Patent Publication Number: US-2023136130-A1

Title: Hematocrit sensor based on impedance measurement in cardiovascular implantable electronic devices

Description:
RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application Ser. No. 63/274,295, filed August Nov. 1, 2021, the entire contents of each of which are incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The disclosure relates to medical devices, and, more particularly, to cardiovascular medical device systems configured to sense hematocrit in a patient. 
     BACKGROUND 
     Implantable cardioverter defibrillators (ICDs) and implantable artificial pacemakers may provide cardiac pacing therapy to a patient&#39;s heart when the natural pacemaker and/or conduction system of the heart fails to provide synchronized atrial and ventricular contractions at rates and intervals sufficient to sustain healthy patient function. Such antibradycardial pacing may provide relief from symptoms, or even life support, for a patient. Cardiac pacing may also provide electrical overdrive stimulation, e.g., ATP therapy, to suppress or convert tachyarrhythmias, again supplying relief from symptoms and preventing or terminating arrhythmias that could lead to sudden cardiac death. Cardiac resynchronization therapy (CRT) is another type of cardiac pacing that may help enhance cardiac output by resynchronizing the electromechanical activity of the ventricles of the heart. Ventricular desynchrony may occur in patients that suffer from heart failure. 
     Treatment of end stage heart failure may include implant of a mechanical circulatory support device (e.g., a ventricular assist device, such as a left ventricular assist device) to aid the heart in pumping blood to the body. A ventricular assist device may be used to sustain life until a heart transplant procedure may be performed (e.g., as a bridge to transplant), as a permanent solution to reduce the symptoms of heart disease (e.g., destination therapy), or as a temporary measure to treat a reversible condition (such as, e.g., myocarditis). Though ventricular assist devices may be effective in the treatment or management of symptoms of heart failure, ventricular assist patients may experience an increased risk of a stroke. 
     Additionally, some medical devices, such as an insertable cardiac monitor or pressure monitor, may monitor physiological parameters of a patient. For example, some medical devices are configured to sense cardiac electrogram (EGM) signals, e.g., electrocardiogram (ECG) signals, indicative of the electrical activity of the heart via electrodes. 
     SUMMARY 
     Hematocrit is a relatively important parameter for managing patients with heart failure and other chronic diseases. In combination with the existing diagnostics in cardiac implantable electronic devices (such as intrathoracic impedance), a hematocrit sensor can improve remote patient management. For example, a hematocrit sensor may be used to detect anemia in a patient, which is a common comorbidity of heart failure. 
     Hematocrit of blood samples (in-vitro, in a fixed geometry) may be determined by sensing the conductance of blood because the conductivity of blood is inversely correlated with the hematocrit. When the impedance is measured intracardially (in-vivo), however, there are many confounding factors, such as changes in the sample volume/geometry and motion. 
     30% to 50% of congestive heart failure (CHF) patients have anemia, which may be defined as low hemoglobin or low hematocrit values, and the prevalence of anemia generally increases with disease severity. Anemia is an independent risk factor for a number of adverse outcomes. Routine detection of and management of anemia in patients with chronic conditions such as CHF may be desirable. A reduced hemoglobin/hematocrit can result from either a reduced red blood cell (RBC) volume (which may be referred to herein as “true anemia”) or from an increased plasma volume and fluid overload. Both causes of anemia (true anemia and fluid overload) may require different treatments. For example, treatment for true anemia may depend on pathophysiology, for example, intravenous administration of iron in the case of iron deficiency. Treatment for fluid overload may include, for example, the administration of diuretics to the patient. Therefore, there may be a need to, relatively quickly, distinguish between true anemia and fluid overload in patients and provide an indication of which condition a patient may be suffering from, thereby facilitating the administration by a clinician of the appropriate treatment for the condition of the patient. A device capable of detecting anemia, and differentiating true anemia from fluid overload, may improve patient management by enabling earlier detection and treatment of the underlying cause of the anemia. 
     In one example, this disclosure is directed to a method including: determining, by processing circuitry, a first impedance associated with a heart of a patient; determining, by the processing circuitry, a second impedance associated with the heart of the patient; determining, by the processing circuitry, at least one of a measure of hematocrit, an indication of fluid overload, or an indication of true anemia based at least in part on the first impedance and the second impedance; and outputting, by the processing circuitry, an indication of the measure of hematocrit, the indication of fluid overload, or the indication true anemia. 
     In another example, this disclosure is directed to a device including: memory configured to store a first impedance and a second impedance, each associated with a heart of a patient; and processing circuitry communicatively coupled to the memory and configured to: determine at least one of a measure of hematocrit, an indication of fluid overload, or an indication of true anemia based at least in part on the first impedance and the second impedance; and output an indication of the measure of hematocrit, the indication of fluid overload, or the indication true anemia. 
     In a further example, this disclosure is directed to a non-transitory computer-readable storage medium having stored thereon instructions which, when executed, cause processing circuitry to: determine at least one of a measure of hematocrit, an indication of fluid overload, or an indication of true anemia based at least in part on a first impedance and a second impedance associated with a heart of a patient; and output an indication of the measure of hematocrit, the indication of fluid overload, or the indication true anemia. 
     This summary is intended to provide an overview of the subject matter described in this disclosure. It is not intended to provide an exclusive or exhaustive explanation of the apparatus and methods described in detail within the accompanying drawings and description below. The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG.  1    is a conceptual diagram illustrating an example implantable medical device system. 
         FIG.  2    is a block diagram illustrating an example configuration of an external device of  FIG.  1   . 
         FIG.  3    is a block diagram illustrating an example configuration of a pacemaker/cardioverter/defibrillator of the implantable medical device system of  FIG.  1   . 
         FIG.  4    is a graphical diagram illustrating an example phase shift between in input current and an output voltage. 
         FIG.  5 A  is a graphical diagram illustrating an example of conductivity of heart and blood tissue as a function of frequency. 
         FIG.  5 B  is a graphical diagram illustrating an example of permittivity of heart and blood tissue as a function of frequency. 
         FIG.  6    is a chart illustrating an example relationship between impedance measurements which may be used to discriminate between true anemia and fluid overload according to the techniques of this disclosure. 
         FIG.  7 A  is a conceptual diagram illustrating an example positioning of leads and electrodes used to sense an intrathoracic impedance according to the techniques of this disclosure. 
         FIG.  7 B  is a conceptual diagram illustrating an example positioning of leads and electrodes used to sense an intracardiac impedance according to the techniques of this disclosure. 
         FIGS.  8 A and  8 B  are conceptual diagrams illustrating example electrode locations. 
         FIG.  9    is a flow diagram illustrating example hematocrit sensing techniques of this disclosure. 
     
