may also be coupled to a return electrode or an indifferent electrode (not shown) that may be combined with each electrode 112 for unipolar sensing.

In some examples, about 12 to about 50 electrodes 112 and about 12 to about 50 acoustic sensors 120 may be spatially distributed around the torso of the patient. Other configurations may have more or fewer electrodes 112 and more or fewer acoustic sensors 120. It should be understood that the electrodes 112 and acoustic sensors 120 may not be arranged or distributed in an array that extends all the way around or completely around the patient 14. Rather, the electrodes 112 and acoustic sensors 120 may be arranged in an array that extends around only a portion of the patient 14 or partially around the patient. For example, the electrodes 112 and acoustic sensors 120 may be distributed on the front, back, and left sides of the patient with fewer or no electrodes and acoustic sensors near the right side (including the back and front regions of the right side of the patient).

The computing device 140 may record and analyze torso-surface potential signals sensed by the electrodes 112 and acoustic signals sensed by the acoustic sensors 120, which are amplified/conditioned by the interface/amplifier circuitry 116. The computing device 140 may be configured to analyze the electrical signals from the electrodes 112 to provide Electrocardiogram (ECG) signals, information, or data from the patient's heart, as will be further described herein. The computing device 140 may be configured to analyze the electrical signals from the acoustic sensor 120 to provide acoustic signals, information, or data from the patient's body and/or a device implanted therein, such as a left ventricular assist device.

Additionally, the computing apparatus 140 and the remote computing device 160 may be configured to provide a graphical user interface 132, 172 depicting various information related to the electrode apparatus 110 and data collected or sensed using the electrode apparatus 110. For example, the graphical user interface 132, 172 may depict an ECG containing a QRS complex obtained using the electrode apparatus 110 and sound data containing sound waves obtained using the acoustic sensor 120, as well as other information related thereto. The illustrative systems and methods may non-invasively use electrical information collected with the electrode device 110 and acoustic information collected with the acoustic sensor 120 to assess cardiac health of the patient and assess and configure cardiac therapy delivered to the patient.

Further, the electrode device 110 may further include reference electrodes and/or drive electrodes positioned, for example, around the lower torso of the patient 14, which may further be used by the system 100. For example, electrode device 110 may contain three reference electrodes, and signals from the three reference electrodes may be combined to provide a reference signal. Further, electrode apparatus 110 may use three tail reference electrodes (e.g., instead of the standard reference used in Wilson Central Terminal) to obtain a "true" unipolar signal with less noise by averaging the three tail located reference signals.

Fig. 3 illustrates another illustrative electrode device 110 including a plurality of electrodes 112 configured to surround the heart of the patient 14 and record or monitor electrical signals associated with depolarization and repolarization of the heart after the signals have propagated through the torso of the patient 14, and a plurality of acoustic sensors 120 configured to surround the heart of the patient 14 and record or monitor sound signals associated with the heart after the signals have propagated through the torso of the patient 14. The electrode apparatus 110 may comprise a vest 114 to which a plurality of electrodes 112 and a plurality of acoustic sensors 120 may be attached or to which the electrodes 112 and acoustic sensors 120 may be coupled. In at least one embodiment, the plurality of electrodes 112 or the array of electrodes may be used to collect electrical information, such as, for example, surrogate electrical activation times. Similar to electrode device 110 of fig. 2, electrode device 110 of fig. 3 may contain interface/amplifier circuitry 116 electrically coupled to each of electrode 112 and acoustic sensor 120 by wired connection 118 and configured to transmit signals from electrode 112 and acoustic sensor 120 to computing device 140. As illustrated, the electrodes 112 and acoustic sensors 120 may be distributed over the torso of the patient 14, including, for example, a posterior position, a lateral position, a posterolateral position, an anterolateral position, and an anterior position of the torso of the patient 14.

The vest 114 may be formed of fabric with the electrodes 112 and acoustic sensors 120 attached to the fabric. The vest 114 may be configured to maintain the positioning and spacing of the electrodes 112 and acoustic sensors 120 on the torso of the patient 14. Further, the vest 114 may be marked to assist in determining the location of the electrodes 112 and acoustic sensors 120 on the surface of the torso of the patient 14. In some examples, about 25 to about 256 electrodes 112 and about 25 to about 256 acoustic sensors 120 may be distributed around the torso of the patient 14, although other configurations may have more or fewer electrodes 112 and more or fewer acoustic sensors 120.

The illustrative systems and methods may be used to provide non-invasive assistance to a user in assessing a patient's cardiac health and/or assessing and configuring cardiac therapy currently delivered to the patient (e.g., via an implantable medical device, via an LVAD, etc.). For example, the illustrative systems and methods may be used to assist a user in configuring and/or adjusting one or more cardiac therapy settings, such as, for example, optimizing a-V intervals or delays and a-V intervals or delays for pacing therapy (e.g., left ventricular-only or left mono-ventricular pacing therapy), and V-V intervals or delays for pacing therapy (e.g., bi-ventricular pacing therapy).

Further, it should be understood that the computing apparatus 140 and the remote computing device 160 may be operatively coupled to each other in a number of different ways in order to perform or perform the functions described herein. For example, in the depicted embodiment, computing device 140 may be wirelessly operatively coupled to remote computing device 160, as depicted by the wireless signal lines emanating therebetween. Further, as opposed to a wireless connection, one or more of the computing apparatus 140 and the remote computing device 160 may be operatively coupled by one or more wired electrical connections.

An illustrative method 200 of evaluating and configuring cardiac therapy is depicted in fig. 4. The illustrative method 200 may generally be described as being used in non-invasive assessment and configuration (e.g., optimization) of cardiac therapy. The illustrative method 200 may be described as non-invasive in that the method does not use an invasive device to perform the evaluation and configuration of cardiac therapy. However, the delivered cardiac therapy may be described as invasive, such as when, for example, one or more pacing electrodes are implanted near the patient's heart. Thus, the illustrative method 200 may be used to evaluate and configure such invasive cardiac therapies.

The illustrative method 200 may generally be described as determining pacing settings for each of a left ventricular only pacing therapy and a biventricular pacing therapy. Pacing settings may be determined for each of a plurality of different heart rates, e.g., for use by a pacing device (such as the IMD described herein) to deliver adaptive cardiac therapy. For example, as shown in fig. 4 and described further herein, method 200 may determine a-V intervals and V-V intervals for a plurality of different heart rates or a range of heart rates for biventricular pacing therapy, and a-V intervals for a plurality of different heart rates or a range of heart rates for left ventricular only pacing therapy.

The illustrative 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 electrode device 110 as described herein with respect to fig. 1-3. For example, the plurality of external electrodes may be part of or incorporated into a vest or strap that is positioned around the torso of the patient. More specifically, the plurality of electrodes may be described as surface electrodes positioned in an array configured to be positioned adjacent to the skin of the torso of the patient. The electrical activity monitored during process 202 prior to delivery of cardiac therapy may be referred to as "baseline" electrical activity because no therapy is delivered to the patient, leaving the patient's heart in its natural or intrinsic rhythm.

The illustrative method 200 may include measuring or monitoring an intrinsic a-V delay or transit time 204 of a patient's heart at a current heart rate. The intrinsic a-V delay may be measured from a single intrinsic a-V conduction time over a single cardiac cycle or heartbeat (e.g., 833ms at a heart rate of 72 beats per minute). Further, the intrinsic a-V delay may be an average, a mode, a median, and/or any other statistical measure of the plurality of measured intrinsic a-V transit times. For example, the intrinsic A-V delay may be an average of the intrinsic A-V delay for a selected number of heartbeats at a selected heart rate. For example, when more than 3 heartbeats are measured at a heart rate of 70 beats per minute (bpm), the patient's average intrinsic a-V delay may be 200 ms.

During or concurrently with monitoring or collecting electrical activity 202, the illustrative method 200 may initiate delivery of cardiac therapy 206 (such as, for example, left ventricular-only or left single ventricular pacing therapy or biventricular pacing therapy). Cardiac therapy 206 may be delivered by at least one electrode configured to electrically stimulate (e.g., depolarize, pace, etc.) the patient's left ventricle after atrial sensing or atrial pacing in left ventricular only pacing or to electrically stimulate (e.g., depolarize, pace, etc.) the patient's left and right ventricles after atrial sensing or atrial pacing in biventricular pacing. Cardiac therapy may be delivered to the left ventricle using an a-V interval or delay, which is the time period between an atrial event (e.g., a pacing depolarization or intrinsic depolarization) and left ventricular pacing, and cardiac therapy may be delivered to the right ventricle using a V-V interval or delay, which is the time period between a left ventricular event (e.g., a pacing depolarization or intrinsic depolarization) and right ventricular pacing.

