Detection of myocardial ischemia from the time sequence of implanted sensor measurements

A system including a plurality of implantable sensors, a processor, and a response circuit. Each sensor produces an electrical sensor signal related to physiologic cardiovascular events of a subject. The processor includes an event sequence detector to permit real-time detection of a time-wise sequential cascade of physiologic cardiovascular events related to myocardial ischemia of a subject and a decision module. The time-wise cascade includes at least first, second, and third physiologic cardiovascular events. The decision module declares whether an ischemic event occurred using at least one rule applied to a temporal relationship of the first, second, and third physiologic cardiovascular events. The response circuit provides a specified response if the ischemic event is declared.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to the following commonly assigned U.S. patent applications: Ser. No. 10/703,175, entitled “A DUAL USE SENSOR FOR RATE RESPONSIVE PACING AND HEART SOUND MONITORING,” filed on Nov. 6, 2003, now issued as U.S. Pat. No. 7,248,923, Ser. No. 10/334,694 entitled “METHOD AND APPARATUS FOR MONITORING OF DIASTOLIC HEMODYNAMICS,” filed on Dec. 30, 2002, Ser. No. 10/746,874 entitled “A THIRD HEART SOUND ACTIVITY INDEX FOR HEART FAILURE MONITORING,” filed on Dec. 24, 2003, now issued as U.S. Pat. No. 7,115,096, Ser. No. 60/631,742 entitled “CARDIAC ACTIVATION SEQUENCE MONITORING FOR ISCHEMIA DETECTION,” filed on Nov. 30, 2004, Ser. No. 11/129,050, entitled “METHOD AND APPARATUS FOR CARDIAC PROTECTION PACING,” filed on May 16, 2005, Ser. No. 11/148,107, entitled “ISCHEMIA DETECTION USING HEART SOUND SENSOR,” filed on Jun. 8, 2005, U.S. Pat. No. 6,666,826, entitled “METHOD AND APPARATUS FOR MEASURING LEFT VENTRICULAR PRESSURE,” filed Jan. 4, 2002, and U.S. patent application Ser. No. 10/795,126, entitled “WIRELESS ECG IN IMPLANTABLE DEVICES,” filed on Mar. 5, 2004, now issued as U.S. Pat. No. 7,299,086, each of which is hereby incorporated by reference.

TECHNICAL FIELD

The field generally relates to implantable medical devices and, in particular, but not by way of limitation, to systems and methods for detecting myocardial ischemia.

BACKGROUND

Implantable medical devices (IMDs) are devices designed to be implanted into a patient. Some examples of these devices include cardiac function management (CFM) devices such as implantable pacemakers, implantable cardioverter defibrillators (ICDs), cardiac resynchronization devices, and devices that include a combination of such capabilities. The devices are typically used to treat patients using electrical or other therapy and to aid a physician or caregiver in patient diagnosis through internal monitoring of a patient's condition. The devices may include one or more electrodes in communication with sense amplifiers to monitor electrical heart activity within a patient, and often include one or more sensors to monitor one or more other internal patient parameters. Other examples of implantable medical devices include implantable diagnostic devices, implantable drug delivery systems, or implantable devices with neural stimulation capability.

Additionally, some IMDs detect events by monitoring electrical heart activity signals. In addition to electrical events, CFM devices may measure hemodynamic parameters related to chamber filling and contractions. Ischemia occurs when blood flow to cardiac muscles decreases below the metabolic requirements of the heart. Detecting ischemia early is critical to the health of the patient and allows early initiation of treatment. Cardiac muscle cells that are ischemic are electrically irritable and may be more susceptible to abnormal heart rhythms (e.g., fibrillation). Further, ischemia impairs the pumping function of the heart. If left untreated the underlying cause of ischemia which is commonly artherosclerotic disease may lead to myocardial infarction (i.e., heart attack).

SUMMARY

This document discusses, among other things, systems and methods for monitoring cardiac function of a patient or subject. A system example includes a plurality of sensors, a processor, and a response circuit. At least one of the sensors is an implantable sensor. Each sensor produces an electrical sensor signal related to physiologic cardiovascular events of a subject. The processor includes an event sequence detector to permit real-time detection of a time-wise sequential cascade of physiologic cardiovascular events related to myocardial ischemia of the subject and a decision module. The time-wise cascade includes at least first, second, and third physiologic cardiovascular events. The decision module declares whether an ischemic event occurred using at least one rule applied to a temporal relationship of the first, second, and third physiologic cardiovascular events. The response circuit provides a specified response if the ischemic event is declared.

A method example includes sensing first, second, and third implantable sensor signals, each sensor signal including physiologic cardiovascular information, detecting first, second, and third physiologic cardiovascular events from the first, second, and third implantable sensor signals, and declaring whether an ischemic event occurred using at least one rule applied to a temporal relationship of the first, second, and third physiologic cardiovascular events.

