Patent Application
20110184301
The present invention generally relates to implantable medical devices, such as pacemakers or implantable cardioverter/defibrillators (ICDs), and in particular to techniques for detecting and predicting changes of heart conditions, such as heart failure, at an early stage within a patient in which a medical device is implanted.
Heart failure is a debilitating disease in which abnormal function of the heart may lead to inadequate blood flow to fulfil the needs of tissues and organs of the body or increased filling pressures. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately eject or fill with blood between heartbeats and the valves regulating blood flow become leaky, allowing regurgitation or back-flow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness and the inability to carry out daily tasks may result. Not all heart failure patients suffer debilitating symptoms immediately and some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive. As heart failure progresses, it tends to be increasingly difficult to manage. A particularly severe form of heart failure is congestive heart failure (CHF) wherein the weak pumping of the heart leads to build-up of fluid in the lungs and other organs and tissues.
New medical and device-based therapies for heart failure improve survival and reduce hospitalization rates. However, total hospitalization continues to rise with the growing prevalence of heart failure. In fact, only in Europe approximately 14 million people suffer from heart failure and about 3.6 million new cases are diagnosed every year. The 5 year mortality is approximately 50%. Consequently, treating HF poses a huge stress on all European countries as well as USA's economic systems and, for example, in United States heart failure is one of the most costly diseases in healthcare budgets, with 70% of the expenses going to the treatment of acute heart failure de-compensation.
Patients with HF eventually experience episodes of HF exacerbation requiring some kind of intervention—in some cases even hospitalization. These exacerbations may be triggered by a number of factors such as non-compliance to drugs, development of AF, changes in diet or alcohol intake, influenza etc., but may also be idiopathic. By predicting these exacerbations or more closely following the patient's HF status, early intervention is possible which may prevent the need for costly hospitalization. This also improves patient care, and in the long run, may even improve survival. Although regular monitoring of heart failure patients is recommended in management programs, none of these measures has shown conclusive impact on heart failure morbidity.
Incipient CHF is often present without the patient knowing it. An indicator of incipient CHF would therefore be of great value since treatment by addition of drugs or electrical stimulation therapy could then be introduced at an early stage of CHF to slow down the progression of CHF. This would prolong the survival of the patient. Such an indicator could also be used to alert the patient or the physician about new conditions, so that appropriate measures can be taken to avoid hospitalization. The first signs of CHF can be observed in the left atrium of the heart by monitoring its mechanical behaviour, such as volume and pressure changes. If the pumping ability of the left ventricle is reduced, the volume of the left atrium will increase due to excessive filling of blood.
Thus, as mentioned above, symptoms leading to heart failure hospitalization usually occur late in the course of de-compensation. Therefore, a reliable means of chronic fluid status monitoring in HF patients is needed to detect early de-compensation when appropriate intervention is possible.
Both literature and clinical and pre-clinical work have shown that impedance, both intracardiac and intrathoracic, decrease as HF progresses and drops significantly prior to an acute HF exacerbation. For example, US 2006/0235325 discloses a congestive heart failure monitor that measures the impedance over the left atrium, which reflects volume changes in the left atrium. Specifically, the mean value of the impedance and the quotient between the maximum value and the minimum value of the impedance during a cardiac cycle are monitored to detect CHF.
Thus, an object of the present invention is to provide an improved medical device and method for such a device for detecting incipient congestive heart failure.
According to a first aspect of the present invention, there is provided a heart failure detector for detecting incipient heart failure of a patient that includes an impedance measuring unit adapted to acquire impedance signals reflecting volume changes of the right ventricle of a heart of the patient. The impedance measuring unit is connectable to at least two electrodes adapted to be located in or at the right side of the heart including in the right ventricle or in the vicinity of the right ventricle, in the right atrium or in the vicinity of the right atrium such that volume changes of the right ventricle and/or the right atrium are reflected by the impedance signals. Further, a computerized impedance processing unit is configured to receive the impedance signals from the impedance measuring unit and to process the impedance signals to determine a first impedance parameter substantially reflecting a volume of the right ventricle, and a computerized heart failure status determining unit is configured to determine a heart failure status based on the first impedance parameter, wherein a decreasing first impedance parameter is determined to be an indication of a deterioration of the heart failure status.
According to a second aspect of the present invention, there is provided a method for detecting incipient heart failure of a patient comprising acquiring impedance signals reflecting volume changes of the right ventricle of a heart of the patient, using at least two electrodes adapted to be located in or at the right side of the heart including in the right ventricle or in the vicinity of the right ventricle, in the right atrium or in the vicinity of the right atrium such that volume changes of the right ventricle and/or the right atrium are reflected by the impedance signals; processing the impedance signals to determine a first impedance parameter substantially reflecting a volume of the right ventricle; and determining a heart failure status based on the first impedance parameter, wherein a decreasing first impedance parameter is determined to be an indication of a deterioration of the heart failure status.
