Abstract:
Described herein are methods and systems for delivering pacing therapy to HF patients who do not exhibit a reduced EF. Such patients do not have systolic dysfunction and generally do not benefit from established HF therapies that either augment contractile function or counteract conduction abnormalities. In one embodiment, a HF patient with a normal EF is tested for the adequacy of heart rate response during exercise. If the patient is found to be chronotropically incompetent, a rate-adaptive pacing mode is employed in order improve functional capacity.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application is related to co-pending, commonly assigned U.S. patent application Ser. No. 10/038,936, “METHOD AND APPARATUS FOR MEASURING LEFT VENTRICULAR PRESSURE,” filed on Jan. 4, 2002, U.S. patent application Ser. No. 10/314,910, “METHOD AND APPARATUS FOR OPTIMIZING VENTRICULAR SYNCHRONY DURING DDD RESYNCHRONIZATION THERAPY USING ADJUSTABLE ATRIO-VENTRICULAR DELAYS,” filed on Dec. 9, 2002, U.S. patent application Ser. No. 10/314,899, “METHOD AND APPARATUS FOR OPTIMIZING STROKE VOLUME DURING DDD RESYNCHRONIZATION THERAPY USING ADJUSTABLE ATRIO-VENTRICULAR DELAYS,” filed on Dec. 9, 2002, U.S. patent application Ser. No. 10/402,324, “METHOD AND APPARATUS FOR QUANTIFICATION OF CARDIAC WALL MOTION ASYNCHRONY,” filed on Mar. 28, 2003, and U.S. patent application Ser. No. 10/703,398, “ELECTRICAL THERAPY FOR DIASTOLIC DYSFUNCTION,” filed on Nov. 7, 2003, all assigned to Cardiac Pacemakers, Inc., which are hereby incorporated by reference. 
     
    
     TECHNICAL FIELD  
       [0002]     This document relates generally to cardiac rhythm management devices and, in particular, to the use of such devices in heart failure patients.  
       BACKGROUND  
       [0003]     Heart failure (HF) is a debilitating global disease whose incidence is increasing dramatically. Heart failure refers to a clinical syndrome in which an abnormality of cardiac function causes a below normal cardiac output that can fall below a level adequate to meet the metabolic demand of peripheral tissues. Heart failure can be due to a variety of etiologies with ischemic heart disease being the most common. Heart failure can be treated with a drug regimen designed to augment cardiac function or by pacing therapy. It has been shown that some heart failure patients suffer from intraventricular and/or interventricular conduction defects (e.g., bundle branch blocks) such that their cardiac outputs can be increased by improving the synchronization of ventricular contractions with electrical stimulation. In order to treat these problems, implantable cardiac devices have been developed that provide appropriately timed electrical stimulation to one or more heart chambers in an attempt to improve the coordination of atrial and/or ventricular contractions, termed cardiac resynchronization therapy (CRT). Ventricular resynchronization is useful in treating heart failure because, although not directly inotropic, resynchronization can result in a more coordinated contraction of the ventricles with improved pumping efficiency and increased cardiac output. Currently, a most common form of CRT applies stimulation pulses to both ventricles, either simultaneously or separated by a specified biventricular offset interval, and after a specified atrio-ventricular delay interval with respect to the detection of an intrinsic atrial contraction or delivery of an atrial pace.  
