Patent Description:
This document relates generally to medical devices, and more particularly, to a system for detecting and managing cardiac arrhythmias.

Implantable medical devices (IMDs) have been used for monitoring patient health condition or disease states and delivering therapies. For example, implantable cardioverter-defibrillators (ICDs) may be used to monitor for certain abnormal heart rhythms and to deliver electrical energy to the heart to correct the abnormal rhythms. Some IMDs may be used to monitor for chronic worsening of cardiac hemodynamic performance, such as due to congestive heart failure (CHF), and to provide cardiac stimulation therapies, including cardiac resynchronization therapy (CRT) to correct cardiac dyssynchrony within a ventricle or between ventricles.

Some IMDs are capable of detecting cardiac arrhythmias, such as atrial fibrillation (AF). AF is the most common clinical arrhythmia affecting millions of people. During AF, disorganized electrical pulses originated from regions in or near an atrium may lead to irregular conductions to ventricles, thereby causing inappropriately fast and irregular heart rate. AF may be paroxysmal that may last from minutes to days before it stops by itself, persistent that may last for over a week and typically requires medication or other treatment to revert to normal sinus rhythm, or permanent where a normal heart rhythm cannot be restored with treatment. Timely detection of AF may be clinically important for assessing progression of AF.

For example, document <CIT> describes a method and apparatus for detecting atrial arrhythmias and discriminating atrial fibrillation (AF) and organized atrial tachycardia (OAT) that includes defining a threshold detection criteria for a cluster signature evidence metric corresponding to a Lorenz distribution of ventricular cycle lengths representative of AF or OAT. Using a signal containing VCL information, a number of consecutive ventricular cycle lengths are determined during a selected time interval for generating a one-dimensional or a two-dimensional histogram as a numerical representation of a Lorenz plot of VCLs. A number of cluster signature metrics are computed using the stored ventricular cycle length information, and a cluster signature evidence metric is computed from the cluster signature metrics. AF or OAT is detected if a comparative analysis of a corresponding cluster signature evidence metric meets a respective threshold detection criteria.

As a further example, document <CIT> describes techniques for detecting atrial fibrillation (AF) based on variations in ventricular intervals detected by a pacemaker, implantable cardioverter-defibrillator (ICD) or implantable cardiac monitor (ICM). In one example, ventricular beats are detected and intervals between the ventricular beats are measured, such as RR intervals. Irregular ventricular beats are identified, including ectopic beats, bigeminal beats, and the like. The degree of variability within the ventricular intervals is then determined while excluding any intervals associated with irregular beats. AF is then detected based on the degree of variability. That is, AF is detected based on variability occurring within ventricular intervals after ectopic beats and other irregular beats have been eliminated, thus mitigating detection problems that might arise if the variability were instead calculated based on all ventricular beat intervals. Techniques are also described herein for distinguishing AF from sinus tachycardia, which can also cause a high degree of variability in RR intervals.

Document <CIT> describes an implantable anti-tachyarrhythmia device which delivers anti-tachyarrhythmia therapies to a patient's heart in response to detection of tachyarrhythmias. The device defines first criteria indicating the presence of atrial tachycardia and second criteria indicating the presence of atrial fibrillation, and compares the time elapsed since the either the first or second criteria were initially met to a defined time duration. In response to the defined duration having passed and either of the first or second criteria being met, the device triggers delivery of an appropriate anti-tachyarrhythmia therapy. The timer is reset on detection of termination of atrial tachyarrhythmia, but not on failure of the first and second criteria to be met. The first and second criteria are defined such that they can not be concurrently met.

Implantable medical devices are capable of detecting physiological events, such as cardiac arrhythmias or progression of chronic heart diseases, and obtaining sampled values of cardiac electrical activity signals such as electrograms. Some IMDs may further be communicated with multiple physiological sensors that may measure various physiological signals. The IMD may be programmed to monitor and store data sensed from some or all of the physiological sensors.

Capturing accurate electrogram or other physiological sensor information obtained over a longer period of time, such as chronically between regularly-scheduled outpatient office visits, may help the physician re-program the device, if needed, or to diagnose and assess the patient's condition. In an IMD programmed to detect cardiac arrhythmias such as atrial fibrillation (AF) episodes, noise, motion artifacts, or cardiac rhythms other than the AF episode may be inappropriately detected as AF episodes. Inappropriate arrhythmia detection may reduce detection specificity and result in inappropriate AF therapy. Alerts to clinicians of inappropriately detected arrhythmic events, or presenting to clinicians a large volume of inappropriately detected arrhythmic events for review or adjudication, may adversely affect the device efficacy and unwarrantedly increase the cost associated with patient management. For at least these reasons, the present inventors have recognized, among other things, substantial challenges and a demand for a more efficient arrhythmic detection and reporting system.

This document discusses, among other things, systems, devices, and non-claimed methods for detecting cardiac arrhythmias such as AF.

The first example is a system in accordance with the invention for detecting cardiac arrhythmia. The system may comprise a sensor circuit configured to sense a physiological signal. The system comprises a heartbeat processor, and an arrhythmia detector coupled to the heartbeat processor. The heartbeat processor is configured to determine cardiac cycle lengths (CLs) from a physiological signal sensed from a subject (e.g., sensed by means of the sensor circuit); recognize a plurality of beat patterns based on respective two or more consecutive CLs, where the beat pattern indicates a temporal relationship between the two or more consecutive cardiac cycles; and generate a repetitiveness indicator of the beat pattern based on a statistical measurement of the plurality of beat patterns, where the repetitiveness indicator indicates randomness of the CLs. The arrhythmia detector is configured to detect atrial fibrillation (AF) based on the repetitiveness indicator of the beat pattern. Further details of the system according to the invention are defined in claim <NUM>.

In an example, the system may optionally include a therapy circuit configured to generate and deliver an AF therapy in response to the detection of the AF.

The beat pattern includes a cycle length statistic of consecutive cardiac cycles, and the repetitiveness indicator includes a count of the computed cycle length statistics that are substantially identical within a specified tolerance. The arrhythmia detector is configured to detect the AF when the count of the computed cycle length statistics falls below an AF threshold.

The cycle length statistic includes one of a maximum cycle length and a minimum cycle length, and optionally a median cycle length, each computed from the consecutive cardiac cycles within a time window.

The count of the computed cycle length statistics that may include a relative count, and the arrhythmia detector is configured to detect the AF when the computed count of the computed cycle length statistics exceeds a threshold value of at least <NUM>%.

In an example, the cycle length statistic may be computed from consecutive cardiac cycles within a time window having a specified time duration or specified number of cardiac cycles.

In an example, the beat patterns may include an ascending CL sequence of two or more consecutive cardiac cycles progressively increasing by at least a specified step size, and a descending CL sequence of two or more consecutive cardiac cycles progressively decreasing by at least a specified step size; wherein the heartbeat processor is configured to determine the repetitiveness indicator using a first count of ascending CL sequences and a second count of descending CL sequences from the determined cardiac cycles; and wherein the arrhythmia detector is configured to detect the AF when the generated repetitiveness indicator falls below an AF threshold.

In an example, the beat patterns may further include an identical CL sequence of two or more consecutive cardiac cycles of substantially identical CL. The heartbeat processor is configured to generate the repetitiveness indicator further using a third count of identical CL sequences.

In an example, the heartbeat processor may be configured to generate the repetitiveness indicator using (<NUM>) an accumulative observed count including the first count of ascending CL sequences and the second count of descending CL sequences, (<NUM>) an expected count computed using the first and second counts, and (<NUM>) a standard deviation of counts of the ascending and descending CL sequences.

In an example, the arrhythmia detector may be further configured to detect atrioventricular conduction abnormality (ACA) when the repetitiveness indicator exceeds an ACA threshold.

In an example, the atrioventricular conduction abnormality may include Wenckebach rhythm.

In an example, the system may include an ambulatory device that may include at least a portion of one or more of the sensor circuit, the heartbeat processor, or the arrhythmia detector.

In an example, the ambulatory device may include an implantable or wearable device.

In an example, the heartbeat processor may be further configured to compute a stability of the CLs; and the arrhythmia detector is configured to detect the AF further based on the stability of the CLs and the repetitiveness indicator of the beat pattern.

In an example, the stability of the CLs includes a CL distribution according to a histogram of the CLs.