In at least one embodiment, each of the electrodes may be coupled to one or more leads implanted in or near the patient's heart. Further, in at least one embodiment, the cardiac therapy 206 may be delivered by leadless electrodes. Illustrative cardiac therapies using implantable electrodes and leads may be further described herein with reference to fig. 6-8. Although the systems and devices of fig. 6-8 include three leads, it should be understood that the illustrative systems and methods described herein may be used with any type of cardiac pacing system including leadless, less than three leads, and more than three leads. As described herein, although cardiac therapy delivery may be described as invasive, the illustrative methods and systems may be described as non-invasive in that the illustrative methods and systems may only initiate delivery of cardiac therapy and configure cardiac therapy, and the illustrative methods and systems may further use electrical signals that are non-invasively monitored or acquired from the patient. Further, illustrative cardiac therapies may utilize either a leaded or a leadless implantable cardiac device, comprising a tissue-piercing electrode implantable from the Koch triangle region of the right atrium through the right atrial endocardium and central corpus fibrosum, to deliver cardiac therapy to or sense electrical activity of the left ventricle in the basal and/or septal region of the left ventricular myocardium of the patient's heart, as described in U.S. provisional patent application serial No. 62/647,414 entitled "VfA cardiac therapy (VfA CARDIAC THERAPY)" and filed on 23.3.2018 and U.S. provisional patent application serial No. 62/725,763 entitled "ADAPTIVE VfA cardiac therapy (ADAPTIVE VfA CARDIAC THERAPY)" and filed on 31.8.8.2018, each of which is incorporated herein by reference in its entirety.

The monitored electrical activity may be used to generate Electrical Heterogeneity Information (EHI)208 for the current a-V interval and/or the V-V interval at the current heart rate. The EHI may be described as information or data representing at least one of mechanical cardiac function and electrical cardiac function. EHI and other cardiac therapy information may be described in U.S. provisional patent application No. 61/834,133 entitled "metric OF ELECTRICAL dynamics and ELECTRICAL ACTIVATION PATTERNS FROM SURFACE ECG ELECTRODES" (measuring OF ELECTRICAL system dynamics AND ELECTRICAL activity patient FROM ECG ELECTRODES) "and filed on 12.6.2013, which is hereby incorporated by reference in its entirety.

Electrical heterogeneity information (e.g., data) may be defined as information indicative of at least one of mechanical or asynchronous movement of the heart and/or electrical or asynchronous movement of the heart. In other words, the electrical heterogeneity information may represent a surrogate for the actual mechanical and/or electrical function of the patient's heart. In at least one embodiment, the relative change in electrical heterogeneity information (e.g., from baseline heterogeneity information to therapy heterogeneity information, from a first set of heterogeneity information to a second set of therapy heterogeneity information, etc.) may be used to determine a surrogate value that represents a change in hemodynamic response (e.g., an abrupt change in LV pressure gradient). Left ventricular pressure can typically be monitored invasively with a pressure sensor located in the left ventricle of the patient's heart. As such, the use of electrical heterogeneity information to determine an alternative value indicative of 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, for example, some or all of the external electrodes of electrode device 110. Further, local or regional electrical heterogeneity information may include standard deviation and/or average of activation times measured using electrodes located in certain anatomical regions of the torso. For example, external electrodes on the left side of the patient's torso may be used to calculate local or regional left electrical heterogeneity information.

One or more different systems and/or methods may be used to generate the electrical heterogeneity information. For example, electrical heterogeneity information may be generated using an array or multiple surface electrodes of an imaging system and/or surface electrodes as described in: U.S. patent application publication No. 2012/0283587a1, published on 8.11.2012 and entitled "assessing intra-CARDIAC ACTIVATION PATTERNS and electrical DYSSYNCHRONY (ASSESSING INRA-CARDIAC ACTIVATION PATTERNS AND ELECTRICAL DYSSYNCHRONY"), U.S. patent application publication No. 2012/0284003a1, published on 8.11.2012 and entitled "assessing intra-CARDIAC ACTIVATION PATTERNS", and U.S. patent No. 8,180,428B2, published on 15.5.2012 and entitled "method and system FOR selecting CARDIAC pacing sites (methodology AND SYSTEMS FOR USE IN SELECTING CARDIAC PACING SITES)".

The electrical heterogeneity information may comprise one or more metrics or indices. For example, one of the measures or indices of electrical heterogeneity may be the Standard Deviation of Activation Times (SDAT) measured using some or all of the electrodes on the surface of the patient's torso. In some instances, the SDAT may be calculated using estimated cardiac activation times on the surface of the model heart.

Another measure or index of electrical heterogeneity may be the left standard deviation of surrogate electrical activation time (LVED) monitored by an external electrode located near the left side of the patient. Further, another measure or index of electrical heterogeneity may comprise an average of surrogate electrical activation times (LVATs) monitored by an external electrode located near the left side of the patient. LVED and LVAT may be determined (e.g., calculated, etc.) from electrical activity measured only by electrodes near the left side of the patient (which may be referred to as "left" electrodes). A left electrode may be defined as any surface electrode located near the left ventricle that encompasses the area of the patient's sternum and left side of the spine. In one embodiment, the left electrode may include all anterior electrodes on the left side of the sternum and all posterior electrodes on the left side of the spine. In another embodiment, the left electrode may comprise all anterior electrodes and all posterior electrodes on the left side of the sternum. In yet another embodiment, the left electrode may be designated based on contours of the left and right sides of the heart as determined using an imaging device (e.g., x-ray, fluoroscopy, etc.).

Another illustrative metric or index of dyssynchrony may be an activation time Range (RAT), which may be calculated as the difference between the maximum and minimum torso-surface or cardiac activation times (e.g., overall or for a region). RAT reflects the span of activation times, while SDAT gives an estimate of dispersion from the mean activation time. SDAT also provides an estimate of heterogeneity in activation times, because if activation times are spatially heterogeneous, individual activation times will be further away from the average activation time, indicating that activation of one or more regions of the heart has been delayed. In some instances, the RATs may be calculated using estimated cardiac activation times on the surface of the model heart.

Another illustrative metric or index of electrical heterogeneity information may include an estimate of the percentage of surface electrodes located within a particular region of interest of the torso or heart whose associated activation time is greater than some percentile, e.g., the 70 th percentile, of the measured QRS complex duration or the determined activation time of the surface electrodes. The region of interest may be, for example, a posterior, left anterior, and/or left ventricular region. An illustrative metric or index may be referred to as Percent Late Activation (PLAT). A PLAT may be described as providing an estimate of the percentage of regions of interest that are activated later (e.g., posterior and left anterior regions associated with the left ventricular region of the heart). A large value of PLAT may imply delayed activation of a large portion of the region (e.g., the left ventricle) and the potential benefit of electrical resynchronization through CRT by pre-energizing late regions of, for example, the left ventricle. In other examples, PLAT may be determined for other electrode subsets in other regions (e.g., the right anterior region) to assess delayed activation in the right ventricle. Further, in some instances, the PLAT may be calculated using estimated cardiac activation times on the surface of the model heart for the entire heart or for particular regions of the heart (e.g., the left ventricle or the right ventricle).