         [0004]     The treatments for HF discussed above are most appropriately used to treat patients with systolic dysfunction. In such patients, the fraction of the blood accumulated during diastolic filling of one or both ventricles that is pumped out during systole, referred to as the ejection fraction, is below normal. Recent epidemiological reports, however, have documented that a large percentage of HF patients maintain a normal left ventricular ejection fraction (EF)&gt;50%. Although current treatment modalities have improved prognosis among individuals with a depressed EF, the application of these therapeutic strategies to the condition of HF with a normal EF have not had such favorable outcomes  
       SUMMARY  
       [0005]     Described herein are methods and systems for delivering pacing therapy to HF patients who do not exhibit a reduced EF. Such patients do not have systolic dysfunction and generally do not benefit from established HF therapies that either augment contractile function or counteract conduction abnormalities. In one embodiment, a HF patient with a normal EF is tested for the adequacy of heart rate response during exercise. If the patient is found to be chronotropically incompetent, a rate-adaptive pacing mode is employed in order improve functional capacity. The rate-adaptive pacing mode may be employed with any appropriate pacing configuration including conventional bradycardia pacing to an atrium and/or ventricle, CRT, or pacing designed to improve diastolic function (e.g., ventricular septal pacing). In order to prevent the rate-adaptive pacing mode from unduly compromising diastolic filling in patients with diastolic dysfunction, one or more rate-adaptive pacing parameters are adjusted in accordance with an evaluation of the patient&#39;s diastolic function as the heart rate is increased. Such evaluation of the patient&#39;s diastolic function may be performed clinically with the appropriately adjusted rate-adaptive pacing parameters then being programmed into the pacing system. Alternatively, evaluation of diastolic function and adjustment of the rate-adaptive pacing parameters may be performed by the pacing system automatically.  
         [0006]     In one embodiment, a cardiac pacing system includes a sensing circuit, a pacing circuit, a diastolic performance sensor, a signal processor, and a pacing controller. The diastolic performance sensor senses a signal indicative of a diastolic function. The signal processor receives and processes the signal indicative of the diastolic function, and includes a diastolic performance parameter generator that produces a diastolic performance parameter based on the signal indicative of the diastolic function. The pacing controller receives the diastolic performance parameter and adjusts one or more rate-adaptive pacing parameters in accordance with the diastolic performance parameter. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]      FIG. 1A  is a schematic/block diagram illustrating one embodiment of a cardiac pacing system for treating the diastolic dysfunction and portions of an environment in which the system is used.  
         [0008]      FIG. 1B  is a schematic/block diagram illustrating one embodiment of a pacing controller of the cardiac pacing system of  FIG. 1A .  
         [0009]      FIG. 2  is a schematic/block diagram illustrating one embodiment of portions a cardiac rhythm management (CRM) system including the cardiac pacing system of  FIG. 1A  and portions of an environment in which the CRM system is used.  
         [0010]      FIG. 3  is a flow chart illustrating one embodiment of a method for controlling rate-adaptive pacing in a diastolic heart failure patient. 
     
    
     DETAILED DESCRIPTION  
       [0011]     Although the mechanisms of HF with a normal EF are incompletely understood, diastolic dysfunction is thought to be a central component. The increasing recognition that HF may arise in the absence of significant systolic dysfunction has lead to the use of the term diastolic heart failure (DHF) when describing patients who exhibit HF and a normal EF. The term DHF will be used similarly herein.  
         [0012]     Rate-adaptive pacing (RAP) has been demonstrated to improve response to physical activity in patients with inadequate chronotropic response, and improvements are most pronounced in patients who are chronotropically incompetent. Chronotropic incompetentce (CI) is clinically defined as an attenuated exercise heart rate response, commonly perceived as an inability to achieve a predetermined percentage of predicted maximal heart rate, and is diagnosed through various types of exercise stress tests. The benefit of RAP, in conjunction with cardiac resynchronization therapy, on exercise performance has also been demonstrated in HF patients with a reduced EF and CI (See Tse, H.F., et al., The incremental benefit of rate-adaptive pacing on exercise performance during cardiac resynchronization therapy. J Am Coll Cardiol, 2005. 46(12): p. 2292-7). A severely blunted heart rate response (as attenuated peak heart rate and diminished heart rate acceleration) to incremental cycle exercise has also been observed in patients with HF and a normal EF (See Borlaug, B., Melenovsky, V., Shively, L., Swiger, K., and Kass, D A., Impaired Systolic and Vasodilator Reserve in Patients with Heart Failure and a Normal Ejection Fraction, in American Heart Association Scientific Sessions. 2005: Dallas, Tex.).  