The present disclosure provides a method for detecting cardiac arrhythmia. The method, which does not form part of the claimed invention and is provided for illustrative purposes only, comprises sensing a physiological signal; determining cardiac cycle lengths (CLs) from the sensed physiological signal; recognizing a plurality of beat patterns using respective two or more consecutive CLs, the beat pattern indicating a temporal relationship between the two or more consecutive cardiac cycles; generating a repetitiveness indicator of the beat pattern based on a statistical measurement of the plurality of beat patterns, the repetitiveness indicator indicating randomness of the determined CLs; and detecting atrial fibrillation (AF) based on the repetitiveness indicator of the beat pattern.

In an example, the non-claimed method optionally includes generating and delivering an AF therapy in response to the detection of AF.

In an example, the beat pattern may include a cycle length statistic of consecutive CLs; and the repetitiveness indicator includes a count of the computed cycle length statistics that are substantially identical within a specified tolerance; wherein the detection of AF includes detecting AF when the count of the computed cycle length statistics falls below an AF threshold.

In an example, the non-claimed method optionally includes wherein the cycle length statistic includes one of a maximum cycle length, a minimum cycle length, or a median cycle length each computed from the consecutive CLs within a time window.

In an example, the non-claimed method optionally includes the beat patterns that may include an ascending CL sequence of two or more consecutive cardiac cycles progressively increasing by at least a specified step size, and a descending CL sequence of two or more consecutive cardiac cycles progressively decreasing by at least a specified step size. The repetitiveness indicator may be generated using a first count of ascending CL sequences and a second count of descending CL sequences from the determined cardiac cycles; and detecting AF includes detecting AF when the generated repetitiveness indicator falls below an AF threshold.

In an example, the non-claimed method optionally includes the beat patterns that may further include an identical CL sequence of two or more consecutive cardiac cycles of substantially identical CL, and wherein determining the repetitiveness indicator further includes using a third count of identical CL sequences.

In an example, the non-claimed method optionally includes detecting an atrioventricular conduction abnormality (ACA) when the repetitiveness indicator exceeds an ACA threshold.

In an example, the non-claimed method optionally includes computing a stability of the CLs, wherein the detection of AF further includes detecting AF based on the stability of the CLs and the repetitiveness indicator of the beat pattern.

In an example, a system may optionally combine any portion or combination of any portion of any one or more of the aforementioned examples to include "means for" performing any portion of any one or more of the functions or methods of the aforementioned examples, or a "non-transitory machine-readable medium" including instructions that, when performed by a machine, cause the machine to perform any portion of any one or more of the functions or methods of the aforementioned examples.

Although the discussion herein focuses on cardiac arrhythmia detection, this is meant only by way of example and not limitation. The systems, devices, and non-claimed methods discussed in this document, such as the beat patterns and repetitiveness indicator indicating a degree of organization of the rhythm, may also be used for monitoring physiologic events other than cardiac arrhythmias, including progression of a chronic disease, such as a worsening heart failure, heart failure decompensation, pulmonary edema, pulmonary condition exacerbation, asthma and pneumonia, myocardial infarction, dilated cardiomyopathy, ischemic cardiomyopathy, valvular disease, renal disease, chronic obstructive pulmonary disease, peripheral vascular disease, cerebrovascular disease, hepatic disease, diabetes, anemia, or depression, among others.

This Overview is an overview of some of the teachings of the present application and not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details about the present subject matter are found in the detailed description and appended claims. Other aspects of the disclosure will be apparent to persons skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which are not to be taken in a limiting sense. The scope of the present invention is defined by the appended claims and their legal equivalents.

Disclosed herein are systems, devices, and non-claimed methods for detecting cardiac arrhythmias such as an atrial fibrillation (AF). The AF detection system includes a sensor circuit to sense a physiological signal, a heartbeat processor to recognize beat patterns using cycle length of two more consecutive cardiac cycles. The beat pattern can be indicative of temporal relationship between the consecutive cardiac cycles. The heartbeat processor may generate a repetitiveness indictor based on a statistical measurement of various beat patterns. The AF detection system includes an arrhythmia detector to detect AF based on the repetitiveness indictor, and to discriminate AF from other arrhythmias with atrio-ventricular conduction abnormalities.

<FIG> illustrates generally an example of a Cardiac Rhythm Management (CRM) system <NUM> and portions of an environment in which the CRM system <NUM> may operate. The CRM system <NUM> may include an ambulatory medical device, such as an implantable medical device (IMD) <NUM> that may be electrically coupled to a heart <NUM> such as through one or more leads 108A-C, and an external system <NUM> that may communicate with the IMD <NUM> such as via a communication link <NUM>. The IMD <NUM> may include an implantable cardiac device such as a pacemaker, an implantable cardioverter-defibrillator (ICD), or a cardiac resynchronization therapy defibrillator (CRT-D). In some examples, the CRM system may include one or more monitoring or therapeutic devices such as a subcutaneously implanted device, a neural stimulator, a drug delivery device, a biological therapy device, an ambulatory medical device, or a wearable external device such as a smartphone, a smartwatch, a wearable fitness or activity tracker, or a wearable health monitor. The IMD <NUM> may be coupled to, or may be substituted by a monitoring medical device such as a bedside or other external monitor.

The IMD <NUM> may include a hermetically sealed can housing <NUM> that may house an electronic circuit that may sense a physiological signal in the heart <NUM> and may deliver one or more therapeutic electrical pulses to a target region, such as in the heart, such as through one or more leads 108A-C. The CRM system <NUM> may include only one lead such as 108B, or may include two leads such as 108A and 108B.

The lead 108A may include a proximal end that may be configured to be connected to IMD <NUM> and a distal end that may be configured to be placed at a target location such as in the right atrium (RA) <NUM> of the heart <NUM>. The lead 108A may have a first pacing-sensing electrode <NUM> that may be located at or near its distal end, and a second pacing-sensing electrode <NUM> that may be located at or near the electrode <NUM>. The electrodes <NUM> and <NUM> may be electrically connected to the IMD <NUM> such as via separate conductors in the lead 108A, such as to allow for sensing of the right atrial activity and optional delivery of atrial pacing pulses. The lead 108B may be a defibrillation lead that may include a proximal end that may be connected to IMD <NUM> and a distal end that may be placed at a target location such as in the right ventricle (RV) <NUM> of heart <NUM>. The lead 108B may have a first pacing-sensing electrode <NUM> that may be located at distal end, a second pacing-sensing electrode <NUM> that may be located near the electrode <NUM>, a first defibrillation coil electrode <NUM> that may be located near the electrode <NUM>, and a second defibrillation coil electrode <NUM> that may be located at a distance from the distal end such as for superior vena cava (SVC) placement. The electrodes <NUM> through <NUM> may be electrically connected to the IMD <NUM> such as via separate conductors in the lead 108B. The electrodes <NUM> and <NUM> may allow for sensing of a ventricular electrogram and may allow delivery of one or more ventricular pacing pulses, and electrodes <NUM> and <NUM> may allow for delivery of one or more ventricular cardioversion/defibrillation pulses. In an example, the lead 108B may include only three electrodes <NUM>, <NUM> and <NUM>. The electrodes <NUM> and <NUM> may be used for sensing or delivery of one or more ventricular pacing pulses, and the electrodes <NUM> and <NUM> may be used for delivery of one or more ventricular cardioversion or defibrillation pulses. The lead 108C may include a proximal end that may be connected to the IMD <NUM> and a distal end that may be configured to be placed at a target location such as in a left ventricle (LV) <NUM> of the heart <NUM>. The lead 108C may be implanted through the coronary sinus <NUM> and may be placed in a coronary vein over the LV such as to allow for delivery of one or more pacing pulses to the LV. The lead 108C may include an electrode <NUM> that may be located at a distal end of the lead 108C and another electrode <NUM> that may be located near the electrode <NUM>. The electrodes <NUM> and <NUM> may be electrically connected to the IMD <NUM> such as via separate conductors in the lead 108C such as to allow for sensing of the LV electrogram and allow delivery of one or more resynchronization pacing pulses from the LV. Additional electrodes may be included in or along the lead 108C. In an example, as illustrated in <FIG>, a third electrode <NUM> and a fourth electrode <NUM> may be included in the lead <NUM>. In some examples (not shown in <FIG>), at least one of the leads 108A-C, or an additional lead other than the leads 108A-C, may be implanted under the skin surface without being within at least one heart chamber, or at or close to heart tissue.

