Determining CRT response

Abstract

Systems and methods are disclosed for determining an indication of a patient's predictive response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on a patient metric determined using received physiological information of the patient, the physiological information includes at least one of heart sound information or breathing information from a first period of time prior to CRT or MSP therapy.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 420,270, filed December 5, 2022, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates generally to medical devices and, more particularly, to using a patient's physiological information to determine a predictive indicator of response to cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy. Background Art

[0004] Heart failure (HF) is a decreased ability of the heart to deliver enough blood to meet the body's needs. Patients with heart failure typically present with an enlarged heart and weakened myocardium, resulting in decreased contractility and poor cardiac output. Signs of heart failure include pulmonary congestion, edema, and difficulty breathing. Heart failure is usually a chronic disease, but it can also occur suddenly, affecting the left, right, or both sides of the heart. Causes of heart failure include coronary artery disease, myocardial infarction, hypertension, atrial fibrillation, valvular heart disease, alcoholism, infection, cardiomyopathy, or one or more other conditions that reduce the heart's pumping efficiency.

[0005] Medical devices, including ambulatory, implantable, subcutaneous, wearable, or one or more other medical devices, can monitor, detect, or treat various conditions, including heart failure, atrial fibrillation, and the like. The medical device may include a sensor for sensing physiological information from a patient, and one or more circuits for using the sensed physiological information to detect one or more physiological events or transmitting the sensed physiological information or detected physiological events to one or more remote devices. In addition, the medical device may be configured to provide electrical stimulation or one or more other therapies or treatments to the patient, such as to improve cardiac function.

[0006] Frequent patient monitoring can provide early detection of worsening patient conditions, including worsening heart failure or atrial fibrillation. Accurate identification of patients or groups of patients at increased risk for future adverse events can control mode or feature selection or resource management of one or more medical devices, control notifications or messages in a connected system to various users associated with a particular patient or group of patients, organize or schedule doctor or patient contact or treatment, or prevent or reduce patient hospitalizations. Correctly identifying and safely managing the risk of worsening patient conditions can avoid unnecessary medical interventions, extend the life of medical devices, and reduce medical costs. In addition, correctly monitoring, detecting and identifying patient status (including improvement or worsening of the patient's condition) and modifying one or more medical device functions accordingly, where different operating modes, functions or therapies are available, can improve medical device efficiency, such as by reducing unnecessary resource consumption, thereby extending the life of mobile medical devices. Summary of the Invention

[0007] Systems and methods are disclosed for determining an indication of a patient's predicted response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on patient metrics determined using received physiological information of the patient, the physiological information including at least one of heart sound information or respiratory information from a first time period prior to the CRT or MSP therapy.

[0008] An example (e.g., “Example 1”) of the subject matter (e.g., a medical device system) may include a signal receiver circuit configured to receive physiological information of a patient, the physiological information including at least one of heart sound information or respiratory information; and an evaluation circuit configured to: determine a patient metric using the received physiological information from a first time period; determine an indication of a predicted response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on the determined patient metric, wherein the first time period precedes the CRT or MSP therapy; and provide an indication of the determined predicted response to a user or process.

[0009] In Example 2, the subject matter according to Example 1 can optionally include a first medical device configured to sense physiological information from a patient during a first time period; and a second implantable medical device different from the first medical device, the second implantable medical device including a stimulation circuit configured to generate a stimulation signal to be provided to the patient's heart during a second time period after the first time period, wherein the evaluation circuit is configured to determine a patient metric using the received physiological information from the first medical device.

[0010] In Example 3, the subject matter described in any one or more of Examples 1 to 2 can optionally be configured such that to determine an indication of a predictive response, the evaluation circuit is configured to compare the determined patient metric to one or more thresholds, and wherein the predictive response includes one of: an indication that the patient will respond to at least one of CRT or MSP therapy; or an indication that the patient will not respond to either CRT or MSP therapy.

[0011] In Example 4, the subject matter according to any one or more of Examples 1 to 3 can optionally be configured such that the heart sound information includes at least one of S1 or S3 information, and the respiratory information includes rapid shallow breathing index (RSBI) information.

[0012] In Example 5, the subject matter according to any one or more of Examples 1 to 4 can optionally be configured such that the evaluation circuit is configured to determine the patient metric as a function of the S3 information to the S1 information and the RSBI information.

[0013] In Example 6, the subject matter of any one or more of Examples 1 to 5 can optionally be configured such that the S3 information includes S3 amplitude or energy, and the S1 information includes S1 amplitude or energy.

[0014] In Example 7, the subject matter according to any one or more of Examples 1 to 6 can optionally be configured such that the respiratory information includes a measurement of tidal volume (TV).

[0015] In Example 8, the subject matter according to any one or more of Examples 1 to 7 can optionally be configured such that the patient's physiological information includes thoracic impedance information, and the evaluation circuit is configured to determine the patient metric as a function of the thoracic impedance information and at least one of heart sound information and respiratory information.

[0016] An example (e.g., “Example 9”) of the subject matter (e.g., a method) may include: using a signal receiver circuit to receive physiological information of a patient, the physiological information including at least one of heart sound information or respiratory information; and using an evaluation circuit to: determine a patient metric using the received physiological information from a first time period; determine an indication of a predictive response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on the determined patient metric, wherein the first time period precedes the CRT or MSP therapy; and providing an indication of the determined predictive response to a user or process.

[0017] In Example 10, the subject matter of any one or more of Examples 1 to 9 may optionally include sensing physiological information from a patient during a first time period using a first medical device, wherein using the evaluation circuit includes using a second implantable medical device different from the first medical device, the second implantable medical device including a stimulation circuit configured to generate a stimulation signal to be provided to the patient's heart during a second time period after the first time period, and wherein determining the patient metric includes using the received physiological information from the first medical device.

[0018] In Example 11, the subject matter described in any one or more of Examples 1-10 can optionally be configured such that determining an indication of a predictive response includes comparing the determined patient metric to one or more thresholds, and the predictive response includes one of: an indication that the patient will respond to at least one of CRT or MSP therapy; or an indication that the patient will not respond to either CRT or MSP therapy.

[0019] In Example 12, the subject matter according to any one or more of Examples 1 to 11 can optionally be configured such that the heart sound information includes at least one of S1 or S3 information, and the respiratory information includes rapid shallow breathing index (RSBI) information.

[0020] In Example 13, the subject matter according to any one or more of Examples 1 to 12 can optionally be configured such that determining the patient metric comprises as a function of the S3 information to the S1 information and the RSBI information.

[0021] In Example 14, the subject matter of any one or more of Examples 1 to 13 can optionally be configured such that the S3 information includes S3 amplitude or energy, and the S1 information includes S1 amplitude or energy.

[0022] In Example 15, the subject matter according to any one or more of Examples 1 to 14 can optionally be configured such that the respiratory information includes a measurement of tidal volume (TV).

[0023] In Example 16, the subject matter according to any one or more of Examples 1 to 15 can optionally be configured such that the patient's physiological information includes thoracic impedance information, and the patient measurement is included as a function of the thoracic impedance information and at least one of heart sound information and respiratory information.

[0024] An example (e.g., “Example 17”) of the subject matter (e.g., a system) may include: a device for receiving physiological information of a patient, the physiological information including at least one of heart sound information or respiratory information; and a device for determining a patient metric using the received physiological information from a first time period, determining an indication of a predictive response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on the determined patient metric, and providing the indication of the determined predictive response to a user or process, wherein the first time period precedes the CRT or MSP therapy.

[0025] In Example 18, the subject matter according to any one or more of Examples 1 to 17 can optionally be configured such that the device for receiving physiological information of a patient includes a signal receiver circuit configured to receive physiological information of the patient, the physiological information including at least one of heart sound information or respiratory information; and the device for determining a patient metric, determining an indication of a predicted response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy, and providing an indication of the determined predicted response to a user or process includes an evaluation circuit configured to use the received physiological information from a first time period to determine a patient metric, determine an indication of a predicted response to at least one of CRT or MSP therapy based on the determined patient metric, and provide an indication of the determined predicted response to a user or process.

[0026] In Example 19, the subject matter according to any one or more of Examples 1 to 18 may optionally include a first medical device and a second implantable medical device, the first medical device being configured to sense physiological information from the patient during a first time period, the second implantable medical device being distinguishable from the first medical device, the second implantable medical device including a stimulation circuit configured to generate a stimulation signal to be provided to the patient's heart during a second time period after the first time period, wherein the evaluation circuit is configured to determine a patient metric using the received physiological information from the first medical device.

[0027] In Example 20, the subject matter of any one or more of Examples 1 to 19 can optionally be configured such that the heart sound information includes at least one of S1 or S3 information, the respiratory information includes rapid shallow breathing index (RSBI) information, and the means for determining the patient metric includes means for determining the patient metric as a function of the ratio of the S3 information to the S1 information and the RSBI information.

[0028] In Example 21, the subject matter (e.g., a system or apparatus) may optionally combine any portion or combination of any portions of any one or more of Examples 1 to 20 to include a "device" or at least one "non-transitory machine-readable medium" for performing any portion of any one or more of the functions or methods of Examples 1 to 20, the non-transitory machine-readable medium including instructions that, when executed by a machine, cause the machine to perform any portion of any one or more of the functions or methods of Examples 1 to 20.

