Atty Ref. No.: A0012141WO01 MEDICAL SYSTEM CONFIGURED FOR CONTINUOUS QT INTERVAL MONITORING DURING ANTIARRYTHMIC LOADING HOSPITALIZATION [0001] This application claims the benefit of U.S. Provisional Patent Application Serial No.63/610,169, filed December 14, 2023, the entire content of which is incorporated herein by reference. TECHNICAL FIELD [0002] This disclosure generally relates to systems including medical devices and, more particularly, to monitoring of patient health using such systems. BACKGROUND [0003] Cardiac signal analysis may be performed by a variety of devices, such as implantable medical devices (IMDs), insertable cardiac monitors (ICMs) and external devices (e.g., smart watches, fitness monitors, mobile devices, Holter monitors, wearable defibrillators, or the like). For example, devices may be configured to process cardiac signals (e.g., cardiac electrograms (ECGs) and electrocardiograms (ECGs)) sensed by one or more electrodes. Features of cardiac signals may include the P-wave, Q-wave, R-wave, S-wave, QRS-complex, and T-wave. A QT interval is the time from the beginning of the QRS complex to the end of the T-wave. A QTc interval is a QT interval that has been normalized or corrected with respect to a heart rate using a formula. Accurate detection and delineation of features in cardiac signals, such as QT intervals or QTc intervals, may be of importance for monitoring patient health, such as risk of sudden cardiac death. SUMMARY [0004] In general, the disclosure describes techniques for combining detection of acute health events, such as lethal tachyarrhythmia and SCA, with QT interval monitoring during a monitoring period associated with medication initiation. Certain medications, such as antiarrhythmic medications to treat AF, may cause prolongation of the QT interval in patients. Prolongation of the QT interval can predispose patients to Torsades de Pointes, which is a ventricular tachyarrhythmia that may lead to SCA. Since medication-
Atty Ref. No.: A0012141WO01 induced tachyarrhythmias tend to occur shortly after initiation of the medication and can be life-threatening, it is common practice to hospitalize patients for drug initiation under continuous ECG surveillance. [0005] Usually, patients are hospitalized for a few days for antiarrhythmic drug loading in order to monitor for drug induced cardiotoxicity when introducing such a drug to a patient. During such a hospitalization, QT intervals are usually measured at static intervals (e.g., a few times every day) from a 12-lead ECG device. However, static measurements taken a few times each day may not be sufficient to determine variability in the QT intervals over the day and to measure the changes in QT before and after medication intake. [0006] An insertable cardiac monitor (ICM) capable of continuously monitoring QT interval over a long period may be a useful tool for evaluating and managing patients taking QT prolonging drugs, such as antiarrhythmic drugs. Continuous monitoring may include triggered, episodic, and/or periodic sensing of patient signals, without requiring human intervention. Such an ICM may continuously determine QT interval values. In some examples, the continuous determination of QT interval values may include the exclusion of QT interval values for heart beats determined to be noisy. As such, the use of “continuous” is not intended to indicate that there will necessarily be a QT interval value associated with every heartbeat. [0007] According to the techniques of this disclosure, a device or system may continuously monitor QT intervals during the hospitalization period for antiarrhythmic loading using an ICM. The ICM may detect a T-wave and determine the QT and/or QTc (QT corrected) intervals for each beat, thus facilitating the monitoring of continuous long term QT interval trends. The QT intervals before and after medication intake may be recorded and if any QT prolongation is detected after medication, then the dosage can be changed to prevent cardiotoxicity. The ICM can also continuously monitor for the occurrence of arrhythmias such as PVCs, VT/VF and if any arrhythmias are detected coupled with QT interval changes, a clinician may change the drug dosage (or change the drug) to reach an optimal level. [0008] In one example, a system includes: one or more memories configured to store a plurality of QT interval values; and processing circuitry coupled to the one or more memories and configured to: continuously determine, based on an electrocardiogram
Atty Ref. No.: A0012141WO01 (ECG) of a patient sensed by sensing circuitry of an implantable medical device, the plurality of QT interval values; determine at least one of whether a first QT interval value of the plurality of QT interval values meets a first threshold or whether a change in magnitude of a difference between two QT interval values of the plurality of QT interval values meets a second threshold; and based on at least one of a determination that the first QT interval value meets the first threshold or the change in magnitude of the difference between the two QT interval values meets the second threshold, generate a first indication for output. [0009] In another example, a method includes any of the techniques of this disclosure. [0010] In another example, a non-transitory, computer-readable storage medium stores instructions, which when executed, cause processing circuitry to perform any of the techniques of this disclosure. [0011] The summary is intended to provide an overview of the subject matter described in this disclosure. It is not intended to provide an exclusive or exhaustive explanation of the systems, device, and methods described in detail within the accompanying drawings and description below. Further details of one or more examples of this disclosure are set forth in the accompanying drawings and in the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF DRAWINGS [0012] FIG.1 illustrates the environment of an example medical system in conjunction with a patient. [0013] FIG.2 is a functional block diagram illustrating an example configuration of the insertable cardiac monitor (ICM) of the medical system of FIG.1. [0014] FIG.3A is a perspective drawing illustrating an insertable cardiac monitor. [0015] FIG.3B is a perspective drawing illustrating another insertable cardiac monitor. [0016] FIG.4 is a functional block diagram illustrating an example configuration of the external device of FIG.1.