In one or more embodiments, the electrical heterogeneity information may include indicators of favorable changes in global cardiac electrical activation, as described, for example, in Sweeney et al, "Analysis of Ventricular Activation Using Surface electrocardiogram to Predict Left Ventricular inverse volume Remodeling During Cardiac Resynchronization Therapy (Analysis of venous Activation Using Surface electrical simulation to pre-di Left Ventricular reversal Volumetric Remodeling)" loop (Circulation), day 2/2010, day 9, 121(5):626-34 and/or Van Deursen et al, "vector electrocardiography as a Tool for Easy Optimization of Cardiac Resynchronization Therapy in Canine LBBB heart (vector diagnostics as a Tool for Easy Optimization of Cardiac Resynchronization Therapy in Canine LBBB Hearts)" [ circulatory Arrhythmia and Electrophysiology (Circulation Arrhytmia and Electrophysiology), 6.1.2012, (5) (3): 544-52. Heterogeneity information may also include measurements of improved cardiac mechanical function measured by imaging or other systems, as described, for example, in Ryu et al, "simultaneous electrical and mechanical mapping using a 3D cardiac mapping system: novel methods for Optimal Cardiac Resynchronization Therapy (Simultaneous Electrical and Mechanical Mapping Using 3D Heart Mapping System: Novel Approach for Optimal Cardiac Resynchronization Therapy), "Journal of Cardiovascular Electrophysiology (Journal of Cardiovascular Electrophysiology), month 2 2010, 21(2): 219-22; sperzel et al, "Intraoperative Characterization of Interventricular Mechanical asynchrony Using an electroanatomical Mapping System — Feasibility Study (Intra operative Characterization of International Cardiac Mechanical asynchrony Using electro imaging System-A Feasibility Study)", "International Journal of Cardiac Electrophysiology (Journal of International Cardiac Electrophysiology), 11/2012, 35(2):189-96 and/or entitled" METHOD FOR optimizing CRT therapy (METHOD FOR OPTIMIZING CRT THERAPY) "and described in U.S. patent application publication No. 2009/0099619A1, published on 16/4/2009.

Additionally, although not depicted in the block diagram of fig. 4, electrical heterogeneity information 208, which may be referred to as baseline electrical heterogeneity information, may be generated for electrical activity monitored without or prior to delivery of cardiac therapy.

Once the Electrical Heterogeneity Information (EHI)208 has been generated for the current a-V interval and/or V-V interval at the current heart rate, the illustrative method 200 may further adjust one or both of the a-V interval from the previous a-V interval and the V-V interval 210 from the previous V-V interval according to the therapy type, and return to delivering left ventricular-only or biventricular pacing therapy 206 and generating an EHI 208 from the monitored electrical activity.

For example, the A-V and/or V-V intervals may be adjusted (e.g., increased or decreased) based on the step value of the previous value. It may be described that the a-V intervals and/or V-V intervals "sweep" from the initial short a-V intervals and/or V-V intervals until intrinsic ventricular events 212 are sensed (e.g., depolarized), for example, because the a-V intervals are adjusted to be too "long". In at least one embodiment, the first or initial A-V interval may be about 60 milliseconds (ms). The first or initial A-V interval may be greater than or equal to about 25ms, greater than or equal to about 35ms, greater than or equal to about 45ms, greater than or equal to about 55ms, greater than or equal to about 65ms, greater than or equal to about 75ms, greater than or equal to about 85ms, or the like. Further, the first or initial A-V interval may be less than or equal to about 120ms, less than or equal to about 100ms, less than or equal to about 90ms, less than or equal to about 80ms, less than or equal to about 70ms, less than or equal to about 60ms, or the like.

The A-V interval may be increased by one step until an intrinsic ventricular event is sensed 212. As used herein, an "intrinsic" ventricular event or conduction is a ventricular event or conduction that occurs naturally or is conducted (e.g., across the a-V node of the heart, from the atrium to the ventricle, etc.). In at least one embodiment, the step size or increment can be about 20 ms. The step size or increment can be greater than or about 5ms, greater than or equal to about 10ms, greater than or equal to about 15ms, greater than or equal to about 20ms, greater than or equal to about 25ms, greater than or equal to about 30ms, greater than or equal to about 45ms, and the like. Further, the step size or increment can be less than or equal to about 70ms, less than or equal to about 60ms, less than or equal to about 50ms, less than or equal to about 40ms, less than or equal to about 35ms, less than or equal to about 30ms, and the like.

Thus, the illustrative method 200 may continue to deliver left ventricular only or biventricular pacing therapy 206 to monitor electrical activity 202 and generate electrical heterogeneity information 208 for each adjusted a-V and/or V-V interval 210 until an intrinsic ventricular event 212 is sensed. In other words, the method 200 may continue to repeat the same cycle (e.g., monitoring electrical activity 202 and generating electrical heterogeneity information 208) for different a-V and/or V-V intervals 210 until an intrinsic ventricular event 212 is sensed.

It may be described that the illustrative methods and systems initiate delivery of left mono-ventricular or bi-ventricular pacing therapy at a plurality of different a-V and/or V-V intervals 210 (e.g., different a-V intervals per cycle) and monitor electrical activity 202 for each of a plurality of different a-V and/or V-V intervals at a current heart rate. Further, electrical heterogeneity information 208 representing at least one of mechanical cardiac function and electrical cardiac function may be generated for each of a plurality of different a-V and/or V-V intervals at the current heart.

After sensing an intrinsic ventricular event (e.g., when the a-V interval becomes too "long" such that intrinsic depolarization will occur before ventricular pacing is to occur or delivered according to the current a-V interval) 212, the illustrative method 200 may select or identify an a-V interval, and may also select or identify a V-V interval 214 based on electrical heterogeneity information generated at the current heart rate when biventricular pacing is delivered. Thus, for a current heart rate or a given heart rate, the illustrative method 200 will attempt or test a number of different pacing settings, such as a-V intervals, V-V intervals, using both left ventricular only pacing and biventricular pacing, and then determine or select a-V intervals for use with left ventricular only pacing therapy at the current heart rate and a-V intervals and V-V intervals for use with biventricular pacing therapy at the current heart rate. The implantable medical device may be configured to use and utilize the selected pacing settings for providing adaptive pacing therapy at the current heart for which pacing settings are evaluated and selected, as will be further described herein with reference to fig. 5.

As described herein, the A-V and/or V-V intervals 214 for the current heart rate may be selected using EHIs generated from the monitored electrical activity. For example, one or more of the EHI metrics described herein may be used individually or together to select the A-V interval and/or the V-V interval for the current heart rate. In one or more embodiments, an EHI metric may be selected that indicates the most effective cardiac therapy at the current heart rate. For example, SDAT may be measured using EHI, and the A-V intervals and V-V intervals of SDAT that provide the indication of the most effective cardiac therapy may be selected.

In one embodiment, A-V and/or V-V intervals that generate one or more of a lowest global Standard Deviation (SDAT), a lowest left standard deviation (LVED), and a lowest left average (LVAT) of surrogate electrical activation times may be identified. The identified a-V and/or V-V intervals may be referred to as optimal or optimized and/or effective a-V and/or V-V intervals because, for example, the identified a-V and/or V-V intervals may provide optimal and/or effective cardiac therapy at the current heart rate based on the generated heterogeneity information.

The illustrative method 200 may continue with determining and selecting pacing settings (a-V intervals, V-V intervals, etc.) for both left-only and biventricular pacing at a plurality of different rates. As shown, the illustrative method 200 includes adjusting 216 the patient's heart rate and then returning to measuring the intrinsic a-V delay at the current heart rate.

The patient's heart rate 216 may be adjusted in a number of different ways. For example, the patient may be instructed or guided to perform or avoid performing a certain amount of work or exercise (e.g., using a supine bicycle) to increase the patient's heart rate. Further, for example, an implanted atrial pacing device may be used for atrial pacing to induce multiple different heart rates. Still further, for example, a controlled dose of one or more drugs (e.g., beta-blockers) can be used to titrate (e.g., increase or decrease) the heart rate of the patient.

Optionally, for each selected or determined a-V interval for each different heart rate, method 200 may determine or generate an a-V interval adjustment value 215 for each different heart rate based on the selected a-V interval and the measured intrinsic a-V interval. During delivery of cardiac pacing therapy, the a-V interval adjustment value may adjust the a-V interval based on the sensed intrinsic a-V delay, as will be further described herein. The a-V interval adjustment value may be any suitable modification parameter that provides an optimal a-V pacing delay in response to the measured intrinsic a-V delay. In particular, the A-V interval adjustment value may be associated with a heart rate and may be applied to an intrinsic A-V delay measured at the corresponding heart rate.