DETAILED DESCRIPTION

In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and specific embodiments in which the invention may be practiced are shown by way of illustration. It is to be understood that other embodiments may be used and structural or logical changes may be made without departing from the scope of the present invention.

The functions or algorithms described herein are typically implemented in software or a combination of software and human implemented procedures in one embodiment. The software typically comprises computer executable instructions stored on computer readable media such as memory or other type of storage devices. Further, such functions typically correspond to modules, which are software, hardware, firmware or any combination thereof. Multiple functions are performed in one or more modules as desired, and the embodiments described are merely examples. The software is typically executed on a digital signal processor, ASIC, microprocessor, or other type of processor. The processor may operate as part of an implantable medical device or the processor may operate on a computer system, such as a personal computer, server or other computer system.

An implantable medical device (IMD) may include one or more of the features, structures, methods, or combinations thereof described herein. For example, a cardiac monitor or a cardiac stimulator may be implemented to include one or more of the advantageous features and/or processes described below. It is intended that such a monitor, stimulator, or other implantable or partially implantable device need not include all of the features described herein, but may be implemented to include selected features that provide for unique structures and/or functionality. Such a device may be implemented to provide a variety of therapeutic or diagnostic functions.

The IMDs may be configured with a variety of electrode arrangements, including transvenous, endocardial, and epicardial electrodes (i.e., intrathoracic electrodes), and/or subcutaneous, non-intrathoracic electrodes, including can, header, and indifferent electrodes, and subcutaneous array or lead electrodes (i.e., non-intrathoracic electrodes). Monitoring of electrical signals related to cardiac activity may provide early, if not immediate, diagnosis of ischemia.

Evidence of myocardial ischemia in a subject can become manifest in various ways. Occurrences of coronary blood flow occlusion typically result in an immediate increase in heart rate and a decrease in myocardial shortening, particularly in an ischemic heart-wall segment. Dyssynergy in ventricular contractions also often occurs. Sometimes, abnormalities are detectable after the occlusion in an electrocardiograph (ECG) within thirty seconds to one minute after the occlusion. Myocardial ischemia depresses the peak negative rate of change of pressure (dP/dt) in the left ventricle (LV) and also depresses the LV peak positive dP/dt. Coronary blood flow occlusion may also result in decreased peak endocardial acceleration.

Implantable cardiac rhythm management (CRM) devices are sometimes equipped with implantable sensors that have the capability to detect various physiological variables associated with cardiac and pulmonary function. These sensors are typically used in applications such as rate responsive pacing and advanced patient management. Because myocardial ischemia can result in changes in the various physiological variables, these sensors may also be used for early detection of myocardial ischemia. The difficulty with using such sensors to detect ischemia is that while each sensor may experience a change due to ischemia, the sensor output may not be tailored to be specific to ischemia. Myocardial ischemia results in a series of physiological events that occur in a particular sequence in time beginning with heart-wall abnormalities and ending with S-T segment elevation. Thus, the specificity of ischemia detection can be improved by detecting this time-wise sequence of events using a plurality of sensors that each measure a part of the time sequence of events.

FIG. 1is a block diagram of portions of a system100that uses an implantable medical device (IMD)110. As one example, the system100shown is used to treat a cardiac arrhythmia. The IMD110typically includes an electronics unit coupled by a cardiac lead108, or additional leads, to a heart105of a patient102, or otherwise associated with the heart105. Examples of IMD110include, without limitation, a, pacemaker, a cardioverter, a defibrillator, a cardiac resynchronization therapy (CRT) device, and other cardiac monitoring and therapy delivery devices, including cardiac devices that include or work in coordination with neuro-stimulating devices, drugs, drug delivery systems, or other therapies. System100also typically includes an IMD programmer or other external device170that communicates wireless signals160with the IMD110, such as by using radio frequency (RF) or other telemetry signals.

Cardiac lead108includes a proximal end that is coupled to IMD110and a distal end, coupled by an electrode or electrodes to one or more portions of a heart105. The electrodes typically deliver cardioversion, defibrillation, pacing, or resynchronization therapy, or combinations thereof to at least one chamber of the heart105. The electronics unit of the IMD110typically includes components that are enclosed in a hermetically-sealed canister or “can.” Other electrodes may be located on the can, or on an insulating header extending from the can, or on other portions of IMD110, such as for providing pacing energy, defibrillation energy, or both, in conjunction with the electrodes disposed on or around a heart105. The lead108or leads and electrodes may also typically be used for sensing intrinsic or other electrical activity of the heart105.