         [0013]     Described herein are methods and systems for treating DHF patients with pacing therapy in which such patients are identified by measurement of EF and/or evaluation of diastolic function. If a DHF patient is also found to have CI, a rate-adaptive pacing mode is employed to deliver the pacing therapy. The pacing therapy delivered in the RAP mode may be conventional bradycardia pacing to an atrium and/or ventricle, CRT, or pacing designed to improve diastolic function (e.g., ventricular septal pacing). An evaluation of diastolic function is performed on the patient to determine if such rate-adaptive pacing adversely affects diastolic filling of the ventricles. If the patient is found to have diastolic dysfunction, one or more rate-adaptive pacing parameters are adjusted in accordance with an evaluation of the patient&#39;s diastolic function as the heart rate is increased. The evaluation of the patient&#39;s diastolic function may be performed clinically with the appropriately adjusted rate-adaptive pacing parameters then being programmed into the pacing system. Alternatively, evaluation of diastolic function and adjustment of the rate-adaptive pacing parameters may be performed by the pacing system automatically. Described below are various embodiments of methods and systems for treating DHF patients with RAP, the features of which may be arbitrarily combined in any manner. The methods and systems described herein may also be combined in any manner with the methods and systems for delivering pacing therapy to treat diastolic dyssynchrony described in the aforementioned U.S. patent application Ser. No. 10/703,398.  
         [0000]     1. Cardiac Pacing System  
         [0014]      FIG. 1A  is a schematic/block diagram illustrating one embodiment of a cardiac pacing system. In the illustrated embodiment, cardiac pacing system  100  includes leads  110 A-B, a sensing circuit  112 , a pacing circuit  114 , a diastolic performance sensor  116 , a signal processor  130 , and a pacing controller  120 . Leads  110 A-B are intracardiac pacing leads each including one or more electrodes for sensing electrograms from and delivering pacing pulses to a predetermined region within a heart  101 . Leads  110 A-B provide for electrical connections between sensing circuit  112  and heart  101  and between pacing circuit  114  and heart  101 . In one embodiment, diastolic performance sensor  116  is also incorporated into one of leads  110 A-B for intracardiac placement. In the embodiment illustrated in  FIG. 1 , lead  110 A is an atrial pacing lead with one or more electrodes for placement in the right atrium (RA) of heart  101 , and lead  110 B is a ventricular pacing lead with one or more electrodes for placement in the right ventricle (RV) and/or left ventricle (LV) of heart  101 . The ventricular electrodes may be disposed to pace either septum or a free wall of the LV or RV. In other embodiments, cardiac pacing system  100  includes one or more pacing leads in additional to leads  110 A-B to provide access to additional intracardiac regions, such as regions within the right RV and/or LV. In the embodiment illustrated in  FIG. 1A , sensing circuit  112  senses RA and RV electrograms through leads  110 A-B, and pacing circuit  114  delivers pacing pulses to the RV and/or LV through lead  110 B. In other embodiments, where additional leads are included, sensing circuit  112  senses additional electrograms and, when necessary, pacing circuit  114  delivers pacing pulses to additional sites through the additional leads.  