In one embodiment, the A-V interval adjustment value may be the difference between the selected A-V interval and the measured intrinsic A-V delay. In other words, the A-V interval adjustment value may be described as an offset that may be applied to the measured intrinsic A-V delay. For example, an offset may be added to or subtracted from the measured intrinsic A-V delay to arrive at an A-V adjustment value. Non-limiting examples of offset A-V interval adjustment values include plus or minus (+/-) approximately 0ms, 10ms, 20ms, 30ms, 40ms, 50ms, 60ms, 70ms and 80ms, and any suitable range between any of these values. For example, if the measured intrinsic a-V delay is about 220ms and the a-V adjustment value is 55ms, the optimal a-V pacing interval calculated by applying the a-V adjustment value will be 220-55 ms to 165 ms.

In one embodiment, the A-V interval adjustment value may be a percentage of the selected A-V interval and the measured intrinsic A-V delay. In other words, the A-V interval adjustment value is a percentage that may be applied to the measured intrinsic A-V delay. For example, the percentage may be multiplied or even divided by the measured intrinsic A-V delay to arrive at an A-V interval adjustment value. Non-limiting examples of percent a-V interval adjustment values include about 20 percent (%), 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100%, and any suitable range between any of these values. For example, if the measured intrinsic a-V delay is about 200ms and the percentage a-V adjustment value is 70%, the optimal a-V pacing interval calculated by applying the percentage a-V adjustment value will be 200ms x 70% ═ 140 ms.

Additionally, since the EHIs may be generated for selected a-V intervals and V-V intervals of bi-ventricular cardiac therapy at the current heart rate and for selected a-V intervals of left ventricular cardiac therapy only at the current heart rate, the EHIs of the two therapies may be compared to determine which of the two therapies should be performed at the current heart rate 217. For example, if an EHI generated during left ventricular only cardiac therapy at a current heart rate indicates more effective cardiac therapy than bi-ventricular cardiac therapy at the current heart rate, left ventricular only cardiac therapy may be selected for initial delivery to the patient at the current heart rate.

Selected or determined a-V interval and V-V interval information (e.g., selected a-V intervals and V-V intervals, a-V interval adjustment values, etc.) for a biventricular cardiac pacing therapy and a-V interval information (e.g., selected a-V intervals, a-V interval adjustment values, etc.) for a left ventricular cardiac pacing therapy for each of a plurality of different heart rates may be stored (e.g., in a memory, in a "lookup" table, etc.) for use with a cardiac therapy device, such as an IMD. In this way, A-V and/or V-V interval information may be "looked up" or invoked based on a currently measured or monitored heart rate. In other words, the a-V interval and V-V interval configuration information used to provide adaptive therapy across a range of heart rates may be the result of illustrative method 200, which may then be used by a cardiac therapy device to provide such adaptive cardiac therapy, e.g., adaptive CRT.

An illustrative method 250 of performing or delivering adaptive cardiac therapy is depicted in fig. 5. The method 250 first includes providing a pre-excitation interval 252, such as selected a-V intervals and V-V intervals used with a plurality of different heart rates during biventricular pacing therapy and selected a-V intervals used with a plurality of different heart rates during left ventricular only pacing therapy. Such pre-excitation intervals may be provided or determined using method 200 described herein with reference to fig. 4, and may be used in method 250 to provide adaptive pacing therapy. The pre-excitation interval may be provided 252 and programmed to the cardiac therapy device automatically by the illustrative systems and methods described herein and/or manually by a user may use such illustrative systems and methods.

The illustrative method 250 may include pausing or stopping an ongoing pacing therapy 254, measuring a heart rate 256, and measuring an intrinsic a-V delay or conduction time 258. Illustrative systems and methods for measuring or Sampling Intrinsic a-V delay may be described in U.S. patent No. 8,744,576 entitled Sampling Intrinsic AV Conduction Time and issued 6/3 2014, which is incorporated by reference herein in its entirety. As previously described, the intrinsic a-V delay may be a single measured intrinsic a-V delay over a single cardiac cycle or an average, mode, median, and/or any other statistical measure of multiple measured intrinsic a-V delays for multiple cardiac cycles.

Using the measured heart rate 256 and the measured intrinsic a-V delay 258, the illustrative method 250 may then adjust the a-V and/or V-V intervals 260 of the pacing therapy according to the provided pre-excitation interval. In other words, the measured A-V interval adjustment value for the heart rate and the measured intrinsic A-V delay may be used to generate a new A-V interval and/or the provided V-V interval for the measured heart rate may be programmed as a new V-V interval in biventricular pacing.

For example, if the patient's measured intrinsic A-V delay is 200ms at a heart rate of 90bpm and the A-V interval of 90bpm is adjusted by a difference ratio of 1.5, the process 260 may divide the measured intrinsic delay by the difference ratio to generate a new A-V interval of approximately 133 ms. Further, for example, if the patient's measured intrinsic A-V delay is 150ms at a heart rate of 125bpm and the A-V interval adjustment value of 125bpm is a difference ratio of 1.5, the process 260 may divide the measured intrinsic A-V delay by the difference ratio to generate an A-V interval of approximately 100 ms.

Further, for example, if the patient's measured intrinsic A-V delay is 200ms at a heart rate of 100bpm and the A-V interval adjustment value of 100bpm is a difference period of 50ms, the process 260 may subtract the difference period to form the measured intrinsic A-V delay, thereby generating an A-V interval of approximately 150 ms. Further, for example, if the patient's measured intrinsic A-V delay is 180ms at a heart rate of 110bpm and the A-V interval of 110bpm is adjusted for a difference period of 60ms, the process 260 may subtract the difference period to form the measured intrinsic A-V delay to generate an A-V interval of approximately 120 ms.

After the A-V intervals and/or V-V intervals have been generated or calculated 260, the A-V intervals and/or V-V intervals may be evaluated to determine whether the generated A-V intervals and V-V intervals should be used in cardiac therapy. For example, if the generated A-V interval is too "long," the generated A-V interval may not provide effective and/or optimal pacing therapy to the patient. For example, the generated or calculated A-V interval may be compared to a threshold, and if the A-V interval is greater than or equal to the threshold, the A-V interval may not be used for cardiac therapy, and the A-V interval may be set to a nominal value (e.g., the sensed A-V interval (SAV) may be set to 100ms and the paced A-V interval (PAV) may be set to 150 ms). Likewise, if the A-V interval is less than the threshold, the A-V interval may be used for cardiac therapy. The threshold can be greater than or equal to about 200ms, greater than or equal to about 210ms, greater than or equal to about 220ms, greater than or equal to about 240ms, greater than or equal to about 250ms, greater than or equal to about 270ms, greater than or equal to about 300ms, and the like. Further, the threshold value may be less than or equal to about 230ms, less than or equal to about 260ms, less than or equal to about 280ms, less than or equal to about 310ms, less than or equal to about 350ms, less than or equal to about 370ms, less than or equal to about 400ms, or the like. If the A-V interval and the V-V interval are determined to be acceptable for pacing therapy, such A-V interval and V-V interval may be set or programmed in a cardiac therapy device (e.g., IMD).

Pacing therapy may be resumed 262 and periodically, pacing therapy may be suspended again 254 to adjust the cardiac pacing therapy according to the current heart rate and the intrinsic measured a-V delay. It should be appreciated that suspending cardiac therapy and adjusting the frequency of cardiac pacing therapy may occur at any rate in order to provide effective cardiac pacing to a patient. In one embodiment, the time period between adjusting cardiac pacing and adjusting cardiac pacing again may be every 1 minute. In other embodiments, the time period between adjusting cardiac pacing and adjusting cardiac pacing again may be between about every 30 seconds and about every 15 minutes.

Additionally, the method 250 may further include a pacing type or configuration, switching process 270. As shown, the patient's heart rate 272 and intrinsic a-V delay 274 may be evaluated, and based on this evaluation, the process 270 may switch pacing therapy 276 before resuming pacing therapy 262.

The switching process 270 may switch from left ventricular only pacing therapy to biventricular pacing therapy or from biventricular pacing therapy to left ventricular only pacing therapy based on evaluating the heart rate 272. In one embodiment, the heart rate may be evaluated by comparing the heart rate to a threshold heart rate switch value. More specifically, for example, if the heart rate exceeds the threshold rate switch value and the current pacing therapy is left ventricular only pacing, the pacing therapy may switch to biventricular pacing, and conversely, if the heart rate is less than the threshold rate switch value and the current pacing therapy is biventricular pacing, the pacing therapy may switch to left ventricular only pacing. For example, if the heart rate is greater than 100bpm and the current pacing configuration is left ventricular only, the device may switch to biventricular pacing.