    
    
     DETAILED DESCRIPTION 
       FIG.  1    is a schematic diagram of an example implantable medical device system  100  in conjunction with a patient  114 . As illustrated in  FIG.  1   , a medical device system  100  for sensing cardiac events (e.g., P-waves, R-waves, QRS complexes, etc.) and detecting tachyarrhythmia episodes may include an implantable medical device (IMD)  110 , right ventricular lead  118 , left ventricular lead  120 , and atrial lead  121 . In one example, IMD  110  may be embodied as an implantable cardioverter-defibrillator (ICD) or pacemaker/cardioverter/defibrillator (PCD) capable of delivering pacing, cardioversion and defibrillation therapy to the heart  116  of a patient  114 . Right ventricular lead  118 , left ventricular lead  120  and atrial lead  121  are electrically coupled to PCD  110  and extend into the patient&#39;s heart  116  via a vein. Right ventricular lead  118  includes electrodes  122  and  124  shown positioned on the lead in the patient&#39;s right ventricle (RV) for sensing ventricular electrogram signals and pacing in the RV. Left ventricular lead  120  includes one or more electrodes  130  positioned in the patient&#39;s left ventricle (LV) for sensing ventricular electrogram signals and pacing the LV. Atrial lead  121  includes electrodes  126  and  128  positioned on the lead in the patient&#39;s right atrium (RA) for sensing atrial electrogram signals and pacing in the RA. 
     In the illustrated example, each of right ventricular lead  118 , left ventricular lead  120 , and atrial lead  121  may carry a high voltage coil electrode  142 ,  132 , and  144 , respectively, used to deliver cardioversion and defibrillation shocks. In other examples, system  100  may include any number of high voltage coil electrodes on any one or more leads. In some examples, right ventricular lead  118  may include two high voltage coil electrodes, e.g., a first high voltage coil electrode in the RV and a second high volage coil electrode in the RA or superior vena cava (SVC). The techniques disclosed herein may be applicable to systems including any number of electrodes and/or leads, including systems that do not include high voltage coil electrodes and IMDs that do not deliver antitachyarrhythmia shocks. 
     Implantable medical device circuitry configured for performing the functions of PCD  110  described herein and associated battery or batteries are housed within a sealed housing  112 . Housing  112  may be conductive so as to serve as an electrode for use as an indifferent electrode during pacing or sensing or as an active electrode during defibrillation. As such, housing  112  is also referred to herein as “housing electrode”  112 . Each of left ventricular lead  120 , right ventricular lead  118 , and atrial lead  121  may be used to acquire intracardiac electrogram signals and hematocrit measurements from the patient  114  and/or to deliver therapy in response to the acquired data. PCD  110  may utilize two or more electrodes on the leads, or one or more electrodes on the leads in combination with housing electrode  112 , for sensing and therapy. 
     EGM signal data, hematocrit data, and/or true anemia or fluid overload data acquired by PCD  110  may be transmitted to an external device  21 . External device  21  may be embodied as a programmer, e.g., used in a clinic or hospital to communicate with PCD  110  via wireless telemetry. External device  21  may be coupled to a remote patient monitoring system, such as Carelink™, available from Medtronic plc, of Dublin, Ireland. External device  21  is used to program commands or operating parameters into PCD  110  for controlling PCD function and to interrogate PCD  110  to retrieve data, including device operational data as well as physiological data accumulated in a memory of PCD  110 . Examples of communication techniques used by PCD  110  and external device  21  include low frequency or radiofrequency (RF) telemetry, which may be an RF link established via Bluetooth®, WiFi, medical information communication service (MICS), or another public or proprietary communication protocol. 
     External device  21  may be configured to communicate with PCD  110 . In some examples, external device  21  comprises a handheld computing device, computer workstation, or networked computing device. External device  21  may include a user interface that receives input from a user. In other examples, the user may also interact with external device  21  remotely via a networked computing device. The user may interact with external device  21  to communicate with PCD  110 . For example, the user may interact with external device  21  to send an interrogation request and retrieve therapy delivery data, update therapy parameters that define therapy, or perform any other activities with respect to PCD  110 . In some examples, external device  21  may receive from PCD  110  an indication of a measurement of hematocrit, an indication of true anemia, or an indication of fluid overload, which a clinician may use to guide treatment of patient  114 . Although the user is a physician, technician, surgeon, electrophysiologist, or other healthcare professional, the user may be patient  14  in some examples. 
     External device  21  may also allow the user to define how PCD  110  senses electrical signals (e.g., ECGs), detects arrhythmias such as tachyarrhythmias, detects hematocrit, detects true anemia, detects fluid overload, delivers therapy, and communicates with other devices of system  100 . For example, external device  21  may be used to change tachyarrhythmia detection parameters. In another example, external device  21  may be used to manage therapy parameters that define therapies such as CRT or ATP therapy. 
     External device  21  may communicate with PCD  110  via wireless communication using any techniques known in the art. Examples of communication techniques are described above with reference to  FIG.  1   . In some examples, external device  21  may include a programming head that may be placed proximate to patient  14 &#39;s body near the PCD  110  implant site in order to improve the quality or security of communication between PCD  110  and external device  21 . 
     The example illustrated in  FIG.  1    should not be considered limiting of the techniques described herein. The techniques disclosed herein may be applicable to systems that do not include any leads and/or that do not provide any electrical stimulation therapies, such as insertable/implantable cardiac monitors, implantable pressure sensors, or other implantable systems. 
       FIG.  2    is a functional block diagram illustrating an example configuration of external device  21 . External device  21  may include processing circuitry  400 , memory  402 , communication circuitry  408 , user interface  406 , and power source  404 . Processing circuitry  400  controls user interface  406  and communication circuitry  408  and stores and retrieves information and instructions to and from memory  402 . External device  21  may be configured for use as a clinician programmer or a patient programmer. Processing circuitry  400  may comprise any combination of one or more processors including one or more microprocessors, DSPs, ASICs, FPGAs, or other equivalent integrated or discrete logic circuitry. Accordingly, processing circuitry  400  may include any suitable structure, whether in hardware, software, firmware, or any combination thereof, to perform the functions ascribed herein to processing circuitry  400 . 
     A user, such as a clinician or patient  114 , may interact with external device  21  through user interface  406 . User interface  406  may include a display, such as an LCD or LED display or other type of screen, to present information. In some examples, user interface  406  may be configured to alert a clinician of a measure of hematocrit, an indication of true anemia, or an indication of fluid overload of patient  114 , such that the clinician may take the appropriate measures to treat patient  114 . In addition, user interface  406  may include an input mechanism to receive input from the user. The input mechanisms may include, for example, buttons, a keypad (e.g., an alphanumeric keypad), a peripheral pointing device or another input mechanism that allows the user to navigate through user interfaces presented by processing circuitry  400  of external device  21  and provide input. 
     In some examples, at least some of the techniques described herein may be implemented by processing circuitry  400  of external device  21 . For example, processing circuitry  400  may determine hematocrit values based on impedance values measured by PCD  110 , and/or may determine whether to indicate fluid overload or anemia of patient  114  based on data received from PCD  110 . 
