Abstract:
A method for monitoring a patient includes measuring a series of consecutive pulse transit times (PTT&#39;s) of the patient, and processing the resulting PTT signal to detect a presence or absence of central sleep apnea (CSA). The method further includes determining an effectiveness of congestive heart failure therapy, which is being provided to the patient, based on the detected presence or absence of CSA. A system incorporating the method includes an electrode of an implantable medical device, which is adapted to pick up the patient&#39;s ventricular depolarization signals, a sensor, which is adapted to pick up peripheral arterial pulse signals of the patient, and a signal processor, which is adapted to receive the two types of signals and to process the signals according to the method. The system may provide the therapy via cardiac resynchronization pacing and, upon detection of CSA, the system may adjust at least one pacing parameter.

Description:
TECHNICAL FIELD 
       [0001]    The present invention pertains to congestive heart failure (CHF) therapy and more particularly to sleep apnea monitoring and classification, utilizing an implanted medical device, to evaluate an effectiveness of CHF therapy delivered from the device. 
       BACKGROUND 
       [0002]    Because congestive heart failure (CHF) may cause and/or be caused by a person&#39;s abnormal breathing patterns, including periodic breathing, particularly manifest in the form of sleep apnea, sleep apnea may be an indication of developing heart failure in that person. In general, there are two types of sleep apnea, obstructive and central. Obstructive sleep apnea (OSA), which is caused by an airway obstruction, for example, collapse of the pharynx, can adversely impact attempts to treat heart failure. Central sleep apnea (CSA) is frequently associated with CHF, and may be a manifestation of worsening CHF. Because of the limited response of the heart suffering from CHF to supply blood, to meet demand, blood CO 2  levels, which are detected by peripheral vascular chemoreceptors, change slowly. This slow response may introduce control system instability in the physiological loop that regulates breathing; this instability leads to periodic breathing in which respiration fluctuates between hypopnea/apnea and hyperpnea. A well known type of periodic breathing is known as Cheyne-Stokes Respiration (CSR). 
         [0003]    In recent years implantable medical devices (IMD&#39;s) have been adapted to treat congestive heart failure via bi-ventricular pacing, which provides cardiac resynchronization therapy (CRT). Further adaptation of these types of devices, for the detection and therapeutic treatment of sleep apneas, has been described, for example, in commonly-assigned patent application Ser. No. 10/419,404, entitled APPARTAUS AND METHOD FOR MONITORING FOR DISORDERED BREATHING, salient portions of which are hereby incorporated by reference. The effectiveness of congestive heart failure therapy is typically monitored via measurement of one or more hemodynamic parameters, examples of which include, intra-cardiac pressure and left ventricular ejection fraction. The detection of sleep apnea events can provide another means for monitoring the effectiveness of heart failure therapy. However, because not all types of sleep apnea are influenced by heart failure, there is a need for monitoring systems and methods that can distinguish between the types of sleep apnea. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0004]    The following drawings are illustrative of particular embodiments of the present invention and therefore do not limit the scope of the invention. The drawings are not to scale (unless so stated) and are intended for use in conjunction with the explanations in the following detailed description. Embodiments of the present invention will hereinafter be described in conjunction with the appended drawings, wherein like numerals denote like elements. 
           [0005]      FIG. 1  is a schematic depiction of various elements that may be incorporated by a system, according to some embodiments of the present invention. 
           [0006]      FIG. 2  is an exemplary functional block diagram for an implantable medical device such as is shown in  FIG. 1 , according to some embodiments of the present invention. 
           [0007]      FIG. 3  is a group of tracings illustrating a measure of pulse transit time, according to some embodiments of the present invention. 
           [0008]      FIG. 4A  is a plot representative of a pulse transit time signal corresponding to a central sleep apnea event. 
           [0009]      FIG. 4B  is a plot representative of a pulse transit time signal corresponding to an obstructive sleep apnea event. 
           [0010]      FIG. 5  is a flow chart defining some methods of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0011]    The following detailed description is exemplary in nature and is not intended to limit the scope, applicability, or configuration of the invention in any way. Rather, the following description provides practical illustrations for implementing exemplary embodiments of the present invention. Examples of constructions, materials, dimensions, and manufacturing processes are provided for selected elements, and all other elements employ that which is known to those of skill in the field of the invention. Those skilled in the art will recognize that many of the examples provided have suitable alternatives that can be utilized. 