[0029] This summary is intended to provide an overview of the subject matter of this patent application. It is not intended to provide an exclusive or exhaustive explanation of the present disclosure. The detailed description is included to provide further information about this patent application. Other aspects of the present disclosure will become apparent to those skilled in the art upon reading and understanding the following detailed description and reviewing the accompanying drawings, each of which should not be construed as limiting. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In the accompanying drawings, which are not necessarily drawn to scale, similar numerals may describe similar components in different views. Similar numerals with different letter suffixes may represent different instances of similar components. By way of example and not limitation, the accompanying drawings generally illustrate various embodiments discussed in this document.

[0031] Figure 1 An example process for using determined patient parameters to control transitions between therapy modes is shown.

[0032] Figure 2 An example process is shown for determining one or more patient metrics prior to ultimately selecting or implanting a second medical device.

[0033] Figure 3A -C shows example heart sound information of a patient during a first time period after implantation of a CRT device.

[0034] Figure 4A -C shows example RSBI information for a patient during a first time period after implantation of a CRT device.

[0035] Figure 5 Determined odds ratios of physiological information associated with response to CRT are shown.

[0036] Figure 6 An exemplary implantable medical device (IMD) electrically coupled to a heart is shown.

[0037] Figure 7 An exemplary medical device system is shown.

[0038] Figure 8 An exemplary patient management system is shown.

[0039] Figure 9 A block diagram illustrating an example machine upon which any one or more of the techniques discussed herein may be executed. DETAILED DESCRIPTION

[0040] The medical device can be implanted in the patient or otherwise positioned on or around the patient to monitor patient physiological information (such as heart sound information, respiratory information (e.g., respiration rate (RR), tidal volume (TV), rapid shallow breathing index (RSBI)), impedance information (e.g., intrathoracic impedance (ITTI)), pressure information, electrocardiographic information (e.g., heart rate), physical activity information, or other physiological information or one or more other physiological parameters of the patient), or provide electrical stimulation or one or more other therapies or treatments to optimize or control the contraction of the patient's heart. For example, the medical device may include one or more implantable medical devices (IMDs), such as cardiac resynchronization therapy (CRT) devices, which are configured to receive cardiac electrical information from one or more electrodes located in, on, or near the heart (such as coupled to one or more leads and located in one or more chambers of the heart or within the vasculature of the heart near one or more chambers or otherwise attached to or in contact with the heart) and, in some examples, provide electrical stimulation to the heart.

[0041] Stimulation signals can be generated and provided to one or more chambers of the heart (e.g., often two or more of the right ventricle (RV), left ventricle (LV) (e.g., typically via the cardiac vascular system), or right atrium (RA), etc.) to improve cardiac function, such as improving coordination of contractions between different chambers of the heart (e.g., right ventricle and left ventricle, right atrium and right ventricle, etc.), or otherwise improving cardiac output or efficiency. However, different therapy modes can provide different therapies that have different power and resource requirements and different efficacy for different respective patients. Patients may use multiple therapy modalities, but not all patients receive the optimal medical device, therapy mode, or therapy setting.

[0042] Among other things, the inventors have recognized that, in certain examples, systems and methods are provided for using physiological information from a respective patient to determine which of multiple therapies may be more effective for a respective patient before providing one or more therapy modes, or before switching from a first therapy mode to a second therapy mode.

[0043] Conventional CRT involves generating and applying stimulation signals to one or more chambers of the heart to improve the coordination of contractions of the different chambers, or otherwise improve cardiac output or efficiency. CRT can include biventricular pacing of the right and left ventricles of the heart, but can also include single chamber pacing (e.g., right ventricular pacing, left ventricular pacing, etc.), sensing or pacing in one or more other chambers or combinations of chambers, etc. The timing of the stimulation signal in the cardiac cycle or relative to one or more cardiac events typically varies depending on a number of factors, including the placement of the leads or electrodes, the propagation of the stimulation signal through the tissue, the stimulation amplitude, etc.

[0044] In contrast, multi-site pacing (MSP) (or multiple site pacing) therapy generally refers to applying one or more stimulation signals to multiple electrodes (e.g., two or more) in or near a first chamber (e.g., typically the left ventricle, but in some examples also the right ventricle, right atrium, or a combination thereof) for a single cardiac cycle. During MSP therapy, the same or different stimulation signals can be applied to different electrodes in or near the first chamber at the same time, different times (e.g., delayed), or a combination thereof for a single cardiac cycle.

[0045] Some heart failure patients respond to (e.g., benefit from) MSP therapy but do not respond to CRT. Other patients do not respond either. Pacing therapy is frequently evaluated to ensure that the applied pacing therapy provides some benefit to the patient, to determine whether the pacing therapy should be adjusted, or to determine whether the pacing therapy should be switched. For example, a study titled "Usefulness of Multisite Ventricular Pacing in Nonresponders to Cardiac Resynchronization Therapy" published by Samir Saba et al. in the February 1, 2022 issue of the American Journal of Cardiology (hereinafter referred to as the "Saba Study") found that 25% to 40% of heart failure patients with myocardial dysfunction did not respond to conventional CRT at an assessment of 6 months after implantation, but also found that more than half (51.3%) of CRT non-responders at 6 months subsequently responded to 6 months of MSP therapy in the left ventricle at an assessment of 12 months after implantation. The assessment in the Saba study was based on evaluation of patient mortality, heart failure event rates, global patient assessment, and NYHA general classification of heart failure.

[0046] Although the conversion from CRT to MSP therapy in the left ventricle is physiologically largely free of complications, switching from conventional CRT to MSP therapy may provide at least some cardiac stress and also require additional resources from the implantable medical device. In some estimates, implementing MSP therapy in a device capable of both MSP therapy and CRT would reduce the estimated lifespan of the device by 11-13%. Even a single six-month evaluation of MSP therapy on an IMD would have a relatively large and often unnecessary impact on the lifespan of the IMD.

[0047] The inventors have recognized that, among other things, certain physiological information sensed from a patient over one or more time periods can be used to determine one or more MSP response metrics, and that such one or more determined MSP response metrics can be used to provide an alert or notification, or otherwise control transitions between different medical device modes (e.g., a first stimulation mode, a second stimulation mode, etc.), which in some examples includes being used to: (1) control transitions from a non-MSP therapy mode to an MSP therapy mode; (2) control transitions from an MSP therapy mode to a non-MSP therapy mode; or (3) enable or disable an MSP therapy mode.

[0048] Furthermore, the inventors have recognized that specific physiological information sensed from a patient after implementation of a stimulation mode can be used to determine an MSP response metric that is configured to determine an indication of a predicted patient response to the stimulation mode, such that in some examples, the stimulation mode can be evaluated without entering the stimulation mode. In particular, the inventors have recognized that specific physiological information or a combination of physiological information can be determined to evaluate a stimulation mode or predict a positive response of a patient to a particular stimulation mode, such as using a response to another stimulation mode, etc. In an example, physiological information sensed or detected during a CRT mode can be used to determine whether a patient is likely to respond to (e.g., benefit from) an MSP therapy mode before implementing or enabling the MSP therapy mode.

[0049] In an example, the inventors have recognized that, among other things, one or more of impedance information (e.g., ITTI) and respiratory information (e.g., RSBI) over one or more time periods (e.g., a 60-day period, a 150-day period, etc.), or a combination thereof, can be used to determine an indication that a patient will respond to an MSP therapy mode before implementing or enabling the MSP therapy mode. An example is provided below, namely, equation (1).

[0050] p(MSP response )∝(α×ITTI)+(β×RSBI)(1)

[0051] In equation (1), p(MSP response) is a patient metric (e.g., an MSP response metric), ITTI is a measure of the patient's intrathoracic impedance, RSBI is a ratio of a measure of the patient's respiratory rate (RR) or frequency to a measure of tidal volume (TV) (e.g., RR / TV, etc.), and α and β are variables. In other examples, the patient metric can be determined using only one of ITTI or RSBI information, or as a different function of one or more such physiological parameters in combination with one or more other physiological parameters. Using physiological information from a time period in a therapy mode prior to implementation of the MSP therapy mode (e.g., from within a conventional CRT mode), the inventors were able to determine a positive MSP response using equation (1) and a threshold (TH) with an area under the ROC curve of 0.8309 and a confidence interval of 95%. Once in the MSP therapy mode, the inventors were able to determine a positive MSP response using equation (1) and a threshold (TH) with an area under the ROC curve of 0.78527 and a confidence interval of 95%. Such a determination is highly sensitive.

[0052] Figure 1 An example process 100 for controlling transitions between therapy modes using determined patient parameters is shown. Based on training data, patient metrics can be determined with a true positive rate of 50% and a true negative rate of 0%. In some examples, a high sensitivity determination, such as by adjusting equation (1) or one or more thresholds, may be required before transitioning to an MSP therapy mode to conserve medical device resources and avoid unnecessary cardiac stress associated with the transition.

[0053] At step 101, for example, in some examples, a CRT mode can be implemented for the first time. Although described herein as starting with implementing the CRT mode, in other examples, the process can start with one or more other therapy modes, or with a monitoring mode without therapy. In some examples, the stimulation circuit can generate and provide one or more stimulation signals in one or more stimulation modes, and the evaluation circuit can be configured to control the stimulation circuit to, for example, adjust one or more parameters or switch between different therapy modes.

