The invention relates to the administration of tests for cardiovascular autonomic neuropathy, and more specifically, to the administration of cardiovascular autonomic neuropathy tests in a patient having an implanted medical device.
Diabetes is a relatively common affliction in which a person's body does not produce or properly use the hormone called insulin that is needed to convert sugar, starches and other food into energy. By some estimates, about seven percent of the population of the United States has diabetes. The symptoms of diabetes are often not recognized, and it is estimated that about one-third of people with the disease do not realize they have it.
Compared to the general population, diabetes is estimated to be even more common within the population of patients who have an implanted cardiac rhythm management device. In one estimate, approximately 11-13% of patients with implantable pacemakers have diabetes, approximately 30-38% of patients having implantable cardioverter defibrillators have diabetes, and approximately 39-45% of patients having cardiac resynchronization therapy (CRT) devices have diabetes.
A common complication of diabetes is called Diabetic Autonomic Neuropathy (DAN). DAN is a condition that develops at some point after onset of diabetes and then progresses slowly over the course of the diabetic disease. By some estimates, almost 100% of patients with diabetes will eventually develop some form of DAN. DAN generally impairs a patient's ability to conduct activities of daily living and lowers quality of life. Moreover, DAN creates a risk of serious complications for the patient, the most important being that it diminishes the patient's ability to sense a hypoglycemic state and also diminishes the patient's ability to sense an incipient heart attack and seek appropriate medical attention. These and other risks create an elevated mortality rate, such that by some estimates the 5-year mortality rate in patients with DAN is three times higher than in diabetic patients without autonomic involvement. Furthermore, DAN also accounts for a large portion of the cost of care of a diabetic patient.
Although the mechanisms that cause DAN are not entirely understood, it is believed that the condition results, at least in part, from diabetic microvascular injury to the small blood vessels that supply nerves. DAN involves injury to a number of different autonomic functions, but one of the most clinically important is cardiovascular autonomic neuropathy (CAN). CAN results in impairment to autonomic control of cardiovascular function, typically resulting in abnormal heart rate and blood pressure reflexes, and is linked to increased patient mortality.
CAN is a degenerative disease that progresses slowly, but inexorably, in a patient. CAN is capable, however, of being managed through intensive glycemic control that can slow its progression. Furthermore, there are a variety of pharmacologic and nonpharmacologic therapies that are available to treat the symptoms of autonomic neuropathy. Therefore, it is desirable to monitor a patient for indications of the presence and degree of CAN in order to be able to properly manage the disease.
Improved techniques for monitoring diabetic patients for CAN are needed. In particular, techniques are needed for monitoring diabetic patients for CAN that are convenient for the patient, are less imposing on the resources of the medical care system, and are readily conducted at regular intervals.
A test for cardiovascular autonomic neuropathy is disclosed that incorporates an implanted medical device. One aspect of the invention relates to a system for performing cardiovascular autonomic neuropathy (CAN) testing in a diabetic patient. The system has an implantable medical device (IMD) that includes a plurality of implantable physiological sensors and that is configured to transmit a wireless signal corresponding to a sensed physiological activity and to receive wireless signals. The system further includes one or more non-implantable physiological sensors, where the non-implantable physiological sensors are each configured to transmit a signal corresponding to a sensed physiological parameter, and a monitor device having a patient interface. The monitor device is configured to interface with a patient, including directing the patient to answer health related questions and use one or more of the non-implantable physiological sensors. The monitor device is also configured to receive signals, including signals from the IMD and the non-implantable physiological sensors. The system is configured to provide an indication of the presence or progression of CAN.
Another aspect of the invention relates to a method of testing for cardiovascular autonomic neuropathy (CAN) in a diabetic patient. The method includes providing an implanted medical device (IMD) that includes a plurality of implantable physiological sensors, where the IMD is configured to transmit a wireless signal corresponding to a sensed physiological activity and to receive wireless signals. The method further includes providing a plurality of non-implantable physiological sensors, where the non-implantable physiological sensors are each configured to transmit a signal corresponding to a sensed physiological parameter, and providing a monitor device having a patient interface. The method also includes directing a patient through the patient interface to answer health related questions, interface with one or more of the non-implantable physiological sensors, and to perform a diagnostic procedure. The method further involves receiving signals at the monitor device, including signals from the IMD and the non-implantable physiological sensors, and using an implantable physiological sensor to verify that the patient properly performed the diagnostic procedure.