The IMD <NUM> may include an electronic circuit that may sense a physiological signal. The physiological signal may include an electrogram or a signal representing mechanical function of the heart <NUM>. The hermetically sealed can housing <NUM> may function as an electrode such as for sensing or pulse delivery. For example, an electrode from one or more of the leads 108A-C may be used together with the can housing <NUM> such as for unipolar sensing of an electrogram or for delivering one or more pacing pulses. A defibrillation electrode from the lead 108B may be used together with the can housing <NUM> such as for delivering one or more cardioversion/defibrillation pulses. In an example, the IMD <NUM> may sense impedance such as between electrodes located on one or more of the leads 108A-C or the can housing <NUM>. The IMD <NUM> may be configured to inject current between a pair of electrodes, sense the resultant voltage between the same or different pair of electrodes, and determine impedance using Ohm's Law. The impedance may be sensed in a bipolar configuration in which the same pair of electrodes may be used for injecting current and sensing voltage, a tripolar configuration in which the pair of electrodes for current injection and the pair of electrodes for voltage sensing may share a common electrode, or tetrapolar configuration in which the electrodes used for current injection may be distinct from the electrodes used for voltage sensing. In an example, the IMD <NUM> may be configured to inject current between an electrode on the RV lead 108B and the can housing <NUM>, and to sense the resultant voltage between the same electrodes or between a different electrode on the RV lead 108B and the can housing <NUM>. A physiological signal may be sensed from one or more physiological sensors that may be integrated within the IMD <NUM>. The IMD <NUM> may also be configured to sense a physiological signal from one or more external physiological sensors or one or more external electrodes that may be coupled to the IMD <NUM>. Examples of the physiological signal may include one or more of thoracic impedance, intracardiac impedance, arterial pressure, pulmonary artery pressure, RV pressure, LV coronary pressure, coronary blood temperature, blood oxygen saturation, one or more heart sounds, physical activity or exertion level, posture, respiration, body weight, or body temperature.

The arrangement and functions of these leads and electrodes are described above by way of non-limiting example and not by way of limitation. Depending on the need of the patient and the capability of the implantable device, other arrangements and uses of these leads and electrodes are contemplated.

As illustrated, the CRM system <NUM> includes a cardiac arrhythmia detector <NUM> for detecting an arrhythmic event such as an atrial fibrillation (AF) episode using a physiological signal detected from the patient. The cardiac arrhythmia detector <NUM> determines a heart rate (HR) pattern or, in accordance with the invention, a cardiac cycle length (CL) pattern using heart rates or, in accordance with the invention, cycle lengths determined from the physiological signal. Using various HR or CL patterns, the cardiac arrhythmia detector <NUM> generates a repetitiveness indicator indicative of randomness of the heart rates or cycle lengths. A more repetitive CL or HR pattern may weigh against AF, while a less repetitive or more random CL or HR pattern may weigh toward AF. The cardiac arrhythmia detector <NUM> detects AF based on the repetitiveness indicator. In some examples, the cardiac arrhythmia detector <NUM> may further discriminate AF from other types of arrhythmias such as arrhythmias with atrio-ventricular conduction abnormalities. Examples of the cardiac arrhythmia detector <NUM> are described below, such as with reference to <FIG>.

The external system <NUM> may allow for programming of the IMD <NUM> and may receive information about one or more signals acquired by IMD <NUM>, such as may be received via a communication link <NUM>. The external system <NUM> may include a local external IMD programmer. The external system <NUM> may include a remote patient management system that may monitor patient status or adjust one or more therapies such as from a remote location.

The communication link <NUM> may include one or more of an inductive telemetry link, a radio-frequency telemetry link, or a telecommunication link, such as an internet connection. The communication link <NUM> may provide for data transmission between the IMD <NUM> and the external system <NUM>. The transmitted data may include, for example, real-time physiological data acquired by the IMD <NUM>, physiological data acquired by and stored in the IMD <NUM>, therapy history data or data indicating IMD operational status stored in the IMD <NUM>, one or more programming instructions to the IMD <NUM> such as to configure the IMD <NUM> to perform one or more actions that may include physiological data acquisition such as using programmably specifiable sensing electrodes and configuration, device self-diagnostic test, or delivery of one or more therapies.

The cardiac arrhythmia detector <NUM>, although as illustrated in <FIG> included within the IMD <NUM>, may alternatively be implemented in a subcutaneously implanted device, a wearable external device, a neural stimulator, a drug delivery device, a biological therapy device, or one or more diagnostic devices. In some examples, the cardiac arrhythmia detector <NUM> may be implemented in the external system <NUM>. The external system <NUM> may include a health status monitor, which may be configured to detect worsening heart failure (WHF) using data extracted from the IMD <NUM> or data stored in a memory within the external system <NUM>. The external system <NUM> may include a user interface that may display information about detection of AF or other cardiac events. In an example, portions of the cardiac arrhythmia detector <NUM> may be distributed between the IMD <NUM> and the external system <NUM>.

Portions of the IMD <NUM> or the external system <NUM> may be implemented using hardware, software, or any combination of hardware and software. Portions of the IMD <NUM> or the external system <NUM> may be implemented using an application-specific circuit that may be constructed or configured to perform one or more particular functions, or may be implemented using a general-purpose circuit that may be programmed or otherwise configured to perform one or more particular functions. Such a general-purpose circuit may include a microprocessor or a portion thereof, a microcontroller or a portion thereof, or a programmable logic circuit, or a portion thereof. For example, a "comparator" may include, among other things, an electronic circuit comparator that may be constructed to perform the specific function of a comparison between two signals or the comparator may be implemented as a portion of a general-purpose circuit that may be driven by a code instructing a portion of the general-purpose circuit to perform a comparison between the two signals. While described with reference to the IMD <NUM>, the CRM system <NUM> may include a subcutaneous medical device (e.g., subcutaneous ICD, subcutaneous diagnostic device), wearable medical devices (e.g., patch based sensing device), or other external medical devices.

<FIG> illustrates generally an example of an arrhythmia detection system <NUM> in accordance with the invention that is configured to detect a cardiac arrhythmia from a patient, such as an atrial fibrillation (AF) episode. The arrhythmia detection system <NUM> is an embodiment of the cardiac arrhythmia detector <NUM>. The arrhythmia detection system <NUM> includes an optional sensor circuit <NUM>, a heartbeat processor <NUM>, an arrhythmia detector <NUM>, an optional controller circuit <NUM>, and an optional user interface unit <NUM>. The arrhythmia detection system <NUM> may be configured as a cardiac monitor or diagnostic device for monitoring patient health status. In some examples, the arrhythmia detection system <NUM> may additionally include an optional therapy circuit <NUM> and configured as a therapeutic device.

The sensor circuit <NUM> may include a sense amplifier circuit to sense a physiological signal sensed from a patient via one or more implantable, wearable, or otherwise ambulatory sensors or electrodes associated with the patient. Examples of the physiological signals may include surface electrocardiography (ECG) such as sensed from electrodes on the body surface, subcutaneous ECG such as sensed from electrodes placed under the skin, intracardiac electrogram (EGM) sensed from the one or more electrodes of the leads 108A-C or the can housing112, thoracic or cardiac impedance signal, arterial pressure signal, pulmonary artery pressure signal, left atrial pressure signal, RV pressure signal, LV coronary pressure signal, coronary blood temperature signal, blood oxygen saturation signal, heart sound signal such as sensed by an ambulatory accelerometer or acoustic sensors, physiological response to activity, apnea hypopnea index, one or more respiration signals such as a respiration rate signal or a tidal volume signal, brain natriuretic peptide (BNP), blood panel, sodium and potassium levels, glucose level and other biomarkers and bio-chemical markers, among others. The sensor circuit <NUM> may include one or more other sub-circuits to digitize, filter, or perform other signal conditioning operations on the received physiological signal.

In some examples, the physiological signals may be stored in a storage device such as an electronic medical record (EMR) system. The sensor circuit <NUM> may be configured to retrieve a physiological signal from the storage device in response to a command signal that is provided by a system user, or automatically generated in response to occurrence of a specified event.