[0054] At step 102, physiological information may be received from one or more sensors, such as using a signal receiver circuit. The received physiological information may include, but is not limited to, patient ITTI information, patient RSBI information, or one or more other types of patient information, such as described herein.

[0055] At step 103 , patient metrics (such as one or more MSP response metrics) may be determined based on the received physiological information, such as described with respect to equation (1) or otherwise described herein, in some examples using an evaluation circuit.

[0056] At step 104, the determined patient metric can be compared to a threshold value (TH), such as using an evaluation circuit. If the determined patient metric exceeds the threshold value, then at step 105, an MSP therapy mode can be implemented (e.g., switching from a CRT mode to an MSP therapy mode), and the process can return to step 102. In other examples, rather than implementing an MSP therapy mode, an indication can be provided to implement the MSP therapy mode, such as providing the indication to a clinician or one or more other machines or processes via a notification or alert. If the determined patient metric does not exceed the threshold value, then at step 106, the MSP therapy mode can remain off, and the process can return to step 101.

[0057] Regarding the above Figure 1 Unlike the description, the inventors have additionally recognized that certain physiological information sensed from a patient over one or more time periods can be used to determine one or more CRT response metrics, and that such one or more determined CRT response metrics can be used to provide alerts or notifications, or otherwise control transitions between different medical device modes, including, in some examples, for: (1) controlling a transition from a CRT mode to a non-CRT mode; (2) controlling a transition from a CRT mode to an MSP therapy mode; or (3) enabling or disabling a CRT mode. In some examples, the alert itself is a notification that a determination has been made, which obtains information from multiple sensors or sources and arrives at the determination.

[0058] In an example, the inventors have recognized that CRT responders and non-responders can be distinguished using, among other things, differences in patient physiological information, which includes one or more of: heart sound information (e.g., first heart sound (S1) information, third heart sound (S3) information, etc.), ITTI information, activity level information, respiratory rate information, RSBI information, or a permutation or combination thereof.

[0059] In some examples, prior to implanting a second medical device (e.g., an implantable medical device) capable of or configured to provide one or both of CRT and MSP therapy, a first medical device (such as one or more wearable or ambulatory medical devices) may be used to sense physiological information from a patient to assess whether the patient is likely to be a responder to one or both of CRT or MSP therapy. The first medical device may sense or collect physiological information of the patient from one or more sensors in the first or one or more other medical devices. Prior to implanting the second medical device, the sensed or collected physiological information of the patient may be analyzed to determine a recommended type of second medical device (e.g., a device having a therapy mode that is consistent with the determined CRT response metric), determine recommended settings (such as a therapy mode or parameters based on the analyzed physiological information, etc.).

[0060] As described above with respect to the Saba study, the current process for determining whether a CRT device is to be implanted is based on the patient's condition (e.g., diagnosis of heart failure with myocardial dysfunction, etc.), which results in 25% to 40% of CRT non-responders. Even for non-responders, there is monitoring value in having an implanted CRT device because the CRT device will detect the patient's physiological information, determine the patient's status, and in some examples provide one or more other non-CRT functions (e.g., atrial or ventricular backup pacing, defibrillator function, etc.). Although half of CRT non-responders respond to MSP therapy, this still results in 12% to 30% of patients undergoing a CRT device implantation procedure who are unresponsive to CRT or MSP therapy. In addition, even switching to an MSP therapy mode results in additional use of CRT device resources that could otherwise be used to perform or extend the life of one or more other device functions. It is important to make a determination as to whether switching to MSP is worth the resource use (even in non-CRT responders).

[0061] Using a first medical device to determine one or both of a CRT response metric or an MSP response metric prior to implanting a second medical device can assist in selecting or providing one or more alerts or notifications indicating a recommended second medical device, which in some examples can reduce unnecessary lead placements, simplify the implantation procedure, or even omit the implantation procedure of the second medical device altogether.

[0062] Figure 2 An example process 200 for determining one or more patient metrics prior to ultimately selecting or implanting a second medical device is shown. In some examples, the one or more determined patient metrics can be used to select or determine a specific device for implantation, a specific modality or therapy to be applied by a specific device, or even to omit implantation entirely.

[0063] At step 201, a first medical device, such as a wearable medical device (e.g., a patch-based medical device configured to be worn during an assessment period, etc.), can be used to receive physiological information of a patient from one or more sensors during a first time period, in some examples, by using a signal receiver circuit. In some examples, the one or more sensors can include sensors of the first medical device. In other examples, the first medical device can receive information from one or more sensors external to the first medical device. The received physiological information can include one or more of the following: heart sound information (e.g., S1, S3, etc.), ITTI information, activity level information, respiratory rate information, RSBI information, or permutations or combinations thereof.

[0064] At step 202, patient metrics (such as one or more CRT or MSP response metrics) available for use with respect to a second medical device can be determined based on the received physiological information (such as described above), in some examples, by using an evaluation circuit. One or more determined patient metrics can be compared to one or more thresholds, in some examples, as a combined metric or a combination of physiological information and a threshold, as a comparison of a single metric to a specific threshold, or a combination or permutation thereof. The one or more determined patient metrics can be used to determine whether a particular second medical device should be implanted in the patient, and if so, which mode should be implemented in the second medical device.

[0065] At step 203, the determined patient metric can be compared to a first threshold value (TH1), such as using an evaluation circuit. If the determined patient metric does not exceed the first threshold value, then at step 204, the second medical device associated with the determined patient metric is not recommended (e.g., via an alert, notification, etc.). If the determined patient metric does exceed the first threshold value, then the second medical device associated with the determined patient metric (e.g., a device having or capable of providing a CRT mode, etc.) is recommended (e.g., via an alert, notification, etc.), and the process can continue to step 205 to additionally determine whether a specific mode (e.g., an MSP therapy mode) should be implemented on the second medical device.

[0066] At step 205, the determined patient metric can be compared to a second threshold value (TH2), such as by using an evaluation circuit. If the determined patient metric does not exceed the second threshold value, then at step 206, a second medical device associated with the determined patient metric (e.g., having or capable of providing a CRT mode, etc.) is recommended (e.g., via an alert, notification, etc.). If the determined patient metric does exceed the second threshold value, then a second medical device associated with the determined patient metric (e.g., having or capable of providing a CRT mode, etc.) is recommended, and a specific mode (e.g., MSP therapy mode) is activated at step 207.

[0067] In some examples, once determined, one or more recommendations can be provided to one or more other machines or processes, or one or more alerts can be provided to a clinician or user indicating that a recommendation (resulting from processing different data from different sensors or sources) has been determined, including an indication of a final recommendation.

[0068] For example, if the CRT response metric indicates a likely responder, the second medical device may be determined or selected as a device capable of CRT or having a CRT mode, and an indication may be determined to implant the second medical device with the CRT mode turned on, in some examples, at an initially suggested setting determined using information from the first medical device. If the CRT response metric indicates a likely non-responder (e.g., a CRT response metric below a threshold), and the MSP response metric indicates a likely responder, the second medical device may be determined or selected as a device capable of MSP therapy or having an MSP therapy mode, and an indication may be provided to implant the second medical device with the MSP therapy mode turned on, in some examples, at an initially suggested or recommended setting determined using information from the first medical device.

[0069] In examples, rather than the example patch or wearable device being the first medical device, in other examples the first medical device may include a second medical device that is only partially implanted, or in a pocket (e.g., implanted subcutaneously in the patient's chest, etc.) where the pocket is not closed during the first time period of information collection to leave the position open for different lead placements, etc. Alternatively, the second medical device may be implanted and used during the first time period before a decision is made to implement CRT or MSP therapy in the patient using the second medical device, such that the second medical device can be used as a data collection and analysis device before providing one or more therapies or implementing CRT or MSP therapy, etc.

[0070] To determine one or more patient metrics, different physiological information is analyzed over a first time period or one or more other time periods (e.g., longer or shorter than the first time period). For example, heart sound information (e.g., S3 / S1, etc.) and RSBI information are analyzed over a first time period (e.g., 60 days after implantation of the second medical device, etc.). In addition, ITTI information and RSBI information are analyzed over a second time period (e.g., 150 days after implantation, which includes the first time period, etc.). The above equation (1) can be used to determine whether a patient is likely to respond to an MSP therapy mode using one or both of the ITTI information and the RSBI information. In an example, the inventors have recognized that heart sound information (in some examples, particularly S3 / S1) is particularly well correlated with determining whether a patient is likely to respond to a CRT mode (or a CRT mode or an MSP therapy mode) compared to non-responders (e.g., there is a difference in heart sound information between responders and non-responders). The inventors also recognized that RSBI information is also well correlated. In an example, the CRT response metric may be determined using one or both of heart sound information (such as S3 / S1, etc.) and RSBI information, and in some examples, may also be determined in combination with one or more other parameters. An example is provided below, namely equation (2).