         [0015]     The controller  120  may be implemented as microprocessor that controls the overall operation of the device in accordance with programmed instructions stored in memory. The controller  120  interprets electrogram signals from the sensing circuit and controls the delivery of paces in accordance with a pacing mode. The sensing circuitry of the device generates atrial and ventricular electrogram signals from the voltages sensed by the electrodes of a particular sensing circuit. When an electrogram signal from an atrial or ventricular sensing circuit exceeds a specified threshold, the controller detects an atrial or ventricular sense, respectively, which pacing algorithms may employ to trigger or inhibit pacing. Bradycardia pacing modes are most commonly employed, whether to treat bradycardia or to deliver CRT. Bradycardia pacing modes refer to pacing algorithms used to pace the atria and/or ventricles in a manner that enforces a certain minimum heart rate. Because of the risk of inducing an arrhythmia with asynchronous pacing, most pacemakers for treating bradycardia are programmed to operate synchronously in a so-called demand mode where sensed cardiac events occurring within a defined interval either trigger or inhibit a pacing pulse. Inhibited demand pacing modes utilize escape intervals to control pacing in accordance with sensed intrinsic activity. In an inhibited demand mode, a pacing pulse is delivered to a heart chamber during a cardiac cycle only after expiration of a defined escape interval during which no intrinsic beat by the chamber is detected.  
         [0016]     Patients with sinus node dysfunction (e.g, sinus bradyeardia, sinus arrest, paroxysmal supraventricular tachycardia alternating with periods of bradycardia or even asystole) may exhibit symptoms of their arrhythmias, and according to the ACC/AHA/NASPE Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices, such symptoms are essential in deciding whether a permanent pacemaker is indicated. Sinus node dysfunction may also express itself as chronotropic incompetence, resulting in exercise intolerance for the patient and limiting their ability to carry out normal physical activity.  
         [0017]     In pacemaker patients who are chronotropically incompetent, atrial triggered pacing modes cannot be used (or relied upon) so the heart rate is determined solely by the pacemaker in the absence of intrinsic cardiac activity. That heart rate is determined by the programmed escape intervals of the pacemaker which cause paces to be delivered to the atria and/or ventricles, depending upon the pacing mode, if no intrinsic beats occur before expiration of the escape intervals. Pacing the heart at a fixed rate as determined by the length of the programmed escape intervals, however, does not allow the heart rate to increase with increased metabolic demand. It is for this reason that rate-adaptive pacemakers have been developed which vary the programmed escape intervals in accordance with one or more physiological parameters related to metabolic demand such as obtained from an accelerometer or minute ventilation sensor.  
         [0018]     To provide rate-adaptive pacing capability, also interfaced to the controller is an exertion level sensor  199 , which may be an accelerometer, a minute ventilation sensor, or other sensor that measures a parameter related to metabolic demand that indicates the body&#39;s need for an increased heart rate. The exertion level sensor  199  may also represent multiple exertion level sensing modalities. The exertion level sensor enables the controller to adapt the atrial and/or ventricular pacing rate in accordance with changes in the patient&#39;s physical activity in a rate-adaptive pacing mode. In a rate-adaptive pacing mode, one or more escape intervals are adjusted in accordance with a measured exertion level so that the pacing rate varies with metabolic demand. The modified pacing rate dictated by a rate-adaptive algorithm is referred to as the sensor-indicated rate. The rate-adaptive algorithm calculates the sensor-indicated rate by mapping a measured exertion level to a particular heart rate in accordance with a rate response function. In the case of a linear function, the response factor is the slope of the rate response curve. Various pacing parameters may be specified for a particular rate-adaptive pacing mode including the type of rate-response function, slope(s) of the rate-response curve, location of breakpoints that vary the slope of the rate-response curve, and a maximum heart rate.  
         [0019]     The embodiment illustrated in  FIG. 1A  also includes a diastolic performance sensor that  116  senses a signal indicative of a diastolic function and a signal processor  130  that processes the sensed signal. The signal processor  130  may be a separate hardware component from the controller  120  or implemented as a part thereof. In one embodiment, signal processor  130  includes a diastolic performance parameter generator  132  to produce the diastolic performance parameter based on the signal indicative of the diastolic function.  