Another embodiment of the invention is a system for performing testing for cardiovascular autonomic neuropathy (CAN) in a diabetic patient, the system including an implanted medical device (IMD) system that includes a plurality of implantable physiological sensors, the IMD system being configured to transmit a wireless signal corresponding to a sensed physiological activity and receive wireless signals. The system further includes a plurality of non-implantable physiological sensors, where the non-implantable physiological sensors are each configured to transmit a signal corresponding to a sensed physiological parameter. The system further includes a monitor device configured to receive signals including signals from the IMD system and the non-implantable physiological sensors. The monitor device includes a patient interface and is configured to direct a patient through the patient interface to answer health related questions, interface with one or more of the non-implantable physiological sensors, and perform a diagnostic procedure. The IMD system further includes an implantable physiological sensor to verify that the patient properly performed the diagnostic procedure.
The invention may be more completely understood by considering the detailed description of various embodiments of the invention that follows in connection with the accompanying drawings.
While the invention may be modified in many ways, specifics have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives following within the scope and spirit of the invention as defined by the claims.
Cardiovascular autonomic neuropathy (CAN) is one aspect of diabetic autonomic neuropathy (DAN). CAN is a serious complication of diabetes that can create quality of life problems and increases the risk of patient mortality. Because CAN can be managed through appropriate medical treatment, it is important to test diabetic patients for the presence of the condition. Testing is preferably conducted early after a patient is diagnosed with diabetes and then at regular intervals until CAN is identified. Once the existence of CAN is identified, it is desirable to continue to monitor the patient for worsening progression of CAN. However, one problem is that many diabetic patients are not regularly followed by a specialist who is monitoring the patient for CAN, and therefore not all patients receive the appropriate testing at the appropriate intervals. It is desirable to have a CAN testing regime that does not require the oversight or direct involvement of a specialist.
Testing is a key aspect of overall diabetes and DAN management. In one standard treatment protocol, a patient who is diagnosed with Type 1 diabetes is tested for symptoms of CAN five years after diagnosis, although it is possible, and even desirable, to test such a patient earlier and more frequently. It is also standard treatment protocol to test a patient who is diagnosed with Type 2 diabetes for symptoms of CAN immediately after diagnosis. If a patient is tested and the test is negative for symptoms of CAN, then the patient is retested annually until symptoms arise. Once symptoms have been identified, then therapy is initiated, including treatment of symptoms and appropriate further diagnostic tests. A key aspect of control of CAN and DAN is intensive glycemic control. In fact, some studies have shown that intensive glycemic control can reduce the prevalence of the symptoms and effects of DAN by over 50%.
CAN involves degeneration of the autonomic control of cardiac function. Symptoms of CAN include, for example, lack of heart rate variability in response to breathing or exercise, and also the possibility of associated poor exercise tolerance. Furthermore, an excessively rapid resting heart rate (tachycardia) is an indication of the presence of CAN. Some patients having CAN will experience blunted symptoms of coronary artery disease, such as painless ischemia and silent myocardial infarction (MI). These are particularly important aspects of the disease because of the potential that the patient will not realize the presence of a condition that requires immediate medical attention.
A testing protocol for CAN generally includes tests of autonomic control of heart function. CAN tests measure heart rate variability and blood pressure response to various activities and circumstances. The following tests can be used to evaluate the existence and nature of CAN in a diabetic patient. These tests will also be described later herein in the context of administering these tests using certain embodiments of the invention:
(1) Test resting heart rate. A heart rate of greater than 100 beats per minute is abnormal.
(2) Measure beat-to-beat heart rate variation while lying supine and breathing six times per minute. A difference in heart rate of less than 10 beats per minute is abnormal, compared to prior to the patient regulating breathing.
(3) Measure beat-to-beat heart rate variation for inspiration compared to exhalation. An exhalation:inspiration R-R ratio of greater than 1.17 is abnormal. The R-R interval is the amount of time between two consecutive R waves of an electrocardiogram.