         [0012]      FIG. 1  is a schematic depiction of various elements that may be incorporated by a system, according to some embodiments of the present invention.  FIG. 1  illustrates an IMD  100  implanted in a patient and including a first electrical lead  102 , a second electrical lead  104 , and a device housing  105  on which a connector module  103  is mounted to facilitate the coupling of leads  102 ,  104  to a battery and electronic components (not shown) enclosed within housing  105 ; configurations and construction details concerning such housing and connector module couplings for electrical leads are well known to those skilled in the art. First lead  102  is shown implanted within a coronary vein and including an electrode  112  positioned for sensing and stimulation of a left ventricle (LV) of the patient&#39;s heart, while second lead  104  is shown implanted in a right ventricle (RV) and including a tip electrode  114  positioned in an apex of the RV for sensing and stimulation in conjunction with that of LV electrode  112 . Although not shown, IMD  100  may further include another electrode positioned in a right atrium (RA) of the patient&#39;s heart, either coupled to one of leads  102 ,  104  or coupled to another, atrial lead (not shown). According to the illustrated embodiment, IMD  100  is adapted to provide CRT via bi-ventricular pacing carried out by at least, LV electrode  112  and RV electrode  114 , according to methods known to those skilled in the art. 
         [0013]      FIG. 2  is an exemplary functional block diagram for the electronic components enclosed within housing  105  of IMD  100 , according to some embodiments of the present invention. Each of the aforementioned electrodes  112 ,  114  of leads  102 ,  104  is electrically coupled, via a conductor extending within leads  102 ,  104 , to a connector of each lead  102 ,  104 , each of which are electrically coupled to an electrical contact within connector module  103 ; the contacts within module  103  are coupled via electrical feedthroughs to terminals  212  and  214 , which correspond to electrodes  112  and  114  respectively. Each of electrodes  112 ,  114  may be one of a bipolar pair, for example,  FIG. 2  shows a terminal  314  which may correspond to another electrode forming a bipolar pair with electrode  114 , and a terminal  312  which may correspond to another electrode forming a bipolar pair with electrode  112 . According to the illustrated embodiment, terminals  212 ,  312 ,  214  and  314  electrically connect corresponding electrodes to sense amplifiers which provide the appropriate signals to a pacer timing and control circuit  212  according to respective preset thresholds.  FIG. 2  further illustrates a switch matrix  208 , under control of a microprocessor/controller  224 , which is used to select, via bus  218 , the electrodes which are to be coupled to a wide band amplifier  210  for use in digital signal analysis; the signals from the selected electrodes are directed through a multiplexer  220  and thereafter converted by an A/D converter  222  for storage in random access memory (RAM)  226 , which is under the control of a direct memory access (DMA) circuit  228 . Microprocessor  224  includes an associated ROM for storing programs that allow microprocessor  224  to analyze signals, transmitted thereto via bus  218 , and to control the delivery of the appropriate therapy, for example, via pacing timing and control circuitry  212 . 
         [0014]      FIG. 1  further illustrates an external signal processor  110  hardwired to an external pressure cuff sensor  116 , for example of the type used for blood pressure monitoring, and to a pulse-oximeter sensor  118 , for example, a PureLight® sensor commercially available from Nonin Medical, Inc. of Plymouth, Minn. An implantable pressure cuff sensor  120 , for example, as is described in commonly assigned U.S. Pat. No. 6,106,477, salient portions of which are hereby incorporated by reference, is also shown coupled to a radial artery, and an implantable pulse-oximeter sensor  107  is shown mounted to IMD housing  105 .  FIG. 2  further illustrates a terminal  227  for electrically connecting either of sensors  107 ,  120  to sensor processing circuitry  342 , which is coupled to microprocessor  224  via data/address bus  218 , for the transmission of sensor signals. 