The present invention is based on the insight that there is a high positive correlation between the left atrial pressure and the right ventricular pressure, particularly, at volume overload. It is well documented that patients with congestive heart failure may develop elevated systemic venous pressure indicated by e.g. jugular vein stasis. This is a direct consequence of an increased left atrial blood pressure. Since the right side of the heart and in particular the right ventricle has a higher compliance than the left side, the increased left atrial pressure will swiftly propagate through the pulmonary vessels to the right ventricle and atrium. Thus, by measuring the pressure or volume change in the right ventricle (and/or right atrium) an early and accurate indication of incipient heart failure can be achieved. The inventors have further identified a negative correlation between impedance signals measured between the right atrium and the right ventricle and the end-systolic volume of the right ventricle and a negative correlation between the measured impedance signal and the right ventricular pressure. Moreover, the inventors have also observed that the peak to peak impedance value decreases with increased left atrial pressure, which is a result of a dilatation of the right atrium and right ventricle due to increased pressure load where especially the end-systolic volume is increased. Consequently, the inventors have come to the conclusion that the impedance measured in the right ventricle (and/or right atrium) is a good parameter for detection of right ventricle dilatation and right atrium dilatation at congestive heart failure, and that this parameter in combination with the peak to peak value of the impedance provides an even more accurate indicator. This increased dilatation of the right ventricle and right atrium is a direct consequence of an increased left atrial pressure, which is well known to be an early indicator of left heart failure. This increased dilatation of the right ventricle and right atrium is caused by the differences in tissue composition between the right side and the left side of the heart. The wall of the left ventricle is thick and can thus withstand high pressure without significant volume changes, while the right ventricle, as mentioned above, is compliant to be able to pump varying volumes with low pressures. This means that a pressure increase in the left side of the heart will be to some extent “transmitted backwards” to the right heart resulting in an amplified volume change.
According to an embodiment of the present invention, the impedance processing unit is adapted to receive the impedance signals from the impedance measuring unit and to process the impedance signals to determine a first impedance parameter substantially reflecting a volume of the right ventricle, or, specifically, an end-systolic right ventricle volume. The impedance signals may be synchronized with ECG/IEGM signals in order to locate the end of the contraction phase in the cardiac cycle, for example, by identifying the end of the T-wave. Further, the end-systolic right ventricle volume may be determined by identifying a maximum impedance in a time window between to successive QRS complexes, for example, between two successive R-waves, wherein the maximum impedance substantially reflects the end-systolic volume.
In embodiments of the present invention, the impedance processing unit is adapted to process the impedance signals to determine an impedance parameter substantially reflecting the diastolic right ventricle volume and/or the right atrial volume. As above, the impedance signals may be synchronized with ECG/IEGM signals. The measurement of the impedance at the end-systolic right ventricle volume can be combined with measurements of impedances reflecting or related to the diastolic right ventricle volume and/or the right atrial volume.
The present invention is preferably implemented in an implantable heart stimulator such as a pacemaker e.g. a biventricular pacemaker. However, the invention is also applicable to other types of cardiac stimulators such as dual chamber stimulators, implantable cardioverter defibrillators (ICDs), etc.
According to an embodiment of the present invention, the impedance signals are processed to determine a second impedance parameter substantially reflecting a difference between diastolic and systolic volume. In a further alternative, the impedance signals are processed to determine a second impedance parameter substantially reflecting a right ventricular ejection-fraction.
Thus, according to embodiments of the present invention, the first impedance parameter, which decreases with increasing right ventricle volume and left atrial pressure, and the second impedance parameter, which decreases with decreasing difference between diastolic and systolic volume right ventricle ejection fraction, are monitored over time for early detection of impaired left ventricle or right ventricle function. If both the first and second impedance parameters have decreased during a predetermined period of time, this is a strong indication of a worsening heart failure condition. This is caused by dilatation or blood accumulation in the right side of the heart. By using both the first and second impedance parameters in the monitoring, the specificity of the HF detection can be significantly improved. In fact, there are a number of situations where the right ventricle volume increases or where the peak to peak amplitude decreases, which is not caused by heart failure. These situations may be identified by monitoring both the first impedance parameter and the second impedance parameter and determining the heart failure status based on the development of both these parameters. A non exhaustive number of examples of such situations or conditions include:
In a further embodiment of the present invention, a rate of change of the first and/or the second impedance parameter are/is calculated for each cardiac cycle or for a number of cardiac cycles, and a heart failure status of the patient is determined to be deteriorating if a rate of change of a decrease of the first impedance parameter is higher than a predetermined threshold and/or a rate of change of a decrease of the second impedance parameter is higher than a predetermined threshold. This indicates a fast change of the right ventricle congestion, i.e. increased left atrial pressure. Such a fast change may be an early indication of acute worsening, which may be further communicated to the patient and/or the hospital. As a response to such an indication, the therapy can be changed and hospitalization may thereby be avoided. In an alternative embodiment, two thresholds may be used, where the first indicates a fast change and a second, lower threshold may indicate a worsening which is not acute. Thereby, slow impairments or slow improvements can be followed, for example, at changed drug titration or pacing therapy. Furthermore, the rate of change of the first and/or the second impedance parameter may be calculated over longer period than a cardiac cycle of a few consecutive cardiac cycles, for example, for a period of a couple of days or weeks.