[0071] p(CRT response )∝(α×(S3 / S1))+(β×RSBI)(2)

[0072] In equation (2), p(CRT response ) is a patient metric (e.g., a CRT response metric), S3 is a third heart sound parameter (e.g., the amplitude or power of the third heart sound, etc.), S1 is a first heart sound parameter (e.g., the amplitude or power of the first heart sound, etc.), RSBI is a ratio of a measure of the patient's respiratory rate (RR) or frequency to a measure of tidal volume (e.g., RR / TV, etc.), and α and β are variables. In other examples, the patient metric can be determined using a combination of this or other heart sound information (e.g., in addition to S3 / S1, etc.), using only one of the heart sound or RSBI information, using information over different time periods (e.g., a 60-day period, a 150-day period, etc.), or as a different function of one or more such physiological parameters in combination with one or more other physiological parameters.

[0073] For example, a relatively high S3 / S1 ratio may indicate that the patient is likely to be a responder to CRT or MSP therapy. However, a relatively low S3 / S1 ratio may be combined with other information (such as one or more parameters from equation (1) above) to determine whether the patient is likely to be a responder to MSP therapy (rather than CRT). Relatively high and low ratios may be proportional to individual measurements or may be determined by comparing data from responders and non-responders. In some examples, individual parameters may include differences, such as indicating the change or variance of daily values ​​over a period of time.

[0074] Figure 3A -C shows example heart sound information 300 (eg, S3 / S1 ) of a patient within a first time period (eg, 60 days) after implantation of a CRT device. Figure 3A Example heart sound information is shown for initial responders to CRT (labeled "C"), subsequent responders to MSP therapy (labeled "M"), and non-responders to CRT and MSP therapy (labeled "N"). Figure 3B Example heart sound information is shown for initial responders (labeled "C") and others (labeled "O") (eg, including subsequent responders to MSP therapy, non-responders, etc.). Figure 3C Example heart sound information is shown for subsequent responders to MSP therapy (marked "M") and subsequent non-responders to MSP therapy (marked "X"). Each shown example also includes an average representation of the corresponding information, as shown by the wider filled line (marked "A").

[0075] In some examples, as described above, heart sound information may be particularly suitable for distinguishing initial responders from non-responders to CRT, or distinguishing initial responders to CRT from other patients (e.g., subsequent responders to MSP therapy or non-responders to CRT and MSP therapy, etc.).

[0076] Figure 4A -C shows example RSBI information 400 for a patient during a first time period (eg, 60 days) after implantation of a CRT device. Figure 4A Example RSBI information is shown for initial responders to CRT (labeled "C"), subsequent responders to MSP therapy (labeled "M"), and non-responders to CRT and MSP therapy (labeled "N"). Figure 4B Example RSBI information is shown for initial responders (labeled "C") and others (labeled "O") (eg, including subsequent responders to MSP therapy, non-responders, etc.). Figure 4C Example RSBI information is shown for subsequent responders to MSP therapy (labeled "M") and subsequent non-responders to MSP therapy (labeled "X"). Each illustrated example also includes an average representation of the corresponding information, as shown by the wider fill line (labeled "A").

[0077] In certain examples, as described above, RSBI information may be particularly suitable for distinguishing initial responders to CRT from other patients (e.g., subsequent responders to MSP or non-responders to both CRT and MSP therapies, etc.), distinguishing subsequent responders to MSP from other patients (e.g., initial responders to CRT or non-responders to both CRT and MSP therapies, etc.), or distinguishing subsequent responders to MSP therapy from subsequent non-responders to MSP therapy.

[0078] In other examples, one or more other patient metrics may be determined using sensed or received patient physiological information, or frequently a combination of sensed or received patient physiological information. The inventors contemplate a variety of different physiological information for determining patient response metrics, including heart sound information (particularly S1 and S3 information), ITTI information, respiratory rate information, RSBI information, nighttime heart rate information, activity information, and a multi-sensor HeartLogic Index.

[0079] The HeartLogic Index is a composite heart failure risk indicator determined using a combination of different physiological information, including heart sound information (including S1 and S3), respiratory rate and volume information, ITTI information, heart rate information (e.g., particularly the patient's nighttime heart rate determined between midnight and 6 a.m.), and the patient's daily activity information (e.g., the number of hours per day above an activity threshold).

[0080] From a randomly selected 60% developmental patient set (183 CRT responders and 40 CRT non-responders), based on the first 150-day period after implantation of the cardiac rhythm therapy device, the following statistical measures were calculated for each parameter: overall mean (μ150), mean of the first 30 days (μF30) or last 30 days (μL30) of the period, and standard deviation (σ150). To assess the effect of each measure on response or non-response, odds ratios were calculated and tested for significance. Based on the initial univariate analysis, measures with p-values ​​<0.15 were subsequently included in the multivariate logistic regression model and backward elimination was performed to achieve p <0.05 for the remaining variables.

[0081] In univariate models, increases in the 150-day variability (σ150) of S3, S3 / S1 ratio, RSBI, respiratory rate, and HeartLogic Index were significantly associated with a decreased odds of a positive response to CRT. Similarly, increases in the mean RSBI, respiratory rate, and HeartLogic Index were significantly associated with a decreased odds of a positive response to CRT. Multiple device-based physiological parameters differed significantly between CRT responders and non-responders. Respiratory rate variability and daily activities remained significant in multivariate analysis.

[0082] Thus, the inventors unexpectedly recognized that respiratory variability information (e.g., respiratory rate variability (e.g., 1 BPM changes), etc.) and daily activity information (e.g., the amount of time that patient activity exceeds a threshold, the number of hours that patient activity exceeds a threshold, etc.) are strong indicators of CRT response or non-response. In some examples, patient metrics can be determined using one or more of the respiratory variability information or daily activity information to identify patients who may respond to one or both of CRT or MSP therapy, identify patients who may benefit from switching from CRT to MSP therapy, and in some examples distinguish between MSP therapy responders and non-responders once MSP therapy is provided. The evaluation circuitry can be configured to provide one or more alerts, make one or more recommendations, or provide one or more control signals to control the generation or delivery of one or more stimulation signals, or the implementation of one or more different stimulation modes.

[0083] Figure 5Determined odds ratios 500 for physiological information associated with CRT response are shown, with 95% confidence intervals for each 1 unit or standard deviation change. An odds ratio of 1 has no effect on the outcome. In contrast, odds ratios further away from 1 indicate a greater effect on the outcome, with odds ratios greater than 1 associated with a higher odds of the outcome and odds ratios less than 1 associated with a lower odds of the outcome. The different odds are marked on a line centered on a diamond, with patterned odds indicating significant values ​​compared to unpatterned odds. The multivariate model started with measures with p-values ​​< 15 in the univariate analysis and was simplified using backward elimination to identify the most significant indicators. Although respiratory variability and daily activities are the most significant, other physiological information is still of great value, including heart sound information (e.g., S3, S3 / S1, etc.), RSBI information, and in some examples, the HeartLogic Index.

[0084] In an example, a patient metric can be determined using patient physiological information (such as one or more of respiratory variability information or daily activity information, or in some examples, heart sound information, RSBI information, or a combination or permutation thereof). In some examples, the determined patient metric can indicate the need for CRT, MSP therapy, or a combination thereof, or indicate that the patient is likely to be a responder or non-responder to CRT or MSP therapy. In other examples, the determined patient metric can be used to control transitions between therapy modes, such as transitioning to, between, or out of one or more of a CRT mode and an MSP therapy mode.

[0085] The following features were found to be associated with CRT response and were identified as the most significant indicators, as described above: HeartLogic Index (e.g., HeartLogic Index rough pattern, number of days that HeartLogic Index exceeded the group mean); ITTI (e.g., ITTI maximum real FFT (Fast Fourier Transform); respiratory rate (e.g., RR standard deviation); activity (e.g., change in activity from the first 30 days to the last 30 days of the assessment period); etc.

[0086] The following features were found to be associated with subsequent responders to MSP therapy and were identified as the most significant indicators, as described above: ITTI (e.g., ITTI coarse pattern, number of days that ITTI exceeded the group mean), RSBI (e.g., RSBI power spectral density (PSD) peak width, number of days that RSBI exceeded the group mean), etc. In other examples, other significant features may include: RR (e.g., RR FFT image maximum, RR mean, RR mean over the past 30 days (the last 30 days of the assessment period)), S3 (e.g., late S3 mean), RSBI (e.g., RSBI mean for the 30 days before switching from CRT to MSP therapy, RSBI mean for the last 30 days), ITTI (e.g., ITTI standard deviation), HR (e.g., HR delta), etc.

[0087] Respiration and intrathoracic impedance drive the prediction of CRT and subsequent MSP response. HeartLogic and activity level were also useful in predicting initial CRT response. RSBI was found to be more influential in determining the MSP response metric compared to RR. Therefore, regarding MSP response, tidal volume (TV) may be a driving factor in determining the MSP response metric.

[0088] Figure 6 An implantable medical device (IMD) 600 is shown electrically coupled to a heart 605, such as via one or more leads coupled to the IMD 600 via one or more lead ports, such as first, second, or third lead ports 641, 642, 643 in a header 602 of the IMD 600. In an example, the IMD 600 may include an antenna (such as in the header 602) configured to enable communication with an external system and one or more electronic circuits (e.g., evaluation circuitry, etc.) in a hermetically sealed housing (CAN) 601.