Atty Ref. No.: A0012141WO01 [0017] FIG.5 is a block diagram illustrating an example system that includes an access point, a network, external computing devices, such as a server, and one or more other computing devices, which may be coupled to the medical device and external device of FIGS.1–4, in accordance with one or more examples of the present disclosure. [0018] FIGS.6A and 6B are conceptual diagrams illustrating example primary and secondary sensing channels for an R-wave and a T-wave detector according to the techniques of this disclosure. [0019] FIG.7 is a graphical diagram illustrating an example ensemble average plot of QTc intervals computed from IMD 10 data collected during an entire antiarrhythmic hospitalization period for 5 patients in a clinical study. [0020] FIG.8 is a graphical diagram illustrating example ensemble QTc trends observed for a period of 2 hours after each dosage of antiarrhythmic drugs during hospitalization period for 5 patients computed from IMD 10 data collected during the clinical study. [0021] FIG.9 is a flow diagram illustrating example QT monitoring techniques according to one or more aspects of this disclosure. DETAILED DESCRIPTION [0022] Continuous monitoring of QT intervals may allow identification of long QT intervals, which may indicate a need for medical intervention. In some examples, continuous monitoring of QT intervals may be performed using an insertable cardiac monitor (ICM). This disclosure describes an example algorithm which may monitor the QT interval with an ICM, such as a Reveal LINQ™ or LINQ II™ available from Medtronic, Inc., of Minneapolis, Minnesota, which may be inserted subcutaneously. [0023] An ICM capable of continuously monitoring QT intervals may be a useful tool for evaluating and managing patients taking QT prolonging drugs, such as antiarrhythmic drugs, such as during a hospitalization period for drug initiation. [0024] A variety of types of medical devices sense cardiac ECGs. Some medical devices that sense cardiac ECGs are non-invasive, e.g., using a plurality of electrodes placed in contact with external portions of the patient, such as at various locations on the skin of the patient. The electrodes used to monitor the cardiac ECG in these non-invasive
Atty Ref. No.: A0012141WO01 processes may be attached to the patient using an adhesive, strap, belt, or vest, as examples, and electrically coupled to a monitoring device, such as an electrocardiograph, Holter monitor, or other electronic device. The electrodes are configured to sense electrical signals associated with the electrical activity of the heart or other cardiac tissue of the patient, and to provide these sensed electrical signals to the electronic device for further processing and/or display of the electrical signals. The non-invasive devices and methods may be utilized on a temporary basis, for example to monitor a patient during a clinical visit, such as during a doctor’s appointment, or for example for a predetermined period of time, for example for one day (twenty-four hours), or for a period of several days. [0025] Some implantable medical devices (IMDs) also sense and monitor cardiac ECGs. The electrodes used by IMDs to sense cardiac ECGs are typically integrated with a housing of the IMD and/or coupled to the IMD via one or more elongated leads. Example IMDs that monitor cardiac ECGs include pacemakers and implantable cardioverter- defibrillators, which may be coupled to intravascular or extravascular leads, as well as pacemakers with housings configured for implantation within the heart, which may be leadless. An example of pacemaker configured for intracardiac implantation is the Micra™ Transcatheter Pacing System, available from Medtronic plc. Some IMDs that do not provide therapy, e.g., implantable patient monitors, sense cardiac ECGs. Examples of such an IMD include Reveal LINQ™ and LINQ II™. Such IMDs may facilitate relatively longer-term monitoring of patients during normal daily activities, and may periodically transmit collected data to a network service, such as the Medtronic Carelink™ Network. [0026] While this disclosure discusses techniques for measuring QT intervals with an example ICM, any medical device configured to sense a cardiac ECG (which may also be referred to as a cardiac electrogram (EGM)) via implanted or external electrodes, including the examples identified herein, may implement the techniques of this disclosure for measuring QT intervals. The techniques include evaluation of the cardiac ECG using criteria configured to provide a desired sensitivity and specificity of QT interval detection despite noise and depolarization morphology variations due to varying electrode positions. The techniques of this disclosure for identifying QT intervals may facilitate determinations of cardiac wellness, and risk of sudden cardiac death, and may lead to clinical interventions to suppress the risk of sudden cardiac death.
Atty Ref. No.: A0012141WO01 [0027] FIG.1 illustrates the environment of an example medical system 2 in conjunction with a patient 4, in accordance with one or more techniques of this disclosure. The example techniques may be used with an IMD 10, which may be in wireless communication with at least one of external device 12 and other devices not pictured in FIG.1. In some examples, IMD 10 is implanted outside of a thoracic cavity of patient 4 (e.g., subcutaneously in the pectoral location illustrated in FIG.1). IMD 10 may be positioned near the sternum near or just below the level of the heart of patient 4, e.g., at least partially within the cardiac silhouette. IMD 10 includes a plurality of electrodes (not shown in FIG.1), and is configured to sense a cardiac ECG via the plurality of electrodes. In some examples, IMD 10 takes the form of the Reveal LINQ™ or LINQ II™ ICM, or another ICM similar to, e.g., a version or modification of, the Reveal LINQ™ or LINQ II™ ICM. [0028] External device 12 may be a computing device with a display viewable by the user and an interface for providing input to external device 12 (i.e., a user input mechanism). In some examples, external device 12 may be a notebook computer, tablet computer, workstation, one or more servers, cellular phone, personal digital assistant, or another computing device that may run an application that enables the computing device to interact with IMD 10. External device 12 is configured to communicate with IMD 10 and, optionally, another computing device (not illustrated in FIG.1), via wireless communication. External device 12, for example, may communicate via near-field communication technologies (e.g., inductive coupling, NFC or other communication technologies operable at ranges less than 10–20 cm) and far-field communication technologies (e.g., RF telemetry according to the 802.11 or Bluetooth® specification sets, or other communication technologies operable at ranges greater than near-field communication technologies). [0029] External device 12 may be used to configure operational parameters for IMD 10. External device 12 may be used to retrieve data from IMD 10, such as QT intervals. The retrieved data may include values of physiological parameters measured by IMD 10, indications of episodes of arrhythmia or other maladies detected by IMD 10, and physiological signals recorded by IMD 10. For example, external device 12 may retrieve information related to detection of QT intervals by IMD 10, such as QT interval trends or QT metrics over a time period. The time period may be predetermined, for example,
Atty Ref. No.: A0012141WO01 hourly, daily or weekly, or may be otherwise based on the timing of the last retrieval of information by external device 12, or may be determined by a user of external device 12, such as by entering a command on external device 12 requesting the information from IMD 10. In some examples, the time period may be 2 hours. External device 12 may also retrieve cardiac electrogram (ECG) segments recorded by IMD 10, e.g., due to IMD 10 determining that an episode of arrhythmia or another malady occurred during the segment, or in response to a request to record the segment from patient 4 or another user. [0030] Processing circuitry of medical system 2, e.g., of IMD 10, external device 12, and/or of one or more other computing devices, may be configured to perform the example techniques of this disclosure for monitoring QT intervals such as when patient 4 is in a hospital for drug introduction. In some examples, the processing circuitry of medical system 2 may analyze a cardiac ECG sensed by IMD 10 to determine QT intervals in the cardiac ECG. Although described in the context of examples in which IMD 10 that senses the cardiac ECG comprises an insertable cardiac monitor, example systems including one or more implantable or external devices of any type configured to sense a cardiac ECG may be configured to implement the techniques of this disclosure. [0031] FIG.2 is a functional block diagram illustrating an example configuration of IMD 10 of FIG.1 in accordance with one or more techniques described herein. In the illustrated example, IMD 10 includes electrodes 16A and 16B (collectively “electrodes 16”), antenna 26, processing circuitry 50, sensing circuitry 52, communication circuitry 54, storage device 56, switching circuitry 58, and sensors 62. Although the illustrated example includes two electrodes 16, IMDs including or coupled to more than two electrodes 16 may implement the techniques of this disclosure in some examples. [0032] Processing circuitry 50 may include fixed function circuitry and/or programmable processing circuitry. Processing circuitry 50 may include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or equivalent discrete or analog logic circuitry. In some examples, processing circuitry 50 may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry. The functions attributed to processing circuitry 50 herein may be embodied as software, firmware, hardware or any combination thereof.