Pacing therapy for heart failure patients can be altered as changed AV-delay, PV-delay, or VV-delay. If several pacing sites are available using multiple electrode leads, the pacing therapy can be optimized or the optimal pacing site(s) can be made automatically using the first and/or second impedance parameter(s) as input. After changing a timing combination of pacing location, the change of impedance is recorded and compared to the values prior to the change. If the first impedance parameter increases (i.e. indicating an improvement of the heart failure status), the new setting is favourable and may be stored as the new setting. This may be an iterative procedure to optimize the pacing therapy and/or pacing site.
In embodiments of the present invention, a first electrode configuration includes a first electrode located in the right atrium (e.g. a ring electrode), a second electrode located in the right ventricle (e.g. a ring electrode), a third electrode located in the right atrium (e.g. a tip electrode), and a fourth electrode located in the right ventricle (e.g. a tip electrode), and wherein a second alternative electrode configuration includes a first electrode (e.g. a ring electrode) and a second electrode (e.g. a tip electrode) located in the right ventricle. There are other conceivable alternative electrode configurations that provides impedance signals that substantially reflect volume changes of the right ventricle and/or the right atrium, for example four electrodes located in the right ventricle, e.g. three ring electrodes and one tip electrode, or one coil electrode, one ring electrode and one tip electrode.
According to further embodiments of the present invention, impedance signals are acquired during consecutive cardiac cycles, wherein each impedance signal is acquired/obtained in synchronization with a specific cardiac event in respective cardiac cycle, and wherein the impedance processing unit is adapted to process the received impedance signal to determine the first impedance parameter to be a mean impedance value of the impedance signals and the second impedance parameter to be a peak-to-peak value of the impedance signal between a cardiac event in two consecutive cardiac cycles.
In accordance with embodiments of the present invention, the acquisition of impedance signals is synchronized with the respiration cycle.
In accordance with embodiments of the present invention, the impedance signals are processed to calculate average impedance values from which the first and second impedance parameters are determined, wherein each average value is calculated over a predetermined number of cardiac cycles, or wherein the impedance processing unit is adapted to process the impedance signals to determine the first and second impedance parameter as average values over a predetermined number of cardiac cycles.
According to an embodiment of the present invention, a maximum impedance is identified in a time window between to successive QRS complexes, for example, between two successive R-waves, or between to successive T-waves and the first impedance parameter is determined to be the identified maximum impedance. This maximum impedance coincides with the time-point for the end-systolic volume, i.e. the minimum volume, and will thus substantially reflect the end-systolic volume or the minimum volume. The time window may further be set to ¼T to ¾T of the period T, where the period T may be set to the period of time between the successive R-waves.
In accordance with a further embodiment of the present invention, the heart failure status is compared with a predetermined patient specific threshold and, if the heart failure status exceeds the patient specific threshold, a warning signal that triggers an alarm function is issued. Preferably, the threshold is programmable. The threshold will be different for different methods of determining the patient status and for predicting the HF status and will also be patient specific. Since the impedance is affected not only by the HF status but also by lead location, blood constituents, if the patient is on dialysis, diet, exercise, posture, etc, the impedance (and hence the index) variability will be different for different patients. The alarm may be sent to the physician of the patient via a communication system using a system for remote follow-up. The physician may call the patient for a visit, or the device may notify the patient that he or she should seek contact with the/a physician.
According to an embodiment of the present invention, the patient data is transferred to and displayed on an external device such as programmer during a follow-up and a trend of the patient's heart failure status can be reviewed by, for example, a physician.
In a further embodiment of the present invention, the patient status is regularly transferred to and displayed on an external device such as a home monitoring device located at the patient's home, and/or a programmer device located at the health care provider of the patient.
As the skilled person realizes, steps of the methods according to the present invention, as well as preferred embodiments thereof, are suitable to realize as computer program or as a computer readable medium.