The heartbeat processor <NUM> may be coupled to the sensor circuit <NUM> to analyze beat patterns. The heartbeat processor <NUM> includes a cycle length/heart rate detector <NUM> and optionally a beat pattern analyzer <NUM>. In an example, the sensor circuit <NUM> may sense a cardiac electrical signal such as a ECG, a subcutaneous ECG, or an intracardiac EGM, and the cycle length/heart rate detector <NUM> may detect from the cardiac electrical signal electrophysiological events indicative of cardiac depolarization or repolarization at a portion of the heart, such as an atrium, a ventricle, a His-bundle, or a septum. Examples of the sensed electrophysiological events may include P wave, Q wave, R wave, QRS complex, or T wave in a surface or subcutaneous ECG or an intracardiac EGM. The sensor circuit <NUM> may additionally or alternatively include one or more sensors configured to sense cardiac mechanical activity indicative of heart contractions, and the cycle length/heart rate detector <NUM> may detect from the sensed cardiac mechanical activity mechano-physiological events indicative of one or more of atrial contraction, ventricular contraction, end of filling, end of emptying, or other specified phase during a cardiac contraction cycle. Examples of the sensors for sensing cardiac mechanical activity may include an accelerometer or a microphone configured to sense a heart sound signal or an endocardial acceleration signal from the heart, an impedance sensor configured to sense cyclic changes in cardiac impedance as a result of cardiac contractions, or a blood pressure sensor or a blood flow sensor for sensing pulsatile arterial pressure or flow as a result of cyclic cardiac contractions and opening/closure of heart valves, among other sensors. Examples of the mechano-physiological events may include: S1, S2, S3, or S4 heart sound from the sensed heart sound signal, peak or trough impedance from the cardiac impedance signal, or peak or trough blood pressure from the blood pressure signal, among others.

The cycle length/heart rate detector <NUM> may detect HR or CL using the detected electrophysiological or mechano-physiological events. In an example, the CL, in a unit of second or millisecond, may be measured a time interval between two adjacent R waves (R-R interval) or P waves (P-P interval), or between adjacent impedance peaks or adjacent impedance troughs from the cardiac impedance signal, or an interval between two adjacent blood pressure peaks (i.e., systolic pressure) or adjacent blood pressure troughs (i.e., diastolic pressure) from the blood pressure signal, among others. The HR, in a unit of beats per minute (bpm), may be computed using the CL such as according to HR = <NUM> seconds/CL.

The beat pattern analyzer <NUM>, which is coupled to the cycle length/heart rate detector <NUM>, recognizes a plurality of beat patterns using the HR measurements or, in accordance with the invention, CL measurements. The beat patterns indicate temporal relationships between the two or more consecutive cardiac cycles. In an example, the beat patterns may be recognized using respective two or more consecutive CLs, including a consecutively ascending CL pattern characterized by lengthening of CL of the present cardiac cycle from the immediately previous cardiac cycle, a consecutively descending CL pattern characterized by shortening of CL of the present cardiac cycle from the immediately previous cardiac cycle, or an identical CL pattern characterized by consecutive cardiac cycles having substantially identical cycle length, among other beat patterns. The beat pattern analyzer <NUM> performs a statistical analysis of a plurality of beat patterns, and generates a repetitiveness indicator of the beat pattern indicating a degree of randomness of the determined CLs. Examples of the beat pattern analyzer <NUM> are discussed below, such as with reference to <FIG> and <FIG>.

The arrhythmia detector <NUM> is coupled to the beat pattern analyzer <NUM> to detect a cardiac arrhythmia at least based on the repetitiveness indicator of the beat patterns. Examples of cardiac arrhythmias may include atrial fibrillation (AF), atrial flutter (AFL), atrial tachycardia, paroxysmal supraventricular tachycardia (PSVT), Wolff-Parkinson-White (WPW) syndrome, ventricular tachycardia, ventricular fibrillation, bradycardia, or sinus pauses, among others. In an example, the arrhythmia detector <NUM> may be configured to discriminate between AF and unstable but substantially organized rhythms such as cardia rhythms with various degrees of atrio-ventricular conduction abnormalities (such as Wenckebach rhythm) or premature atrial contractions (PACs). Although such unstable and organized rhythms may manifest variable HR or CL which may resemble atrial arrhythmias such as AF, they nevertheless may have more organized (or less random) beat patterns and thus a higher degree of repetitiveness than a typical AF episode. In an example, the arrhythmia detector <NUM> may trend the repetitiveness indicator over time. In accordance with the invention, if the repetitiveness indicator falls below a specified threshold, a more disorganized beat pattern is indicated and an AF episode is detected. In another example, the arrhythmia detector <NUM> may include a first arrhythmia detector and a different second arrhythmia detector. The first arrhythmia detector may be sensitive but less specific to AF, and detects AF based on HR or CL stability. The second arrhythmia detector may be more specific to AF, and employs a beat pattern and repetitiveness based method to confirm, reject, or other modify the detection provided by the first arrhythmia detector. The second arrhythmia detector may additionally distinguish an AF episode from an unstable and organized rhythm. Examples of the arrhythmia detector <NUM> are discussed below, such as with reference to <FIG>.

As illustrated in <FIG>, the heartbeat processor <NUM> or the arrhythmia detector <NUM> may respectively include circuit sets comprising one or more other circuits or sub-circuits. The circuits or sub-circuits may, alone or in combination, perform the functions, methods, or techniques described herein. In an example, hardware of the circuit set may be immutably designed to carry out a specific operation (e.g., hardwired). In an example, the hardware of the circuit set may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) including a computer readable medium physically modified (e.g., magnetically, electrically, moveable placement of invariant massed particles, etc.) to encode instructions of the specific operation. In connecting the physical components, the underlying electrical properties of a hardware constituent are changed, for example, from an insulator to a conductor or vice versa. The instructions enable embedded hardware (e.g., the execution units or a loading mechanism) to create members of the circuit set in hardware via the variable connections to carry out portions of the specific operation when in operation. Accordingly, the computer readable medium is communicatively coupled to the other components of the circuit set member when the device is operating. In an example, any of the physical components may be used in more than one member of more than one circuit set. For example, under operation, execution units may be used in a first circuit of a first circuit set at one point in time and reused by a second circuit in the first circuit set, or by a third circuit in a second circuit set at a different time.

In various examples, the heartbeat processor <NUM> or the arrhythmia detector <NUM> may be implemented as a part of a microprocessor circuit. The microprocessor circuit may be a dedicated processor such as a digital signal processor, application specific integrated circuit (ASIC), microprocessor, or other type of processor for processing information including the physiological signals received from the sensor circuit <NUM>. Alternatively, the microprocessor circuit may be a general purpose processor that may receive and execute a set of instructions of performing the functions, methods, or techniques described herein.

The controller circuit <NUM> may control the operations of the sensor circuit <NUM>, the heartbeat processor <NUM>, the arrhythmia detector <NUM>, the user interface unit <NUM>, and the data and instruction flow between these components. The controller circuit <NUM> may control the heartbeat pattern analysis and arrhythmia detection, and configure the user interface unit <NUM> to output the beat patterns, the repetitiveness indicator, or the detected cardiac arrhythmia to a user or a process. The user interface unit <NUM> may include an input unit <NUM> and an output unit <NUM>. In an example, at least a portion of the user interface unit <NUM> may be implemented in the external system <NUM>. The input unit <NUM> may receive a user's programming input, such as respective parameters for beat pattern analysis or parameters for arrhythmia detection. The input unit <NUM> may include an input device such as a keyboard, on-screen keyboard, mouse, trackball, touchpad, touch-screen, or other pointing or navigating devices. The input device may enable a system user to program the parameters used for sensing the physiological signals, detecting the arrhythmias, and generating alerts, among others. The output unit <NUM> may generate a human-perceptible presentation of information including one or more of the detection of the target cardiac arrhythmia, confidence indicators associated with the detected arrhythmic events, alerts generated for the detected arrhythmias, or other system information. The output unit <NUM> may include a display for displaying the information. The information may be presented in a table, a chart, a diagram, or any other types of textual, tabular, or graphical presentation formats, for displaying to a system user. The presentation of the output information may include audio or other media format to alert the system user of the detected physiological events.

The optional therapy circuit <NUM> may be configured to deliver a therapy to the patient in response to the detection of the arrhythmia. Examples of the therapy may include electrostimulation therapy delivered to the heart, a nerve tissue, other target tissues, a cardioversion therapy, a defibrillation therapy, or drug therapy including delivering drug to a tissue or organ. In some examples, the therapy circuit <NUM> may modify an existing therapy, such as adjust a stimulation parameter or drug dosage.

<FIG> illustrate generally examples of beat pattern analyzer for analyzing the beat patterns to determine a degree of randomness of a cardiac rhythm. Beat pattern analyzer <NUM> as illustrated in <FIG> in accordance with the invention and beat pattern analyzer <NUM> as illustrated in <FIG> may each be an embodiment of the beat pattern analyzer <NUM>.