[0089] IMD 600 may include an implantable medical device (IMD), such as an implantable cardiac monitor (ICM), a pacemaker, a defibrillator, a cardiac resynchronizer, or other subcutaneous IMD or cardiac rhythm management (CRM) device, configured to be implanted in the chest of a subject, having one or more leads for positioning one or more electrodes or other sensors at various locations in or near the heart 605 (such as one or more of the atria or ventricles). Separately from or in addition to the one or more electrodes or other sensors of the leads, IMD 600 may include one or more electrodes or other sensors (e.g., a pressure sensor, an accelerometer, a gyroscope, a microphone, etc.) powered by a power source in IMD 600. The one or more electrodes or other sensors of the leads, IMD 600, or a combination thereof may be configured to detect physiological information from the patient or to provide one or more therapies or stimuli to the patient.

[0090] IMD 600 can include one or more electronic circuits configured to sense one or more physiological signals (such as electrograms or signals representing the mechanical function of heart 605). In some examples, CAN 601 can be used as an electrode, such as for sensing or pulse delivery. For example, electrodes from one or more leads can be used with CAN 601, such as for unipolar sensing of an electrogram or for delivering one or more pacing pulses. Defibrillation electrodes (e.g., first defibrillation coil electrode 628, second defibrillation coil electrode 629, etc.) can be used with CAN 601 to deliver one or more cardioversion / defibrillation pulses.

[0091] In an example, the IMD 600 can sense impedance between electrodes, such as those located on one or more leads or the CAN 601. The IMD 600 can be configured to inject current between a pair of electrodes, sense a resultant voltage between the same or different electrode pairs, and determine impedance, such as using Ohm's law. Impedance can be sensed in a bipolar configuration (in which the same electrode pair can be used for injecting current and sensing voltage), a tripolar configuration (in which the electrode pair used for current injection and the electrode pair used for voltage sensing can share a common electrode), or a quadrupole configuration (in which the electrode used for current injection can be different from the electrode used for voltage sensing), etc. In an example, the IMD 600 can be configured to inject current between an electrode on one or more of the first, second, third, or fourth leads 620, 625, 630, 635 and the CAN 601, and sense a resultant voltage between the same or different electrode and the CAN 601.

[0092] Figure 6An exemplary lead configuration in includes first, second, and third leads 620, 625, 630 in conventional lead placement in the coronary vein 616 (e.g., the coronary sinus) over the right atrium (RA) 606, right ventricle (RV) 607, left atrium (LA) 608, and left ventricle (LV) 609, respectively, and a fourth lead 635 positioned near the bundle of His 611 in the RV 607 between the AV node 610 and the left and right bundle branches 612, 613, and the Purkinje fibers 614, 615. Each lead can be configured to position one or more electrodes or other sensors at various locations in or near the heart 605 to detect physiological information or provide one or more therapies or stimulations.

[0093] A first lead 620, positioned in the RA 606, includes a first tip electrode 621 located at or near the distal end of the first lead 620 and a first ring electrode 622 located near the first tip electrode 621. A second lead 625 (dashed line), positioned in the RV 607, includes a second tip electrode 626 located at or near the distal end of the second lead 625 and a second ring electrode 627 located near the second tip electrode 626. A third lead 630, positioned in the coronary vein 616 above the LV 609, includes a third tip electrode 631 located at or near the distal end of the third lead 630, a third ring electrode 632 located near the third tip electrode 631, and two additional electrodes 633 and 634. A fourth lead 635, positioned near the His bundle 611 in the RV 607, includes a fourth tip electrode 636 located at or near the distal end of the fourth lead 635 and a fourth ring electrode 637 located near the fourth tip electrode 636. The tip and ring electrodes may include pace / sense electrodes configured to sense electrical activity or provide pacing stimulation.

[0094] In addition to the tip and ring electrodes, one or more leads may also include one or more defibrillation coil electrodes configured to sense electrical activity or deliver cardioversion or defibrillation shock energy. For example, the second lead 625 includes a first defibrillation coil electrode 628 located near the distal end of the second lead 625 in the RV 607 and a second defibrillation coil electrode 629 located a distance from the distal end of the second lead 625, such as where the electrode is placed in or near the superior vena cava (SVC) 617.

[0095] Different CRM devices include different numbers of leads and lead placements. For example, some CRM devices are single-lead devices with one lead (e.g., RV only, RA only, etc.). Other CRM devices are multi-lead devices with two or more leads (e.g., RA and RV; RV and LV; RA, RV, and LV, etc.). CRM devices suitable for His bundle pacing typically use a lead port designated for the LV or RV lead to deliver stimulation to the His bundle 611.

[0096] Figure 7 An example system 700 (e.g., a medical device system) is shown. In an example, one or more aspects of the example system 700 can be a component of, or communicatively coupled to, a medical device (such as an implantable medical device (IMD)), an insertable cardiac monitor, an ambulatory medical device (AMD), or the like. The system 700 can be configured to monitor, detect, or treat various physiological conditions of the body, such as cardiac conditions associated with a reduced ability of the heart to adequately deliver blood to the body, including heart failure, arrhythmias, cardiac dyssynchrony, or one or more other physiological conditions, and in some examples, can be configured to provide electrical stimulation or one or more other therapies or treatments to a patient.

[0097] System 700 may include a single medical device or multiple medical devices implanted in or otherwise positioned on or about a patient to monitor patient physiological information of the patient using one or more sensors, such as sensor 701 . In an example, sensor 701 may include one or more of the following: a respiratory sensor configured to receive respiratory information (e.g., respiratory rate, respiratory volume (tidal volume), etc.); an acceleration sensor (e.g., accelerometer, microphone, etc.) configured to receive cardiac acceleration information (e.g., cardiac vibration information, pressure waveform information, heart sound information, endocardial acceleration information, acceleration information, activity information, body position information, etc.); an impedance sensor (e.g., intrathoracic impedance sensor, transthoracic impedance sensor, thoracic impedance sensor, etc.) configured to receive impedance information; a cardiac sensor configured to receive cardiac electrical information; an activity sensor configured to receive information about body movement (e.g., activity, steps, etc.); a body position sensor configured to receive body position or location information; a pressure sensor configured to receive pressure information; a volume flowmeter sensor (e.g., photoplethysmography sensor, etc.); a chemical sensor (e.g., electrolyte sensor, pH sensor, anion gap sensor, etc.); a temperature sensor; a skin elasticity sensor; or one or more other sensors configured to receive physiological information of the patient.

[0098] The example system 700 may include a signal receiver circuit 702 and an evaluation circuit 703. The signal receiver circuit 702 may be configured to receive physiological information of a patient (or group of patients) from the sensor 701. The evaluation circuit 703 may be configured to receive information from the signal receiver circuit 702 and use the received physiological information to determine one or more parameters (e.g., physiological parameters, stratification factors, etc.) or an indication of an existing or changing patient condition (e.g., an indication of patient dehydration, respiratory condition, cardiac condition (e.g., heart failure, arrhythmia), sleep-disordered breathing, etc.), such as described herein. The physiological information may include, among other things, cardiac electrical information, impedance information, respiratory information, heart sound information, activity information, body position information, temperature information, or one or more other types of physiological information.

[0099] In some examples, the evaluation circuit 703 can aggregate information from multiple sensors or devices, use the information from each sensor or device, individually or in combination, to detect various events, update a detection status for one or more patients based on the information, and transmit a message or alert to one or more remote devices that a detection has been performed on one or more patients or that information has been stored or transmitted so that one or more additional processes or systems can use the stored or transmitted detection or information for one or more other examinations or processes.

[0100] In some examples, such as to detect improvement or deterioration of a patient's condition, some initial assessment is typically required to establish a baseline level or condition based on one or more sensors or physiological information. Subsequent detection of deviations from the baseline level or condition can be used to determine improvement or deterioration of the patient's condition. However, in other examples, the amount of deviation or change (e.g., relative or absolute change) in physiological information over different time periods can be used to determine the risk of an adverse medical event, or to predict or stratify the risk of a patient experiencing an adverse medical event (e.g., a heart failure event) over a period of time following the detected change, either in combination with or separately from any baseline level or condition.

[0101] Variations in different physiological information can be aggregated and weighted based on one or more patient-specific stratifiers and, in some examples, compared to one or more thresholds, for example, to have clinical sensitivity and specificity for a particular condition (such as heart failure) across a target population, and for one or more specific time periods, such as daily values, short-term averages (e.g., daily values ​​aggregated over several days), long-term averages (e.g., daily values ​​aggregated over multiple short-term time periods or more days (sometimes different (e.g., non-overlapping) days than used for short-term averages), etc.

[0102] The evaluation circuit 703 can be configured to provide an output to a user, such as to a display or one or more other user interfaces, including a score, trend, alert, or other indication. In other examples, the evaluation circuit 703 can be configured to provide an output to another circuit, machine, or process, such as a therapy circuit 704 (e.g., a cardiac resynchronization therapy (CRT) circuit, a chemotherapy circuit, a stimulation circuit, etc.) to control, adjust, or stop a therapy of a medical device, a drug delivery system, etc., or otherwise change one or more processes or functions of one or more other aspects of a medical device system, such as one or more CRT parameters, drug delivery, dose determination or recommendations, etc. In an example, the therapy circuit 704 can include one or more of a stimulation control circuit, a cardiac stimulation circuit, a neural stimulation circuit, a dose determination or control circuit, etc. In other examples, the therapy circuit 704 can be controlled by the evaluation circuit 703 or one or more other circuits, etc.