(4) Determine heart rate response to standing. Generally, this involves measuring the R-R interval on an electrocardiogram at the fifteenth and the thirtieth beats after standing. An increase in the heart rate of less than 3 percent from the fifteenth to the thirtieth beats is abnormal.
(5) Test heart rate response to the Valsalva maneuver, where the patient forcibly exhales into the mouthpiece of a manometer at a pressure of 40 mm Hg for 15 seconds. A ratio of the longest R-R interval to the shortest of less than 1.2 is abnormal.
(6) Measure systolic blood pressure response to standing, where a first blood pressure measurement is taken when the patient is lying down and a second blood pressure measurement is taken two minutes after the patient stands. A decrease in systolic blood pressure in response to standing of more than 30 mm Hg is abnormal, and a decrease of 10 to 29 mm Hg is borderline.
(7) Measure diastolic blood pressure in response to isometric exercise. This test involves having a patient squeeze a handgrip dynamometer to establish a maximum exertion, and then having the patient squeeze the grip at 30 percent of maximum for five minutes. A rise in diastolic blood pressure of less than 16 mm Hg in the contralateral arm is abnormal.
(8) Conduct electrocardiography and determine a corrected QT interval (QTc). Because the actual QT interval is affected by the patient's heart rate, a corrected QT interval is one that is corrected for the heart rate so that various QT interval measurements can be compared against each other. A QTc of more than 440 ms is abnormal.
(9) Conduct electrocardiography and determine heart-rate variability. Testing for reduced heart-rate variability using electrocardiography over a longer period of time, such as over 24 hours, can reveal CAN earlier than reflex tests, like those determining the body's response to standing. By recording of the heart-rate over a 24-hour period, abnormal circadian rhythms can be detected, thereby revealing problems with sympathovagal activity. One measure of heart rate variability is a frequency domain measure. A common frequency domain method is to apply a discrete Fourier transform to the patient's beat-to-beat interval time series. The result expresses the amount of variation for different frequencies. Several frequency bands of interest have been defined in humans, including the High Frequency band (HF) between 0.15 and 0.4 Hertz. The High Frequency band is driven by respiration and appears to derive mainly from vagal activity. The Low Frequency band is between 0.04 and 0.15 Hz and derives from both vagal and sympathetic activity. The Very Low Frequency band is between 0.0033 and 0.04 Hz. A depressed very-low frequency peak indicates sympatho-vagal imbalance, and a depressed high frequency peak indicates parasympathetic dysfunction. A lowered low-frequency to high-frequency ratio indicates sympathetic imbalance. The exact values expected for the low and high frequency peaks will vary depending on the patient's age and other factors. A description of methods of analyzing heart rate variability for assessing autonomic balance is described in commonly-owned U.S. Pat. Nos. 7,069,070, 7,215,992 and U.S. Published Patent Application 2004-0158295, which patent documents are hereby incorporated herein by reference.
These tests are traditionally performed in a physician's office or other medical facility. Because many of these tests require the patient to perform a certain motion, such as standing up, they typically require the direction and monitoring of a medical professional. Because of the inconvenience, cost, and time involved in conducting these tests, they are often conducted at intervals of about a year or greater. However, it is desirable to reduce the inconvenience, cost, and time involved in conducting the screening tests. This is advantageous to the patient and the medical system. Furthermore, it may as a practical matter allow the screening test to be conducted more often, and in doing so, to identify symptoms of CAN earlier and to provide for earlier and more effective treatment. This earlier and more effective treatment may slow the progression of the disease, thereby reducing mortality and increasing quality of life. The screening tests may also be more accurate.
As discussed above, there tends to be overlap between the population of diabetics and the population of heart patients who have implantable medical devices such as cardiac rhythm management (CRM) devices. The inventors have devised a CAN test protocol that can be executed by or in conjunction with a patient's implantable medical device. This arrangement utilizes some of the capabilities inherent in an implantable medical device, and further incorporates additional sensors and telemetric communications to accomplish a CAN test. The CAN test protocol has the advantage that it can be conducted in a patient's home or other convenient location, and does not require a visit to a medical facility and the direct attention of trained medical personnel. These advantages may, as a practical effect, allow the test to be performed more frequently, thereby leading to earlier diagnosis and treatment. Furthermore, there is less inconvenience to the patient and less expense for the medical system.