The beat pattern analyzer <NUM> includes a cycle length statistics generator <NUM> and a beat counter <NUM>. The cycle length statistics generator <NUM> generates a beat pattern including a cycle length statistic based on cycle lengths of a plurality of consecutive cardiac cycles. In accordance with the invention, the CL statistic includes one of a maximum cycle length (maxCL) or a minimum cycle length (minCL), each computed from a plurality of consecutive CLs within respective time windows. Further examples of CL statistics are a median cycle length (medCL), or an average cycle length (avgCL), each computed from a plurality of consecutive CLs within respective time windows. The beat counter <NUM>, coupled to the CL statistics generator, generates a repetitiveness indicator including a percentage of the computed CL statistics that are substantially identical within a specified tolerance.

In an example, in analyzing a cardiac rhythm from a physiological signal, the CL statistics generator <NUM> may apply multiple data windows {W} = (W1, W2,. , Wn) to the consecutive HRs or CLs, and compute the statistics such as maxCL, minCL, medCL, or avgCL using the HRs or CLs within the data windows {W}. The data window may be defined as a specified time duration or a specified number of cardiac cycles. The beat counter <NUM> may identify and count the data windows associated with the CL statistics satisfying a specified condition such as being substantially identical within a specified tolerance. In an example where the maxCL statistics {maxCL} = (maxCL1, maxCL2,. , maxCLn) are computed respectively for the data windows {W} = (W1, W2,. , Wn), the substantially identical CL statistics may include those falling within a specified range defined a lower bound (LB) and an upper bound (UB) of maxCL. The LB and UB may respectively be determined using a central tendency µ (e.g., an average) and a standard deviation σ of all or a portion of {maxCL}. In an example, LB = µ- c1*σ and UB = µ+ c2*σ, where c1 and c2 are constants controlling the tolerance for identicalness. In an example, the c1 and c2 may be approximately <NUM>-<NUM>%. The beat counter <NUM> may determine a relative count, such as a fraction or a percentage, of the maxCL that falls within the range defined by the LB and UB. The arrhythmia detector <NUM> may detect the AF when the percentage of the CL statistics fall below an AF threshold. In an example, the AF threshold is approximately <NUM>%. Examples of the repetitiveness indicator based on CL statistics are discussed below, such as with reference to <FIG>.

The beat pattern analyzer <NUM> as illustrated in <FIG> may include a beat pattern generator <NUM>, a beat counter <NUM>, and a statistical analyzer <NUM>. The beat pattern generator <NUM> may generate one or more beat patterns indicative of temporal relationship between two or more consecutive cardiac cycles. By way of non-limiting example, the beat patterns may include one or more ascending CL sequences <NUM> of consecutive cardiac cycles progressively increasing by at least a specified step size δ<NUM> and descending CL sequences <NUM> of two or more consecutive cardiac cycles progressively decreasing by at least a specified step size δ<NUM>. The step size δ<NUM> may be different than the step size δ<NUM>.

The beat pattern generator <NUM> may compute various beat patterns in an automated process, which includes computing a difference CL sequence {ΔCL} = {ΔCL1, ΔCL2,. , ΔCLn} where ΔCLi denotes a difference between two adjacent cycle lengths CL(i+<NUM>) and CL(i), that is, ΔCLi = CL(i+<NUM>) - CL(i). The difference ΔCLi may be assigned a symbol "L" denoting CL lengthening if ΔCLi is positive and ΔCLi> δ<NUM>, or a symbol "S" denoting CL shortening if ΔCLi is negative and ΔCLi < δ<NUM>, or a symbol "I" denoting identical CL if δ<NUM> < ΔCLi < δ<NUM>. As such, the difference CL sequence {ΔCL} may then be transformed into a symbolic sequence comprising one or more of "S", "L", and "I".

In an example, the ascending CL sequences <NUM> may include an ascending sequence of two consecutive cardiac cycles with cycle lengths CL1<CL2, represented by an "L" sequence or a "+<NUM>" pattern indicating CL2 longer than the previous CL1 by at least δ<NUM>. In another example, the ascending CL sequences <NUM> may include an ascending sequence of three consecutive cardiac cycles with cycle lengths CL1<CL2<CL3, represented by an "LL" sequence or a "+<NUM>" pattern indicating CL2 longer than the previous CL1 by at least δ<NUM>, and CL3 longer than the previous CL2 by at least δ<NUM>. In an example, the descending CL sequences <NUM> may include a descending sequence of two consecutive cardiac cycles with cycle lengths CL1> CL2, represented by an "S" sequence or a "-<NUM>" pattern indicating CL2 shorter than the previous CL1 by at least δ<NUM>. In another example, the descending CL sequences <NUM> may include a descending sequence of three consecutive cardiac cycles with cycle lengths CL1>CL2>CL3, represented by an "SS" sequence or a "-<NUM>" pattern indicating CL2 shorter than the previous CL1 by at least δ<NUM>, and CL3 shorter than the previous CL2 by at least δ<NUM>. In some examples, the beat patterns generated by the beat pattern generator <NUM> may additionally include an identical CL sequence <NUM> represented by an "I" sequence or a "<NUM>" pattern. The identical CL sequence <NUM> may include two or more consecutive cardiac cycles of substantially identical cycle length within a specified tolerance, such as the difference between the consecutive cycle lengths CL1 and CL2 falling between δ<NUM> and δ<NUM>, that is, δ<NUM> < CL2-CL1 < δ<NUM>. Table <NUM> below shows examples of the symbolic sequence and the corresponding beat patterns.

The beat counter <NUM> may identify and count various beat patterns from a sequence of HRs or CLs measured from a physiological signal. For example, a symbolic sequence of X = LSSLSSLLSSI that is transformed from {ΔCL} includes three "SS" sequences, one "I" sequence, two "L" sequences, and one "LL" sequence. Accordingly, the beat counter <NUM> may determine pattern counts as shown in Table <NUM>.

The statistical analyzer <NUM> may determine a repetitiveness indicator based on the beat pattern counts such as those illustrated in Table <NUM>. In an example, positive beat patterns, such as corresponding to beat patterns of "+<NUM>", "+<NUM>", "+<NUM>" etc. are accumulated to produce a first count (N1) of ascending CL sequences. Similarly, negative beat patterns, such as corresponding to beat patterns of "-<NUM>", "-<NUM>", "-<NUM>" etc. are accumulated to produce a second count (N2) of descending CL sequences. For the symbolic sequence X discussed above, according to Table <NUM>, the first and second counts may be determined as N1 = <NUM>+<NUM> = <NUM>, and N2 = <NUM>. In some examples, the "I" sequences or "<NUM>" beat patterns, if any, may be counted towards either the ascending or the descending CL sequences, such that the first or second count (N1 or N2) may include a count of the "I" sequences or "<NUM>" beat patterns.

The statistical analyzer <NUM> may use N1 and N2 to determine one or more composite measures, including an accumulative observed count (R), an expected count (E), and a standard deviation (SD) of counts of the ascending and descending CL sequences each using N1 and N2. These composite measures may be determined according to Equation (<NUM>) below: <MAT>.

The statistical analyzer <NUM> may determine a repetitiveness indicator using the composite measures O, E and SD, such as a Z statistic according to Equation (<NUM>) below: <MAT>.

The Z statistic as computed according to Equation (<NUM>) may indicate a degree of randomness of the CL or HR sequence being analyzed. A larger Z statistic weighs toward more organized (i.e., less random) CL or HR sequence, thus indicating the underlying rhythm being less likely an AF rhythm. Conversely, a smaller Z statistic weighs toward more random or disorganized CL or HR sequence, thus indicating the underlying rhythm being more likely an AF rhythm. The arrhythmia detector <NUM> may compare the repetitiveness indicator Z to an AF threshold, and detect an AF episode when the Z statistic falls below an AF threshold. In some examples, if R is substantially larger than E (e.g., R is greater than E by at least approximately <NUM>), then the arrhythmia detector <NUM> may decide that the underlying rhythm is an organized rhythm, rather than an AF episode.

When N1 and N2 are sufficiently large (such as when N1 and N2 are each greater than <NUM>), the repetitiveness indicator Z may follow a standard normal distribution, with a mean of zero and standard deviation of one. The repetitiveness indicator Z may be compared to a threshold representing a specified significance level (such as X%) that the underlying rhythm is not from a random process. For example, according to the standard normal distribution, at <NUM>% significance level, the threshold is <NUM>. If the absolute value of the Z statistic is greater than <NUM>, then with a <NUM>% confidence, the underlying rhythm is decided not from a random process. That is, the cardia rhythm under analysis is not an AF episode.