     Memory  402  may include instructions for operating user interface  406  and communication circuitry  408 , and for managing power source  404 . Memory  402  may also store any data retrieved from PCD  110 . The clinician may use this therapy data to determine the progression of the patient condition in order to determine future treatment. Memory  402  may include any volatile or nonvolatile memory, such as RAM, ROM, EEPROM or flash memory. Memory  402  may also include a removable memory portion that may be used to provide memory updates or increases in memory capacities. A removable memory may also allow sensitive patient data to be removed before external device  21  is used by a different patient. 
     Wireless telemetry in external device  21  may be accomplished by use of communication circuitry  408 , which may communicate with a proprietary protocol or industry-standard protocol such as using the Bluetooth® specification set. Accordingly, communication circuitry  408  may be similar to the communication circuitry contained within by PCD  110 . In alternative examples, external device  21  may be capable of infrared communication or direct communication through a wired connection. In this manner, other external devices may be capable of communicating with external device  21  without needing to establish a secure wireless connection. 
     Power source  404  may deliver operating power to the components of external device  21 . Power source  404  may include a battery and a power generation circuit to produce the operating power. In some examples, the battery may be rechargeable to allow extended operation. Recharging may be accomplished by electrically coupling power source  308  to a cradle or plug that is connected to an alternating current (AC) outlet. In addition, recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within external device  21 . In other examples, traditional batteries (e.g., nickel cadmium or lithium ion batteries) may be used. In addition, external device  21  may be directly coupled to an alternating current outlet to operate. Power source  404  may include circuitry to monitor power remaining within a battery. In this manner, user interface  406  may provide a current battery level indicator or low battery level indicator when the battery needs to be replaced or recharged. In some cases, power source  404  may be capable of estimating the remaining time of operation using the current battery. 
     According to the techniques of this disclosure, external device  21  may be used to receive from PCD  110  and/or determine an indication of a measurement of hematocrit, an indication of true anemia, or an indication of fluid overload. For example, external device  21  may provide such indications to a clinician or other device to help guide treatment of patient  114 . 
       FIG.  3    is a functional block diagram illustrating an example configuration of pacemaker/cardioverter/defibrillator (PCD)  110 . As illustrated in  FIG.  3   , in one example, PCD  110  includes sensing circuitry  422 , pulse generation circuitry  420 , processing circuitry  416  and associated memory  418 , communication circuitry  424 , power source  426 , and switch circuitry  428 . The electronic components may receive power from power source  426 , which may be a rechargeable or non-rechargeable battery. In other examples, PCD  110  may include more or fewer electronic components. The described circuitry may be implemented together on a common hardware component or separately as discrete but interoperable hardware or software components. Depiction of different features as circuitry is intended to highlight different functional aspects and does not necessarily imply that such circuitry must be realized by separate hardware or software components. Rather, functionality associated with one or more circuitries may be performed by separate hardware or software components or integrated within common or separate hardware or software components. 
     Sensing circuitry  422  receives cardiac electrical signals from electrodes  112 ,  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142  and  144  carried by right ventricular lead  118 , left ventricular lead  120 , and atrial lead  121 , along with housing electrode  112  associated with the housing  112 , for sensing cardiac events attendant to the depolarization of myocardial tissue, e.g., P-waves and R-waves, and sensing impedances indicative of hematocrit, true anemia, and/or fluid overload. In some examples, as illustrated in  FIG.  3   , PCD  110  may include switch circuitry  428  for selectively coupling electrodes  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142 ,  144 , and housing electrode  112  to sensing circuitry  422 . Switch circuitry  428  may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable to selectively couple one or more of the electrodes to sensing circuitry  422 . In some examples, processing circuitry  416  selects the electrodes to function as sense electrodes, or the sensing vector, via switch circuitry  428 . In some examples, PCD  110  may not include switch circuitry  428 . 
     According to the techniques of this disclosure, processing circuitry  416  may determine a first impedance associated with a heart of patient  114  and determine a second impedance associated with the heart of patient  114 . Processing circuitry  416  may determine a measure of hematocrit, an indication of fluid overload, or an indication of true anemia based at least in part on the first impedance and the second impedance. Processing circuitry  416  may output an indication of the measure of hematocrit, the indication of fluid overload, or the indication true anemia, for example, to external device  21  via communication circuitry  242 , to inform a clinician. 
     Sensing circuitry  422  may include multiple sensing channels, each of which may be selectively coupled to respective combinations of electrodes  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142 ,  144  and housing  112  to detect electrical activity of a particular chamber of heart  116 , e.g., an atrial sensing channel and a ventricular sensing channel. Each sensing channel may comprise a sense amplifier that outputs an indication to processing circuitry  416  in response to sensing of a cardiac depolarization, in the respective chamber of heart  116 . In this manner, processing circuitry  416  may receive sense event signals corresponding to the occurrence of sensed R-waves and P-waves in the respective chambers of heart  116 . Sensing circuitry  422  may further include digital signal processing circuitry for providing processing circuitry  416  with digitized electrogram signals, which may be used for cardiac rhythm discrimination. 
     The components of sensing circuitry  422  may be analog components, digital components or a combination thereof. Sensing circuitry  422  may, for example, include one or more sense amplifiers, filters, rectifiers, threshold detectors, analog-to-digital converters (ADCs) or the like. Sensing circuitry  422  may convert the sensed signals to digital form and provide the digital signals to processing circuitry  416  for processing or analysis. For example, sensing circuitry  422  may amplify signals from the sensing electrodes and convert the amplified signals to multi-bit digital signals by an ADC. Sensing circuitry  422  may also compare processed signals to a threshold to detect the existence of atrial or ventricular depolarizations (e.g., P- or R-waves) and indicate the existence of the atrial depolarization (e.g., P-waves) or ventricular depolarizations (e.g., R-waves) to processing circuitry  416 . In addition to detecting and identifying specific types of cardiac rhythms, sensing circuitry  422  may also sample the detected intrinsic signals to generate an electrogram or other time-based indication of cardiac events. 
     Processing circuitry  416  may process the signals from sensing circuitry  422  to monitor electrical activity of the heart of the patient. Processing circuitry  416  may store signals obtained by sensing circuitry  422  as well as any generated electrogram waveforms, marker channel data or other data derived based on the sensed signals in memory  418 . Processing circuitry  416  may analyze the electrogram waveforms and/or marker channel data to detect cardiac events (e.g., tachycardia). In response to detecting the cardiac event, processing circuitry  416  may control pulse generation circuitry  420  to deliver the desired therapy to treat the cardiac event, e.g., ATP therapy. 
     In examples in which PCD  110  includes more than two electrodes for therapy delivery, processing circuitry  416  may use switch circuitry  428  to select which of the available electrodes are used to deliver pacing pulses. In some instances, the same switch circuitry may be used by both pulse generation circuitry  420  and sensing circuitry  422 . In other instances, each of sensing circuitry  422  and pulse generation circuitry  420  may have separate switch circuitry. 