An embodiment of a medical system for testing diabetic patients for CAN that is constructed according to the principles of the present invention is depicted in
The implantable medical device of
Testing system 20 of
Monitor device 24 may also be capable of communicating with a remote computer 32 (also called a remote station 32) through telecommunications, such as over a conventional phone line 34, through cellular phone communications, via the Internet, or any other wired or wireless form of communication. In some embodiments, monitor device 24 is configured to inquire regularly about the patient's general health conditions, such as physical activity and symptoms of disease. Inquiring about the patient's health generally involves displaying one or more health-related questions on an interface such as screen 27 and requesting the patient provide input such as through a touch sensitive screen or buttons 29. The monitor device 24 may also be configured to receive information from the implanted medical device 22 regarding the operation of the device, as well as any information or data stored in the device. The monitor device 24 may be further configured to transmit this information to a remote computer 32, where the information is received and can be further analyzed to determine the patient's medical condition.
A schematic representation of functional elements of an embodiment of a monitor device 24 is depicted in
User input to the monitor device may be provided by a number of means. For example, user input 955 may be a touch sensitive screen, buttons or keys, voice recognition, or some combination of these. DMA controller 960 is provided for performing direct memory access to system RAM 910. A visual display is generated by a video controller 965, which controls video display 970. Monitor device can also include a telemetry interface 990 which allows the monitor device to interface and exchange data with an implantable medical device.
Testing system 20 of
In addition, the embodiment of
The testing system 20 further includes a plurality of non-implantable sensors 41. In the embodiment of
Testing system 20 is also shown in
Testing system 20 is further shown in
In an embodiment, monitor device 24 is programmed or commanded to initiate a CAN test at a regular interval. For example, in one embodiment monitor device 24 is configured to initiate a CAN test at a one month interval, and in another embodiment, to initiate a CAN test at a two month interval, and in yet another embodiment, to initiate a CAN test at a six month interval, and in a further embodiment, to initiate a CAN test at a one year interval. Other intervals are usable. In another embodiment, monitor device 24 initiates a CAN test when commanded to do so, such as by a physician or medical professional.
An embodiment of a CAN test protocol is depicted in
There are many usable embodiments of questions to ask the patient. Examples of appropriate questions are the following:
1. How do you feel today?
2. Do you feel tired?
3. Do you have a difficult time performing physical tasks?
4. Do you occasionally feel out of breath?
5. When did you last drink coffee?
6. Has your blood sugar been difficult to control lately, and if so, when?
7. Have you been lightheaded?
8. Have you had a change in your vision?
9. Have you experienced any burning, tingling, or numbness in your hands or feet?
The monitor device 24 stores the answers to these questions and may transmit them to remote computer 32 at a later time.
After the questions are asked at step 102, the monitor device 24 provides instructions to the patient to perform the various aspects of a CAN screening test. At step 104, the monitor device 24 requests that the patient either sit or lie down and stay at rest for a period of time, and during this time the patient's resting heart rate is recorded. Measuring the patient's resting heart rate involves receiving cardiac electrical signals at electrode 28, which are then passed through lead 26 to electronic circuitry 40 of CRM device 22. Electronic circuitry 40 may be configured to determine a heart rate based on the received cardiac signal and to transmit this information to monitor device 24, or alternatively, the CRM device 22 may transmit the raw cardiac signal to monitor device 24 where the heart rate is determined. In one embodiment, the electronic circuitry 40 determines the heart rate based on an interval in the electrocardiogram, such as an R-R interval. In another embodiment, the electronic circuitry determines the QT interval from the electrocardiogram and corrects the determined QT interval for the heart rate (denoted QTc).