         [0020]     In one embodiment, diastolic performance sensor  116  includes a pressure sensor to sense a signal indicative of an LV pressure. In one specific embodiment, diastolic performance sensor  116  is placed in the LV to directly sense the LV pressure. In other embodiments, diastolic performance sensor  116  indirectly senses the LV pressure, by sensing another pressure having a known or predictable relationship with the LV pressure. Examples of pressures having known or predictable relationships with the LV pressure during all or a portion of the cardiac cycle include an LA pressure and a coronary vein pressure. One specific example of measuring the LV pressure using a coronary vein pressure sensor is discussed in U.S. patent application Ser. No. 10/038,936, “METHOD AND APPARATUS FOR MEASURING LEFT VENTRICULAR PRESSURE,” filed on Jan. 4, 2002, assigned to Cardiac Pacemakers, Inc., which is hereby incorporated by reference in its entirety. In one embodiment, diastolic performance parameter generator  132  includes a diastolic pressure detector to detect a left ventricular end diastolic pressure (LVEDP) from the signal indicative of the LV pressure. The diastolic performance parameter is the LVEDP. In another embodiment, diastolic performance parameter generator  132  includes a diastolic pressure timer to measure a time constant (tau) related to a decrease in the left ventricular pressure. The diastolic performance parameter is that time constant.  
         [0021]     In another embodiment, diastolic performance sensor  116  includes a pulmonary flow sensor to sense a signal indicative of a pulmonary venous blood flow. In one specific embodiment, the pulmonary flow sensor includes a pulmonary impedance sensing circuit to sense the pulmonary impedance, indicative of the pulmonary blood volume. Diastolic performance parameter generator  132  includes a velocity detector to calculate an antegrade pulmonary venous blood velocity based on the signal indicative of the pulmonary venous blood flow. The diastolic performance parameter is the pulmonary venous blood velocity.  
         [0022]     In another embodiment, diastolic performance sensor  116  includes a mitral flow sensor to sense a signal indicative of blood flow through the mitral valve. In one specific embodiment, the mitral flow sensor includes an impedance sensor to a measure an LV volume. The LV volume is derived from an impedance measured between electrodes in the right ventricle and in a left ventricular coronary vein. One example of such an impedance sensor and measurement is discussed in U.S. Pat. No. 6,278,894, “MULTI-SITE IMPEDANCE SENSOR USING CORONARY SINUS/VEIN ELECTRODES,” assigned to Cardiac Pacemakers, Inc., which is hereby incorporated by reference in its entirety. The time-derivative of this LV volume signal during diastole (after the opening of the mitral valve at the end of ejection) is a measure of the blood flow through the mitral valve. The peak blood flow during diastole, the duration of the rapid initial blood flow during diastole, and the time constant of the decrease in the blood flow during diastole are all useful measures of diastolic performance. Diastolic performance parameter generator  132  includes one or more of a peak detector to detect the peak blood flow, a timer to measure the duration of the rapid initial blood flow, and another timer to measure the time constant of the decrease in the blood flow. The diastolic performance parameter includes one of the peak blood flow, the duration of the rapid initial blood flow, and the time constant of the decrease in the blood flow during diastole.  
         [0023]     In another embodiment, diastolic performance sensor  116  includes an acoustic sensor to sense a signal indicative of heart sounds. In one specific embodiment, the acoustic sensor includes an accelerometer. In another specific embodiment, the acoustic sensor includes a microphone. Diastolic performance parameter generator  132  includes a heart sound analyzer to detect a diastolic acoustic noise from the signal indicative of heart sounds. The diastolic performance parameter is the diastolic acoustic noise. The diastolic acoustic noise is the total acoustic noise measured over the diastolic phase of one cardiac cycles. Examples of methods for calculating the total acoustic noise measured over a predetermined time period are discussed in U.S. Pat. No. 6,044,298, “OPTIMIZATION OF PACING PARAMETERS BASED ON MEASUREMENT OF INTEGRATED ACOUSTIC NOISE,” and U.S. Pat. No. 6,058,329, “OPTIMIZATION OF PACING PARAMETERS BASED ON MEASUREMENT OF ACOUSTIC NOISE,” both assigned to Cardiac Pacemakers, Inc., which are hereby incorporated by reference in their entirety.  