     Memory  418  may include computer-readable instructions that, when executed by processing circuitry  416 , cause PCD  110  to perform various functions attributed throughout this disclosure to PCD  110  and processing circuitry  416 . The computer-readable instructions may be encoded within memory  418 . Memory  418  may comprise computer-readable storage media including any volatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media. 
     Processing circuitry  416  may include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or equivalent discrete or integrated logic circuitry or state machine. In some examples, processing circuitry  416  may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry or state machines. The functions attributed to processing circuitry  416  herein may be embodied as software, firmware, hardware or any combination thereof. 
     Pulse generation circuitry  420  is electrically coupled to electrodes  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142 ,  144 , and  112 . In the illustrated example, pulse generation circuitry  420  is configured to generate and deliver electrical therapy to a heart of a patient. For example, pulse generation circuitry  420  may deliver the electrical therapy to a portion of cardiac muscle within the heart via any combination of electrodes  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142 ,  144 , and  112 . In some examples, pulse generation circuitry  420  may deliver pacing stimulation, e.g., bradycardia therapy, CRT, or ATP therapy, in the form of voltage or current electrical pulses. In other examples, pulse generation circuitry  420  may deliver stimulation in the form of other signals, such as sine waves, square waves, or other substantially continuous time signals. 
     In some examples, in addition to cardiac pacing, PCD  110  may deliver cardioversion or defibrillation pulses. Pulse generation circuitry  420  may include one or more pulse generators, capacitors, and/or other components capable of generating and/or storing energy to deliver as pacing therapy, defibrillation therapy, cardioversion therapy, cardiac resynchronization therapy, other therapy or a combination of therapies. In some instances, pulse generation circuitry  420  may include a first set of components configured to provide pacing therapy and a second set of components configured to provide defibrillation therapy. In other instances, pulse generation circuitry  420  may utilize the same set of components to provide both pacing and defibrillation therapy. In still other instances, pulse generation circuitry  420  may share some of the defibrillation and pacing therapy components while using other components solely for defibrillation or pacing. 
     Processing circuitry  416  may control pulse generation circuitry  420  to deliver electrical therapy to heart  116  according to therapy parameters, which may be stored in memory  418 . Pulse generation circuitry  420  is configured to generate and deliver electrical therapy to heart  116  via selected combinations of electrodes  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142 ,  144 , and housing electrode  112 . For example, pulse generation circuitry  420  may be configured to deliver cardiac pacing via selected combinations of electrodes  122 ,  124 ,  126 ,  128 ,  130 , and housing electrode  112 , and may be configured to deliver antitachyarrhythmia shocks via selected combinations of electrodes  132 ,  142 ,  144 , and  112 . 
     As discussed above, processing circuitry  416  may determine a first impedance associated with a heart of patient  114  and determine a second impedance associated with the heart of patient  114  to determine a hematocrit value of patient  114  according to the techniques of this disclosure. In order to determine impedances, processing circuitry  416  may control pulse generation circuitry  420  to generate measurement or input signals (voltage or current) and sensing circuitry  422  may sense or measure resulting or output signals (current or voltage) via selected combinations of electrodes  122 ,  124 ,  126 ,  128 ,  130 ,  132 ,  142 ,  144 , and housing electrode  112 . Processing circuitry  416  may calculate or determine the impedances based on the memory  418  stores determined impedances  276 , such as a first determined impedance and a second determined impedance. Such impedances may be used by processing circuitry  416  to determine a measure of hematocrit, an indication of true anemia, and/or an indication of fluid overload. Memory  418  may be further configured to store other sensed and detected data, therapy parameters, and any other information related to the therapy and treatment of a patient. In the example of  FIG.  3   , memory  418  may store sensed ECGs, detected arrhythmias, communications from PCD  100 . In other examples, memory  418  may act as a temporary buffer for storing data until it can be uploaded to another implanted device, or external device  21 . 
     Communication circuitry  424  is used to communicate with external device  21  for transmitting data accumulated by PCD  110  and for receiving interrogation and programming commands to and/or from external device  21 . Communication circuitry  268  includes any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as external device  21  ( FIGS.  1  and  2   ), a clinician programmer, a patient monitoring device, or the like. For example, communication circuitry  424  may include appropriate modulation, demodulation, frequency conversion, filtering, and amplifier components for transmission and reception of data. Under the control of processing circuitry  416 , communication circuitry  424  may receive downlink telemetry from and send uplink telemetry to external device  21  with the aid of an antenna, which may be internal and/or external. Processing circuitry  416  may provide the data to be uplinked to external device  21  and the control signals for the telemetry circuit within communication circuitry  424 , e.g., via an address/data bus. In some examples, communication circuitry  424  may provide received data to processing circuitry  416  via a multiplexer. 
     In some examples, PCD  110  may signal external device  21  to further communicate with and pass the alert through a network such as the Medtronic CareLink® Network developed by Medtronic plc, of Dublin, Ireland, or some other network linking a patient to a clinician. PCD  110  may spontaneously transmit information to the network or in response to an interrogation request from a user. 
     Power source  426  may be any type of device that is configured to hold a charge to operate the circuitry of PCD  110 . Power source  426  may be provided as a rechargeable or non-rechargeable battery. In other example, power source  426  may incorporate an energy scavenging system that stores electrical energy from movement of PCD  110  within patient  114 . 
     The various circuitry of PCD  110  may include any one or more processors, controllers, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or equivalent discrete or integrated circuitry, including analog circuitry, digital circuitry, or logic circuitry. 
     PCD  110  may determine an impedance at two (or more) frequencies to determine a hematocrit level in patient  114 . Impedance-based hematocrit determinations may rely on an inverse relation between hematocrit and the conductivity of blood σ b . For example, σ b ∝1/HCT (hematocrit). However, when sensing hematocrit in-vivo, a possible parallel impedance (e.g., current through surrounding non-blood tissue) may affect a determination of a hematocrit level. This parallel admittance may occur because electrodes used to determine the impedance may be close to non-blood tissue. For example, the electrodes used to determine the impedance may be on right ventricular lead  118  or left ventricular lead  120 . 
     In general, the measured complex admittance (=1/impedance) Y can be written as Y=G b +G p +j2πfC p , where G b =blood conductance (=1/σ b ), and Y p (=G p +j2πf C p ) is the complex parallel admittance 
     The parallel admittance includes a conductance Gp and a capacitance Cp, which are determined by the conductivity (σ p ) and the permissivity (ε p ) of the surrounding tissue, e.g. cardiac tissue. 
       FIG.  4    is a graphical diagram illustrating an example phase shift between input current and an output voltage. In order to account for the parallel admittance, processing circuitry  416  of PCD  110  may determine a phase shift θ  454  between an input current  450  (e.g., a current signal delivered via a combination of electrodes) and an output voltage  452  (e.g., the voltage signal sensed via the combination of electrodes or another combination of electrodes) to determine a real (Re{Y}) and imaginary admittance (Im{Y}). 
     By determining a complex admittance at two (or more) different frequencies (f 1 , f 2 ), e.g., using two (or more) input signals having different frequencies, G b  (blood conductance) can be determined, by exploiting the fact that σ b  is constant whereas σ p  and ε p  vary as a function of frequency. 
     For example, G b  may be determined by combining following formulas: 
     