Atty Ref. No.: A0012141WO01 [0033] Sensing circuitry 52 may be selectively coupled to electrodes 16 via switching circuitry 58, e.g., to select the electrodes 16 and polarity, referred to as the sensing vector, used to sense a cardiac ECG, as controlled by processing circuitry 50. Sensing circuitry 52 may sense signals from electrodes 16, e.g., to produce a cardiac ECG, in order to facilitate monitoring the electrical activity of the heart. Sensing circuitry 52 also may monitor signals from sensors 62, which may include one or more accelerometers, pressure sensors, and/or optical sensors, as examples. In some examples, sensing circuitry 52 may include one or more filters and amplifiers for filtering and amplifying signals received from electrodes 16 and/or sensors 62. [0034] Sensing circuitry 52 and/or processing circuitry 50 may be configured to detect R-waves and T-waves. Sensing circuitry 52 may include one or more rectifiers, filters, amplifiers, comparators, and/or analog-to-digital converters, in some examples. In some examples, sensing circuitry 52 may output an indication to processing circuitry 50 in response to sensing an R-wave or a T-wave. In some examples, processing circuitry 50 may determine an R-wave or a T-wave in an indication from sensing circuitry 52. Processing circuitry 50 may use the indications of detected R-waves and T-waves for determining QT intervals or corrected QT intervals (QTc). [0035] Sensing circuitry 52 may also provide one or more digitized cardiac ECG signals to processing circuitry 50 for analysis, e.g., for use in cardiac rhythm discrimination, and/or for analysis to determine QT intervals or QTc intervals according to the techniques of this disclosure. In some examples, processing circuitry 50 may store the digitized cardiac ECG in storage device 56. Processing circuitry 50 of IMD 10, and/or processing circuitry of another device that retrieves data from IMD 10, may analyze the cardiac ECG to determine QT intervals or QTc intervals according to the techniques of this disclosure. [0036] Communication circuitry 54 may include any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as external device 12, another networked computing device, or another IMD or sensor. Under the control of processing circuitry 50, communication circuitry 54 may receive downlink telemetry from, as well as send uplink telemetry to external device 12 or another device with the aid of an internal or external antenna, e.g., antenna 26. In addition, processing circuitry 50 may communicate with a networked computing device via an
Atty Ref. No.: A0012141WO01 external device (e.g., external device 12) and a computer network, such as the Medtronic plc CareLink® Network. Antenna 26 and communication circuitry 54 may be configured to transmit and/or receive signals via inductive coupling, electromagnetic coupling, Near Field Communication (NFC), Radio Frequency (RF) communication, Bluetooth®, WiFi, or other proprietary or non-proprietary wireless communication schemes. [0037] In some examples, storage device 56 includes computer-readable instructions that, when executed by processing circuitry 50, cause IMD 10 and processing circuitry 50 to perform various functions attributed to IMD 10 and processing circuitry 50 herein. Storage device 56 may include any volatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media. Storage device 56 may store, as examples, programmed values for one or more operational parameters of IMD 10 and/or data collected by IMD 10 for transmission to another device using communication circuitry 54. Data stored by storage device 56 and transmitted by communication circuitry 54 to one or more other devices may include QT interval values, QTc interval values, a maximum QTc value within a time period, a minimum QTc value within the time period, a magnitude of change between the maximum QTc value within the time period and the minimum QTc value within the time period, a time duration between the maximum QTc value within the time period and the minimum QTc within the time period, a time difference between the determination of the occurrence of the administration of a medication and the maximum QTc value within the time period, indications of a QT or QTc interval value meeting a threshold (which may include a time at which such an event occurred), indications of a change QT or QTc interval value over time meeting a threshold (which may include a time at which such an event occurred), and/or digitized cardiac ECGs, as examples. [0038] Processing circuity 50 may monitor QT interval trends continuously based on the QT intervals determined by processing circuitry 50. Processing circuitry 50 may output indications of QT trends, along with any change in QTc intervals over time via communication circuitry 60. For example, if an absolute QTc value (e.g., the value of any particular QTc interval) meets a first threshold (e.g., becomes greater than, or greater than or equal to the first threshold) (e.g., 500 msec) and/or the magnitude of change in QTc interval value meets a second threshold (e.g., becomes greater than, or greater than or
Atty Ref. No.: A0012141WO01 equal to the second threshold) (e.g., 25 msec). If one of the thresholds is met (or, in some examples, if both thresholds are met), processing circuitry 50 may control communication circuitry 60 to send an alert to the clinician to recommend a change in medication dosage. Processing circuitry of IMD 10, computing device 12, HMS 22, and/or any other devices described with respect to FIG.1, may also monitor the time period after each medication dosage to determine any changes in QTc interval values that may be attributable or occurring due to the medication intake. The processing circuitry may record and/or share with a clinician metrics including maximum QTc interval value, minimum QTc interval value, magnitude of change in QTc interval value, and/or time duration between maximum QTc interval value and minimum QTc interval value in a period of time (e.g., 2 hours) after medication intake. [0039] If processing circuitry 50 detects any arrhythmias such as ventricular tachycardia, ventricular fibrillation, premature ventricular contractions, etc., then processing circuitry 50 may control communication circuitry 60 to provide an alert to the clinician to notify the clinician of the arrhythmia(s) and/or to recommend that the clinician modify the drug dosage. Processing circuitry of IMD 10, computing device 12, HMS 22, and/or any other devices described with respect to FIG.1, may correlate QTc interval trends with the occurrence of arrhythmias to determine whether there is any association between the two and may notify the clinician of any such association. [0040] In some examples, processing circuitry 50 may determine one or more baseline QTc intervals from a sensed ECG before the administration of antiarrhythmic drugs. Then, during the hospitalization period, processing circuitry 50 may continuously measure QTc intervals and can determine changes in QTc before and after medication intake events. If any changes in QTc interval values from the baseline are detected, processing circuitry of IMD 10, computing device 12, HMS 22, and/or any other devices described with respect to FIG.1, may provide alerts to the clinician which may include recommend changes to drug dosage to a more optimal level. [0041] FIG.3A is a perspective drawing illustrating an IMD 10A, which may be an example configuration of IMD 10 of FIGS.1 and 2 as an ICM. In the example shown in FIG.3A, IMD 10A may be embodied as a monitoring device having housing 812, proximal electrode 816A and distal electrode 816B. Housing 812 may further comprise first major surface 814, second major surface 818, proximal end 820, and distal end 822.