Further, the switching process 270 may switch from left ventricular only pacing therapy to biventricular pacing therapy or from biventricular pacing therapy to left ventricular only pacing therapy based on evaluating the measured intrinsic a-V delay 274. In one embodiment, the measured intrinsic A-V delay may be evaluated by comparing the measured intrinsic A-V delay to an A-V delay switch value. More specifically, for example, if the intrinsic a-V delay exceeds the a-V delay switch value and the current pacing therapy is left ventricular only pacing, the pacing therapy may switch to biventricular pacing, and conversely, if the intrinsic a-V delay is less than the a-V delay switch value and the current pacing therapy is biventricular pacing, the pacing therapy may switch to left ventricular only pacing. For example, if the patient's intrinsic a-V exceeds some absolute value (e.g., about 300ms to about 350ms) or exceeds a value above a certain threshold (e.g., about 20ms, about 30ms, about 40ms, etc.) and the current pacing configuration is left ventricle only, as compared to the baseline intrinsic a-V delay, the device may switch 276 to biventricular pacing.

Illustrative cardiac therapy systems and devices may be further described herein with reference to fig. 6-8, which may utilize the illustrative systems, interfaces, methods, and processes described herein with respect to fig. 1-5.

Fig. 6 is a conceptual diagram illustrating an illustrative therapy system 10 that may be used to deliver pacing therapy to a patient 14. The patient 14 may, but need not, be a human. The therapy system 10 may include an implantable medical device 16(IMD) that may be coupled to leads 18, 20, 22. The IMD 16 may be, for example, an implantable pacemaker, cardioverter, and/or defibrillator that delivers or provides electrical signals (e.g., paces, etc.) to and/or senses electrical signals from the heart 12 of the patient 14 through electrodes coupled to one or more of the leads 18, 20, 22.

Leads 18, 20, 22 extend into heart 12 of patient 14 to sense electrical activity of heart 12 and/or deliver electrical stimulation to heart 12. In the example shown in fig. 6, Right Ventricular (RV) lead 18 extends through one or more veins (not shown), the superior vena cava (not shown), and right atrium 26, and into right ventricle 28. Left Ventricular (LV) coronary sinus lead 20 extends through one or more veins, the vena cava, right atrium 26, and into coronary sinus 30 to a region adjacent to the free wall of left ventricle 32 of heart 12. Right Atrial (RA) lead 22 extends through one or more veins and the vena cava, and into right atrium 26 of heart 12.

IMD 16 may sense electrical signals attendant to the depolarization and repolarization of heart 12, etc., through electrodes coupled to at least one of leads 18, 20, 22. In some examples, IMD 16 provides pacing therapy (e.g., pacing pulses) to heart 12 based on electrical signals sensed within heart 12. IMD 16 is operable to adjust one or more parameters associated with pacing therapy, such as a-V delay and other various timings, pulse widths, amplitudes, voltages, burst lengths, and the like. Further, IMD 16 is operable to deliver pacing therapy using various electrode configurations, which may be unipolar, bipolar, quadrupolar, or further multipolar. For example, a multipolar lead may contain several electrodes that may be used to deliver pacing therapy. Thus, the multipolar lead system may provide or supply multiple electrical vectors to pace therefrom. 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 a housing or can of an IMD. While the improvement in cardiac function as a result of pacing therapy may depend primarily on the cathode, electrical parameters such as impedance, pacing threshold voltage, current consumption, longevity may be more dependent on the pacing vector, which includes both the cathode and the anode. IMD 16 may also provide defibrillation therapy and/or cardioversion therapy via electrodes located on at least one of leads 18, 20, 22. Further, IMD 16 may detect cardiac arrhythmias of heart 12, such as fibrillation of ventricles 28, 32, and deliver defibrillation therapy to heart 12 in the form of electrical pulses. In some examples, IMD 16 may be programmed to deliver a progression of therapy (e.g., pulses with increasing energy levels) until fibrillation of heart 12 ceases.

Fig. 7A-7B are conceptual diagrams illustrating the IMD 16 and leads 18, 20, 22 of the therapy system 10 of fig. 6 in more detail. Leads 18, 20, 22 may be electrically coupled to a therapy delivery module (e.g., for delivering pacing therapy), a sensing module (e.g., for sensing one or more signals from one or more electrodes), and/or any other module of IMD 16 through connector block 34. In some examples, the proximal ends of leads 18, 20, 22 may include electrical contacts that are electrically coupled to corresponding electrical contacts within connector block 34 of IMD 16. Additionally, in some examples, the leads 18, 20, 22 may be mechanically coupled to the connector block 34 by way of set screws, connecting pins, or another suitable mechanical coupling mechanism.

Each of the leads 18, 20, 22 includes an elongated insulated lead body that may carry a plurality of conductors (e.g., concentric coil conductors, straight conductors, etc.) separated from one another by insulation (e.g., a tubular insulating sheath). In the example shown, the bipolar electrodes 40, 42 are located near the distal end of the lead 18. In addition, bipolar electrodes 44, 45, 46, 47 are located near the distal end of lead 20, and bipolar electrodes 48, 50 are located near the distal end of lead 22.

Electrodes 40, 44, 45, 46, 47, 48 may take the form of ring electrodes, and electrodes 42, 50 may take the form of extendable helix tip electrodes retractably mounted within 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., coil conductors and/or straight conductors) within the lead body of its associated lead 18, 20, 22, and thereby to a respective one of the electrical contacts on the proximal end of the lead 18, 20, 22.

In addition, the electrode surface area of electrodes 44, 45, 46, and 47 may be about 5.3mm²To about 5.8mm². Electrodes 44, 45, 46 and 47 may also be referred to as LV1, LV2, LV3 and LV4, respectively. LV electrodes on lead 20 (i.e., left ventricular electrode 1(LV1)44, left ventricular electrode 2(LV2)45, left ventricular electrode 3(LV3)46, and left ventricle 4(LV4)47, etc.) may be spaced at variable distances. For example, electrode 44 may be spaced from electrode 45 by a distance of, for example, about 21 millimeters (mm), electrodes 45 and 46 may be spaced from each other by a distance of, for example, about 1.3mm to about 1.5mm, and electrodes 46 and 47 may be spaced from each other by a distance of, for example, 20mm to about 21 mm.

Electrodes 40, 42, 44, 45, 46, 47, 48, 50 may further be used to sense electrical signals (e.g., morphology waveforms within an Electrogram (EGM)) that accompany the depolarization and repolarization of heart 12. Electrical signals are conducted to IMD 16 through respective leads 18, 20, 22. In some examples, IMD 16 may also deliver pacing pulses through electrodes 40, 42, 44, 45, 46, 47, 48, 50 to cause depolarization of cardiac tissue of patient's heart 12. In some examples, as shown in fig. 7A, IMD 16 includes one or more housing electrodes, such as housing electrode 58, which may be integrally formed with an outer surface of a housing 60 (e.g., a hermetic housing) of IMD 16 or otherwise coupled to housing 60. Any of electrodes 40, 42, 44, 45, 46, 47, 48, 50 may be used in combination with housing electrode 58 for unipolar sensing or pacing. It is generally understood by those skilled in the art that other electrodes may also be selected to define or be used for pacing and sensing vectors. Further, any of the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, when not used to deliver pacing therapy, may be used to sense electrical activity during pacing therapy.

As described in further detail with reference to fig. 7A, the housing 60 may enclose a therapy delivery module that may contain 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 contain elongated electrodes 62, 64, 66, respectively, which may take the form of coils. IMD 16 may deliver defibrillation shocks to heart 12 via any combination of elongated electrodes 62, 64, 66 and housing electrode 58. Electrodes 58, 62, 64, 66 may also be used to deliver cardioversion pulses to heart 12. Further, the electrodes 62, 64, 66 may be made of any suitable electrically conductive material, such as, but not limited to, platinum alloys, and/or other materials known to be useful 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 and may be used in combination with any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58. In at least one embodiment, RV elongate electrode 62 may be used to sense electrical activity of the patient's heart during delivery of pacing therapy (e.g., in combination with housing electrode 58 or defibrillation electrode-to-housing electrode vectors).