At step 106, the monitor device 24 requests that the patient lie supine (on the back) while breathing at the rate of six breaths per minute. In some embodiments, an implantable respiration sensor 36 is consulted to verify that the patient is breathing at an appropriate rate. The respiration sensor may be a trans-thoracic respiration sensor 36 or an accelerometer 38, or a variety of other sensors that provide information about a patient's respiration. In one embodiment, the monitor device 24 assists the patient in breathing at a rate of six breaths per minute by providing an audible signal once every 10 seconds, such that the patient can use the audible signal to time each breath. The patient's heart rate and heart rate variability is then measured. This can be accomplished in electronic circuitry 40, which may be configured to measure intervals on an electrocardiogram. For example, the circuitry 40 may measure an R-R interval after the patient has slowed breathing, and compare the R-R interval to the R-R interval before the patient's breathing was slowed. The circuitry 40 also determines the beat-to-beat variability in one embodiment. In addition to measuring the heart rate variability over the course of the test, the circuitry 40 may be configured to measure the patient's R-R interval during exhalation and also during inspiration. The heart rate variability and ratio of exhalation to inspiration R-R values is transmitted to monitor device 24. Alternatively, raw cardiac signal data may be transmitted to the monitor device 24, where the appropriate cardiac intervals and ratios are determined.
At step 108, the monitor device 24 requests that the patient sit down or lie down for a period of time, such as 30 seconds, and then stand up and remain standing for a period of time, such as 30 seconds or more. Other time intervals are usable, however, and in some embodiments, it is necessary for the patient to remain standing longer than 30 seconds. In some embodiments, the implantable posture sensor 38 is used to determine when the patient has transitioned from a sitting position to a standing position. At the point that the patient is standing, electronic circuitry monitors the patient's cardiac activity. A typical data collection involves measuring the R-R interval at the 15th beat after standing and at the 30th beat after standing. This information is then transmitted to monitor device 24, or alternatively, the raw cardiac data is transmitted to monitor device 24 and the data is analyzed in the monitor device 24.
In one embodiment, step 108 also includes instructing the patient to utilize non-implantable blood pressure tester 42, where blood pressure tester 42 is present, prior to beginning the procedure. Instructing the patient to use the blood pressure tester 42 generally includes instructing the patient to place a blood pressure cuff on the patient's bicep or other suitable location. In some embodiments, however, a non-implantable blood pressure tester 42 is not used, but instead an implantable blood pressure sensor is available. In either case, step 108 further includes the step of instructing the patient to remain standing for a period of time, such as two minutes. Then blood pressure measurements are taken either by blood pressure tester 42 or by implantable blood pressure tester, at a first time while the patient is sitting or lying down and at a second time two minutes after standing. If a non-implantable blood pressure tester 42 is used, it is configured to automatically inflate and deflate at the appropriate times in order to take a blood pressure measurement. The blood pressure measurements are transmitted to monitor device 24. Alternatively, the change in the patient's blood pressure from the first time to the second time is determined and the calculated difference is transmitted to monitor device 24.
At step 110, the monitor device 24 instructs the patient to use non-implantable manometer 44. The patient is generally instructed to forcibly exhale into a mouthpiece of the manometer 44 and to maintain a pressure of at least 40 mm Hg for at least 15 seconds. As described above, the manometer 44 or the monitor device 24 may provide indications to assist the patient with meeting these requirements, such as an audible signal that indicates that sufficient pressure is achieved and a separate audible signal that indicates that sufficient time has passed. During the 15 seconds where the patient is exhaling at the appropriate pressure, electronic circuitry 40 is configured to measure the R-R interval of each heart beat. The R-R intervals are transmitted to monitor device 24, or alternatively, raw cardiac signal data is transmitted to monitor device 24 where the R-R intervals are determined.
At step 112, the monitor device 24 instructs the patient to use the handgrip dynamometer 45, if available, along with the blood pressure tester 42, if available. The patient is instructed to apply a cuff of the blood pressure tester to one arm if a non-implantable blood pressure tester 42 is used. The patient is then instructed to squeeze the handgrip dynamometer 45 as hard as possible with the arm opposite to the one that has the blood pressure tester 42 on it. This procedure is used to define the patient's maximum handgrip force. Then a value that represents 30 percent of the patient's maximum handgrip force is calculated. The patient is then instructed to squeeze the handgrip dynamometer 45 with the same hand as used to determine the maximum at the 30 percent of maximum value for 5 minutes. In some embodiments, monitor device 24 includes a timer to assist the patient in determining when the appropriate time interval has elapsed and may provide an audible signal to indicate that the patient can relax. While the patient is squeezing the handgrip dynamometer 45, the blood pressure tester 42 monitors the patient's blood pressure in the contralateral arm. This blood pressure information is transmitted to control device 24.