Atty Ref. No.: A0012141WO01 Housing 812 encloses electronic circuitry located inside the IMD 10A and protects the circuitry contained therein from body fluids. Housing 812 may be hermetically sealed and configured for subcutaneous implantation. Electrical feedthroughs provide electrical connection of electrodes 816A and 816B. [0042] In the example shown in FIG.3A, IMD 10A is defined by a length L, a width W and thickness or depth D and is in the form of an elongated rectangular prism wherein the length L is much larger than the width W, which in turn is larger than the depth D. In one example, the geometry of the IMD 10A – in particular a width W greater than the depth D – is selected to allow IMD 10A to be inserted under the skin of the patient using a minimally invasive procedure and to remain in the desired orientation during insertion. For example, the device shown in FIG.3A includes radial asymmetries (notably, the rectangular shape) along the longitudinal axis that maintains the device in the proper orientation following insertion. For example, the spacing between proximal electrode 816A and distal electrode 816B may range from 5 millimeters (mm) to 55 mm, 30 mm to 55 mm, 35 mm to 55 mm, and from 40 mm to 55 mm and may be any range or individual spacing from 5 mm to 60 mm. In addition, IMD 10A may have a length L that ranges from 30 mm to about 70 mm. In other examples, the length L may range from 5 mm to 60 mm, 40 mm to 60 mm, 45 mm to 60 mm and may be any length or range of lengths between about 30 mm and about 70 mm. In addition, the width W of major surface 814 may range from 3 mm to 15, mm, from 3 mm to 10 mm, or from 5 mm to 15 mm, and may be any single or range of widths between 3 mm and 15 mm. The thickness of depth D of IMD 10A may range from 2 mm to 15 mm, from 2 mm to 9 mm, from 2 mm to 5 mm, from 5 mm to 15 mm, and may be any single or range of depths between 2 mm and 15 mm. In addition, IMD 10A according to an example of the present disclosure is has a geometry and size designed for ease of implant and patient comfort. Examples of IMD 10A described in this disclosure may have a volume of three cubic centimeters (cm) or less, 1.5 cubic cm or less or any volume between three and 1.5 cubic centimeters. [0043] In the example shown in FIG.3A, once inserted within the patient, the first major surface 814 faces outward, toward the skin of the patient while the second major surface 818 is located opposite the first major surface 814. In addition, in the example shown in FIG.3A, proximal end 820 and distal end 822 are rounded to reduce discomfort and irritation to surrounding tissue once inserted under the skin of the patient. IMD 10A,
Atty Ref. No.: A0012141WO01 including instrument and method for inserting IMD 10A is described, for example, in U.S. Patent Publication No.2014/0276928, incorporated herein by reference in its entirety. [0044] Proximal electrode 816A is at or proximate to proximal end 820, and distal electrode 816B is at or proximate to distal end 822. Proximal electrode 816A and distal electrode 816B are used to sense cardiac ECG signals, e.g., ECG signals, thoracically outside the ribcage, which may be sub-muscularly or subcutaneously. Cardiac signals may be stored in a memory of IMD 10A, and data may be transmitted via integrated antenna 830A to another device, which may be another implantable device or an external device, such as external device 812. In some example, electrodes 816A and 816B may additionally or alternatively be used for sensing any bio-potential signal of interest, which may be, for example, an ECG, EEG, EMG, or a nerve signal, or for measuring impedance, from any implanted location. [0045] In the example shown in FIG.3A, proximal electrode 816A is at or in close proximity to the proximal end 820 and distal electrode 816B is at or in close proximity to distal end 822. In this example, distal electrode 816B is not limited to a flattened, outward facing surface, but may extend from first major surface 814 around rounded edges 824 and/or end surface 826 and onto the second major surface 818 so that the electrode 816B has a three-dimensional curved configuration. In some examples, electrode 816B is an uninsulated portion of a metallic, e.g., titanium, part of housing 812. [0046] In the example shown in FIG.3A, proximal electrode 816A is located on first major surface 814 and is substantially flat, and outward facing. However, in other examples proximal electrode 816A may utilize the three-dimensional curved configuration of distal electrode 816B, providing a three-dimensional proximal electrode (not shown in this example). Similarly, in other examples distal electrode 816B may utilize a substantially flat, outward facing electrode located on first major surface 814 similar to that shown with respect to proximal electrode 816A. The various electrode configurations allow for configurations in which proximal electrode 816A and distal electrode 816B are located on both first major surface 814 and second major surface 818. In other configurations, such as that shown in FIG.16A, only one of proximal electrode 816A and distal electrode 816B is located on both major surfaces 814 and 818, and in still other configurations both proximal electrode 816A and distal electrode 816B are located on one of the first major surface 814 or the second major surface 818 (e.g., proximal electrode
Atty Ref. No.: A0012141WO01 816A located on first major surface 814 while distal electrode 816B is located on second major surface 818). In another example, IMD 10A may include electrodes on both major surface 814 and 818 at or near the proximal and distal ends of the device, such that a total of four electrodes are included on IMD 10A. Electrodes 816A and 816B may be formed of a plurality of different types of biocompatible conductive material, e.g., stainless steel, titanium, platinum, iridium, or alloys thereof, and may utilize one or more coatings such as titanium nitride or fractal titanium nitride. [0047] In the example shown in FIG.3A, proximal end 820 includes a header assembly 828 that includes one or more of proximal electrode 816A, integrated antenna 830A, anti-migration projections 882, and/or suture hole 834. Integrated antenna 830A is located on the same major surface (i.e., first major surface 814) as proximal electrode 816A and is also included as part of header assembly 828. Integrated antenna 830A allows IMD 10A to transmit and/or receive data. In other examples, integrated antenna 830A may be formed on the opposite major surface as proximal electrode 816A or may be incorporated within the housing 812 of IMD 10A. In the example shown in FIG.3A, anti- migration projections 832 are located adjacent to integrated antenna 830A and protrude away from first major surface 814 to prevent longitudinal movement of the device. In the example shown in FIG.3A, anti-migration projections 832 include a plurality (e.g., nine) small bumps or protrusions extending away from first major surface 814. As discussed above, in other examples anti-migration projections 832 may be located on the opposite major surface as proximal electrode 816A and/or integrated antenna 830A. In addition, in the example shown in FIG.3A, header assembly 828 includes suture hole 834, which provides another means of securing IMD 10A to the patient to prevent movement following insertion. In the example shown, suture hole 834 is located adjacent to proximal electrode 816A. In one example, header assembly 828 is a molded header assembly made from a polymeric or plastic material, which may be integrated or separable from the main portion of IMD 10A. [0048] FIG.3B is a perspective drawing illustrating another IMD 10B, which may be another example configuration of IMD 10 from FIGS.1 and 2 as an ICM. IMD 10B of FIG.16B may be configured substantially similarly to IMD 10A of FIG.3A, with differences between them discussed herein.