FIG. 2illustrates an IMD110coupled by one or more leads108to heart105. Heart105includes a right atrium200A, a left atrium200B, a right ventricle205A, and a left ventricle205B. Lead108includes electrodes (electrical contacts, such as ring electrode225and tip electrode230) disposed in a ventricle205A of heart105for sensing signals, or delivering pacing therapy, or both, to the ventricle205A. Lead108also includes one or more electrodes for placement in the right atrium200A, such as ring electrode235and ring electrode240, for sensing electrical cardiac signals, delivering pacing therapy, or both sensing signals and delivering pacing therapy. Sensing and pacing allows the IMD110to adjust timing of the chamber contractions. For example, IMD110can adjust the timing of ventricular contractions with respect to the timing of atrial contractions delay by sensing a contraction in the right atrium200A and pacing the right ventricle205A at the desired AV delay time. The IMD also includes can electrode250formed on the IMD can245, and header electrode260formed on the IMD header255.

The IMD110optionally also includes additional leads and electrodes, such as for delivering atrial cardioversion, atrial defibrillation, ventricular cardioversion, ventricular defibrillation, or combinations thereof to heart105. Such electrodes typically have larger surface areas than pacing electrodes in order to handle the larger energies involved in defibrillation. Optionally, lead108includes two leads containing two electrodes each. In an example, a first lead includes a tip electrode located in the apex of the right ventricle205A and a first ring electrode located proximal to the tip electrode. A second lead includes a tip electrode located in the right atrium200A and a ring electrode located in the right atrium200A proximal to the tip electrode.

Optionally, IMD110includes an additional cardiac lead that includes ring electrodes for placement in a coronary vein extending along a wall of the left ventricle205B. A lead placed in the left ventricle205B and a lead placed in the right ventricle205A may be used to optionally provide resynchronization therapy to the heart105.

Other forms of electrodes include meshes and patches which may be applied to portions of heart105or which may be implanted in other areas of the body to help “steer” electrical currents produced by IMD110. The present methods and systems will work in a variety of configurations and with a variety of electrodes.FIGS. 3A-Bshow an example of an IMD300that does not use intravascular leads to sense cardiac signals.FIG. 3Ashows that the IMD300includes a thicker end313to hold the power source and circuits. The IMD300also includes electrodes325and327for remote sensing of cardiac signals. Cardioversion/defibrillation is provided through electrodes315and317.FIG. 3Bshows an example of the IMD300positioned within a patient.

Myocardial ischemia results in a series of physiological cardiovascular events that occur in a particular sequence in time, which can be referred to as a time-wise cascade of physiological cardiovascular events. Table 1 is a non-exhaustive list of some examples of the physiological cardiovascular events in the time-wise sequential ischemic cascade and includes examples of sensor used to detect the events.

The list includes an approximate magnitude of the change when ischemia occurs, the time after ischemia that the event occurs, and whether the change is monophasic or biphasic. Monophasic refers to the indicated change remaining after an ischemic event. Biphasic refers to the change appearing and then disappearing as the heart compensates in response to the ischemic event.

The Table shows that if myocardial ischemia results in regional shortening of a heart wall, it happens fairly quickly. This change can be manifested as left ventricle (LV) wall motion abnormality for example. Myocardial ischemia often results in a reduction in LV contractility which can be detected through measurements of heart sounds and cardiac impedance.

Heart sounds are associated with mechanical vibrations from activity of a patient's heart and the flow of blood through the heart. Heart sounds recur with each cardiac cycle and are separated and classified according to the activity associated with the vibration. The first heart sound (S1) is the vibrational sound made by the heart during tensing of the mitral valve. The second heart sound (S2) marks the beginning of diastole. The third heart sound (S3) and fourth heart sound (S4) are related to filling pressures of the left ventricle during diastole. A heart sound sensor produces an electrical signal which is representative of mechanical activity of a patient's heart. Regional shortening causes changes in the heart sounds detectable with a heart sound sensor. A description of systems and methods for sensing wall motion is found in the commonly assigned, co-pending U.S. patent application Ser. No. 11/135,985, entitled “SYSTEMS AND METHODS FOR MULTI-AXIS CARDIAC VIBRATION MEASUREMENTS,” filed May 24, 2005, which is incorporated herein by reference.

An accelerometer can be used to provide acceleration signals each indicative of regional cardiac wall motion. One or more accelerometers can be incorporated into a portion of a lead positioned on or in the heart. The accelerometers detect the wall motion abnormality as an abrupt decrease in the amplitude of local cardiac accelerations.

A cardiac impedance sensor senses an electrical impedance signal between electrodes interposed in the heart. For example, inFIG. 2a cardiac impedance sensor can sense intracardiac impedance of the right ventricle205A between an electrode placed at the apex of the right ventricle205A and an electrode placed in the right atrium200A. A predetermined excitation current is delivered between the electrodes and the impedance is determined from a voltage sensed between the electrodes. A transthoracic impedance of a subject can be measured between the ring electrode225and can electrode250or header electrode260.