         [0024]      FIG. 1B  is a schematic/block diagram illustrating one embodiment of pacing controller  120 . Pacing controller  120  receives the diastolic performance parameter and uses it to determine and/or adjust one or more pacing parameters. Pacing controller  120  includes a pacing parameter optimization module  124  and a pacing algorithm execution module  122 . Pacing parameter optimization module  124  receives the diastolic performance parameter and calculates one or more approximately optimal pacing parameters based on at least the diastolic performance parameter. In one embodiment, the approximately optimal pacing parameter is a pacing parameter predicted to provide a target value (including a maximum or minimum value) for the diastolic performance parameter. In another embodiment, the approximately optimal pacing parameter is a pacing parameter predicted to maintain a threshold value for the diastolic performance parameter. In one specific embodiment, the target or threshold value for the diastolic performance parameter is determined based on systemic considerations including both systolic and diastolic performance of heart  101 . As described below, the pacing parameter optimization module  124  adjusts the rate-adaptive pacing algorithm in a manner so as not to unduly compromise diastolic function. In one embodiment, the pacing controller is programmed to adjust one or more rate-adaptive pacing parameters in accordance with the diastolic performance parameter. The pacing controller may be further programmed to adjust one or more rate-adaptive pacing parameters if a comparison of the diastolic performance parameter with a specified threshold value indicates diastolic filling is unduly compromised. In another embodiment, the pacing controller is further programmed to adjust one or more rate-adaptive pacing parameters in a manner that maximizes diastolic performance, either continuously or intermittently according to a defined schedule.  
         [0025]     In another embodiment, pacing parameter optimization module  124  includes a pacing site selector to select one or more pacing sites and a pacing timing calculator to calculate one or more pacing timing parameters such as atrioventricular and interventricular pacing delays. Pacing algorithm execution module  122  controls the delivery of the pacing pulses by executing a predetermined pacing algorithm using the one or more approximately optimal pacing parameters. In one embodiment, the predetermined pacing algorithm defines an atrial tracking pacing mode such as a DDD or a VDD mode. The one or more approximately optimal pacing parameters include an atrioventricular pacing delay. In one embodiment, wherein multiple ventricular leads are applied to provide sensing and pacing of multiple ventricular sites, the one or more approximately optimal pacing parameters include one or more atrioventricular pacing delays, one or more interventricular pacing delays, and/or one or more pacing sites to which pacing pulses are actually delivered.  
         [0026]      FIG. 2  is a schematic/block diagram illustrating one embodiment of portions of a cardiac rhythm management (CRM) system  200  and portions of the environment in which system  200  is used. CRM system  200  incorporates cardiac pacing system  100  to provide a pacing therapy to heart  101 . In one embodiment, CRM system  200  includes an implantable system  235 , an external system  255 , and a telemetry link  245  providing for bidirectional communication between implantable system  235  and external system  255 . Implantable system  235  includes an implantable device  240  and a lead system  210 . Implantable device  240  is implanted within a body  202  and coupled to heart  101  via lead system  210 . Examples of implantable device  240  include pacemakers, pacemaker/defibrillators, cardiac resynchronization devices, cardiac remodeling control devices, and any other implantable medical devices with a pacing function. In one embodiment, lead system  210  includes leads  110 A-B and additional pacing leads, if any. In another embodiment, diastolic performance sensor  116  is incorporated in a lead of lead system  210 . In one embodiment, external system  255  is a patient management system including an external device  250  in proximity of implantable device  240 , a remote device  270  in a relatively distant location, and a telecommunication network  260  linking external device  250  and remote device  270 . An example of such a patient management system is discussed in U.S. patent application Ser. No. 10/323,604, “ADVANCED PATIENT MANAGEMENT FOR DEFINING, IDENTIFYING AND USING PREDETERMINED HEALTH-RELATED EVENTS,” filed on Dec. 18, 2002, assigned to Cardiac Pacemakers, Inc., which is incorporated herein by reference in its entirety. The patient management system allows access to implantable system  235  from a remote location, for purposes such as monitoring patient status and adjusting therapies. In another embodiment, external system  255  includes a programmer. In one embodiment, telemetry link  245  is an inductive telemetry link. In an alternative embodiment, telemetry link  245  is a far-field radio-frequency telemetry link. In one embodiment, telemetry link  245  provides for data transmission from implantable device  240  to external system  255 . This may include, for example, transmitting real-time physiological data acquired by implantable device  240 , extracting physiological data acquired by and stored in implantable device  240 , extracting therapy history data stored in implantable device  240 , and extracting data indicating an operational status of implantable device  240  (e.g., battery status and lead impedance). In a further embodiment, telemetry link  245  provides for data transmission from external system  255  to implantable device  240 . This may include, for example, programming implantable device  240  to acquire physiological data, programming implantable device  240  to perform at least one self-diagnostic test (such as for a device operational status), programming implantable device  240  to alter therapy parameters and programming implantable device  240  to deliver at least one therapy.  