Atty Ref. No.: A0012141WO01 [0049] IMD 10B may include a leadless, subcutaneously-implantable monitoring device, e.g., an ICM. IMD 10B includes housing having a base 840 and an insulative cover 842. Proximal electrode 816C and distal electrode 816D may be formed or placed on an outer surface of cover 842. Various circuitries and components of IMD 10B, e.g., described above with respect to FIG.2, may be formed or placed on an inner surface of cover 842, or within base 840. In some examples, a battery or other power source of IMD 10B may be included within base 840. In the illustrated example, antenna 830B is formed or placed on the outer surface of cover 842 but may be formed or placed on the inner surface in some examples. In some examples, insulative cover 842 may be positioned over an open base 840 such that base 840 and cover 842 enclose the circuitries and other components and protect them from fluids such as body fluids. The housing including base 840 and insulative cover 842 may be hermetically sealed and configured for subcutaneous implantation. [0050] Circuitries and components may be formed on the inner side of insulative cover 842, such as by using flip-chip technology. Insulative cover 842 may be flipped onto a base 840. When flipped and placed onto base 840, the components of IMD 10B formed on the inner side of insulative cover 842 may be positioned in a gap 844 defined by base 840. Electrodes 816C and 816D and antenna 830B may be electrically connected to circuitry formed on the inner side of insulative cover 842 through one or more vias (not shown) formed through insulative cover 842. Insulative cover 842 may be formed of sapphire (i.e., corundum), glass, parylene, and/or any other suitable insulating material. Base 840 may be formed from titanium or any other suitable material (e.g., a biocompatible material). Electrodes 816C and 846D may be formed from any of stainless steel, titanium, platinum, iridium, or alloys thereof. In addition, electrodes 846C and 846D may be coated with a material such as titanium nitride or fractal titanium nitride, although other suitable materials and coatings for such electrodes may be used. [0051] In the example shown in FIG.3B, the housing of IMD 10B defines a length L, a width W and thickness or depth D and is in the form of an elongated rectangular prism wherein the length L is much larger than the width W, which in turn is larger than the depth D, similar to IMD 10A of FIG.3A. For example, the spacing between proximal electrode 816C and distal electrode 816D may range from 5 mm to 50 mm, from 30 mm to 50 mm, from 35 mm to 45 mm, and may be any single spacing or range of spacings from 5
Atty Ref. No.: A0012141WO01 mm to 50 mm, such as approximately 40 mm. In addition, IMD 10B may have a length L that ranges from 5 mm to about 70 mm. In other examples, the length L may range from 30 mm to 70 mm, 40 mm to 60 mm, 45 mm to 55 mm, and may be any single length or range of lengths from 5 mm to 50 mm, such as approximately 45 mm. In addition, the width W may range from 3 mm to 15 mm, 5 mm to 15 mm, 5 mm to 10 mm, and may be any single width or range of widths from 3 mm to 15 mm, such as approximately 8 mm. The thickness or depth D of IMD 10B may range from 2 mm to 15 mm, from 5 mm to 15 mm, or from 3 mm to 5 mm, and may be any single depth or range of depths between 2 mm and 15 mm, such as approximately 4 mm. IMD 10B may have a volume of three cubic centimeters (cm) or less, or 1.5 cubic cm or less, such as approximately 1.4 cubic cm. [0052] In the example shown in FIG.3B, once inserted subcutaneously within the patient, outer surface of cover 842 faces outward, toward the skin of the patient. In addition, as shown in FIG.3B, proximal end 846 and distal end 848 are rounded to reduce discomfort and irritation to surrounding tissue once inserted under the skin of the patient. In addition, edges of IMD 10B may be rounded. [0053] FIG.4 is a block diagram illustrating an example configuration of components of external device 12. In the example of FIG.4, external device 12 includes processing circuitry 80, communication circuitry 82, storage device 84, and user interface 86. [0054] Processing circuitry 80 may include one or more processors that are configured to implement functionality and/or process instructions for execution within external device 12. For example, processing circuitry 80 may be capable of processing instructions stored in storage device 84. Processing circuitry 80 may include, for example, microprocessors, DSPs, ASICs, FPGAs, or equivalent discrete or integrated logic circuitry, or a combination of any of the foregoing devices or circuitry. Accordingly, processing circuitry 80 may include any suitable structure, whether in hardware, software, firmware, or any combination thereof, to perform the functions ascribed herein to processing circuitry 80. [0055] Communication circuitry 82 may include any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as IMD 10. Under the control of processing circuitry 80, communication circuitry 82 may receive downlink telemetry from, as well as send uplink telemetry to, IMD 10, or another device. Communication circuitry 82 may be configured to transmit or receive signals via inductive
Atty Ref. No.: A0012141WO01 coupling, electromagnetic coupling, Near Field Communication (NFC), Radio Frequency (RF) communication, Bluetooth®, WiFi, or other proprietary or non-proprietary wireless communication schemes. Communication circuitry 82 may also be configured to communicate with devices other than IMD 10 via any of a variety of forms of wired and/or wireless communication and/or network protocols. [0056] Storage device 84 may be configured to store information within external device 12 during operation. Storage device 84 may include a computer-readable storage medium or computer-readable storage device. In some examples, storage device 84 includes one or more of a short-term memory or a long-term memory. Storage device 84 may include, for example, RAM, DRAM, SRAM, magnetic discs, optical discs, flash memories, or forms of EPROM or EEPROM. In some examples, storage device 84 is used to store data indicative of instructions for execution by processing circuitry 80. Storage device 84 may be used by software or applications running on external device 12 to temporarily store information during program execution. [0057] Data exchanged between external device 12 and IMD 10 may include operational parameters. External device 12 may transmit data including computer readable instructions which, when implemented by IMD 10, may control IMD 10 to change one or more operational parameters and/or export collected data, such as QT intervals or QTc intervals. For example, processing circuitry 80 may transmit an instruction to IMD 10 which requests IMD 10 to export collected data (e.g., QT interval data, QTc interval data and/or digitized cardiac ECGs) to external device 12. In turn, external device 12 may receive the collected data from IMD 10 and store the collected data in storage device 84. Processing circuitry 80 may implement any of the techniques described herein to analyze cardiac ECGs received from IMD 10, e.g., to determine QT intervals or QTc intervals. [0058] A user, such as a clinician or patient 4, may interact with external device 12 through user interface 86. In some examples, a clinician or patient 4 may interact with external device 12 to input an indication that patient 4 has taken medication and/or to view alerts and/or indications relating to QT intervals and/or arrhythmia detection. User interface 86 includes a display (not shown), such as a liquid crystal display (LCD) or a light emitting diode (LED) display or other type of screen, with which processing circuitry 80 may present information related to IMD 10, e.g., cardiac ECGs, indications of QT