The configuration of the illustrative therapy system 10 shown in fig. 6-8 is but 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 shown in fig. 6. Additionally, in other examples, therapy system 10 may be implanted in/around the cardiac space without a transvenous lead (e.g., leadless/wireless pacing system) or with a lead implanted (e.g., transvenously implanted or using the method) into the left chamber of the heart (in addition to or in place of the transvenous lead placed in the right chamber of the heart as shown in fig. 6). Further, in one or more embodiments, IMD 16 need not be implanted within patient 14. For example, IMD 16 may deliver various cardiac therapies to heart 12 via percutaneous leads that extend through the skin of patient 14 to various locations within or outside of heart 12. In one or more embodiments, system 10 may sense cardiac activation using wireless pacing (e.g., using energy transmission to one or more intracardiac pacing components via ultrasound, inductive coupling, RF, etc.) and using electrodes on the can/housing and/or on subcutaneous leads.

In other examples of therapy systems that provide electrical stimulation therapy to heart 12, such therapy systems may include any suitable number of leads coupled to IMD 16, and each of the leads may extend to any location within or near heart 12. For example, other examples of therapy systems may include three transvenous leads positioned as shown in fig. 6-8. Still further, other therapy systems may include a single lead extending from IMD 16 into right atrium 26 or right ventricle 28 or two leads extending into a respective one of right atrium 26 and right ventricle 28.

Fig. 8A is a functional block diagram of one illustrative configuration of IMD 16. As shown, IMD 16 may include a control module 81, a therapy delivery module 84 (which may include a stimulation generator, for example), a sensing module 86, and a power source 90.

Control module or device 81 may include a processor 80, memory 82, and telemetry module or device 88. Memory 82 may contain computer readable instructions that, when executed, for example, by processor 80, cause IMD 16 and/or control module 81 to perform various functions attributed to IMD 16 and/or control module 81 described herein. Further, the memory 82 may comprise any volatile, non-volatile, magnetic, optical, and/or electrical media, such as 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 illustrative CAPTURE MANAGEMENT module may be the Left Ventricular CAPTURE MANAGEMENT (LVCM) module described in U.S. patent No. 7,684,863 entitled LV THRESHOLD MEASUREMENT AND CAPTURE MANAGEMENT (LV THRESHOLD MEASUREMENT AND CAPTURE MANAGEMENT) AND issued on 23/3/2010.

The processor 80 of the control module 81 may include any one or more of the following: 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, 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 functionality attributed to processor 80 herein may be embodied as software, firmware, hardware, or any combination thereof.

Control module 81 may control therapy delivery module 84 to deliver therapy (e.g., electrical stimulation therapy such as pacing) to heart 12 according to the selected one or more therapy programs, which may be stored in memory 82. More specifically, control module 81 (e.g., processor 80) may control various parameters of the electrical stimulation delivered by therapy delivery module 84, such as, for example, a-V delay, V-V delay, pacing pulses having amplitudes, pulse widths, frequencies, 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, therapy delivery module 84 is electrically coupled to electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, for example, by conductors of respective leads 18, 20, 22 or, in the case of housing electrode 58, by electrical conductors 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 heart 12 using one or more of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66.

For example, therapy delivery module 84 may deliver pacing stimuli (e.g., pacing pulses) through ring electrodes 40, 44, 45, 46, 47, 48 coupled to leads 18, 20, 22 and/or spiral tip electrodes 42, 50 of leads 18, 22. Further, therapy delivery module 84 may deliver defibrillation shocks to heart 12 through at least two of electrodes 58, 62, 64, 66, for example. 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 to deliver one or more of these types of stimulation in the form of other signals (e.g., sine waves, square waves, and/or other substantially continuous time signals).

IMD 16 may further include a switching module 85, and control module 81 (e.g., processor 80) may use switching module 85 to select 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, e.g., via a data/address bus. Switch module 85 may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable for selectively coupling sensing module 86 and/or therapy delivery module 84 to one or more selected electrodes. More specifically, therapy delivery module 84 may include a plurality of pacing output circuits. Each of the plurality of pacing output circuits may be selectively coupled to one or more of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pair of electrodes for delivering therapy to a bipolar or multipolar pacing vector), for example, using switching module 85. In other words, each electrode may be selectively coupled to one of the pacing output circuits of the therapy delivery module using switch module 85.

Sensing module 86 is coupled (e.g., electrically coupled) to a sensing device, which may contain electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitor electrical activity of heart 12, such as Electrocardiogram (ECG)/Electrogram (EGM) signals, among other sensing devices. The ECG/EGM signals may be used to measure or monitor activation times (e.g., ventricular activation times, etc.), Heart Rate (HR), Heart Rate Variability (HRV), heart rate oscillations (HRT), deceleration/acceleration capabilities, deceleration sequence incidence, T-wave alternans (TWA), P-wave to P-wave intervals (also referred to as P-P intervals or a-a intervals), R-wave to R-wave intervals (also referred to as R-R intervals or V-V intervals), P-wave to QRS complex intervals (also referred to as P-R intervals, a-V intervals, or P-Q intervals), QRS complex morphology, ST segments (i.e., segments connecting QRS complexes and T waves), T-wave changes, QT intervals, electrical vectors, and the like.

Switching module 85 may also be used with sensing module 86 to select which of the available electrodes are used or enabled, for example, to sense electrical activity of the patient's heart (e.g., one or more electrical vectors of the patient's heart using any combination of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66). Likewise, switching module 85 may also be used with sensing module 86 to select which of the available electrodes are not used (e.g., disabled), for example, to sense electrical activity of the patient's heart (e.g., one or more electrical vectors of the patient's heart using any combination of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66), and so forth. In some examples, control module 81 may select an electrode that serves as a sense electrode through a switching module within sensing module 86 (e.g., providing a signal through a data/address bus).

In some examples, sensing module 86 includes channels including amplifiers having relatively wider passbands than R-wave or P-wave amplifiers. The signal from the selected sensing electrode may be provided to a multiplexer and thereafter converted by an analog-to-digital converter to a multi-bit digital signal for storage in memory 82, for example as an Electrogram (EGM). In some examples, the storage of such EGMs in memory 82 may be under the control of direct memory access circuitry.

In some examples, control module 81 may operate as an interrupt driven device and may be responsive to interrupts from the pacemaker timing and control module, where the interrupts may correspond to the occurrence of sensed P-waves and R-waves and the generation of cardiac pacing pulses. Any necessary mathematical calculations may be performed by processor 80, and any updates to the values or intervals controlled by the pacemaker timing and control module may occur after such interrupts. A portion of memory 82 may be configured as a plurality of recirculation buffers capable of holding one or more series of measured intervals that may be analyzed by, for example, processor 80 in response to the occurrence of a pacing or sensing interruption to determine whether patient's heart 12 is currently exhibiting atrial or ventricular tachyarrhythmia.

Telemetry module 88 of 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 processor 80, telemetry module 88 may receive downlink telemetry from and send uplink telemetry to a programmer by way of an antenna (which may be internal and/or external). Processor 80 may provide data to be uplinked to the programmer and control signals for telemetry circuitry within telemetry module 88, for example, via an address/data bus. In some examples, telemetry module 88 may provide the received data to processor 80 through a multiplexer.

The various components of IMD 16 are further coupled to a power source 90, which may include rechargeable or non-rechargeable batteries. 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. 8B is another embodiment depicting a functional block diagram of IMD 16 without LA CS pace/sense electrodes and coupled with bipolar RA lead 22, bipolar RV lead 18, and bipolar LV CS lead 20 with Implantable Pulse Generator (IPG) circuitry 31 having programmable modes and parameters of the bi-ventricular DDD/R type known in the pacing art. In turn, the sensor signal processing circuit 91 is indirectly coupled to the timing circuit 43 and to the microcomputer circuitry 33 via a data and control bus. The IPG circuit 31 is shown in a functional block diagram generally divided into a microcomputer circuit 33 and a pacing circuit 21. Pacing circuit 21 includes digital controller/timer circuit 43, output amplifier circuit 51, sense amplifier circuit 55, RF telemetry transceiver 41, activity sensor circuit 35, and many other circuits and components described below.