A cardiac impedance sensor can be used to track an impedance signal along with cardiac contractions and create a baseline impedance or normal impedance signal pattern. Because cardiac impedance is responsive to cardiac contractions, changes due to regional shortening may change the morphology of the impedance swings that occur with each cardiac contraction. In some examples, the impedance signal morphology is compared against the baseline pattern. When the pattern is significantly different, e.g. based on fiducial points in the signal or based on an amplitude distance between the signals (such as a mean absolute deviation or a root-mean-square (RMS) difference), an ischemic event is declared. In some examples, the morphology is compared by assigning a morphology score to the impedance signal. An ischemic event is declared if the morphology score is different from a predetermined threshold score by a specified amount. The morphological changes are typically confirmed by other sensor measurements.

The regional shortening is followed by an increase in the heart rate of a subject. Some subjects may experience about a forty percent increase in rate. Examples of sensors that can detect a heart rate increase include a cardiac signal sensing circuit that includes electrodes as shown inFIG. 2. Some subjects may experience an increase in a ratio of sympathetic cardiac activity to parasympathetic cardiac activity. This can be detected using the sensing electrodes and a measure of variability of ventricular time intervals. In some examples, the change in the sympathetic/parasympathetic ratio can be obtained by sampling of the signal. A morphology template is compared to the stored signals. A morphology score for a normal sinus rhythm is used to the asses the rhythm. Because knowledge of the activity of a subject is useful in obtaining a measure of sympathetic cardiac activity to parasympathetic cardiac activity, such measurements are sometimes made in association with an activity sensor, such as an accelerometer.

The change in heart rate is followed by a decrease in chamber relaxation and by a decrease in chamber contractility. The change in relaxation and contractility is manifested as a change in intra-chamber blood pressure. Rate of pressure change (dP/dt) is an after-load independent measure of left ventricular contraction strength. Some subjects may experience a decrease in heart chamber relaxation as measured by a maximum negative dP/dt of forty percent. Some subjects may experience a decrease in heart chamber contractility as measured by a maximum positive dP/dt of twenty percent.

Examples of sensors that can detect a change in heart chamber contractility or relaxation include a cardiac impedance sensor or electrodes for sensing heart signals. Cardiac impedance changes measure changes in chamber volumes. Regional changes in cardiac relaxation may be measured using measurements of cardiac impedance using an impedance sensor. Similarly, the strength of contraction may be inferred from changes in the rate of decrease of cardiac impedance during cardiac contraction. Peak positive dP/dt may be also inferred from the magnitude of the S1 heart sound.

Changes in heart chamber relaxation and contractility can also be detected using electrodes by measuring the systolic time intervals (STIs). A shortening of an STI may indicate a change in contractility. The availability of intracardiac impedance changes that are sensitive of cardiac volume, electrogram (egram) for cardiac electrical activity, and heart sounds, allows the measurement of systolic time intervals such as the electromechanical systole from the Q wave to the S2 heart sound.

A change in heart chamber contractility can also be measured using a heart sound sensor. Because ischemia is associated with a decrease in ventricular chamber contractility, ischemia is correlated to a decrease in the loudness of the S1 heart sound. A description of systems and methods for monitoring heart sounds is found in U.S. patent application Ser. No. 10/334,694, entitled “METHOD AND APPARATUS FOR MONITORING OF DIASTOLIC HEMODYNAMICS,” filed on Dec. 30, 2002, which is incorporated herein by reference.

Near the time of the change in chamber relaxation and in chamber contractility, a subject may experience an increase in filling pressure of the left ventricle. Examples of sensors that can detect an increase in the filling pressure include an implantable cardiac pressure sensor and a heart sound sensor. An implantable cardiac pressure sensor can be used to measure chamber pressure of the left ventricle. In an example, a pressure sensor is implanted in a coronary vessel to determine left ventricle pressure by direct measurement of coronary vessel pressure. A description of systems and methods that use such an implantable pressure sensor is found in Salo et al., U.S. Pat. No. 6,666,826, entitled “METHOD AND APPARATUS FOR MEASURING LEFT VENTRICULAR PRESSURE,” filed Jan. 4, 2002, which is incorporated herein by reference. Other cardiac pressure sensors examples include a right ventricle (RV) chamber pressure sensor, a pulmonary artery pressure sensor, and a left atrial chamber pressure sensor.

A heart sound sensor can also be used to detect increased filling pressure. An increase in S3 heart sound activity is known to be an indication of elevated filing pressures. Systems and methods that use an index derived from the S3 heart sound to detect ischemic events are described in commonly assigned, co-pending U.S. patent application Ser. No. 10/746,874, entitled “A THIRD HEART SOUND ACTIVITY INDEX FOR HEART FAILURE MONITORING,” filed Dec. 24, 2003, which is incorporated herein by reference.