       
         
           
             
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                       } 
                     
                   
                   
                     2 
                     ⁢ 
                     π 
                     ⁢ 
                     
                       f 
                       2 
                     
                   
                 
               
             
           
         
       
     
     where the subscripts 1 and 2 refer to 2 different frequencies used. 
     If the ratio (σ p /ε p ) is known (at either frequency), G b  can be calculated using one of the above equations. This is, however, typically not the case as these tissue properties differ across patients and may change over time. Using a common value across patients (e.g., retrieved from literature) for the ratio (σ p /ε p ) may provide an approximate value for G b . 
     To determine G b  more accurately, additional information about the relation between the ratio (σ p /ε p ) at the different frequencies may be used (because the frequency dependence is more stable across patients, and over time). For example, if the ratio at the 2 nd  frequency (σ p,2 /ε p,1 ) can be written as K×(σ p,1 /ε p,1 ), G b  may be determined using the following formula: 
     
       
         
           
             
               G 
               b 
             
             = 
             
               
                 
                   Re 
                   ⁢ 
                   
                     { 
                     
                       Y 
                       ⁡ 
                       ( 
                       
                         f 
                         1 
                       
                       ) 
                     
                     } 
                   
                 
                 - 
                 
                   Re 
                   ⁢ 
                   
                     { 
                     
                       Y 
                       ⁡ 
                       ( 
                       
                         f 
                         2 
                       
                       ) 
                     
                     } 
                   
                   ⁢ 
                   
                     1 
                     K 
                   
                   ⁢ 
                   
                     ( 
                     
                       
                         f 
                         2 
                       
                       
                         f 
                         1 
                       
                     
                     ) 
                   
                   ⁢ 
                   
                     
                       Im 
                       ⁢ 
                       
                         { 
                         
                           Y 
                           ⁡ 
                           ( 
                           
                             f 
                             1 
                           
                           ) 
                         
                         } 
                       
                     
                     
                       Im 
                       ⁢ 
                       
                         { 
                         
                           Y 
                           ⁡ 
                           ( 
                           
                             f 
                             2 
                           
                           ) 
                         
                         } 
                       
                     
                   
                 
               
               
                 1 
                 - 
                 
                   
                     1 
                     K 
                   
                   ⁢ 
                   
                     ( 
                     
                       
                         f 
                         2 
                       
                       
                         f 
                         1 
                       
                     
                     ) 
                   
                   ⁢ 
                   
                     
                       Im 
                       ⁢ 
                       
                         { 
                         
                           Y 
                           ⁡ 
                           ( 
                           
                             f 
                             1 
                           
                           ) 
                         
                         } 
                       
                     
                     
                       Im 
                       ⁢ 
                       
                         { 
                         
                           Y 
                           ⁡ 
                           ( 
                           
                             f 
                             2 
                           
                           ) 
                         
                         } 
                       
                     
                   
                 
               
             
           
         
       
     
     The factor K may be determined from literature, or independent measurements of the electrical properties (σ, ε) of (cardiac) tissue. 
     An alternative embodiment uses information from a second set of impedance measurements in the same tissue but at a different condition (providing different admittance measurements). For example, such second set of data can be obtained from measurements at different states of contraction of the heart (e.g., systole vs diastole). In this case, for example, G b  may be determined using the following formula: 
     
       
         
           
             
               G 
               b 
             
             = 
             
               
                 
                   Re 
                   ⁢ 
                   
                     { 
                     
                       Y 
                       ⁡ 
                       ( 
                       
                         f 
                         2 
                       
                       ) 
                     
                     } 
                   
                 
                 - 
                 
                   
                     ( 
                     
                       
                         Im 
                         ⁢ 
                         
                           { 
                           
                             Y 
                             ⁡ 
                             ( 
                             
                               f 
                               2 
                             
                             ) 
                           
                           } 
                         
                       
                       
                         Im 
                         ⁢ 
                         
                           { 
                           
                             
                               Y 
                               c 
                             
                             ( 
                             
                               f 
                               2 
                             
                             ) 
                           
                           } 
                         
                       
                     
                     ) 
                   
                   [ 
                   
                     
                       Re 
                       ⁢ 
                       
                         { 
                         
                           
                             Y 
                             c 
                           
                           ( 
                           
                             f 
                             1 
                           
                           ) 
                         
                         } 
                       
                     
                     - 
                     
 
                     