         [0027]     The physical distribution of cardiac pacing system  100  in CRM system  200  depends on practical factors such as the size and power constraints for an implantable device, computational power of the implantable device, and convenience of implementation and use. In one embodiment, cardiac pacing system  100  is included in implantable system  235 . This embodiment allows for a diastolic performance based feedback loop (including diastolic performance sensor  116 , signal processor  130 , pacing controller  120 , and pacing circuit  114 ) to operate continuously, without the need to communicate with external system  255 . In another embodiment, portions of cardiac pacing system  100  are included in implantable system  235 , and the remaining portions are included in external system  255 . In one specific embodiment, external system  255  includes diastolic performance parameter generator  132  and pacing parameter optimization module  124 . The signal sensed by diastolic performance sensor  116  is transmitted to external system  255  via telemetry link  245 . One or more approximately optimal pacing parameters are transmitted to implantable device  240  via telemetry  245 . Including portions of cardiac pacing system  100  in external system reduces size, power, and/or computational demands on implantable device  240 .  
         [0000]     2. Rate-Adaptive Pacing in HF Patients  
         [0028]     A patient with symptomatic heart failure may first be identified as having diastolic heart failure by measurement of his or her ejection fraction. If the patient is also found to be chronotropically incompetent, the patient is treated with pacing therapy using a rate-adaptive pacing mode. An evaluation of the patient&#39;s diastolic function may then be performed. Diastolic dysfunction may involve dyssynchronous relaxation of the ventricles and/or a non-compliant ventricle due to many causes. At higher heart rates brought about by rate-adaptive pacing, the ventricles may not have time to fill adequately if diastolic dysfunction is present. Such lessened diastolic filling would then lessen cardiac output. Therefore, if the patient is found to also exhibit diastolic dysfunction, a determination is made as to whether the rate-adaptive pacing adversely affects cardiac function at higher heart rates by compromising diastolic filling. If so, one or more rate-adaptive pacing parameters are adjusted in accordance with a sensed diastolic performance parameter so that diastolic filling is not unduly compromised.  
         [0029]      FIG. 3  is a flow chart illustrating one embodiment of a method for improving diastolic performance by cardiac pacing. The method determines and adjusts one or more rate-adaptive pacing parameters based on a sensed signal indicative of a diastolic function. Such rate-adaptive pacing parameters may include maximum heart rate, a slope of the rate response curve, type of rate response function, and cessation or initiation of rate adaptive pacing. In one embodiment, the sensed signal indicative of diastolic function is obtained in a clinical setting by appropriate instrumentation and may include any of the diastolic performance parameters discussed above as well as other modalities appropriate for evaluating diastolic function such as echocardiography. In another embodiment, the method is performed by a cardiac pacing system such as described above in a closed-loop manner.  