In some subjects, the increase in filling pressure may be followed by abnormalities in a subject's ECG. An example of such an abnormality is having an S-wave to T-wave (“ST”) interval of the ECG that is elevated by a specified amount from an ST interval of a baseline ECG. An example of a sensing circuit that can detect an abnormality is a wireless ECG sensing circuit. A wireless ECG is a signal approximating the surface ECG and is acquired without using surface (skin contact) electrodes. An example of a circuit for sensing the wireless ECG is discussed in commonly assigned, co-pending U.S. patent application Ser. No. 10/795,126, entitled “WIRELESS ECG IN IMPLANTABLE DEVICES,” filed on Mar. 5, 2004, which is incorporated herein by reference. An example of a wireless ECG-based ischemia detector is discussed in commonly assigned, co-pending U.S. patent application Ser. No. 11/079,744, entitled “CARDIAC ACTIVATION SEQUENCE MONITORING FOR ISCHEMIA DETECTION,” filed on Mar. 14, 2005, which is incorporated herein by reference.

Table 1 includes an entry for subject pain and/or discomfort. This occurs about the same time as the ECG abnormalities and is important information in making a decision about whether the subject is experiencing an ischemic event. It can be seen from the Table that many of the changes in the various physiological variables occur within a minute or so of an ischemic event. The Table thus shows that an IMD can provide early detection of myocardial ischemia.

FIG. 4is a block diagram of portions of an embodiment of a system400to detect myocardial ischemia. The system400includes a plurality of implantable sensors405. Each of the implantable sensors405, when implanted in a subject, produces an electrical sensor signal that is related to physiologic cardiovascular events of the subject. The system400also includes a processor410in electrical communication with the implantable sensors405. The term electrical communication refers to devices arranged to communicate using electrical signals that influence the operation of the devices. In some examples, the devices are coupled directly. In some examples, the devices communicate electrical signals through intermediate devices, such as devices that include digital or analog circuits. Some of the implantable sensors405may include an interface circuit415to condition an electrical signal to be compatible for communication with the processor410.

Examples of the implantable sensors405include, without limitation, a heart sound sensor, a three-dimensional (3D) heart sound sensor, a transthoracic impedance measurement circuit, an intracardiac impedance measurement circuit, an electrical cardiac signal sensing circuit, an accelerometer, a blood pressure sensor, and a patient activity sensor.

In some examples, the processor410is operable by executing instructions in firmware. In some examples, the processor410is operable by executing software instructions. In some examples, the processor410is operable through any combination of hardware, software and/or firmware. The processor410includes an event sequence detector420to permit real-time detection of a time-wise sequential cascade of physiologic cardiovascular events related to myocardial ischemia of a subject. The time-wise cascade includes at least first, second, and third physiologic cardiovascular events. The physiologic cardiovascular events do not have to come from three different sensors. For example, a single heart sound sensor can provide indications of a change in regional wall shortening, an increase in filling pressure, and an increase in heart chamber contractility.

The system400also includes a decision module425and a response circuit430. The decision module425declares whether an ischemic event occurred using at least one rule applied to a temporal relationship of the first, second, and third physiologic cardiovascular events. For example, the decision module425may declare an ischemic event if regional shortening is detected, followed by an increase in heart rate, followed by an ECG abnormality. In another example, subsequent events must fall within a timed duration before the decision module425declares an ischemic event. In some examples, the decision module425assigns weights to the first, second, and third physiologic cardiovascular events, the weights indicating a likelihood that the corresponding event indicates ischemia.

The response circuit provides a specified response if the ischemic event is declared. Following myocardial infarction (MI), cardiac remodeling begins with expansion of the region of the infarcted tissue and progresses to a chronic expansion in the size and a change in the shape of the entire left ventricle. The consequences include a further impaired hemodynamic performance and a significantly increased risk of developing heart failure, as well as a risk of suffering recurrent MI.

In some examples, the system400is included in an implantable medical device (IMD) that includes a therapy circuit, such as a pacing therapy circuit. The response circuit430initiates the pacing therapy circuit to provide pacing to protect the heart from ischemic damage caused by the detected ischemic event by delivering a pacing post-conditioning therapy followed by a prophylactic pacing preconditioning therapy. Systems and methods that use post-ischemic event cardiac protection pacing are described in commonly assigned, co-pending U.S. patent application Ser. No. 11/129,050, entitled “METHOD AND APPARATUS FOR CARDIAC PROTECTION PACING,” filed on May 16, 2005, which is incorporated herein by reference.

In some examples, the response circuit430initiates an indication of the ischemic event. In an example, the response circuit430activates an alarm, such as a buzzer or other audible indication to indicate that an ischemic event occurred. In some examples, the system400is included in an IMD that includes a communication circuit coupled to the response circuit430and the system400communicates information about the ischemic event to an external device. The detection of ischemia may trigger a drug delivery device to automatically administer a drug. An indication or alarm provided to the subject has further uses, such as to direct the patient to take a drug, adjust medication, or to seek immediate medical assistance.