Crystal oscillator circuit 89 provides a basic timing clock to pacing circuit 21 when power is supplied by battery 29. The power-on-reset circuit 87 is responsive to the initial connection of the circuit to the battery for defining an initial operating condition and, similarly, resets the operating state of the device in response to detecting a low battery condition. Reference mode circuitry 37 generates stable voltage references and currents for analog circuitry within pacing circuit 21. Analog-to-digital converter (ADC) and multiplexer circuitry 39 digitizes the analog signals and voltages to provide real-time telemetry of, for example, cardiac signals from sense amplifiers 55 for uplink transmission through RF transmitter and receiver circuitry 41. The 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 the illustrative implantable cardiac pacemaker.

If the IPG is programmed into a rate response mode, the signal output by one or more physiological sensors is used as a Rate Control Parameter (RCP) to derive physiological escape intervals. For example, escape intervals are adjusted in proportion to the level of patient activity generated in Patient Activity Sensor (PAS) circuit 35 in the depicted illustrative 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 an RCP. The sensor 27 generates an electrical signal in response to the sensed physical activity, which is processed by the activity circuit 35 and provided to the digital controller/timer circuit 43. The activity circuit 35 AND associated sensor 27 may correspond to the circuitry disclosed in U.S. patent No. 5,052,388 entitled "METHOD AND APPARATUS FOR performing activity sensing in a PULSE GENERATOR (METHOD AND APPARATUS FOR IMPLEMENTING ACTIVITY SENSING IN A PULSE GENERATOR)" AND issued on month 1 of 1991 AND U.S. patent No. 4,428,378 entitled "rate adaptive pacemaker (RATE ADAPTIVE PACER)" AND issued on month 31 of 1984. Similarly, the illustrative systems, devices, and methods described herein may be practiced in conjunction with alternative types of sensors (e.g., oxygenation sensors, pressure sensors, pH sensors, and respiration sensors) for providing rate-responsive pacing capabilities. Alternatively, the QT time may be used as a rate indicating parameter, in which case no additional sensor is required. Similarly, the illustrative embodiments described herein may also be practiced in non-rate-responsive pacemakers.

Data transmission to and from the external programmer is accomplished through telemetry antenna 57 and associated RF transceiver 41 for demodulating both received downlink telemetry and transmitting uplink telemetry. The uplink telemetry capability 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 atria and ventricles).

The microcomputer 33 contains a microprocessor 80 and associated system clock and on-processor RAM chip 82A and ROM chip 82B, respectively. In addition, the microcomputer circuit 33 contains a separate RAM/ROM chip 82C to provide additional memory capacity. Microprocessor 80 typically operates in a reduced power consumption mode and is interrupt driven. Microprocessor 80 wakes up in response to defined interrupt EVENTs, which may include a-TRIG, RV-TRIG, LV-TRIG signals generated by a timer in digital timer/controller circuit 43, and a-EVENT, RV-EVENT, LV-EVENT signals generated by sense amplifier circuit 55, and the like. The specific values of the intervals and delays timed out by digital controller/timer circuit 43 are controlled by microcomputer circuit 33 from programmed parameter values and operating modes via data and control buses. Additionally, if programmed to operate as a rate responsive pacemaker, a timer interrupt may be provided (e.g., every cycle or every two seconds) to allow the microprocessor to analyze the activity sensor data and update the basic A-A, V-A or V-V escape intervals, if applicable. In addition, microprocessor 80 may also be used to define variable, operational A-V delay intervals, V-V delay intervals, 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. However, it is contemplated that other embodiments may be suitable for practicing the present disclosure. For example, an off-the-shelf commercially available microprocessor or microcontroller or custom dedicated 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 microcomputer 33 to control timing and other functions within pacing circuit 21, and contains a set of timing and associated logic circuits, of which certain logic circuits relevant to the present disclosure are depicted. The depicted timing circuit includes a URI/LRI timer 83A, V-V delay timer 83B, an intrinsic interval timer 83C for timing the elapsed V-EVENT to V-EVENT interval or V-EVENT to A-EVENT interval or V-V conduction interval, an escape interval timer 83D for timing the 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 the previous A-EVENT or A-TRIG, a post-ventricular timer 83F for timing the post-ventricular time period, and a date/time clock 83G.

The A-V delay interval timer 83E is loaded with the appropriate delay interval for one ventricular chamber (e.g., A-RVp delay or A-LVp) to begin timing out from the previous A-PACE or A-EVENT. The interval timer 83E triggers pacing stimulus delivery and may be based on one or more previous cardiac cycles (or a data set derived empirically for a given patient).

The post-EVENT timer 83F times out the post-ventricular time period following RV-EVENT or LV-EVENT or RV-TRIG or LV-TRIG and the post-atrial time period following A-EVENT or A-TRIG. The duration of the post-event time period may also be selected as a programmable parameter stored in the microcomputer 33. The post-ventricular periods include PVARP, post-atrial ventricular blanking period (PAVBP), Ventricular Blanking Period (VBP), post-ventricular atrial blanking period (PVARP), and Ventricular Refractory Period (VRP), although other periods may be suitably defined, at least in part, according to the operating circuitry employed in the pacing engine. The post-atrial time period includes an Atrial Refractory Period (ARP), during which A-EVENT is ignored for the purpose of resetting any A-V delays, and an Atrial Blanking Period (ABP), during which atrial sensing is disabled. It should be noted that the post-atrial period and the beginning of the A-V delay may begin substantially simultaneously with the beginning or end of each A-EVENT or A-TRIG, or in the latter case, at the end of the A-PACE, which may follow the A-TRIG. Similarly, the post-ventricular time period and the start of the V-A escape interval may begin substantially simultaneously with the start or end of the V-EVENT or V-TRIG, or in the latter case, at the end of the V-PACE which may follow the V-TRIG. Microprocessor 80 also optionally calculates a-V delays, V-V delays, post-ventricular time periods, and post-atrial time periods that vary with sensor-based escape intervals and/or intrinsic atrial and/or ventricular rates established in response to one or more RCPs.

The output amplifier circuit 51 contains a RA pacing pulse generator (and LA pacing pulse generator if LA pacing is provided), a RV pacing pulse generator, a LV pacing pulse generator, and/or any other pulse generator configured to provide atrial and ventricular pacing. To trigger the generation of an RV-PACE or LV-PACE pulse, the digital controller/timer circuit 43 generates an RV-TRIG signal upon expiration of the A-RVp delay (in the case of RV pre-excitation) provided by the A-V delay interval timer 83E (or V-V delay timer 83B) or generates an LV-TRIG signal upon expiration of the A-LVp delay (in the case of LV pre-excitation). Similarly, digital controller/timer circuit 43 generates an RA-TRIG signal that triggers the output of an RA-PACE pulse (or LA-TRIG signal that triggers the output of a LA-PACE pulse, if provided) at the end of the V-A escape interval timed by escape interval timer 83D.

Output amplifier circuit 51 contains switching circuitry for coupling selected pairs of pacing electrodes from among the lead conductors and IND-CAN electrode 20 to the RA pacing pulse generator (and LA pacing pulse generator if provided), RV pacing pulse generator, and LV pacing pulse generator. Pace/sense electrode pair selection and control circuitry 53 selects lead conductors and associated pacing electrode pairs to couple with atrial and ventricular output amplifiers within output amplifier circuitry 51 for enabling RA, LA, RV, and LV pacing.

Sense amplifier circuitry 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 the voltage difference signals generated across the sensing electrode pairs due to the passage of cardiac depolarization wavefronts. High impedance sense amplifiers use high gain to amplify low amplitude signals and rely on pass band filters, time domain filtering and amplitude threshold comparisons to distinguish P-waves or R-waves from background electrical noise. The digital controller/timer circuit 43 controls the sensitivity settings of the atrial and ventricular sense amplifiers 55.