                       Re 
                       ⁢ 
                       
                         { 
                         
                           
                             Y 
                             c 
                           
                           ( 
                           
                             f 
                             2 
                           
                           ) 
                         
                         } 
                       
                     
                     - 
                     
                       
                         
                             
                           
                             Im 
                             ⁢ 
                             
                               { 
                               
                                 
                                   Y 
                                   c 
                                 
                                 ( 
                                 
                                   f 
                                   1 
                                 
                                 ) 
                               
                               } 
                             
                           
                         
                         
                             
                           
                             Im 
                             ⁢ 
                             
                               { 
                               
                                 Y 
                                 ⁡ 
                                 ( 
                                 
                                   f 
                                   1 
                                 
                                 ) 
                               
                               } 
                             
                           
                         
                       
                       ⁢ 
                       Re 
                       ⁢ 
                       
                         { 
                         
                           
                             Y 
                             c 
                           
                           ( 
                           
                             f 
                             1 
                           
                           ) 
                         
                         } 
                       
                     
                   
                   ] 
                 
               
               
                 1 
                 - 
                 
                   
                     Im 
                     ⁢ 
                     
                       { 
                       
                         Y 
                         ⁡ 
                         ( 
                         
                           f 
                           2 
                         
                         ) 
                       
                       } 
                     
                     ⁢ 
                        
                     Im 
                     ⁢ 
                     
                       { 
                       
                         
                           Y 
                           c 
                         
                         ( 
                         
                           f 
                           1 
                         
                         ) 
                       
                       } 
                     
                   
                   
                     Im 
                     ⁢ 
                     
                       { 
                       
                         Y 
                         ⁡ 
                         ( 
                         
                           f 
                           1 
                         
                         ) 
                       
                       } 
                     
                     ⁢ 
                        
                     Im 
                     ⁢ 
                     
                       { 
                       
                         
                           Y 
                           c 
                         
                         ( 
                         
                           f 
                           2 
                         
                         ) 
                       
                       } 
                     
                   
                 
               
             
           
         
       
     
     where Y c  represents the admittance measured in the alternative condition. 
     Any of the above formulas may provide a quantity which is solely dependent on the conductivity of the blood and is not affected by the surrounding tissue. As the hematocrit is inversely related to the conductivity of the blood, the quantity, as such, can be used to monitor (relative) changes in hematocrit (independent from changes in the surrounding tissue). 
     In order to obtain an absolute value of the hematocrit, a calibration measurement can be performed during which the hematocrit is determined by an independent measurement technique (e.g., blood sampling). 
     
       
         
           
             HCT 
             = 
             
               
                 
                   G 
                   b 
                 
                 
                   G 
                   
                     b 
                     , 
                     c 
                   
                 
               
               ⁢ 
               
                 HCT 
                 c 
               
             
           
         
       
     
     where G b,c  represents the (calculated) blood conductance (using any of the formulas above) from the calibration data, and HCT c  represents the hematocrit value at the time of calibration as determined by an independent hematocrit measurement technique. 
     In some examples, possible changes in volume and/or geometry may: 1) change the ratio G b /σ b  and therefore G b /hematocrit or 2) simultaneously change parallel admittance, which can be estimated by determining admittance (Y) at the two (or more) frequencies f 1  and f 2 . Therefore, calibration using a known hematocrit level may be desirable to take account this effect. In some examples, processing circuitry  416  may determine a first measure of hematocrit based on the blood conductance (e.g., there may be an inverse relationship between hematocrit and blood conductance). In some examples, processing circuitry  416  may receive a second measure of hematocrit from another device (such as a hematocrit sensor), and based on the second measure, determine a calibration factor for processing circuitry  416  to apply to the first measure. 
     For example, the determination of hematocrit may be calibrated using the following formula: 
     
       
         
           
             HCT 
             = 
             
               
                 
                   G 
                   b 
                 
                 
                   G 
                   
                     b 
                     , 
                     c 
                   
                 
               
               ⁢ 
               
                 
                   Δ 
                   ⁢ 
                   
                     G 
                     p 
                   
                 
                 
                   Δ 
                   ⁢ 
                   
                     G 
                     
                       p 
                       , 
                       c 
                     
                   
                 
               
               ⁢ 
               
                 
                   Δ 
                   ⁢ 
                   
                     G 
                     
                       p 
                       , 
                       c 
                     
                   
                 
                 
                   Δ 
                   ⁢ 
                   
                     G 
                     
                       p 
                       , 
                       
                         c 
                         ′ 
                       
                     
                   
                 
               
               ⁢ 
               
                 HCT 
                 c 
               
             
           
         
       