FIG. 5is a block diagram of portions of an embodiment of another system500to detect myocardial ischemia. The system500includes a plurality of implantable sensors505, a processor510, an event sequence detector520, a decision module525, a detection module535, and a response circuit530. The detection module535is in communication with at least one of the implantable sensors505. In some examples, the detection module535is in communication with three or more sensors505. The implantable sensors505, when implanted in a subject, produce an electrical sensor signal that is related to physiologic cardiovascular events.

The detection module535declares the first physiologic cardiovascular event of the time-wise sequential cascade according to a first detection criterion, or criteria, applied to a first sensor signal, declares the second physiologic cardiovascular event according to a second detection criterion, or criteria, applied to a second sensor signal, and declares the third physiologic cardiovascular event according to a third detection criterion, or criteria, applied to a third sensor signal. AlthoughFIG. 5shows each of three sensors505providing a sensor signal, one of the sensors505may provide more than one of the sensor signals. In some examples, more than one sensor signal is used to declare a physiologic cardiovascular event.

In some examples, the system500further includes a timing circuit550in communication with the detection module535. The timing circuit550initiates a timing window triggered by a detected occurrence of the first physiologic cardiovascular event. The response circuit530triggers the specified response upon the second and third physiologic cardiovascular events occurring during the timing window.

Examples of responses include immediately delivering a therapy, communicating an alarm based on the difference between the first sensor signal and the first specified threshold, or both immediately delivering a therapy and communicating an alarm.

In some examples, a detection criterion includes comparing a sensor signal to a predetermined threshold value. In an example, the detection criterion includes detecting that a sensor signal exceeds a predetermined sensor signal amplitude value. In some examples, a detection criterion includes comparing a parameter derived from the sensor signal to predetermined parameter value. In an example, the detection criterion includes a measure of signal variability exceeding a threshold measure. In another example, the detection criterion includes a morphology score for a normal sinus rhythm not meeting a predetermined threshold score value.

In some examples, a detection criterion includes detecting that a sensor signal exceeds a predetermined threshold value for a period of time then not exceeding the predetermined threshold value or being slightly below the value. In some examples, the detection criterion includes hysteresis. For example, a physiologic cardiovascular event is detected when a sensor signal exceeds a first predetermined threshold value for a period of time then not exceeding a second predetermined threshold value. The converse is also possible. A physiologic cardiovascular event is detected when a sensor signal drops below a first predetermined threshold value for a period of time then exceeds a second predetermined threshold value.

In some examples, if at least one of the second and third physiologic events is declared without the first physiologic event being declared, the response circuit530initiates a second look at the first physiologic cardiovascular event by changing a detection parameter such as sensitivity. This may occur if the first sensor output is not tailored to be specific to ischemic events. The response circuit530modifies the first detection criterion and examines the first sensor signal during a time period before the second physiologic cardiovascular event to determine if the first physiologic cardiovascular event was undetected, and determines the specified response to be delivered.

To examine the first sensor signal, some examples of the system500include a sampling circuit to sample the first sensor signal and a memory to store the sampled signal values. In some examples, modifying the detection criterion includes changing a detection threshold for the first sensor signal to determine if the first event was undetected because it was below a threshold (or in some cases above a threshold) of the detection criterion. In some examples, the threshold is applied to the sensor signal itself, such as a signal amplitude threshold. In some examples, the threshold may be applied to a measure derived from the sensor signal, such as a threshold measure of variability of the sensor signal or a morphology score for a normal sinus rhythm not meeting a predetermined threshold value.

If the response circuit530determines that the first event was undetected, the response circuit specifies the response of the system500, such as delivering a therapy or communicating an alarm based on the difference between the first sensor signal and the first specified threshold.

In some examples, the system500includes a response inhibition circuit555. In some examples, the response inhibition circuit555is coupled to the detection module525and the timing circuit550. If at least one of the second and third physiologic cardiovascular events is absent during a timing window triggered by the timing circuit, the response inhibition circuit555inhibits the specified response.

In some examples, if at least one of the second and third physiologic events is declared without the first physiologic event being declared, the response circuit530reduces the detection threshold of one or more of the sensor signals. In some examples, the detection threshold of the sensor signals is set to just above the noise level of the sensor signal. The event sequence detector520then determines if the first physiologic event occurs and determines the specified response to be delivered. In some examples, the event sequence detector520uses a joint probability distribution of the sensor signals to determine whether an ischemic event occurred.

According to some examples, system500can be programmed to customize the criteria used to declare a physiologic cardiovascular event. Suppose that there are 4 events in the cascade that lead to detection of an ischemic event. If only the first two events are used to make an “ischemia detected decision, or declaration, (IDD)” then the detection module535may have a given performance measured in terms of 4 parameters: true positives, false positives, false negatives, and time to detection). For example, the time to detection of the event will be smaller if fewer events are used for making the IDD. However the detection will probably exhibit a large number of false positives which may cause nuisance alarms to issue. If more events are used to make an IDD, typically the time to detection will be longer but the specificity will be higher (fewer false positives). While sometimes sensitivity may increase if fewer detectors are used, sensitivity typically decreases with most detection criteria.