         [0015]    According to embodiments of the present invention, a system for monitoring an effectiveness of CRT delivered by IMD  100 , via leads  102 ,  104 , employs a monitoring method in which times for blood pulses to travel between two arterial sites are measured, collected and analyzed, either by signal processor  224  of IMD  100 , or by external processor  110 ; the system includes electrode  114  to detect ventricular depolarization, and any one of sensors  107 ,  116 ,  118  and  120  to pick up a pulse signal downstream of the patient&#39;s heart. The time that it takes an arterial pulse to travel from the left ventricle, at aortic valve opening, to a arterial peripheral site, downstream, is known as a pulse transit time (PTT); PTT is typically measured as the time delay between each detected ventricular depolarization and each subsequent peripheral pulse signal. PTT signals have been shown to track esophageal pressure, which is commonly measured to detect changes in inspiratory effort resulting from sleep apnea events (Argod, J., et al., Differentiating obstructive and central sleep respiratory events through pulse transit time. Am J Respir Crit Care Med, vol. 158, 1778-1783, 1998). Argod et al. also demonstrate that PTT signals corresponding to events of sleep apnea vary according to the type of sleep apnea, and may be analyzed in order to classify the apnea event as being either central or obstructive. PTT signals indicative of each type of apnea event will be described in greater detail below, in conjunction with  FIGS. 4A-B . 
         [0016]    If external processor  110  is employed in conjunction with one of external sensors  116 ,  118 , the ventricular depolarization signal may be transmitted wirelessly, as indicated by the double-headed arrow in  FIG. 1 , from IMD  100 , for example, via a communications module including a telemetry circuit  330  and an antenna  332  ( FIG. 2 ), to a similar communications module of external processor  110 . External signal processor  110 , in conjunction with sensor  118 , may be similar to a pulse-oximetry monitor programmed to calculate PTT, for example, the Datex Cardiocap II; and signal processor  110  may be adapted to also function as an IMD programmer, for example, similar to the Medtronic CareLink® Programmer. Telemetry circuit  330  and antenna  332  of IMD  100  may also function to wirelessly receive the peripheral pulse signals from external signal processor  110  or any of sensors  116 ,  118 ,  120  so that microprocessor  224  of IMD  100  may carry out the monitoring method. 
         [0017]      FIG. 3  is a group of tracings illustrating a measure of a single PTT, according to some embodiments of the present invention.  FIG. 3  illustrates an EGM trace aligned in time with an oxygen saturation (SpO 2 ) trace, for example, as recorded via pulse-oximetry; the start of PTT is triggered by a detection of ventricular depolarization, marked at a peak  35  of an R-wave, and an end of PTT is defined by an increase in detected oxygen saturation, marked at a point  30 .  FIG. 3  further illustrates an aortic pressure trace  310  and an LV pressure trace  320 , both traces also being aligned in time with the EGM and SpO 2  traces. Although ventricular depolarization is detected just prior to a point  311  when the aortic valve opens, inclusion of pre-ejection time in PTT has been shown to have no significant impact on the effectiveness of the monitoring method. 
         [0018]    Oxygen saturation serves as one type of peripheral pulse signal, for example, being measured by pulse-oximeter sensor  118  clipped to a finger of the patient, or being measured by implanted pulse-oximeter sensor  107  disposed adjacent to subcutaneous pocket arterioles ( FIG. 1 ). Typically, point  30  is either 25% or 50% of a maximum saturation value and is indicative of passage of the arterial pressure pulse. According to alternate embodiments of the present invention, peripheral pulse pressure is measured directly, for example, via one of pressure cuff sensors  116 ,  120 , in order to detect passage of the arterial pressure pulse as the end of PTT. 
         [0019]      FIGS. 4A-B  are plots representative of a PTT signal corresponding to a central sleep apnea (CSA) event, and representative of a PTT signal corresponding to an obstructive sleep apnea (OSA) event, respectively.  FIG. 4A  illustrates hyperpneic episodes  40  each followed by hypopneic/apneic episodes  42  in which there are sustained decreases in a variability of PTT&#39;s, which are typical of CSA events.  FIG. 4B  illustrates periods of relatively normal respiration  43  each followed by crescendo episodes  45  of progressively increasing variability in PTT&#39;s, which are typical of obstructive sleep apnea. According to embodiments of the present invention, PTT signals, such as those shown in  FIGS. 4A-B , may be generated using ventricular depolarization signals collected from electrode  114  and peripheral pulse signals collected from any of sensors  107 ,  116 ,  118 ,  120  ( FIG. 1 ), and analyzed via signal processing, which takes place either in microprocessor  224  of IMD  100 , or in external signal processor  110 , according to pre-programmed methods of the present invention, for example, as outlined by the flow chart in  FIG. 5 . 