     
     where HCT is the hematocrit level, subscripts c and c′ refer to calibration points, and ΔG x =G x (f 2 )−G x (f 1 ). 
     For example, processing circuitry  416  may determine an impedance between an electrode on right ventricular lead  118  and housing electrode  112  and determine fluid in the thorax based on the determined impedance. In some examples, rather than using housing electrode  112 , processing circuitry  416  may use an electrode on a lead, such as right ventricular lead  118 , that is near a proximal end of the lead. Part of the current being used to stimulate presumably goes to lungs (fluid and lungs) of patient  114 . Processing circuitry  416  may use a complex part of impedance to assess the effect that surrounding tissue has on the determined impedance. For example, if sensing circuitry  422  were to determine an impedance in the RV, part of current may travel to tissue which may make a determined value of impedance inaccurate. For example, blood may only be resistive, whereas tissue may be both resistive and conductive. By using complex impedances, PCD  110  may take into account the properties of surrounding tissue. 
       FIG.  5 A  is a graphical diagram illustrating an example of conductivity of heart and blood tissue as a function of frequency. As can be seen in  FIG.  5 A , the conductivity (Y-axis) of blood, shown as line  500 , does not vary with frequency (X-axis). However, the conductivity of the heart muscle, shown as line  502 , does vary with frequency. 
       FIG.  5 B  is a graphical diagram illustrating an example of permittivity of heart and blood tissue as a function of frequency. As can be seen in  FIG.  5 B , the permittivity (Y-axis) of blood, shown as line  504 , does not vary with frequency (X-axis). However, the permittivity of the heart muscle, shown as line  506 , does vary with frequency. At lower frequencies, the permittivity of blood is much smaller than that of the heart muscle. 
       FIG.  6    is a chart illustrating an example relationship between impedance measurements which may be used to discriminate between true anemia and fluid overload according to the techniques of this disclosure. As discussed above, true anemia and fluid overload require different treatments. For example, treatment for true anemia may depend on pathophysiology, for example, intravenous administration of iron in the case of iron deficiency. Treatment for fluid overload may include, for example, the administration of diuretics to the patient. Therefore, it may be desirable to be able to distinguish or discriminate between true anemia and fluid overload and to output an indication of which condition patient  114  may have in order to guide a clinician in administering the appropriate treatment. 
     A determined hematocrit may be used to determine fluid status of patient  114  by taking into account the effect of the blood (hematocrit) on the intrathoracic impedance. In some examples, sensing circuitry  422  may determine intrathoracic impedance between an electrode on right ventricular lead  118  and housing electrode  112  of PCD  110 . The intrathoracic impedance may be influenced by both the tissue and blood. 
     Certain medical devices, such as PCD  110 , may be configured to periodically determine intrathoracic impedance. Such devices may be used to monitor fluid levels in patient  114  and may provide an early warning, for example, to a clinician via external device  21  for fluid-related decompensation. As, in some examples, the intrathoracic impedance is determined between an electrode on right ventricular lead  118  and housing electrode  112  of PCD  110 . The intrathoracic impedance may be sensitive to fluid accumulation in the lungs (and interstitial tissue). Changes in other tissues (such as blood) between right ventricular lead  118  and PCD  110  can also influence these impedance measurements. 
     Processing circuitry  416  of PCD  110  may be configured to determine whether a condition is fluid overload and true anemia. For example, in case of fluid overload, both intrathoracic impedance and intracardiac impedance will decrease due to the decrease in hematocrit (e.g., hemodilution) and the fluid accumulation in the lung/interstitial tissue (between the right ventricle or right atrium and PCD  110 ). In case of “true” anemia, both impedances will also decrease but the effect on the intracardiac impedance will be larger than on the intrathoracic impedance because there is no change in the lung/interstitial fluid status. This difference can be seen in table  600  of  FIG.  6   . For example, sensing circuitry  422  may determine an intracardiac impedance and an intrathoracic impedance. Processing circuitry  416  may determine a relative change in intracardiac impedance compared to a baseline intracardiac impedance. Processing circuitry  416  may determine a relative change in intrathoracic impedance compared to a baseline intrathoracic impedance. Processing circuitry  416  may compare the relative change in intracardiac impedance to the relative change in intrathoracic impedance. Processing circuitry  416  may determine an indication of fluid overload or an indication of true anemia based on the comparison. For example, if the relative change in intracardiac impedance is greater than the relative change in intrathoracic impedance, processing circuitry  416  may determine an indication of true anemia. If the relative change in intracardiac impedance is less than or equal to the relative change in intrathoracic impedance, processing circuitry  416  may determine an indication of fluid overload. In some examples, rather than determining a relative change in intracardiac impedance and intrathoracic impedance, processing circuitry  416  may determine an absolute change in intracardiac impedance and an absolute change in intrathoracic impedance and compare the absolute changes to determine an indication of fluid overload or true anemia. In some examples, other measures may be determined as appropriate to determine an indication of fluid overload or true anemia. 
     In some examples, processing circuitry  416  may determine an indication of true anemia in patient  114 . For example, processing circuitry  416  may determine an intracardiac impedance between electrodes on a pacing and/or defibrillation lead in a right ventricle or atrium, e.g., right ventricular lead  118 . Processing circuitry  416  may determine the intrathoracic impedance between an electrode on a pacing and/or defibrillation lead in a right ventricle or atrium and housing electrode  112 . Processing circuitry  416  may calculate the change in intracardiac and intrathoracic impedance compared to a baseline state of patient  114 , the baseline state being a state where patient  114  has a normal hematocrit and fluid status. Processing circuitry  416  may compare the changes in intracardiac and intrathoracic impedance to determine whether the decrease in impedance is due to true anemia or fluid overload. In some examples, processing circuitry  416  may be configured to determine the condition of true anemia or fluid overload and discriminate therebetween even without quantifying an actual value of intracardiac impedance and an actual value of intrathoracic impedance. 
       FIG.  7 A  is a conceptual diagram illustrating an example positioning of leads and electrodes used to determine an intrathoracic impedance according to the techniques of this disclosure. As shown in the example of  FIG.  7 A , intrathoracic impedance may be determined by stimulating (e.g., delivering an input signal) from a first electrode (e.g., tip electrode  122 ) of right ventricular lead  118  to housing electrode  112  of PCD  110  and sensing (e.g., sensing an output signal) between a second electrode (e.g., ring electrode  124 ) of right ventricular lead  118  and housing electrode  112  of PCD  110 . 
       FIG.  7 B  is a conceptual diagram illustrating an example positioning of leads and electrodes used to determine an intracardiac impedance according to the techniques of this disclosure. As shown in the example of  FIG.  7 B , intracardiac impedance may be determined by stimulating from a first electrode (e.g., tip electrode  122 ) of right ventricular lead  118  to a second electrode (e.g., coil electrode  142 ) of right ventricular lead  118  and sensing between a third electrode (e.g., ring electrode  124 ) of right ventricular lead  118  and the second electrode of right ventricular lead  118 . 
       FIGS.  8 A and  8 B  are conceptual diagrams illustrating example electrode locations. In some examples, if parallel admittance is negligible or not significant, an interelectrode distance  700  may be much smaller than a distance to tissue that is not blood. For example, Gp«G b =&gt;Re Y=|Y|=Gb∝σb. In some examples, the interelectrode distance  700  may be on the order of less than two millimeters, such as 1.2 mm. 
     In such a case, admittance magnitude |Y| may be measured at one frequency rather than two frequencies. An initial calibration may be performed, and the admittance may be used to determine a hematocrit level. For example, HCT=(|Yc|/|Y|)*HCTc where, Yc is the calibrated admittance and HCTc is the calibrated hematocrit level. 
     In the example of  FIG.  8 A , closely space electrodes  3  and  4  may be integrated into a bipolar lead to measure hematocrit in a heart chamber, such as a right atrium or right ventricle. In  FIG.  8 B , electrodes may be integrated into a ventricular assist device, such as a left ventricular assist device, in an outflow graft  702  or cannula to measure hematocrit. 