Most detection criteria have a trade off between sensitivity (true positives divided by true positives plus false negatives) and false positive rate. The time to detection may also be an issue depending on how quickly the therapy needs to be delivered once ischemia is detected and the therapy side effects. Generally, the higher the sensitivity, the higher is the false positive rate. For a particular patient in whom an ischemic episode may be fatal, a physician may require that the detector be set to high sensitivity (and low time to detection) at the cost of a large false positive rate. Thus, the system500can be tailored to a desired response for a particular patient.

Returning toFIG. 4, in some examples, the plurality of implantable sensors405and the processor410are included in an implantable medical device (IMD). The IMD also includes a communication circuit coupled to the processor410. The system400further includes an external device and the IMD communicates information obtained from the implantable sensors405to the external device. In some examples, the external device includes a memory to store data related to physiologic cardiovascular events of the subject and a second processor. The second processor includes a second decision module in communication with the memory. The second decision module declares whether an ischemic event occurred using at least one rule applied to both the temporal relationship of the first, second, and third physiologic cardiovascular events and to the stored data. In some examples, the external device includes an IMD programmer.

In some examples, the external device includes a user interface to receive a user input such as a keyboard, computer mouse, a touch-screen, and the like. The second decision module declares whether an ischemic event occurred using at least one rule applied to a temporal relationship of the first, second, and third physiologic cardiovascular events and the user input. In some examples, the user input includes an indication that the subject is experiencing significant pain or discomfort.

In some system examples, the processor410and the response circuit430are included in an external device and the plurality of implantable sensors405are included in an IMD. An example of such a system600is shown inFIG. 6. The system600includes an external device635and an IMD640. The IMD640includes a plurality of implantable sensors605and a response circuit630. In some examples, the external device635includes the response circuit630. In some examples, both the external device635and the IMD640include a response circuit630. The IMD640also includes a controller circuit650and a communications circuit645. The controller circuit650is coupled to the implantable sensors605and the response circuit630. The communication circuit645is coupled to the controller circuit650and the IMD640communicates information obtained from the implantable sensors605to the external device635.

The external device635includes a processor610having an event sequence detector620and a decision module625. The system600further includes a memory655in communication with the external device635to store data related to physiologic cardiovascular events of the subject. The decision module625is configured to declare whether an ischemic event occurred using at least one rule applied to both the temporal relationship of first, second, and third physiologic cardiovascular events and to the stored data. In some examples, the external device635includes an IMD programmer. In some examples, the external device635includes an input to receive input from the subject. The decision module625is configured to declare whether an ischemic event occurred using at least one rule applied to physiologic cardiovascular events that include input that the subject is experiencing significant pain or discomfort. In some examples, the external device635includes a server in communication with a network660. In some examples, the network660includes a hospital computer network. In some examples, the network660includes the Internet. In some examples, the network660is a communications network such as a cell phone network.

In some examples, the system600further includes additional sensors that are external to the IMD. In an example, the system600includes an external electrocardiograph (ECG) circuit operable to communicate one or more ECG signals to the external device, and wherein the first, second, and third physiologic cardiovascular events include events indicated by the one or more ECG signals.

FIG. 7shows a block diagram of an example of a method700for detecting myocardial ischemia. At705, first, second, and third implantable sensor signals are sensed. Each sensor signal includes physiologic cardiovascular information. Examples of implantable sensors that provide the implantable sensor signals include, without limitation, a heart sound sensor, a three-dimensional (3D) heart sound sensor, a transthoracic impedance measurement circuit, an intracardiac impedance measurement circuit, an electrical cardiac signal sensing circuit, an accelerometer, a cardiac pressure sensor, and a patient activity sensor. In some examples, sensor signals from external sensors are provided in addition to the signals from the implantable sensors. In some examples, one of the physiologic cardiovascular events is detected using an external electrocardiograph (ECG) signal.

At710, first, second and third physiologic cardiovascular events are detected from the first, second, and third implantable sensor signals. Examples of physiologic cardiovascular events that are detected from the signals include, without limitation, ventricle wall motion abnormality, an increase in heart rate, a decrease in a heart relaxation interval, an increase in ventricle filling pressure, ventricular chamber dyssynergy, and a decrease in heart contractility. At715, whether an ischemic event occurred is declared using at least one rule applied to a temporal relationship of the first, second, and third physiologic cardiovascular events. In some examples, one of the physiologic cardiovascular events includes a subject experiencing pain and discomfort. In some examples, the method includes receiving an indication of subject discomfort related to ischemia, and declaring whether an ischemic event occurred at least in part by using the indication.