In each of steps 102 to 112, data is generated concerning the patient's performance or response to each test. This data may be transmitted in a raw or unprocessed form to monitor device 24, or may be processed in an implantable or non-implantable device and then transmitted to monitor device 24 in a summary condition.
In one embodiment, the data generated from testing protocol 100 is analyzed in monitor device 24 to determine whether the patient has symptoms of CAN, and if so, the nature and extent of the symptoms. In another embodiment, the data generated from testing protocol 100 is transmitted to remote computer 32, where it is analyzed to determine whether the patient has symptoms of CAN and the nature and extent of the symptoms. In yet another embodiment, the data generated from testing protocol 100 is transmitted to remote computer 32, where it is presented to a trained medical person who can evaluate it to determine whether the patient has symptoms of CAN and the extent of the symptoms and progression of CAN. Further, the data may be analyzed by a combination of these ways or in all of these ways.
In embodiments where the data from testing protocol 100 is analyzed in monitor device 24 or remote computer 32, parameters may be programmed into or stored within the respective device to form a basis for making an evaluation of CAN. In one aspect of the data analysis, a parameter is provided that is associated with the data from step 104, such that a resting heart rate of greater than 100 beats per minute is an indication of the presence of CAN. Other parameters may be provided that are associated with other aspects of the patient's electrocardiogram, such as a QTc of more than 440 ms.
Another parameter is a heart-rate variability having depressed very-low frequency peak, a depressed high frequency peak, or a lowered low-frequency to high-frequency ratio, where the presence of one or more of these conditions is an indication of the presence of CAN, where these parameters are typically determined by a frequency transform of electrocardiogram data over an extended period, such as a 24 hour period. A description of methods of analyzing heart rate variability for assessing autonomic balance is described in commonly-owned U.S. Pat. Nos. 7,069,070, 7,215,992 and U.S. Published Patent Application 2004-0158295, which patent documents were previously incorporated herein by reference.
In another aspect of the data analysis, a parameter is provided that is associated with the data from step 106, such that a difference in heart rate of less than 10 beats per minute while the patient breaths at the rate of six breaths per minute, and an exhalation to inspiration ratio of greater than 1.17, is an indication of the presence of CAN. In a further aspect of the data analysis, a parameter is provided that is associated with the data from step 108, such that a ratio of the R-R interval at the 30th beat to the R-R ratio at the 15th beat after standing is less than 1.03, and a fall in blood pressure of more than 30 mm Hg, or in some cases more than 10 mm Hg, is an indication of the presence of CAN. In yet another aspect of the data analysis, a parameter is provided that is associated with the data from step 110, such that a ratio of the longest R-R interval to the shortest R-R interval during the Valsalva maneuver of less than 1.2 is an indication of the presence of CAN. In a further aspect of the data analysis, a parameter is provided that is associated with the data from step 112, such that a rise of less than 16 mm Hg in the contralateral arm is an indication of the presence of CAN.
In some embodiments, the determination of whether the patient has CAN is made where any one of the parameters provide an indication of the presence of CAN. In other embodiments, the number of parameters that provide an indication of the presence of CAN and/or the degree to which the patient deviates from the parameters can be used to provide an indication of the extent or progression of the patient's CAN. In some embodiments, where any parameter indicates the presence of CAN, a trained medical person is alerted and analyzes the data further.
In some embodiments, certain testing steps can be done without the patient knowing and without the patient's involvement. For example, a heart rate measurement may be taken any time the posture sensor indicates an appropriate, sudden change in posture, such as would be representative of the patient standing up from a sitting position.
In some embodiments, less than all of the steps of testing protocol 100 shown in
In one embodiment, the monitor device 24 can be programmed to customize which tests are administered to the patient. For example, a physician may program monitor device 24 to administer certain tests and to not administer other tests.
The present invention should not be considered limited to the particular examples described above, but rather should be understood to cover all aspects of the invention as fairly set out in the attached claims. Various modifications, equivalent processes, as well as numerous structures to which the present invention may be applicable will be readily apparent to those of skill in the art to which the present invention is directed upon review of the present specification. The claims are intended to cover such modifications and devices.
The above specification provides a complete description of the structure and use of the invention. Since many of the embodiments of the invention can be made without parting from the spirit and scope of the invention, the invention resides in the claims.