[0103] A technical problem exists in medical devices and medical device systems whereby ambulatory medical devices (e.g., including IMDs) powered by one or more rechargeable or non-rechargeable batteries must balance battery life, or in the case of implantable medical devices with non-rechargeable batteries, device replacement periods, typically including surgical procedures, with the sampling resolution, sampling period, or feature or mode selection of or within the medical device for processing, storage, and transmission of sensed physiological information in a low-power monitoring mode. A medical device may include a higher power mode and a lower power mode. Physiological information (e.g., indicating a potential adverse physiological event) may be used to transition from a low-power mode to a high-power mode. In some examples, a low-power mode may include a low-resource mode characterized by requiring less power, processing time, memory, communication time, or bandwidth (e.g., transmitting less data, etc.) than a corresponding high-power mode. A high-power mode may include a relatively high-resource mode characterized by requiring more power, processing time, memory, communication time, or bandwidth than a corresponding low-power mode. However, when physiological information detected in low-power mode indicates a possible event, valuable information may have been lost and cannot be recorded in high-power mode.

[0104] Vice versa, an erroneous or inaccurate determination of triggering a high-power mode can unnecessarily and inappropriately limit the useful life of certain ambulatory medical devices. Accurately detecting and determining physiological events to avoid unnecessary transitions from low-power to high-power modes and thereby improve utilization of medical device resources is advantageous for a variety of reasons.

[0105] Figure 8An exemplary patient management system 800 and a portion of an environment in which the patient management system 800 can operate are shown. The patient management system 800 can perform a range of activities, including remote patient monitoring and disease condition diagnosis. Such activities can be performed close to the patient 801, such as in the patient's home or office, through a central server, such as in a hospital, clinic, or doctor's office, or through a remote workstation, such as a secure wireless mobile computing device.

[0106] The patient management system 800 may include one or more medical devices, an external system 805, and a communication link 811 that provides for communication between the one or more ambulatory medical devices and the external system 805. The one or more medical devices may include an ambulatory medical device (AMD) (such as an implantable medical device (IMD) 802), a wearable medical device 803, or one or more other implantable, leadless, subcutaneous, external, wearable, or medical devices configured to monitor, sense, or detect information from the patient 801, determine physiological information about the patient 801, or provide one or more therapies to treat various conditions of the patient 801, such as one or more cardiac or non-cardiac conditions (e.g., dehydration, sleep-disordered breathing, etc.).

[0107] In an example, the implantable medical device 802 may include one or more cardiac rhythm management devices implanted in the chest of a patient, having a lead system including one or more transvenous, subcutaneous, or non-invasive leads or catheters to position one or more electrodes or other sensors (e.g., heart sound sensors) in, on, or around the heart, or at one or more other locations in the chest, abdomen, or neck of the patient 801. In another example, the implantable medical device 802 may include a monitor implanted, for example, subcutaneously in the chest of the patient 801, the implantable medical device 802 including a housing containing circuitry and, in some examples, one or more sensors, such as a temperature sensor or the like.

[0108] A cardiac rhythm management device (such as an insertable cardiac monitor, pacemaker, defibrillator, or cardiac resynchronizer) includes an implantable or subcutaneous device having an airtight sealed housing configured to be implanted in the chest of a patient. The cardiac rhythm management device may include one or more leads to position one or more electrodes or other sensors at various locations in or near the heart, such as one or more locations in the atria or ventricles of the heart, etc. Thus, the cardiac rhythm management device may include aspects that are located subcutaneously, although near the distal skin of the patient, and aspects that are located near one or more organs of the patient, such as leads or electrodes. Separately from or in addition to the one or more electrodes or other sensors of the lead, the cardiac rhythm management device may include one or more electrodes or other sensors (e.g., pressure sensors, accelerometers, gyroscopes, microphones, etc.) powered by a power supply in the cardiac rhythm management device. The one or more electrodes or other sensors of the lead, the cardiac rhythm management device, or a combination thereof may be configured to detect physiological information from the patient, or to provide one or more therapies or stimulations to the patient.

[0109] Implantable devices may additionally or solely include a leadless cardiac pacemaker (LCP), which is a small (e.g., smaller than a conventional implantable cardiac rhythm management device, having a volume of approximately 1 cc in some examples, etc.) self-contained device that includes one or more sensors, circuits, or electrodes configured to monitor physiological information from the heart (e.g., heart rate, etc.), detect physiological conditions associated with the heart (e.g., tachycardia), or deliver one or more therapies or stimulation to the heart without the complications associated with conventional leads or implantable cardiac rhythm management devices (e.g., required incisions and pockets, complications associated with lead placement, breakage, or migration, etc.). In some examples, leadless cardiac pacemakers may have more limited power and processing capabilities than conventional cardiac rhythm management devices; however, multiple leadless cardiac pacemakers can be implanted in or around the heart to detect physiological information from one or more chambers of the heart or deliver one or more therapies or stimulation to one or more chambers of the heart. Multiple leadless cardiac pacemakers can communicate with each other or with one or more other implanted devices or external devices.

[0110] The implantable medical device 802 may include an evaluation circuit configured to detect or determine specific physiological information of the patient 801, or to determine one or more conditions, or to provide information or alerts to a user (such as the patient 801 (e.g., a patient), a clinician, or one or more other caregivers or processes), such as described herein. The implantable medical device 802 may alternatively or additionally be configured as a therapy device configured to treat one or more medical conditions of the patient 801. The therapy may be delivered to the patient 801 via a lead system and associated electrodes or using one or more other delivery mechanisms. The therapy may include delivering one or more drugs to the patient 801, such as using the implantable medical device 802 or one or more other ambulatory medical devices. In some examples, the therapy may include CRT to correct dyssynchrony and improve cardiac function in patients with heart failure. In other examples, the implantable medical device 802 may include a drug delivery system, such as a drug infusion pump, for delivering drugs to the patient for the management of arrhythmias or complications caused by arrhythmias, hypertension, hypotension, or one or more other physiological conditions. In other examples, implantable medical device 802 may include one or more electrodes configured to stimulate the patient's nervous system or provide stimulation to muscles of the patient's airway, etc.

[0111] Wearable medical device 803 may include one or more wearable or external medical sensors or devices (e.g., an automated external defibrillator (AED), a Holter monitor, a patch-based device, a smart watch, a smart accessory, a wrist-worn or finger-worn medical device such as a finger-based photoplethysmography sensor, etc.).

[0112] The external system 805 may include a dedicated hardware / software system, such as a programmer, a remote server-based patient management system, or alternatively, a system primarily defined by software running on a standard personal computer. The external system 805 may manage the patient 801 through the implantable medical device 802 or one or more other ambulatory medical devices connected to the external system 805 via a communication link 811. In other examples, the implantable medical device 802 may be connected to the wearable medical device 803, or the wearable medical device 803 may be connected to the external system 805 via the communication link 811. For example, this may include programming the implantable medical device 802 to perform one or more of collecting physiological data, performing at least one self-diagnostic test (such as a self-diagnostic test for the device's operating status), analyzing physiological data, or optionally delivering or adjusting therapy for the patient 801. In addition, the external system 805 may send information to or receive information from the implantable medical device 802 or the wearable medical device 803 via the communication link 811. Examples of information may include real-time or stored physiological data from patient 801, diagnostic data (such as monitoring of the patient's hydration status, hospitalization status, response to therapy delivered to patient 801), or device operating status (e.g., battery status, lead impedance, etc.) of implantable medical device 802 or wearable medical device 803. Communication link 811 may be an inductive telemetry link, a capacitive telemetry link, or a radio-frequency (RF) telemetry link, or wireless telemetry based on, for example, "strong" Bluetooth or IEEE 602.11 Wireless Fidelity (Wi-Fi) interface standards. Other configurations and combinations of patient data source interfaces are possible.

[0113] External system 805 may include an external device 806 located near one or more mobile medical devices and a remote device 808 located relatively remote from the one or more mobile medical devices, communicating with external device 806 via a communication network 807. Examples of external device 806 may include a medical device programmer. Among other possible functions, remote device 808 may be configured to evaluate collected patient or patient information and provide alert notifications. In an example, remote device 808 may include a centralized server that serves as a central hub for storing and analyzing data collected from multiple different sources. The combination of information from multiple sources may be used to make determinations and update individual patient statuses, or to adjust one or more alerts or determinations for one or more other patients. The server may be configured as a single, multiple, or distributed computing and processing system. Remote device 808 may receive data from multiple patients. Data may be collected by one or more mobile medical devices in addition to other data collection sensors or devices associated with patient 801. The server may include a memory device to store the data in a patient database. The server may include alert analyzer circuitry to evaluate the collected data to determine whether specific alert conditions have been met. The satisfaction of an alert condition may trigger the generation of an alert notification, such as an alert notification to be provided by one or more human-perceivable user interfaces. In some examples, the alert condition may alternatively or additionally be evaluated by one or more mobile medical devices, such as implantable medical devices. For example, the alert notification may include a web page update, a phone call or pager, an email, SMS, a text or "instant" message, and a message to the patient and a direct notification to emergency services and clinicians simultaneously. Other alert notifications are possible. The server may include an alert prioritizer circuit configured to prioritize the alert notifications. For example, alerts for a detected medical event may be prioritized using a similarity metric between physiological data associated with the detected medical event and physiological data associated with historical alerts.