During blanking periods before, during, and after delivery of a pacing pulse to any of the pacing electrodes of the pacing system, the sense amplifier may be decoupled from the sense electrodes to avoid saturation of the sense amplifier. Sense amplifier circuitry 55 includes blanking circuitry for decoupling the selected pairs of lead conductors and 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 ABP, PVABP, and VBP. Sense amplifier circuit 55 also includes switching circuitry for coupling selected sense electrode lead conductors and IND-CAN electrode 20 to the RA sense amplifier (and LA sense amplifier if provided), RV sense amplifier and LV sense amplifier. Again, the sense electrode selection and control circuit 53 selects the conductors and associated pairs of sense electrodes to be coupled with the atrial and ventricular sense amplifiers within the output amplifier circuit 51 and sense amplifier circuit 55 for achieving RA, LA, RV, and LV sensing along the desired unipolar and bipolar sensing vectors.

The right atrial depolarization or P-wave in the RA-SENSE signal sensed by the RA SENSE amplifier results in an RA-EVENT signal that is communicated to the digital controller/timer circuit 43. Similarly, left atrial depolarization or P-wave in the LA-SENSE signal sensed by the LA SENSE amplifier (if provided) results in a LA-EVENT signal that is communicated to the digital controller/timer circuit 43. Ventricular depolarization or R-wave in the RV-SENSE signal sensed by the ventricular SENSE amplifier results in the RV-EVENT signal being transmitted to the digital controller/timer circuit 43. Similarly, ventricular depolarization or R-wave in the LV-SENSE signal sensed by the ventricular SENSE amplifiers results in a LV-EVENT signal being transmitted 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 may be unintentionally triggered by electrical noise signals or abnormally conducted depolarization waves rather than the true R-or P-waves.

The techniques described in this disclosure, including the techniques attributed to IMD 16, computing device 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, as embodied in a programmer, such as a physician or patient programmer, stimulator, image processing device, or other device. The terms "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. Additionally, 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 functions ascribed to the systems, devices and techniques described in this disclosure may be embodied as instructions on a computer readable medium (e.g., RAM, ROM, NVRAM, EEPROM, flash memory, magnetic data storage media, optical data storage media, etc.). The instructions may be executed by the processing circuitry and/or one or more processors to support one or more aspects of the functionality described in this disclosure.

Illustrative embodiments

Example 1: a system, comprising:

an electrode apparatus including a plurality of external electrodes for monitoring electrical activity from tissue of a patient; and

a computing device comprising processing circuitry and coupled to the electrode device and configured to:

monitoring electrical activity of the patient's heart using one or more of the plurality of external electrodes during left ventricular only pacing therapy delivered at a plurality of different A-V intervals at a plurality of different heart rates and during biventricular pacing therapy delivered at a plurality of different A-V intervals and V-V intervals at a plurality of different heart rates,

generating Electrical Heterogeneity Information (EHI) from the monitored electrical activity from the electrode device, wherein the EHI represents one or both of mechanical cardiac function and electrical cardiac function,

selecting an A-V interval for left ventricular only pacing therapy for each different heart rate based on the EHIs generated by the monitored electrical activity during left ventricular only pacing therapy, and

selecting an A-V interval and a V-V interval for biventricular pacing therapy for each different heart rate based on the EHIs generated by the monitored electrical activity during biventricular pacing therapy.

Example 2: a method, comprising:

monitoring electrical activity of a heart of a patient using one or more electrodes of a plurality of external electrodes during left ventricular-only pacing therapy delivered at a plurality of different a-V intervals and during biventricular pacing therapy delivered at a plurality of different a-V intervals and V-V intervals at a plurality of different heart rates;

generating Electrical Heterogeneity Information (EHI) from the monitored electrical activity from the electrode device, wherein the EHI represents one or both of mechanical cardiac function and electrical cardiac function;

selecting an A-V interval for left ventricular only pacing therapy for each different heart rate based on the EHI generated from the monitored electrical activity during left ventricular only pacing therapy; and

selecting an A-V interval and a V-V interval for biventricular pacing therapy for each different heart rate based on the EHIs generated by the monitored electrical activity during biventricular pacing therapy.

Embodiment 3. the system or method of any of embodiments 1-2, wherein the computing device is further configured to:

measuring, for each different heart rate, an intrinsic a-V delay during the absence of delivered pacing therapy; and is

For each different heart rate, determining an A-V interval adjustment value to adjust the A-V interval based on intrinsic A-V delays sensed during delivery of pacing therapy, wherein the A-V interval adjustment for each different heart rate is based on the selected A-V interval and measured intrinsic A-V delays corresponding to the different heart rate.

Embodiment 3. the system or method of embodiment 3, wherein determining the A-V interval adjustment value for each different heart rate comprises determining a difference between the selected A-V interval and the measured intrinsic A-V delay.

Embodiment 4. the system or method of embodiment 3, wherein determining the A-V interval adjustment value for each different heart rate comprises determining a percentage of the selected A-V interval to the measured intrinsic A-V delay.

Embodiment 5. the system or method of any of embodiments 1-4, wherein the controller is further configured to select a left ventricular only pacing therapy or a biventricular pacing therapy as an initial pacing therapy modality based on the EHI generated from electrical activity monitored during the left ventricular only pacing therapy and electrical activity monitored during the biventricular pacing therapy.

Embodiment 6. the system or method of any of embodiments 1-5, wherein the EHI comprises a measure of Standard Deviation of Activation Time (SDAT).

Embodiment 7 the system or method of any of embodiments 1-6, wherein the plurality of external electrodes comprises surface electrodes positioned in an array configured to be positioned near the skin of the patient.

Embodiment 8 an implantable medical device, comprising:

a plurality of electrodes including an atrial pacing electrode, a left ventricular pacing electrode, and a right ventricular pacing electrode;

therapy delivery circuitry operably coupled to the plurality of electrodes to deliver cardiac therapy to a heart of a patient;

a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of a heart of a patient; and

a controller comprising processing circuitry operably coupled to the therapy delivery circuitry and the sensing circuitry, the controller configured to:

calibrating the left ventricular only pacing therapy for a plurality of heart rates based on Electrical Heterogeneity Information (EHI) generated from electrical activity monitored from the plurality of external electrodes during the left ventricular only pacing therapy,

calibrating biventricular pacing therapy for a plurality of heart rates based on the EHIs generated from the monitored electrical activity from a plurality of external electrodes during biventricular pacing therapy; and is

Delivering one or both of the calibrated left ventricular-only pacing therapy and the calibrated biventricular pacing therapy.

Embodiment 9 the apparatus of embodiment 8, wherein the calibrated left ventricular only pacing therapy comprises a-V interval adjustment value determined for each different heart rate, wherein delivering the calibrated left ventricular only pacing therapy comprises:

monitoring heart rate;

measuring an intrinsic a-V delay during the absence of delivered pacing therapy; and

adjusting an A-V interval of the calibrated left ventricular only pacing therapy using:

the determined A-V interval adjustment value corresponding to the monitored heart rate; and

the intrinsic a-V retardation measured.

Embodiment 10 the device of embodiments 8-9, wherein the determined A-V interval adjustment value comprises one of a difference between the selected A-V interval and the measured intrinsic A-V delay and a percentage of the selected A-V interval and the measured intrinsic A-V delay.

Embodiment 11 the apparatus of embodiments 8-10, wherein the calibrated biventricular pacing therapy comprises an a-V interval adjustment value determined for each different heart rate and a V-V interval adjustment value determined for each different heart rate, wherein delivering the calibrated biventricular pacing therapy comprises:

monitoring heart rate;

measuring an intrinsic a-V delay during the absence of delivered pacing therapy;

adjusting an A-V interval of the calibrated left ventricular only pacing therapy using:

the determined A-V interval adjustment value corresponding to the monitored heart rate; and

the measured intrinsic A-V retardation; and

adjusting a V-V interval of the calibrated biventricular-only pacing therapy using the determined V-V interval adjustment value corresponding to the monitored heart rate.

Embodiment 12. the apparatus of embodiments 8-11, wherein the controller is further configured to:

monitoring heart rate; and is

Switching from left ventricular only pacing therapy to biventricular pacing therapy based on the monitored heart rate.

Embodiment 13. the apparatus of embodiments 8-12, wherein the controller is further configured to:

measuring an intrinsic a-V delay during the absence of delivered pacing therapy;

switching from left ventricular only pacing therapy to biventricular pacing therapy based on the measured intrinsic A-V delay.

The present disclosure has been provided with reference to illustrative embodiments and is not intended to be construed in a limiting sense. As previously mentioned, 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 from consideration of the specification.