In some examples of the method700, detecting the first physiologic cardiovascular event includes detecting a first sensor signal reaching a first specified sensor threshold value. A duration is timed from the detection of the first physiologic cardiovascular event to a scheduled response. In some examples, the scheduled response includes providing a therapy including a delivery of electrical energy, such as pacing for example. In some examples, the scheduled response includes providing an alarm. In some examples, the scheduled response includes providing both therapy and an alarm.

An occurrence of only one physiologic cardiovascular event may indicate that only a low to medium level alarm should be generated. An episode where only one or two out of three or more physiologic cardiovascular events of an ischemic cascade occur may indicate that an ischemic event has not occurred. This depends on the confidence that the events provide in determining that an ischemic event occurred. In some examples, a weight is assigned to one or more of the first, second, and third events according to a likelihood that the event indicates ischemia. In some examples, the scheduled response is inhibited if at least one of the second and third physiologic cardiovascular events is absent during the timing of the duration triggered by the first event.

The scheduled response is altered if at least one of the second and third physiologic cardiovascular events is detected during the timing of the duration. An occurrence of both the first physiologic cardiovascular event and at least one of the second and third physiologic cardiovascular events can be a strong indication that an ischemic event occurred. The alarm is elevated to a high level in this case. In some examples, the scheduled response is altered by immediately providing the therapy or the alarm. In some examples, the scheduled response is altered by providing the response immediately after the timing of the duration.

In some examples, one of the physiologic cardiovascular events may occur but not meet a detection threshold, i.e. a difference is detected between a measurement based on a first sensor signal and a specified first detection criterion applied to the first sensor signal. The method700includes continuing to detect physiologic cardiovascular events that occur later in the time-wise sequential ischemic cascade. Whether the second physiologic cardiovascular event occurred is declared using a second detection criterion applied to the second sensor signal, and whether the third physiologic cardiovascular event occurred is declared using a third detection criterion applied to the third sensor signal.

If at least one of the second and third events is declared, the first sensor signal is re-examined during a specified time duration before the declaration of the second or third event. The difference between the measurement based on the first sensor signal and the specified first detection criterion is used to determine a response to the ischemic event. In some examples, the specified response is delivered if the at least one of the second or third events occurred based on the difference between the measurement based on the first sensor signal and the specified first detection criterion, i.e. the first sensor signal indicates that a sub-threshold event occurred. The response includes an alarm, an electrical energy delivery, or both an alarm and the electrical energy delivery.

In some examples, if at least one of the second and third events is declared, then a detection threshold is reduced for at least the first sensor signal. In some examples, detection thresholds for all of the sensors are reduced. The method700includes continuing to detect physiologic cardiovascular events. The specified response is delivered if both the first physiologic cardiovascular event and at least one of the second and third physiologic cardiovascular events occur.

FIG. 8is a block diagram of another method for detecting myocardial ischemia. At805it is determined whether an event in an ischemic cascade occurred. If it did occur, a duration timer is started at810. At815, it is determined if the detected event is the earliest in the cascade of events. If the detected event is the earliest event in the cascade, the method800waits for the next event to be measured at835. At840, if a subsequent event in the cascade is not detected, the method800returns to looking for the start of the cascade at805. If one or more subsequent events in the ischemic cascade do occur, the timer is checked at845. If the one or more subsequent events occur during the timed duration, at850a response is initiated immediately. The response can be electrical therapy or drug therapy, or it can be indicating a high level alarm, or it can be both therapy and an alarm. If one or more subsequent events occur but do not occur during the timed duration, a low to medium level alarm is indicated at855. Any scheduled therapy response is not altered and is delivered according to the schedule.

Returning to815, if the first detected event is not the earliest in the ischemic cascade, the event detector is reconfigured to detect evidence of the earlier event at820. In some examples the signal data from a time period before the first event was detected is then examined. At825, it is determined if the earlier event is detected by the detection criterion (such as if the event occurred below a detection threshold for example). If there was not an undetected earlier event, at830it is determined if there is an upcoming event in the ischemic cascade. If there is not, the method800returns to looking for the start of the cascade at805. If there is an upcoming event, the method800waits for the next event to be measured at835.

If there was an undetected earlier event, the timer is checked at845. If the one or more subsequent events occur during the timed duration and there was an undetected earlier event, at850a response is initiated immediately, otherwise a scheduled response is not altered and is delivered according to the schedule.

FIG. 9is a block diagram of another method900for detecting myocardial ischemia. First, second, and third sensor signals are sensed at902. A first cardiovascular event and a second event are detected from at least one of the sensor signals at904and906respectively. If the second event is not next in the cascade at908, then a lower level alert is declared at916. If the second event is next in the cascade at908, then a third event is detected from at least one of the sensor signals at910. If the third event is not next in the cascade at912, then a lower level event is declared at916. If the third event is next in the cascade at912, then ischemia is declared at914.