[0114] In addition, the remote device 808 may include one or more locally configured clients or remote clients securely connected to the server via the communication network 807. Examples of clients may include personal desktop computers, laptop computers, mobile devices, or other computing devices. System users (such as clinicians or other qualified medical experts) can use the client to securely access stored patient data compiled in a database in the server and select and prioritize patients and alerts for health care provision. In addition to generating alert notifications, the remote device 808 (including the server and interconnected clients) can also execute a follow-up plan by sending a follow-up request to one or more mobile medical devices, or by sending a message or other communication as a compliance notification to the patient 801 (e.g., the patient), the clinician, or an authorized third party.

[0115] The communication network 807 can provide wired or wireless interconnectivity. In an example, the communication network 807 can be based on the Transmission Control Protocol / Internet Protocol (TCP / IP) network communication specification, although other types or combinations of networking implementations are also possible. Similarly, other network topologies and arrangements are also possible.

[0116] One or more of the external device 806 or the remote device 808 can output the detected medical event to a system user (such as a patient or clinician) or to a process (e.g., including an instance of a computer program executable in a microprocessor). In an example, the process can include the automatic generation of a recommendation for anti-arrhythmic therapy or a recommendation for further diagnostic testing or treatment. In an example, the external device 806 or the remote device 808 can include a corresponding display unit for displaying physiological signals or functional signals, or issuing an alert, alarm, emergency call, or other form of warning that an arrhythmia has been detected. In some examples, the external system 805 can include an external data processor configured to analyze physiological signals or functional signals received by one or more ambulatory medical devices and confirm or reject the detection of an arrhythmia. Computationally intensive algorithms (such as machine learning algorithms) can be implemented in the external data processor for retrospectively processing data to detect arrhythmias.

[0117] Portions of one or more mobile medical devices or external systems 805 may be implemented using hardware, software, firmware, or a combination thereof. Portions of one or more mobile medical devices or external systems 805 may be implemented using dedicated circuitry that may be constructed or configured to perform one or more functions, or may be implemented using general-purpose circuitry that may be programmed or otherwise configured to perform one or more functions. Such general-purpose circuitry may include a microprocessor or a portion thereof, a microcontroller or a portion thereof, or a programmable logic circuit, memory circuitry, a network interface, and various components for interconnecting these components. For example, a "comparator" may include, among other things, an electronic circuit comparator that may be constructed to perform a specific function of comparing two signals, or the comparator may be implemented as part of a general-purpose circuit that may be driven by code that instructs a portion of the general-purpose circuitry to perform a comparison between two signals. A "sensor" may include an electronic circuit configured to receive information and provide an electronic output representative of such received information.

[0118] The therapy device 810 can be configured to send information to or receive information from one or more ambulatory medical devices or an external system 805 using a communication link 811. In an example, one or more ambulatory medical devices, external device 806, or remote device 808 can be configured to control one or more parameters of the therapy device 810. The external system 805 can allow programming of the one or more ambulatory medical devices and can receive information about one or more signals acquired by the one or more ambulatory medical devices, such as information that can be received via the communication link 811. The external system 805 can include a local external implantable medical device programmer. The external system 805 can include a remote patient management system that can monitor the patient's status or adjust one or more therapies, such as from a remote location.

[0119] The mobile medical device may also include or be configured to receive mechanical acceleration information from one or more accelerometer sensors to determine and monitor patient acceleration information, such as cardiac vibration information associated with blood flow or movement in the heart or patient's vascular system (e.g., heart sounds, heart wall motion, etc.), patient body movement or position information (e.g., patient posture, activity, etc.), respiratory information (e.g., respiratory rate, phase, respiratory sounds, etc.), etc.

[0120] Heart sounds are repetitive mechanical signals associated with cardiac vibrations, accelerations of blood flow through the heart, or other cardiac motions with each cardiac cycle or interval, and can be separated and categorized based on the activity associated with such vibrations, accelerations, motions, pressure waves, or blood flow. Heart sounds include four main characteristics: the first through fourth heart sounds (S1 through S4, respectively). The first heart sound (S1) is the vibration sound emitted by the heart during the closure of the atrioventricular (AV), mitral, and tricuspid valves, and the opening of the aortic valve at systole, or the beginning of ventricular contraction. The second heart sound (S2) is the vibration sound emitted by the heart during the closure of the aortic and pulmonary valves at diastole, or the beginning of ventricular relaxation. The third and fourth heart sounds (S3, S4) are related to the filling pressure of the left ventricle during diastole. A sudden cessation of early diastolic filling may result in the third heart sound (S3). Vibrations caused by atrial expulsion may result in the fourth heart sound (S4). Valve closure and blood movement and pressure changes in the heart may cause acceleration, vibration, or movement of the heart walls, which can be detected using an accelerometer or microphone, providing an output referred to herein as cardiac acceleration information.

[0121] In an example, the heart sound parameters may include an ensemble average of a specific heart sound over a heart sound waveform, such as disclosed in commonly assigned U.S. Patent No. 7,115,096 to Siejko et al., entitled “THIRD HEART SOUND ACTIVITY INDEX FOR HEART FAILURE MOITORING,” or commonly assigned U.S. Patent No. 7,853,327 to Patangay et al., entitled “HEART SOUND TRACKING SYSTEM AND METHOD,” each of which is hereby incorporated herein in its entirety, including their disclosure of ensemble averaging of acoustic signals and determining specific heart sounds of a heart sound waveform.

[0122] In some examples, event storage can be triggered, such as by received physiological information, or in response to one or more detected events or determined parameters reaching or exceeding a threshold (e.g., a static threshold, a dynamic threshold, or one or more other thresholds based on patient or population information, etc.). Information sensed or recorded in high-power mode can be transferred from a short-term storage device (such as in a loop recorder) to long-term or non-volatile memory, or in some examples, prepared for communication to an external device separate from the medical device. In examples, cardiac electrical or mechanical information leading up to a detected atrial fibrillation event can be stored, and in some examples, cardiac electrical or mechanical information of a detected atrial fibrillation event can be included, such as to increase the specificity of detection. In an example, multiple loop recorder windows (e.g., a 2-minute window) can be stored sequentially. In a system without early detection, a loop recorder with a longer time period would be required to record this information, which would require significant additional costs (e.g., power, processing resources, component cost, storage capacity, etc.). Compared to longer loop recorder windows, using this early detection prior to a single event to store multiple windows can provide a complete event assessment while saving power and cost. Additionally, early detection can trigger additional parameter calculation or storage at different resolutions or sampling frequencies without unduly taxing limited system resources.

[0123] In some examples, one or more alerts can be provided, such as to a patient, a physician, or one or more other caregivers (e.g., using a patient smartwatch, cellular or smartphone, computer, etc.), such as in response to a transition to a high power mode, in response to a detected event or condition, or after updating information or transmitting information from a first device to a remote device. In other examples, the medical device itself can provide an audible or tactile alert to alert the patient to a detected condition. For example, an alert can be provided to the patient in response to a detected condition so that they can take corrective action, such as sitting down.

[0124] In some examples, therapy can be provided in response to the detected condition. For example, pacing therapy can be provided, enabled, or adjusted, such as to interrupt or reduce the effects of the detected atrial fibrillation event. In other examples, delivery of one or more drugs (e.g., vasoconstrictors, pressor drugs, etc.) can be triggered, provided, or adjusted (such as using a drug pump) in response to the detected condition, alone or in combination with pacing therapy (such as the pacing therapy described above), such as to increase arterial pressure, maintain cardiac output, and interrupt or reduce the effects of the detected atrial fibrillation event.

[0125] Figure 9 A block diagram of an example machine 900 is shown on which any one or more of the techniques (e.g., methods) discussed herein may be executed. Portions of this description may be applied to the computing framework of one or more of the medical devices described herein (such as wearable medical devices, external programmers, etc.). Furthermore, as described herein with respect to medical device components, systems, or machines, such devices may require regulatory compliance that cannot be achieved by general-purpose computers, components, or machines.

[0126] As described herein, examples may include logic or multiple components or mechanisms within machine 900, or may be operated by them. A circuit system (e.g., processing circuitry, evaluation circuitry, etc.) is a collection of circuits implemented in the tangible physical form of machine 900, including hardware (e.g., simple circuits, gates, logic, etc.). The components of a circuit system may be flexible over time. A circuit system includes components that can, when operated, perform a specified operation, either individually or in combination. In an example, the hardware of a circuit system may be immutably designed to perform a specific operation (e.g., hardwired). In an example, the hardware of a circuit system may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) that include computer-readable media that are physically modified (e.g., magnetically, electrically, by removable placement of immutable aggregated particles, etc.) to encode instructions for a specific operation. When the physical components are connected, the underlying electrical properties of the hardware components change, such as from an insulator to a conductor, or vice versa. The instructions enable embedded hardware (e.g., an execution unit or a loading mechanism) to create components of the circuit system in hardware via variable connections to perform portions of a specific operation when operated. Thus, in examples, the computer-readable medium element is part of a circuit system, or is communicatively coupled to other components of a circuit system when the device is in operation. In examples, any of the physical components can be used in more than one member of more than one circuit system. For example, in operation, an execution unit can be used in a first circuit in a first circuit system at one point in time and reused by a second circuit in the first circuit system, or by a third circuit in the second circuit system, at a different time. The following are additional examples of these components with respect to machine 900.