<FIG> illustrates generally an example of repetitiveness indicator based on CL statistics such as determined by the CL statistics generator <NUM> as shown in <FIG>. A heart rate (HR) sequence <NUM> may be generated by the cycle length/heart rate detector <NUM> such as from a physiological signal sensed from a patient or retrieved from a storage device. The HR sequence <NUM> comprises heart rates (in bpm, on the y-axis) determined from cycle lengths of consecutive cardiac cycles (on the x-axis) detected from the physiological signal. By way of non-limiting examples, <FIG> shows approximately <NUM> cardiac cycles or heartbeats for use in determining if the underlying rhythm is an AF episode or otherwise a more organized cardiac rhythm.

The cycle length statistics generator <NUM> applies a first set of data windows <NUM> to the HR sequence <NUM>, and compute a maximum cycle length (maxCL) within each data of the data windows <NUM>, resulting in maxCL statistics {maxCL} = (maxCL1, maxCL2,. Alternatively or additionally, the cycle length statistics generator <NUM> applies a second set of data windows <NUM> to the HR sequence <NUM>, and compute a minimum cycle length (minCL) within each of the data windows <NUM>, resulting in minCL statistics {minCL} = (minCL1, minCL2,. The length of the data windows <NUM> or <NUM> may be defined as a specified time duration (such as approximately <NUM>-<NUM> seconds) or a specified number of cardiac cycles (such as approximately <NUM>-<NUM> consecutive cardiac cycles). The first data windows <NUM> may have different durations than the second data windows <NUM>. By way of non-limiting example, and as illustrated in <FIG>, the first data windows <NUM> each has a duration of six consecutive cardiac cycles, and the second data windows <NUM> each has a duration of three consecutive cardiac cycles. In some examples, at least some of the data windows <NUM> may be overlapped by a specified amount, or at least some of the data windows <NUM> may be overlapped by a specified amount.

The beat counter <NUM> identifies and counts, out of the first set of data windows <NUM>, the data windows having substantially identical maxCL, such as within a specified lower and upper bounds as previously discussed with reference to <FIG>. The beat counter <NUM> additionally or alternatively identifies and counts, out of the second set of data windows <NUM>, the data windows having substantially identical minCL, such as within a specified lower and upper bounds as discussed with reference to <FIG>. The arrhythmia detector <NUM> detects an AF episode by comparing a percentage of the computed cycle length statistics to an AF threshold, such as approximately <NUM>%. In an example, the beat counter <NUM> may determine <NUM>% of the first data windows <NUM> have substantially identical maxCL values, and/or <NUM>% of the second data windows <NUM> have substantially identical minCL values. Because more than <NUM>% of the first data windows <NUM> have substantially identical maxCL, or more than <NUM>% of the second data windows <NUM> have substantially identical minCL, the arrhythmia detector <NUM> decides that the heart rate sequence <NUM> is organized, and the underlying rhythm is not an AF episode. In an example, the arrhythmia detector <NUM> may generate a composite statistic using two or more of maxCL, minCL, medCL, or avgCL, among other cycle length statistics. The composite statistic may be determined using a linear or nonlinear combination including a voting, weighted combination, decision trees, or neural networks, among others.

<FIG> illustrates generally an example of portions of an arrhythmia detector system such as for detecting an AF episode. The system portion includes a heartbeat processor <NUM> and an arrhythmia detector <NUM>, which are respectively embodiments of the heartbeat processor <NUM> and an arrhythmia detector <NUM>. The heartbeat processor <NUM> includes the cycle length/heart rate detector <NUM> and the beat pattern analyzer <NUM>, which are described previously with reference to <FIG>. As illustrated in <FIG>, the heartbeat processor <NUM> may additionally include a stability analyzer <NUM> configured to calculate a stability of the cycle lengths or heart rates. In an example, the stability may include difference, variance, standard deviation, or other higher-order statistics that characterize the variability of the cycle lengths or heart rates. In another example, the stability may be derived from Lorenz plot (LP) of the HRs or CLs. The LP is a scatterplot of the present CL or HR as a function of the preceding one or more CLs or HRs. The LP-based stability may include geometric indices generated from the LP of the CLs or HRs, such as maximal length of the LP shape, maximal width of the LP shape, a density or spreadness measure of the LP scatterplots, among others.

The arrhythmia detector <NUM> may include a first arrhythmia detector <NUM> and a second arrhythmia detector <NUM>. The first arrhythmia detector <NUM> may be coupled to the stability analyzer <NUM> to perform an initial detection of AF using the stability of the CLs or HRs. In an example, the stability analyzer <NUM> may classify the HRs or CLs into one of a plurality of beat classes including a stable beat class, an unstable beat class, and a random beat class. The stability may be computed as a relative quantity, such as a difference, a ratio, a proportion, or a percentage, using the beat counts of the stable beats, the unstable beats, or the random beats. Examples of the relative quantity may include a ratio of the number of unstable beats to a sum of the numbers of the stable and unstable beats, or a ratio of the number of random beats to a sum of the numbers of the stable and unstable beats. The first arrhythmia detector <NUM> may detect the AF episode in response to the relative quantity satisfying a specified condition, such as those disclosed in the commonly assigned <CIT>, which is hereby incorporated by reference in its entirety, including its disclosure of beats classes and AF detection using at least the beat classes.

In an example, the stability analyzer <NUM> may determine the stability based on a HR or CL distribution such as a HR histogram or a CL histogram. The HR histogram or CL histogram may include percentages of the heart beats during a specified time period that fall within each of a plurality of heart rate bins. Each heart rate bin defines a range of HRs or CLs. The indicator may include a mode of the HR or CL, such as a histogram bin (or a representative heart rate value of that histogram bin) that includes the most heart beats with corresponding HRs or CLs falling within that histogram bin. The indicator may alternatively or additionally include a heart rate density index (HRDI), which may be calculated as a percentage of the heart beats falling within the histogram bin including the mode of the heart rates. The first arrhythmia detector <NUM> may detect the target cardiac arrhythmia such as an AF episode in response to the mode of the heart rate or the HRDI each satisfies a specified condition, such as those disclosed in the commonly assigned <CIT>, which is hereby incorporated by reference in its entirety, including its disclosure of the HRDI and the AF detection using at least the HRDI.

The first arrhythmia detector may additionally or alternatively detect AF using morphology of a plurality of heart beats from the physiological signal. The morphology may include a plurality of morphological features such as samples selected from a portion of a waveform of the signal metric within a beat (or a cardiac cycle). In an example, the morphological features may include characteristic points of the waveform such as a peak, a trough, an inflection point, or one or more intermediate points between the characteristic points. The first arrhythmia detector <NUM> may receive from a user such as via the user interface unit <NUM>, or retrieve from a memory device, a template that represents the morphology of the same signal metric that is obtained during a known rhythm such as a sinus rhythm or a specified arrhythmia such as AF. The first arrhythmia detector <NUM> may compare the morphology measurements of the plurality of beats to the template, and compute a similarity score between the morphology measurements and template. Examples of the similarity score may include a correlation, a sum of differences between the morphology measurements and scaled template, or a distance measure in a multi-dimensional signal feature space. In an example, the arrhythmia detector <NUM> may dynamically update the template using the morphology measurements of previous one or more beats that are morphologically similar to the received or retrieved template (such as the similarity score falling within a specified range). The first arrhythmia detector <NUM> may detect the cardiac arrhythmia in response to the similarity score satisfying a specified condition, such as when the difference falls below a specified detection threshold.

The second arrhythmia detector <NUM>, which is an embodiment of the arrhythmia detector <NUM>, may be coupled to the first arrhythmia detector <NUM> and the beat pattern analyzer <NUM> and detect AF using at least the repetitiveness indicator of the beat pattern, such as the CL statistics-based repetitiveness indicator (as shown in <FIG>) in accordance with the invention or the ascending or descending CL sequences-based repetitiveness indicator (as shown in <FIG>). In an example, the first arrhythmia detector <NUM> may be sensitive but less specific to AF, and the second arrhythmia detector <NUM> may be more specific to AF. The second arrhythmia detector <NUM> may use the repetitiveness indicator to affirm, reject, or modify the AF detection as provided by the fist arrhythmia detector <NUM>, such as to reduce false positive detections of AF episodes. In an example, the second arrhythmia detector <NUM> may be configured to discriminate between an AF episode and an unstable but substantially organized rhythms such as cardia rhythms with various degrees of atrio-ventricular conduction abnormalities (e.g., Wenckebach rhythms), or premature atrial contractions (PACs).