Atty Ref. No.: A0012141WO01 intervals or QTc intervals. In addition, user interface 86 may include an input mechanism to receive input from the user. The input mechanisms may include, for example, any one or more of buttons, a keypad (e.g., an alphanumeric keypad), a peripheral pointing device, a touch screen, or another input mechanism that allows the user to navigate through user interfaces presented by processing circuitry 80 of external device 12 and provide input. In other examples, user interface 86 also includes audio circuitry for providing audible notifications, instructions or other sounds to the user, receiving voice commands from the user, or both. [0059] FIG.5 is a block diagram illustrating an example system that includes an access point 91, a network 93, external computing devices, such as a server 95, and one or more other computing devices 101A–101N (collectively, “computing devices 101”), which may be coupled to IMD 10 and external device 12 via network 93, in accordance with one or more techniques described herein. In this example, IMD 10 may use communication circuitry 54 to communicate with external device 12 via a first wireless connection, and to communicate with an access point 91 via a second wireless connection. In the example of FIG.5, access point 91, external device 12, server 95, and computing devices 101 are interconnected and may communicate with each other through network 93. [0060] Access point 91 may include a device that connects to network 93 via any of a variety of connections, such as telephone dial-up, digital subscriber line (DSL), or cable modem connections. In other examples, access point 91 may be coupled to network 93 through different forms of connections, including wired or wireless connections. In some examples, access point 91 may be a user device, such as a tablet or smartphone, that may be co-located with the patient. IMD 10 may be configured to transmit data, such as patient cardiac activity data and indications of episode data, and/or indications of changes in patient health, to access point 91. Access point 91 may then communicate the retrieved data to server 95 via network 93. [0061] In some cases, server 95 may be configured to provide a secure storage site for data that has been collected from IMD 10 and/or external device 12. In some cases, server 95 may assemble data in web pages or other documents for viewing by trained professionals, such as clinicians, via computing devices 101. One or more aspects of the illustrated system of FIG.5 may be implemented with general network technology and
Atty Ref. No.: A0012141WO01 functionality, which may be similar to that provided by the Medtronic CareLink® Network. [0062] In some examples, one or more of computing devices 101 may be a tablet or other smart device located with a clinician, by which the clinician may program, receive alerts from, and/or interrogate IMD 10. For example, the clinician may enter an indication that patient 4 has taken medication and/or receive alerts or other indications for viewing through a computing device 101. The clinician may also access patient data and/or indications of patient health collected by IMD 10 through a computing device 101, such as when patient 4 is in between clinician visits, to check on a status of a medical condition. In some examples, the clinician may enter instructions for a medical intervention for patient 4 into an application executed by computing device 101, such as based on a status of a patient condition determined by IMD 10, external device 12, server 95, or any combination thereof, or based on other patient data known to the clinician. Device 101 then may transmit the instructions for medical intervention to another of computing devices 101 located with patient 4 or a caregiver of patient 4. For example, such instructions for medical intervention may include an instruction to change a drug dosage, timing, or selection, to schedule a visit with the clinician, or to seek medical attention. In further examples, a computing device 101 may generate an alert to patient 4 based on a status of a medical condition of patient 4, which may enable patient 4 proactively to seek medical attention prior to receiving instructions for a medical intervention. In this manner, patient 4 may be empowered to take action, as needed, to address his or her medical status, which may help improve clinical outcomes for patient 4. [0063] In the example illustrated by FIG.5, server 95 includes a storage device 97, e.g., to store data retrieved from IMD 10, and processing circuitry 99. Although not illustrated in FIG.5 computing devices 101 may similarly include a storage device and processing circuitry. Processing circuitry 99 may include one or more processors that are configured to implement functionality and/or process instructions for execution within server 95. For example, processing circuitry 99 may be capable of processing instructions stored in storage device 97. Processing circuitry 99 may include, for example, microprocessors, DSPs, ASICs, FPGAs, or equivalent discrete or integrated logic circuitry, or a combination of any of the foregoing devices or circuitry. Accordingly, processing circuitry 99 may include any suitable structure, whether in hardware, software, firmware,
Atty Ref. No.: A0012141WO01 or any combination thereof, to perform the functions ascribed herein to processing circuitry 99. Processing circuitry 99 of server 95 and/or the processing circuity of computing devices 101 may implement any of the techniques described herein to analyze information or data received from IMD 10, e.g., to determine whether the health status of a patient has changed. [0064] Storage device 97 may include a computer-readable storage medium or computer-readable storage device. In some examples, storage device 97 includes one or more of short-term memories or long-term memories. Storage device 97 may include, for example, RAM, DRAM, SRAM, magnetic discs, optical discs, flash memories, or forms of EPROM or EEPROM. In some examples, storage device 97 is used to store data indicative of instructions for execution by processing circuitry 99. [0065] FIGS.6A and 6B are conceptual diagrams illustrating example primary and secondary sensing channels for R-wave detection and a T-wave detector. In FIG.6A, sensing circuitry 52 of IMD 10 may sense R-waves by using dual channel sensing techniques of FIGS.6A and 6B. Cardiac signals (e.g., signals from electrode 16A and electrode 16B) may be filtered by band-pass filter 100. In some examples, band-pass filter 100 may have a passband in the range of about 10 Hz to 32 Hz. In some examples, band- pass filter 100 may have a non-linear response as shown. In other examples, band-pass filter 100 may have a generally linear response. The band-passed signal may then be rectified by rectifier 102. [0066] The rectified signal may then be input to an auto adjusting threshold process 104. For example, auto adjusting threshold process may sense an event has occurred in the cardiac signal when the amplitude of rectified signal from rectifier 102 exceeds the auto adjusted threshold. Auto adjusting threshold process 104 may use an auto adjusting sensitivity with a short blanking period (e.g., in the order of 150 ms). During a blanking period, a sensing process, such as auto adjusting threshold process 104 or fixed threshold process 106, may not sense an event in the cardiac signal so as to avoid a single depolarization from resulting in multiple sensed events. Auto adjusting threshold process 104 may form the primary sensing channel 108, which may be the main R-wave sensing mechanism in IMD 10, and may be configured to accommodate the detection of both tachyarrhythmia and bradyarrhythmia.