Further objects and advantages of the present invention will be discussed below by means of exemplifying embodiments.
a is a simplified, schematic diagram illustrating generally one example of an electrode configuration which may be used in the present invention.
b is a simplified, schematic diagram illustrating generally another example of an electrode configuration which may be used in the present invention.
The following is a description of exemplifying embodiments in accordance with the present invention. This description is not to be taken in limiting sense, but is made merely for the purposes of describing the general principles of the invention. Thus, even though particular types of implantable medical devices such as heart stimulators will be described, the invention is also applicable to other types of cardiac stimulators such as dual chamber stimulators, implantable cardioverter defibrillators (ICDs), etc.
Turning now to
The heart stimulator 10 comprises a housing 12 being hermetically sealed and biologically inert, see
As discussed above with reference to
The impedance measuring unit 41 is adapted to carry out impedance measurements of the intracardiac and intrathoracic impedance or admittance of the patient, for example, by applying a current between the RV ring electrode 34 and the RA ring electrode 23 and the measuring the resulting voltage between the RV tip electrode 32 and the RA tip electrode 22. The raw impedance data is then supplied to an impedance processing module 46, which may comprise, for example, amplifiers and filters e.g. FIR or IIR filters. The impedance processing unit 46 performs a pre-processing procedure in which the acquired impedance or admittance signal are pre-processed. According to one embodiment of the present invention, the impedance processing unit 46 determines a first impedance parameter that substantially reflects volume changes of the right ventricle. This first impedance parameter may be determined by low-pass filtering the raw impedance signal, e.g. about 0 to about 5 Hz or about 0 to about 2.5 Hz, and averaging the filtered signal between two detected heart events, for example, two R-waves or two P-waves, which results in one value for each cardiac cycle. In embodiments of the present invention, the resistive part of the impedance is used when determining the impedance parameters.
In one embodiment of the present invention, the first impedance parameter is processed such that is substantially reflects the end-systolic right ventricle volume. The acquired impedance signals (the resistive part of the low-pass filtered signal) may be synchronized with IEGM signals in order to locate the end-systolic right ventricle volume. A maximum impedance may identified in a time window between to successive QRS complexes, for example, between two successive R-waves, or between to successive T-waves and the first impedance parameter may be determined to be the identified maximum impedance. This maximum impedance coincides with the time-point for the end-systolic volume, i.e. the minimum volume, and will thus substantially reflect the end-systolic volume or the minimum volume. The time window may further be set to ¼T to ¾T of the period T, where the period T may be set to the period of time between the successive R-waves. In
Further, in other embodiments, the first impedance parameter substantially reflects the diastolic right ventricle volume and/or the right atrial volume. The first impedance parameter may be determined to reflect a combination of the end-systolic right ventricle volume and/or the diastolic right ventricle volume and/or the right atrial volume.
Moreover, the impedance processing unit 46 may be adapted to determine a second impedance parameter corresponding to a peak to peak value between a maximum impedance and a minimum impedance. The second impedance parameter may be determined by band-pass filtering the raw impedance signal, e.g. about 0.2 to about 100 Hz or about 0.3 to about 65 Hz, and determining the peak to peak amplitude of the band-pass filtered signal between two heart events, which results in one value for each cardiac cycle. In order to reduce the noise, the data acquisition can be synchronized with the respiration frequency, for example, by using cardiac cycles or heart beat from the same relative position in the respiration cycle. Another way to reduce the respiration artefacts, is to determine each impedance parameter (or to use raw impedance data) as an average value over at least two full respiratory cycles.
The impedance parameter, the first and/or second parameter, is/are supplied to a heart failure status determining module 47 adapted to determine a patient status. Thus, the patients' heart failure status can be monitored and tracked and/or acute heart failure exacerbation events in the patient can be predicted, which will be described in more detail hereinafter.
As discussed above, the first impedance parameter decreases with increasing right ventricle volume and left atrial pressure. The second impedance parameter decreases with decreasing difference between diastolic and systolic volume and with decreasing ejection fraction. When the right ventricle dilates as an effect of e.g. increased right ventricle pressure, the wall tension increases which reduces the compliance of the walls. The ventricle becomes more spherical to distribute the tension more evenly. Also, if the stroke volume is unchanged and the right ventricle volume increases, the relative difference between diastolic and systolic volumes will decrease.
Turning now to
With reference now to
In
Although an exemplary embodiment of the present invention has been shown and described, it will be apparent to those having ordinary skill in the art that a number of changes, modifications, or alterations to the inventions as described herein may be made. Thus, it is to be understood that the above description of the invention and the accompanying drawings is to be regarded as non-limiting.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/SE08/00537 | 9/30/2008 | WO | 00 | 3/30/2011 |