       FIG.  9    is a flow diagram illustrating example hematocrit sensing techniques of this disclosure. The example technique of  FIG.  8    is described as being performed by PCD  110 , e.g., by sensing circuitry  422  and processing circuitry  416  of PCD  110 . In some examples, the techniques may be performed in part by processing circuitry of another device, such as processing circuitry  400  of external device  21 , based on data received from PCD  110 . Furthermore, although described in the context of PCD  110 , the techniques of this disclosure may be implemented in systems including other implantable or external devices configured measure impedances, such as other cardiac therapy and/or monitoring devices, ventricular assist devices (VADs), or neurostimulators. 
     PCD  110  may determine a first impedance associated with a heart of a patient ( 800 ). For example, PCD  110  may determine an impedance at a first frequency f 1 . In another example, PCD  110  may determine an intracardiac impedance. 
     PCD  110  may determine a second impedance associated with the heart of the patient ( 802 ). For example, PCD  110  may determine an impedance at a second frequency f 2 . In another example, PCD  110  may determine an intrathoracic impedance. 
     PCD  110  may determine a measure of hematocrit, an indication of fluid overload, or an indication of true anemia based at least in part on the first impedance and the second impedance ( 804 ). For example, PCD  110  may determine a measure of hematocrit using the determined impedance at the first frequency and the determined impedance at the second frequency. In another example, PCD  110  may determine an indication of fluid overload by determining that a relative change in intracardiac impedance is less than or equal to a relative change in intrathoracic impedance. In another example, PCD  110  may determine an indication of true anemia by determining that the relative change in intracardiac impedance is greater than the relative change in intrathoracic impedance. 
     PCD  110  may output an indication of the measure of hematocrit, the indication of fluid overload, or the indication true anemia ( 806 ). For example, PCD  110  may transmit to external device  21  the indication of the measure of hematocrit, the indication of fluid overload, or the indication true anemia. In this manner, a clinician may receive, through external device  21 , the measure of hematocrit, the indication of fluid overload, or the indication of true anemia, and may determine an appropriate treatment for patient  114  based on the received indication. 
     In some examples, PCD  110  may determine a first complex impedance based on the first determined impedance, wherein the first determined impedance is determined at a first frequency; and determine a second complex impedance based on the second determined impedance, wherein the second determined impedance is determined at a second frequency. In some examples, determining the measure of hematocrit is based on the first complex impedance and the second complex impedance. In some examples, PCD  110  may determine a phase shift between an input current and an output voltage to calculate a real admittance and an imaginary admittance. In some examples, PCD  110  may determine blood conductance based on the first complex impedance and the second complex impedance, wherein the determining a measure of hematocrit is further based on the determined blood conductance. In some examples, PCD may calibrate the measure of hematocrit. 
     In some examples, the first impedance comprises an intracardiac impedance, the second impedance comprises an intrathoracic impedance, and the output comprises an indication of fluid overload or an indication of true anemia. In some examples, PCD  110  determines a relative change in intracardiac impedance compared to a baseline intracardiac impedance and determines a relative change in intrathoracic impedance compared to a baseline intrathoracic impedance. In some examples, PCD  110  compares the relative change in intracardiac impedance to the relative change in intrathoracic impedance, wherein the indication of fluid overload or the indication of true anemia is based on the comparison. 
     In some examples, as part of determining the intracardiac impedance, PCD  110  determines an impedance between electrodes in a ventricle or atrium. In some examples, as part of determining the intrathoracic impedance, PCD  110  determines an impedance between an electrode in a ventricle or atrium and a device housing electrode. 
     In some examples, the relative change in intracardiac impedance is greater than or equal to the relative change in intrathoracic impedance and wherein the indication comprises an indication of true anemia. In some examples, the relative change in intracardiac impedance is less than the relative change in intrathoracic impedance and wherein the indication comprises an indication of fluid overload. 
     Any suitable modifications may be made to the techniques described herein and any suitable device, processing circuitry, pulse generation circuitry, and/or electrodes may be used for performing the steps of the methods described herein. The steps of the methods may be performed by any suitable number of devices. For example, a processing circuitry of one device may perform some of the steps while a pulse generation circuitry and/or sensing circuitry of another device may perform other steps of the method, while communication circuitry may allow for communication needed for the processing circuitry to receive information from other devices. This coordination may be performed in any suitable manner according to particular needs. 
     The disclosure contemplates computer-readable storage media comprising instructions to cause a processor to perform any of the functions and techniques described herein. The computer-readable storage media may take the example form of any volatile, non-volatile, magnetic, optical, or electrical media, such as a RAM, ROM, NVRAM, EEPROM, or flash memory. The computer-readable storage media may be referred to as non-transitory. A programmer, such as patient programmer or clinician programmer, or other computing device may also contain a more portable removable memory type to enable easy data transfer or offline data analysis. 
     The techniques described in this disclosure, including those attributed to PCD  110 , external device  21 , and various constituent components, may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, embodied in programmers, such as physician or patient programmers, stimulators, remote servers, or other devices. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry. 
     Such hardware, software, firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. For example, any of the techniques or processes described herein may be performed within one device or at least partially distributed amongst two or more devices, such as between PCD  110  and external device  21 . In addition, any of the described units, circuitry or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as circuitry is intended to highlight different functional aspects and does not necessarily imply that such circuitry must be realized by separate hardware or software components. Rather, functionality associated with one or more circuitry may be performed by separate hardware or software components, or integrated within common or separate hardware or software components. 
     The techniques described in this disclosure may also be embodied or encoded in an article of manufacture including a non-transitory computer-readable storage medium encoded with instructions. Instructions embedded or encoded in an article of manufacture including a non-transitory computer-readable storage medium encoded, may cause one or more programmable processors, or other processors, to implement one or more of the techniques described herein, such as when instructions included or encoded in the non-transitory computer-readable storage medium are executed by the one or more processors. Example non-transitory computer-readable storage media may include random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, a hard disk, a compact disc ROM (CD-ROM), a floppy disk, a cassette, magnetic media, optical media, or any other computer readable storage devices or tangible computer readable media. 
     As used herein, the term “circuitry” refers to an application specific integrated circuit (ASIC), an electronic circuit, a processor (shared, dedicated, or group) and memory that execute one or more software or firmware programs, a combinational logic circuit, or other suitable components that provide the described functionality. 
     In some examples, a computer-readable storage medium comprises non-transitory medium. The term “non-transitory” may indicate that the storage medium is not embodied in a carrier wave or a propagated signal. In certain examples, a non-transitory storage medium may store data that can, over time, change (e.g., in RAM or cache). 
     Various examples have been described for delivering cardiac stimulation therapies as well as coordinating the operation of various devices within a patient. Any combination of the described operations or functions is contemplated. These and other examples are within the scope of the following claims.