Atty Ref. No.: A0012141WO01 [0067] Once primary sensing channel 108 detects an R wave, the threshold of auto adjusting threshold process 104 is set at 65% of the amplitude of the detected R wave (which may be a relatively high threshold so that R waves are not detected immediately). Then the threshold decays from the 65% value to 35 microvolt so that the next R wave may be detected. In some examples, there may be points where the threshold drops sharply such as after anticipated T-waves and P-waves to avoid oversensing of T-waves and/or P-waves. [0068] In some examples, the rectified signal may be input into a fixed threshold process 106. Fixed threshold process 106 may have a fixed threshold and a relatively longer blanking period (e.g., in the order of 520 ms) than auto adjusting threshold process 104 to reduce under-sensing. Similar to auto adjusting threshold process 104, fixed threshold process 106 may sense an event in the cardiac signal when the amplitude of the rectified signal exceeds the fixed threshold. The output of fixed threshold process 106 may form a secondary sensing channel 110. In other examples (not shown), secondary sensing channel 110 may use different filtering and/or different rectification than primary sensing channel 108. [0069] The example dual channel sensing scheme of FIGS.6A and 6B may be employed to avoid under sensing some R-waves, such as those in PVC beats. To capture these beats, a secondary channel, such as secondary sensing channel 110 used with a lower threshold may be used. [0070] For example, when primary sensing channel 108 senses a R-wave, primary sensing channel 108 may blank auto adjusting threshold process 104, as well as the fixed threshold process 106, for a time period, such as 150 ms, to avoid secondary sensing channel 110 from sensing the same beat. If secondary sensing channel 110 senses a R- wave which was not sensed by primary sensing channel 108, secondary sensing channel 110 may blank fixed threshold process 106 for 520 ms after the R-wave sense. In this example, secondary sensing channel 106 may not blank the primary channel from sensing. [0071] To determine the T-wave location, IMD 10 may band-pass the ECG signal, from electrode 16A and electrode 16B, e.g., using band-pass filter 90. In some examples, the band-pass filter may be a 6-20 Hz band-pass filter. The band-passed signal may be rectified by rectifier 92. In FIG.6B, primary sensing channel 108 and secondary sensing
Atty Ref. No.: A0012141WO01 channel 110 determine R-wave senses 95. R-wave senses 95 may be utilized by T-wave sensor 94 to determine a search window for a T-wave. [0072] Further details of example QT interval applications are described in U.S. Patent 11,576,606, “CARDIAC SIGNAL QT INTERVAL DETECTION,” issued on February 14, 2023; U.S. Patent 11,589,794, entitled “CARDIAC SIGNAL QT INTERVAL DETECTION,” issued on February 28, 2023, and U.S. Patent Publication No. US 2023- 0181083A1, published on June 15, 2023, each of which is hereby incorporated by reference. [0073] Prolongation of the QT interval can predispose patients to Torsades de Pointes, which is a ventricular tachyarrhythmia that may lead to SCA. Certain medications, such as antiarrhythmic medications to treat AF, may cause elongation of the QT interval in patients. The commonly used antiarrhythmics for AF rhythm control management belong to Vaughan Williams’ classes, Ic and III, such as Amiodarone and Sotalol. [0074] FIG.7 is a graphical diagram illustrating an example ensemble average plot of QTc intervals computed from IMD 10 data collected during an entire antiarrhythmic hospitalization period for 5 patients in a clinical study. The x-axis represents time, beginning at time 08:00 on a first day and ending after 10:00 on a third day. The y-axis represents CTC in msecs between 360 and 480. Time 902 represents a time of the delivery of a first dose of antiarrhythmic medication. Interval 912 represents a 2-hour period after time 902. Time 904 represents a time of the delivery of a second dose of antiarrhythmic medication. Interval 914 represents a 2-hour period after time 904. Time 906 represents a time of the delivery of a third dose of antiarrhythmic medication. Interval 916 represents a 2-hour period after time 906. Time 908 represents a time of the delivery of a fourth dose of antiarrhythmic medication. Interval 918 represents a 2-hour period after time 908. Time 910 represents a time of the delivery of a fifth dose of antiarrhythmic medication. Interval 920 represents a 2-hour period after time 910. [0075] During the clinical study, QT intervals detected from continuously collected ICM ECG data from patients from three sites were analyzed with the objective of studying the long-term QT interval trends in patients undergoing antiarrhythmic drug loading in an inpatient setting. The ICM ECG was processed through the QT detection algorithm which calculates the QTc interval for every beat to generate continuous long term QTc trends. Ensemble average QTc trends were analyzed over all patients during the hospitalization
Atty Ref. No.: A0012141WO01 period and metrics including maximum and minimum QTc intervals, magnitude of QTc change, and time interval between dosage administration and maximum QTc were analyzed for the time period of 2 hours following each antiarrhythmic dosage for the first 4 dosages administered during the hospitalization period. [0076] During the clinical study, 5 out of 17 patients enrolled (avg. age 71±7.3 years, 40% females) in the QT clinical study had continuous telemetered ICM ECG data available during the index antiarrhythmic loading hospitalization period. All patients were loaded with Sotalol during the hospitalization. The overall ensemble average trend of QTc interval over all patients during the hospitalization period and the QTc interval trends for the 2-hr period after each dosage are shown in FIG.7. The baseline QTc before the first dose was observed to be 412.1±33.5 msec which increased to a baseline of 426±36.6 msec before the second dose (p=0.032, n=5). The baseline QTc before the third dose was 429.7±40.9 msec. A QTc increase of 58.1±52.2 msec (max-min QTc) (p=0.067, n=5) after the first dose and an increase of 34.8±18.2 msec (p=0.013, n=5) after the second dose were observed. The time interval between the first dose and occurrence of maximum QTc interval of 459.5±50.2 msec was 84.2±36.4 mins while the time interval between the second dose and occurrence of maximum QTc interval of 452.4±31.6 msec was 65.6±36.4 mins. [0077] FIG.8 is a graphical diagram illustrating example ensemble QTc trends observed for a period of 2 hours after each dosage of antiarrhythmic drugs during hospitalization period for 5 patients computed from IMD 10 data collected during the clinical study. Metrics such as minimum and maximum QTc values, magnitude of change in the QTc values, and the time interval between the maximum and minimum QTc intervals for the 2-hour period after each dosage are shown for the first, second, third, and fourth dose. [0078] FIG.9 is a flow diagram illustrating example QT monitoring techniques according to one or more aspects of this disclosure. The following techniques may be performed by any of, or any combination of, processing circuitry 50, processing circuitry 80, processing circuitry 99, processing circuitry of one or more of devices 101, and/or processing circuitry of other devices capable of performing such techniques. The processing circuitry may determine one or more baseline QTc intervals before antiarrhythmic drug loading (1100). For example, processing circuitry may determine the