         [0020]      FIG. 5  outlines some methods of the present invention in which PTT signals are generated and analyzed to classify apnea events as either OSA or CSA. The detection of CSA in patients receiving CRT, for example, from IMD  100 , may be an indicator of worsening CHF that warrants an adjustment of therapy or an administration of additional therapy, for example, as illustrated by a step  56  in  FIG. 5 . According to some embodiments of the present invention, CSA detection signals are processed by microprocessor  224  in order to trigger adjustments to CRT, via pacing timing and control circuitry  212  ( FIG. 2 ); CRT may be adjusted by changing at least one pacing parameter, for example, a rate and/or interval, of pacing, which may be delivered from electrodes  112  and  114  ( FIG. 1 ), according to methods known to those skilled in the art. 
         [0021]      FIG. 5  illustrates an initial step  50  in which a series of consecutive PTT&#39;s are measured, for example, over 10 pulse cycles, to generate a PTT signal. According to an embodiment of the present invention, in order to generate the PTT signal, each PTT signal is identified by the detection of a ventricular polarization, which corresponds to the start of the PTT signal, and an increase in detected oxygen saturation, which corresponds to the end of the PTT signal, as described above in reference to  FIG. 3 , for example. 
         [0022]    Step  50  further includes processing of the PTT signal, which is composed of the series of PTT&#39;s plotted versus time, in order to evaluate PTT variability over time. According to some embodiments of the present invention, each successive PTT is compared with a preceding PTT in order to determine if there is progressive increase in variability of PTT&#39;s within the signal, for example, as illustrated by episodes  45  in  FIG. 4B , or if there is a sustained decrease in variability of PTT&#39;s within the signal, for example as illustrated by episodes  42  in  FIG. 4A . According to an embodiment of the present invention, a sustained decrease in variability of PTT&#39;s in the signal is identified when there are sustained decreases in PTT over five or more pulse cycles. Thereforeif such a sustained decrease in variability is detected, absent the detection of progressively increasing variability, a CSA event may be classified. The signal processing of step  50  may employ a Fourier transform function, to calculate an energy of the PTT signal, and then compare the AC signal energy to preset energy thresholds; a signal energy exceeding a preset upper energy threshold may be indicative of progressively increasing PTT variability, while a signal energy below a preset lower energy threshold may be indicative of a sustained decrease in PTT variability absent any episodes of progressively increasing PTT variability. According to the method outlined in  FIG. 5 , a decision point  52  following signal processing in step  50  either leads to a classification of the apnea event as OSA, if progressively increasing variability in the PTT signal is detected, or leads to a second decision point  54 , if progressively increasing variability is not detected. At decision point  54 , if a sustained decrease in variability of the PTT signal is detected, decision point  54  leads to a classification of CSA and a subsequent adjustment of CHF therapy, per step  56 , for example, via adjustment of at least one pacing parameter; if a sustained decrease in variability is not detected, decision point  54  leads back to step  50  wherein a new series of PTT&#39;s are measured and collected into a signal for processing. 
         [0023]    According to some embodiments of the present invention, methods outlined by the flow chart of  FIG. 5  are triggered by detection of an apnea event, for example, via respiration monitoring wherein a disappearance or reduction in respiratory oscillations is detected. According to an exemplary embodiment, electrode  114  and device housing  105 , which acts as a reference electrode, are employed to measure thoracic impedance from which minute volumes may be derived to detect apnea according to cyclical changes in the minute volume. With reference back to  FIG. 2 , a terminal  305  for housing  105  and terminal  314  for electrode  114  are shown connected to an impedance measurement circuit  215 . Circuit  215 , being directed by microprocessor  224 , applies a series of current pulses between housing  105  and electrode  114  and receives back, for input into microprocessor  224 , corresponding potentials, indicative of thoracic impedance, between housing  105  and electrode  114 . Aforementioned commonly assigned patent application Ser. No. 10/419,404 describes a method for monitoring minute volume via impedance measurements, as well as alternative methods for monitoring respiration, such as via heart rate sensing. Once an apnea event is detected via the impedance measurements, ventricular depolarization signals are transmitted to one of microprocessor  224  of IMD  100  and external signal processor  110  for the commencement of PTT measurements, per step  50  of  FIG. 5 . Those skilled in the art will appreciate that embodiments of the present invention can alternatively employ other methods for respiration monitoring to trigger step  50 ; examples of other methods for respiration monitoring include, without limitation, those that utilize measures, direct or indirect, of airflow, lung volume, and/or pleural pressure. 
         [0024]    In the foregoing detailed description, the invention has been described with reference to specific embodiments. However, it may be appreciated that various modifications and changes can be made without departing from the scope of the invention as set forth in the appended claims.