In various examples, the second arrhythmia detector <NUM> may perform AF detection when a low confidence is associated with the detection from the first arrhythmia detector <NUM>. The first and second arrhythmia detectors <NUM> and <NUM> may have different computational power. In an example, the second arrhythmia detector <NUM> may detect cardiac arrhythmia using a computationally more intensive algorithm, or to process larger amount of data for detecting the arrhythmic event than the first arrhythmia detector <NUM>. In an example, the second arrhythmia detector <NUM> may perform retrospective analysis of historical physiological data collected from the patient, while the first arrhythmia detector <NUM> may perform real-time AF detection.

Although the second arrhythmia detector <NUM> is shown to be within the arrhythmia detector <NUM>, this is meant only by example and not limitation. The second arrhythmia detector <NUM> may alternatively be implemented in a separate device than the first arrhythmia detector <NUM>, such as in a programmer, a hand-held, wearable, or other portable device, or a server. In an example, portions of the sub-circuits in the arrhythmia detector <NUM>, such as the first arrhythmia detector <NUM> and the second arrhythmia detector <NUM>, may be distributed between the IMD <NUM> and the external system <NUM>.

<FIG> illustrates generally an illustrative example of a non-claimed method <NUM> for detecting a cardiac arrhythmia from a patient. Examples of cardiac arrhythmias may include atrial fibrillation (AF), atrial flutter (AFL), atrial tachycardia, paroxysmal supraventricular tachycardia (PSVT), Wolff-Parkinson-White (WPW) syndrome, ventricular tachycardia, ventricular fibrillation, bradycardia, or sinus pauses, among others. The method <NUM> may be implemented and executed in an ambulatory medical device such as an implantable or wearable medical device, or in a remote patient management system. In an example, the method <NUM> may be performed by the cardiac arrhythmia detector <NUM> or any embodiment thereof, or by the external system <NUM>.

The method <NUM> begins at <NUM> by sensing a physiological signal from a patient. The physiological signals may include cardiac electrical signals such as electrocardiography (ECG) or intracardiac electrogram (EGM). The physiological signals may additionally or alternatively include signals indicative of cardiac mechanical activity, including thoracic or cardiac impedance signal, arterial pressure signal, pulmonary artery pressure signal, left atrial pressure signal, RV pressure signal, LV coronary pressure signal, heart sounds or endocardial acceleration signal, physiological response to activity, apnea hypopnea index, one or more respiration signals such as a respiration rate signal or a tidal volume signal, among others. The sensed physiological signal may be pre-processed, including one or more of signal amplification, digitization, filtering, or other signal conditioning operations. In an example, a plurality of electrophysiological or mechano-physiological events indicative of heart beats may be detected from the pre-processed physiological signal. In some examples, signal metrics such as timing parameters, or statistical or morphological parameters associated with the beats may be detected from the sensed physiological signal.

At <NUM>, a cardiac cycle length (CL) or heart rate (HR) may be detected using the electrophysiological or mechano-physiological events. The CL may be measured as an interval between two adjacent R waves (R-R interval) or P waves (P-P interval), an interval between adjacent impedance peaks or adjacent impedance troughs from the cardiac impedance signal, or an interval between two adjacent blood pressure peaks (i.e., systolic pressure) or adjacent blood pressure troughs (i.e., diastolic pressure) from the blood pressure signal, among others. The HR, in a unit of beats per minute (bpm), may be computed according to HR = <NUM> seconds/CL where CL is measured in a unit of seconds.

At <NUM>, the HR or CL may be analyzed such as by using one of the beat pattern analyzers <NUM>, <NUM>, or <NUM> as illustrated in <FIG>. The analysis may include computing a plurality of beat patterns at <NUM> based on the HR or CL measurements, and generating a repetitiveness indicator using the beat patterns at <NUM>. The beat patterns may indicate a temporal relationship between the two or more consecutive cardiac cycles. In an example, at <NUM> the beat patterns may include a cycle length statistic, such as one of a maximum cycle length (maxCL), a minimum cycle length (minCL), a median cycle length (medCL), or an average cycle length (avgCL), each computed using CL of a plurality of consecutive cardiac cycles within a time window. In a non-limiting example as illustrated in <FIG>, the data windows used for computing one cycle length statistic (e.g., maxCL) may have different length than the data windows for computing another cycle length statistic (e.g., minCL). At <NUM>, data windows associated with substantially identical CL statistics, such as within a specified tolerance, may be identified. For example, a lower bound (LB) and an upper bound (UB) of maxCL may respectively be determined using a central tendency µ (e.g., an average) and a standard deviation σ of all or a portion of the maxCL computed from the data windows. In an example, LB = µ- c1*σ and UB = µ+ c2*σ, where c1 and c2 are constants. Those maxCL falling within the range of (LB, UB) may be deemed substantially identical, and a relative count such as a percentage of the substantially identical maxCL may be determined as a repetitiveness indicator, which is used for detecting the cardiac arrhythmia such as atrial fibrillation (AF).

In another example, at <NUM> the beat patterns may include ascending CL sequences of consecutive cardiac cycles progressively increasing by at least a specified step size δ<NUM> and descending CL sequences of consecutive cardiac cycles progressively decreasing by at least a specified step size δ<NUM>. As discussed previously with reference to <FIG> and Table <NUM>, the ascending or descending CL sequences may include various beat patterns characterized by consecutive CL shortening or lengthening. The CL sequence may be transformed to a symbolic sequence comprising one or more of "S", "L", and "I" symbols that represent consecutive CL shortening or lengthening. In particular, the symbol "L" denotes CL lengthening if ΔCLi is positive and ΔCLi> δ<NUM>, the symbol "S" denotes CL shortening if ΔCLi is negative and ΔCLi < δ<NUM>, and the symbol "I" denotes identical CL if δ<NUM> < ΔCLi < δ<NUM>.

Various beat patterns may be identified from the symbolic sequence. For example, an ascending sequence of three consecutive cardiac cycles with cycle lengths CL1<CL2<CL3 may be represented by an "LL" sequence or a "+<NUM>" pattern indicating CL2 longer than the previous CL1 by at least δ<NUM>, and CL3 longer than the previous CL2 by at least δ<NUM>. In another example, a descending sequence of three consecutive cardiac cycles with cycle lengths CL1>CL2>CL3 may be represented by an "SS" sequence or a "-<NUM>" pattern indicating CL2 shorter than the previous CL1 by at least δ<NUM>, and CL3 shorter than the previous CL2 by at least δ<NUM>. The beat patterns may additionally include an identical CL sequence of two or more consecutive cardiac cycles with substantially identical cycle length, represented by an "I" sequence or a "<NUM>" pattern. Then at <NUM>, occurrences of various beat patterns may be identified from a sequence of HRs or CLs measured from the physiological signal. A first count (N1) of ascending CL sequences and a second count (N2) of descending CL sequences may be used to determine one or more composite measures including an accumulative observed count (R), an expected count (E), and a standard deviation (SD) of counts of the ascending and descending CL sequences. A repetitiveness indicator may be computed using the composite measures O, E and SD, such as the Z statistic according to Equations (<NUM>) and (<NUM>).

At <NUM>, a cardiac arrhythmia such as atrial fibrillation (AF) may be detected using at least the repetitiveness indicator of the beat pattern. In an example, an AF episode is detected when the percentage of the computed cycle length statistics falls below an AF threshold, such as approximately <NUM>%. In another example, an AF episode is detected if the Z statistic as computed using Equations (<NUM>) and (<NUM>) falls below an AF threshold.

In various examples, detection of AF at <NUM> may additionally include an initial AF detection such as based on the stability of the HR or CL. The arrhythmia detection based on the beat pattern and repetitiveness indicator at steps <NUM> and <NUM> may affirm, reject, or modify the initial AF detection. In some examples, the repetitiveness indicator may be used to distinguish an AF episode from an unstable and organized rhythm. Examples of AF detection and discrimination between AF and unstable but organized rhythms are discussed below, such as with reference to <FIG>.

At <NUM>, a therapy may be delivered to the patient in response to the detection of the cardiac arrhythmia. Examples of the therapy may include electrostimulation therapy delivered to the heart, a nerve tissue, other target tissues, a cardioversion therapy, a defibrillation therapy, or drug therapy including delivering drug to a tissue or organ. In some examples, an existing therapy may be modified to treat the detected arrhythmia, such as adjust a stimulation parameter or drug dosage. The detection of the AF, optionally along with other information such as the beat patterns and repetitiveness indicator, may be output to a system user or a process. In an example, a human-perceptible presentation or alerts about the detected arrhythmias may be generated and presented to a clinician or the patient as via the user interface <NUM>.