Atty Ref. No.: A0012141WO01 one or more baseline QTc intervals based on a sensed ECG signal sensed by IMD 10. The baseline QTc intervals may be determined based on an ECG signal sensed by IMD 10 prior to the patient arriving at the hospital, during the patient arriving at the hospital, or after the patient arrives at the hospital. The baseline QTc intervals are determined based on a sensed ECG signal sensed by IMD 10 prior to administration of an antiarrhythmic drug. [0079] The processing circuitry may continuously determine QTc intervals during a hospitalization period (1102). For example, the processing circuitry may determine QTc intervals while the patient is being monitored for potential cardiotoxicity. In some examples, the continuous determination of QT interval values may include the exclusion of QT interval values for heart beats determined to be noisy. [0080] The processing circuitry may monitor QTc trends and/or determine a magnitude of change in QTc intervals before and after medication (1104). For example, the processing circuitry may monitor a QTc interval value over time and/or a magnitude of a change in QTc interval value over time. [0081] The processing circuitry may determine whether an absolute QTc interval value meets a first threshold (e.g., is greater than, or greater than or equal to the first threshold) and/or if a magnitude of QTc interval value change meets a second threshold (e.g., is greater than, or greater than or equal to the second threshold (1106). If the absolute QTc interval value meets the first threshold and/or the magnitude of QTc interval value change meets the second threshold (the “YES” path from box 1106), the processing circuitry may send an alert (1108) to the clinician. In some examples, the alert may include a recommendation to change a dosage of the medication. [0082] If the absolute QTc interval does not meet the first threshold and/or the magnitude of QTc change does not meet the second threshold (the “NO” path from box 1106), the processing circuitry may continue monitoring for arrhythmia (1110). For example, the processing circuitry may monitor the sensed ECG signal from IMD 10 to monitor for arrhythmia. The processing circuitry may determine whether an arrythmia is detected (1112). For example, the processing circuitry may use any technique discussed herein or any other technique to detect an arrythmia based on a sensed ECG signal. [0083] If an arrhythmia is detected (the “YES” path from box 1112), the processing circuitry may send an alert (1114). The alert may include an indication of the arrythmia
Atty Ref. No.: A0012141WO01 and, in some examples, may include information regarding QTc trends. If an arrhythmia is not detected (the “NO” path from box 1112), the processing circuitry may determine whether the medication is taken or delivered (1116). For example, upon delivering medication or the patient otherwise taking the medication, a clinician may input an indication via computing device 12, that the patient has taken the medication. The processing circuitry may use such an indication to determine whether a patient has taken the medication. [0084] If the processing circuitry determines that the patient has taken the medication (the “YES” path from box 1116), the processing circuitry may monitor QTc trends and arrhythmias for a period of time (e.g., 2 hours) after the medication intake (1118). In some examples, the QTc trends may include QTc metrics such as a maximum QTc, minimum QTc, magnitude of change in QTc, time duration between maximum and minimum QTc, and/or the like during that period of time (e.g., 2 hours) after medication intake. For example, such trends in the period of time after the administration of medication may be useful for a clinician in evaluating antiarrhythmic medication loading of patient 4 and determining an appropriate dosage of the antiarrhythmic medication for patient 4. [0085] The processing circuitry may record and share the QTc trends and any indications of arrhythmias with the clinician (1120). If the processing circuitry determines that the patient has not taken the medication (the “NO” path from box 1116), the processing circuitry may return to box 1102. [0086] While the techniques herein are described as being performed by various elements, such as sensing circuitry 52 and processing circuitry 50, in some examples, other elements or a combination of elements may perform the techniques. For example, sensing circuitry 52 may perform techniques described as being performed by processing circuitry 50, processing circuitry 50 may perform techniques described as being performed by sensing circuitry 52, or a combination of sensing circuitry 52 and processing circuitry 50 may perform techniques described as being performed by either. [0087] The techniques described in this disclosure may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the techniques may be implemented within one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic QRS circuitry, as well
Atty Ref. No.: A0012141WO01 as any combinations of such components, embodied in external devices, such as physician or patient programmers, stimulators, or other devices. The terms “processor,” “processing circuitry,” “controller” or “control module” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry, and alone or in combination with other digital or analog circuitry. [0088] For aspects implemented in software, at least some of the functionality ascribed to the systems and devices described in this disclosure may be embodied as instructions on a non-transitory computer-readable storage medium such as RAM, ROM, NVRAM, EEPROM, FLASH memory, magnetic media, optical media, or the like. The instructions may be executed to support one or more aspects of the functionality described in this disclosure. [0089] Various examples have been described. These and other examples are within the scope of the following claims. [0090] Example 1. A system comprising: one or more memories configured to store a plurality of QT interval values; and processing circuitry coupled to the one or more memories and configured to: continuously determine, based on an electrocardiogram (ECG) of a patient sensed by sensing circuitry of an implantable medical device, the plurality of QT interval values, wherein the patient is hospitalized for antiarrhythmic medication loading; determine at least one of whether a first QT interval value of the plurality of QT interval values meets a first threshold or whether a change in magnitude of a difference between two QT interval values of the plurality of QT interval values meets a second threshold; and based on at least one of a determination that the first QT interval value meets the first threshold or the change in magnitude of the difference between the two QT interval values meets the second threshold, generate a first indication for output. [0091] Example 2. The system of Example 1, wherein the processing circuitry is further configured to: determine, based on the ECG, an indication of an arrhythmia; and based on the determination of the indication of the arrhythmia, generate a second ndication for output. [0092] Example 3. The system of Example 1 or Example 2, wherein the processing circuitry is further configured to: determine an occurrence of an administration of a medication to the patient; determine, based on the administration of the medication and within a time period after the administration of the medication, one or more metrics
Atty Ref. No.: A0012141WO01 associated with the plurality of QT interval values; and generate a third indication for output, the third indication comprising the one or more metrics. [0093] Example 4. The system of Example 3, wherein the occurrence of the administration of the medication to the patient comprises the administration of the medication to the patient by at least one of the patient or a clinician. [0094] Example 5. The system of Example 3 or Example 4, wherein the plurality of QT interval values comprises corrected QT (QTc) interval values, and the one or more metrics comprise at least one of a maximum QTc value within the time period, minimum QTc value within the time period, magnitude of change between the maximum QTc value within the time period and the minimum QTc value within the time period, a time duration between the maximum QTc value within the time period and the minimum QTc within the time period, or a time difference between the determination of the occurrence of the administration of the medication and the maximum QTc value within the time period. [0095] Example 6. The system of Example 5, wherein the time period is of a predetermined length. [0096] Example 7. The system of any of Examples 1-4, wherein the plurality of QT interval values comprises corrected QT (QTc) interval values. [0097] Example 8. The system of any of Examples 1-7, wherein the first indication comprises a recommendation to change a dosage of the medication. [0098] Example 9. The system of any of Examples 1-8, wherein the processing circuitry is further configured to output the first indication. [0099] Example 10. The system of any of Examples 1-9, further comprising the implantable medical device. [0100] Example 11. The system of Example 10, wherein the implantable medical device comprises an insertable cardiac monitor. [0101] Example 12. The system of any of Examples 1-11, wherein as part of continuously determining the plurality of QT interval values, the processing circuitry is configured to: determine a portion of the ECG is noisy; and based on the portion of the ECG being noisy, exclude a QT interval value from the plurality of QT interval values. [0102] Example 13. A method performed by the system of any of Examples 1- 12.
Atty Ref. No.: A0012141WO01 [0103] Example 14. Non-transitory computer-readable storage media storing instructions, which when executed by processing circuitry, cause the processing circuitry to perform the method of Example 13.