[0127] In alternative embodiments, the machine 900 can operate as a standalone device or can be connected (e.g., networked) to other machines. In a networked deployment, the machine 900 can operate as a server machine, a client machine, or both in a server-client network environment. In an example, the machine 900 can act as a peer machine in a peer-to-peer (P2P) (or other distributed) network environment. The machine 900 can be a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a mobile phone, a network appliance, a network router, a switch or a bridge, or any machine capable of executing instructions (sequentially or otherwise) specifying the actions to be taken by the machine. In addition, although only a single machine is shown, the term "machine" should also be deemed to include any collection of machines that individually or jointly execute one (or more) sets of instructions to implement any one or more of the methods discussed herein, such as cloud computing, software as a service (SaaS), and other computer cluster configurations.

[0128] The machine (e.g., a computer system) 900 may include a hardware processor 902 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 904, a static memory 906 (e.g., memory or storage for firmware, microcode, basic input and output (BIOS), unified extensible firmware interface (UEFI), etc.), and a mass storage device 908 (e.g., a hard drive, a tape drive, a flash memory device, or other block device), some or all of which may communicate with each other via an interconnection link 930 (e.g., a bus). The machine 900 may also include a display unit 910, an input device 912 (e.g., a keyboard), and a user interface (UI) navigation device 914 (e.g., a mouse). In an example, the display unit 910, the input device 912, and the UI navigation device 914 may be a touch screen display. The machine 900 may also include a signal generating device 918 (e.g., a speaker), a network interface device 920, and one or more sensors 916, such as a global positioning system (GPS) sensor, a compass, an accelerometer, or one or more other sensors. The machine 900 may include an output controller 928, such as a serial connection (e.g., Universal Serial Bus (USB)), a parallel connection, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection to communicate with or control one or more peripheral devices (e.g., a printer, a card reader, etc.).

[0129] The registers of the hardware processor 902, the main memory 904, the static memory 906, or the mass storage device 908 may be or include a machine-readable medium 922 on which one or more sets of data structures or instructions 924 (e.g., software) are stored that embody or are utilized by any one or more of the techniques or functions described herein. The instructions 924 may also reside, completely or at least partially, within any one of the registers of the hardware processor 902, the main memory 904, the static memory 906, or the mass storage device 908 during execution thereof by the machine 900. In an example, one or any combination of the hardware processor 902, the main memory 904, the static memory 906, or the mass storage device 908 may constitute the machine-readable medium 922. Although the machine-readable medium 922 is illustrated as a single medium, the term "machine-readable medium" may include a single medium or multiple media (e.g., a centralized database or distributed database, and / or associated caches and servers) configured to store one or more instructions 924.

[0130] The term "machine-readable medium" may include any medium that can store, encode, or carry instructions for execution by the machine 900 and that causes the machine 900 to perform any one or more of the techniques described herein, or that can store, encode, or carry data structures used by or associated with such instructions. Non-limiting examples of machine-readable media may include solid-state memory, optical media, magnetic media, and signals (e.g., radio frequency signals, other photon-based signals, sound signals, etc.). In an example, a non-transitory machine-readable medium includes a machine-readable medium having a plurality of particles that have a constant (e.g., stationary) mass and are therefore a composition of matter. Thus, a non-transitory machine-readable medium is a machine-readable medium that does not include a transient propagating signal. Specific examples of non-transitory machine-readable media may include non-volatile memory, such as semiconductor memory devices (e.g., electrically programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0131] The instructions 924 may also be transmitted or received over a communication network 926 using a transmission medium via a network interface device 920 utilizing any of a variety of transmission protocols (e.g., Frame Relay, Internet Protocol (IP), Transmission Control Protocol (TCP), User Datagram Protocol (UDP), Hypertext Transfer Protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), a mobile telephone network (e.g., a cellular network), a plain old telephone (POTS) network, and a wireless data network (e.g., a wireless network known as a cellular network). The Institute of Electrical and Electronics Engineers (IEEE) 802.11 family of standards, known as ), IEEE 802.16 family of standards, IEEE 802.15.4 family of standards, peer-to-peer (P2P) networks, etc. In an example, the network interface device 920 may include one or more physical jacks (e.g., Ethernet jacks, coaxial jacks, or telephone jacks) or one or more antennas to connect to the communication network 926. In an example, the network interface device 920 may include multiple antennas to communicate wirelessly using at least one of single-input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) technology. The term "transmission medium" should be taken to include any intangible medium that is capable of storing, encoding, or carrying instructions for execution by the machine 900, and includes digital or analog communication signals or other intangible media to facilitate communication of such software. A transmission medium is a machine-readable medium.

[0132] Various embodiments are shown in the figures above. One or more features from one or more of these embodiments may be combined to form other embodiments. The method examples described herein may be at least partially machine or computer implemented. Some examples may include a computer-readable medium or machine-readable medium encoded with instructions that are operable to configure an electronic device or system to perform the methods described in the examples above. Implementations of such methods may include code, such as microcode, assembly language code, or high-level language code. Such code may include computer-readable instructions for performing various methods. The code may form part of a computer program product. Further, the code may be tangibly stored on one or more volatile or non-volatile computer-readable media during execution or at other times.

[0133] The above detailed description is intended to be illustrative rather than limiting.The scope of the disclosure should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are legally entitled.

Claims

1. A medical device system comprising: a signal receiver circuit configured to receive physiological information of a patient, the physiological information comprising at least one of heart sound information or respiratory information; as well as Evaluation circuit, which is configured to: determining a patient metric using the received physiological information from the first time period; determining an indication of a predicted response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on the determined patient metric, wherein the first time period precedes the CRT or MSP therapy; as well as An indication of the determined predictive response is provided to a user or process.

2. The system according to claim 1, comprising: a first medical device configured to sense the physiological information from the patient during the first time period; as well as a second implantable medical device, different from the first medical device, the second implantable medical device comprising a stimulation circuit configured to generate a stimulation signal to be provided to a heart of the patient during a second time period following the first time period, Wherein the evaluation circuit is configured to determine the patient metric using the received physiological information from the first medical device.

3. The system according to claim 2, wherein: To determine the indication of the predictive response, the evaluation circuit is configured to compare the determined patient metric to one or more threshold values, and The predictive response includes one of the following: an indication that the patient will respond to at least one of CRT or MSP therapy; or An indication that the patient will not respond to either CRT or MSP therapy.

4. The system according to any one of claims 1 to 3, wherein: The heart sound information includes at least one of S1 or S3 information, and The respiratory information includes rapid shallow breathing index (RSBI) information.

5. The system according to claim 4, wherein: The evaluation circuit is configured to determine the patient metric as a function of: The S3 information is greater than the S1 information; and The RSBI information.

6. The system according to claim 5, wherein: The S3 information includes S3 amplitude or energy, and The S1 information includes S1 amplitude or energy.

7. The system according to any one of claims 1 to 6, wherein: The respiratory information includes a measurement of tidal volume (TV).

8. The system according to any one of claims 1 to 7, wherein: The physiological information of the patient includes chest impedance information, and wherein the evaluation circuit is configured to determine the patient metric as a function of: at least one of the heart sound information and the respiration information; and The thoracic impedance information.

9. A method comprising: receiving physiological information of the patient using a signal receiver circuit, the physiological information including at least one of heart sound information or respiratory information; as well as Use the evaluation circuit to: determining a patient metric using the received physiological information from the first time period; determining an indication of a predicted response to at least one of cardiac resynchronization therapy (CRT) or multi-site pacing (MSP) therapy based on the determined patient metric, wherein the first time period precedes the CRT or MSP therapy; as well as An indication of the determined predictive response is provided to a user or process.

10. The method according to claim 9, comprising: sensing the physiological information from the patient during the first time period using a first medical device, wherein using the evaluation circuit comprises using a second implantable medical device different from the first medical device, the second implantable medical device comprising a stimulation circuit configured to generate a stimulation signal to be provided to the patient's heart during a second time period after the first time period, and Wherein determining the patient metric comprises using received physiological information from the first medical device.

11. The method according to claim 10, wherein: Determining the indication of the predictive response includes comparing the determined patient metric to one or more threshold values, and The predictive response includes one of the following: an indication that the patient will respond to at least one of CRT or MSP therapy; or An indication that the patient will not respond to either CRT or MSP therapy.

12. The method according to any one of claims 9 to 11, wherein The heart sound information includes at least one of S1 or S3 information, and The respiratory information includes rapid shallow breathing index (RSBI) information.

13. The method according to claim 12, wherein: Determining the patient metric includes, as a function of: The S3 information is greater than the S1 information; and The RSBI information.

14. The method according to claim 13, wherein The S3 information includes S3 amplitude or energy, and The S1 information includes S1 amplitude or energy.

15. The method according to any one of claims 9 to 14, wherein The respiratory information includes a measurement of tidal volume (TV).

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