<FIG> illustrates generally an illustrative example of a non-claimed method <NUM> for detecting atrial fibrillation and discriminating AF from unstable and organized rhythms. The method <NUM> may be an embodiment of portions of steps <NUM> and <NUM> of the method <NUM>. In an example, the method <NUM> may be implemented in and executed by the arrhythmia detection system <NUM> in <FIG>.

At <NUM>, cycle length stability or heart rate stability may be computed. The stability may include difference, variance, standard deviation, or other higher-order statistics that characterize the variability of the cycle lengths or heart rates. In an example, the stability may be derived from Lorenz plot (LP) of the HRs or CLs. The LP-based stability measures may include geometric indices generated from the LP of the CLs or HRs, such as maximal length of the LP shape, maximal width of the LP shape, or a density or spreadness measure of the LP scatterplots, among others.

At <NUM>, an initial AF detection may be performed using the CL stability. The stability-based detection may be sensitive but less specific to AF. In an example, an AF is detected if the CL variability exceeds a specified threshold. In an example, the HRs or CLs may be classified into one of a plurality of beat classes including a stable beat class, an unstable beat class, and a random beat class. The stability may be computed as a relative quantity using the beat counts of the stable beats, the unstable beats, or the random beats. An AF is detected at <NUM> if the relative quantity satisfies a specified condition, such as those disclosed in the commonly assigned <CIT>, which is hereby incorporated by reference in its entirety, including its disclosure of beats classes and AF detection using at least the beat classes. In another example, the stability may be based on a HR or CL distribution such as a HR histogram or a CL histogram. The HR histogram or CL histogram may include percentages of the heart beats during a specified time period that fall within each of a plurality of heart rate bins. Each heart rate bin defines a range of HRs or CLs. The indicator may include a mode of the HR or CL, such as a histogram bin (or a representative heart rate value of that histogram bin) that includes the most heart beats with corresponding HRs or CLs falling within that histogram bin. The indicator may alternatively or additionally include a heart rate density index (HRDI), which may be calculated as a percentage of the heart beats falling within the histogram bin including the mode of the heart rates. The initial AF detection may be based on the mode of the heart rate or the HRDI each satisfying a specified condition, such as those disclosed in the commonly assigned <CIT>, which is hereby incorporated by reference in its entirety, including its disclosure of the HRDI and the AF detection using at least the HRDI.

If an AF is deemed detected at <NUM>, then a beat pattern and repetitiveness-based detection method may be used to confirm, reject, or modify the initial AF detection. At <NUM>, beat patterns such as cycle length statistics of consecutive cycle lengths, or ascending and descending CL sequences, may be determined, as previously discussed at step <NUM> of the method <NUM>. At <NUM>, a repetitiveness indicator may be generated. The RI may indicate a degree of randomness of the CLs or HRs. The RI may be computed based on a count of identical CL statistics, or based on counts of ascending or descending CL sequences, as previously discussed at step <NUM> of the method <NUM>.

At <NUM>, the repetitiveness indicator may be compared to an AF threshold. If the repetitiveness indicator falls below an AF threshold, then the AF detection is confirmed at <NUM>. If the repetitiveness indicator exceeds the AF threshold, the underlying rhythm may be characterized by unstable cardiac cycle length but substantially organized rhythms, such as rhythms with various degrees of atrio-ventricular conduction abnormalities (ACAs), or premature atrial contractions (PACs). At <NUM>, the repetitiveness indicator may be compared to a specified ACA threshold. If the repetitiveness indicator exceeds the ACA threshold, an ACA rhythm such as Wenckebach rhythm may be detected at <NUM>. Otherwise, the underlying rhythm may be detected at <NUM> as other types of arrhythmias, which may further be classified using other timing or morphological based rhythm classification method. The detection results, including the absence or presence of AF episodes or ACA rhythms or other cardiac rhythms, may be presented to a system user, or to trigger the delivery or withholding of AF therapy.

<FIG> illustrates generally a block diagram of an example machine <NUM> upon which any one or more of the techniques (e.g., methodologies) discussed herein may perform. Portions of this description may apply to the computing framework of various portions of the LCP device, the IMD, or the external programmer.

Examples, as described herein, may include, or may operate by, logic or a number of components, or mechanisms. Circuit sets are a collection of circuits implemented in tangible entities that include hardware (e.g., simple circuits, gates, logic, etc.). Circuit set membership may be flexible over time and underlying hardware variability. Circuit sets include members that may, alone or in combination, perform specified operations when operating. In an example, hardware of the circuit set may be immutably designed to carry out a specific operation (e.g., hardwired). In an example, the hardware of the circuit set may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) including a computer readable medium physically modified (e.g., magnetically, electrically, moveable placement of invariant massed particles, etc.) to encode instructions of the specific operation. In connecting the physical components, the underlying electrical properties of a hardware constituent are changed, for example, from an insulator to a conductor or vice versa. The instructions enable embedded hardware (e.g., the execution units or a loading mechanism) to create members of the circuit set in hardware via the variable connections to carry out portions of the specific operation when in operation. Accordingly, the computer readable medium is communicatively coupled to the other components of the circuit set member when the device is operating. In an example, any of the physical components may be used in more than one member of more than one circuit set. For example, under operation, execution units may be used in a first circuit of a first circuit set at one point in time and reused by a second circuit in the first circuit set, or by a third circuit in a second circuit set at a different time.

The machine <NUM> may further include a display unit <NUM> (e.g., a raster display, vector display, holographic display, etc.), an alphanumeric input device <NUM> (e.g., a keyboard), and a user interface (UI) navigation device <NUM> (e.g., a mouse). The machine <NUM> may include an output controller <NUM>, such as a serial (e.g., universal serial bus (USB), parallel, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection to communicate or control one or more peripheral devices (e.g., a printer, card reader, etc.).

The term "machine readable medium" may include any medium that is capable of storing, encoding, or carrying instructions for execution by the machine <NUM> and that cause the machine <NUM> to perform any one or more of the techniques of the present disclosure, or that is capable of storing, encoding or carrying data structures used by or associated with such instructions. Non-limiting machine readable medium examples may include solid-state memories, and optical and magnetic media. In an example, a massed machine readable medium comprises a machine readable medium with a plurality of particles having invariant (e.g., rest) mass. Accordingly, massed machine-readable media are not transitory propagating signals. Specific examples of massed machine readable media may include: nonvolatile 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.

The instructions <NUM> may further be transmitted or received over a communications network <NUM> using a transmission medium via the network interface device <NUM> utilizing any one of a number of transfer 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), mobile telephone networks (e.g., cellular networks), Plain Old Telephone (POTS) networks, and wireless data networks (e.g., Institute of Electrical and Electronics Engineers (IEEE) <NUM> family of standards known as WiFi®, IEEE <NUM> family of standards known as WiMax®), IEEE <NUM>. <NUM> family of standards, peer-to-peer (P2P) networks, among others. In an example, the network interface device <NUM> may include one or more physical jacks (e.g., Ethernet, coaxial, or phone jacks) or one or more antennas to connect to the communications network <NUM>. In an example, the network interface device <NUM> may include a plurality of antennas to wirelessly communicate using at least one of single-input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) techniques. The term "transmission medium" shall be taken to include any intangible medium that is capable of storing, encoding or carrying instructions for execution by the machine <NUM>, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software.

The drawings show, by way of illustration, specific embodiments in which the disclosure may be practiced. " Such examples may include elements in addition to those shown or described.

Method examples described herein may be machine or computer-implemented at least in part. Some examples may include a computer-readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods may include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code may include computer readable instructions for performing various methods. Further, in an example, the code may be tangibly stored on one or more volatile, non-transitory, or nonvolatile tangible computer-readable media, such as during execution or at other times. Examples of these tangible computer-readable media may include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like.

Claim 1:
A system (<NUM>) for detecting cardiac arrhythmia, comprising:
a heartbeat processor (<NUM>) configured to:
determine cardiac cycle lengths, CLs, from a physiological signal sensed from a subject;
recognize a plurality of beat patterns based on respective two or more consecutive CLs, the beat pattern including a cycle length statistic of a plurality of consecutive cardiac cycles; and
generate a repetitiveness indicator of the beat pattern using the cycle length statistic; and characterised by an arrhythmia detector (<NUM>) coupled to the heartbeat processor (<NUM>) and configured to detect atrial fibrillation, AF, in response to the repetitiveness indicator of the beat pattern falling below a threshold;
wherein the repetitiveness indicator includes at least one of:
a first count of CL sequences having substantially identical maximum CL values; or
a second count of CL sequences having substantially identical minimum CL values.