         [0030]     A rate-adaptive pacing algorithm to deliver pacing therapy is executed at  300 . The pacing therapy may be conventional bradycardia pacing, CRT, or pacing designed to treat diastolic dysfunction by pre-excitation of the ventricular septum. A signal indicative of the diastolic function is sensed at  310 , and a diastolic performance parameter is derived from that signal at  320 . In one embodiment, the signal indicative of the diastolic function is a signal indicative of an LV pressure, and the diastolic performance parameter is an LVEDP measured from the signal indicative of the LV pressure. In another embodiment, the signal indicative of the diastolic function is a signal indicative of an LV pressure, and the diastolic performance parameter is a minimum left ventricular pressure measured from the signal indicative of the LV pressure. In another embodiment, the signal indicative of the diastolic function is a signal indicative of an LV pressure, and the diastolic performance parameter is an LVEDP measured from the signal indicative of the LV pressure. In another embodiment, the signal indicative of the diastolic function is a signal indicative of an LV pressure, and the diastolic performance parameter is a diastasis pressure measured from the signal indicative of the LV pressure immediately before left atrial systole. In another embodiment, the signal indicative of the diastolic function is a signal indicative of an LV pressure, and the diastolic performance parameter is a time constant (tau) related to a decrease in the LV pressure. In another embodiment, the signal indicative of the diastolic function is a signal indicative of pulmonary arterial pressure and the performance parameter is a pulmonary arterial diastolic pressure. In another embodiment, the signal indicative of the diastolic function is a signal indicative of a pulmonary venous blood flow, and the diastolic performance parameter is an antegrade pulmonary venous blood velocity calculated based on the signal indicative of the pulmonary venous blood flow. In another embodiment, the signal indicative of the diastolic function is a signal indicative of blood flow through the mitral valve, and the diastolic performance parameter is the peak blood flow, the duration of the initial blood flow peak, a time constant related to the decrease in the blood flow during early diastole or a ratio between peak blood flow in early and late diastole. In another embodiment, the signal indicative of the diastolic function is a signal indicative of heart sounds, and the diastolic performance parameter is a diastolic acoustic noise detected from the signal indicative of heart sounds. Other examples of signals indicative of diastolic function are: LA pressure, PA pressure, stroke volume, atrial pressure, and mechanical properties of the inter-ventricular septum such as a strain gauge measurement of contractile force. In another embodiment, the signal indicative of the diastolic function is a signal indicative of an LV volume, and the diastolic performance parameter is a peak derivative of the LV volume, occurring during diastole and indicative of peak blood flow into the heart. In another embodiment, the signal indicative of the diastolic function is a signal indicative of an LV volume, and the diastolic performance parameter is a total LV volume change during diastole.  
         [0031]     As the patient&#39;s heart rate is varied due to the rate-adaptive pacing (either during exercise testing or during everyday activities), the diastolic performance parameter is compared with a specified threshold value. The specified threshold value would be different for each particular diastolic performance parameter and may be determined for an individual patient empirically by correlating the value of the diastolic performance parameter with stroke volume. The threshold value may also be a long term average of the performance parameter or an average measured under specified conditions, such as when the patient is at rest as indicated by heart rate or such parameter. If the diastolic performance parameter is found to be below threshold at an increased HR at  330 , one or more rate-adaptive pacing parameters are adjusted at  340 . (This assumes that the diastolic performance parameter decreases with worsening diastolic function. A diastolic performance parameter could also be defined oppositely.) Otherwise, the rate-adaptive pacing mode continues without adjustment. The steps may be repeated until the rate-adaptive pacing mode results in a diastolic performance parameter that remains above the specified threshold.  
         [0032]     Although the invention has been described in conjunction with the foregoing specific embodiments, many alternatives, variations, and modifications will be apparent to those of ordinary skill in the art. Such alternatives, variations, and modifications are intended to fall within the scope of the following appended claims. What is claimed is: