Abstract:
An implantable leadless pacemaker having a housing and two electrodes arranged on said housing. The two electrodes are made of biocompatible materials that have different sensitivities to pH changes. The two electrodes are connected to an activity monitoring unit that is adapted to determine an open-circuit potential difference between the two electrodes and to generate an activity signal derived from said open-circuit potential difference.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This patent application claims the benefit of co-pending U.S. Provisional Patent Application No. 62/045,568, filed on Sep. 4, 2014, which is hereby incorporated by reference in its entirety. 
     
    
     TECHNICAL FIELD 
       [0002]    The present invention generally relates to an activity monitor and to a rate-adaptive implantable leadless pacemaker comprising an activity monitor. 
       BACKGROUND 
       [0003]    Leadless cardiac pacemakers are small devices implanted directly in a ventricle of a heart. Leadless cardiac pacemakers are preferably rate-adaptive to change pacing output dependent on patient activity. A problem is that sensing patient activity normally requires large circuitry with high power consumption for the application. 
         [0004]    Leadless cardiac pacemakers disclosed in prior art adapt pacing rate based either on an activity sensor (accelerometer) or a temperature sensor, and associated circuitry, hermetically contained within the housing. 
         [0005]    Leadless pacemaker design has strict size and power consumption requirements. A motion-sensing activity sensor (e.g., an accelerometer) contained within the housing to adapt the pacing rate occupies substantial space and its associated circuitry (for signal processing) requires a power consumption level that reduces the lifetime of the device. A temperature sensor-based pacemaker, on the other hand, has a slow response time, which is detrimental to useful pacing rate adaptation. 
         [0006]    In view of the above, there is a need for an improved rate-adaptive implantable leadless pacemaker and activity monitor. 
         [0007]    The present invention is directed toward overcoming one or more of the above-mentioned problems. 
       SUMMARY 
       [0008]    It is an object of the present invention to provide an improved leadless pacemaker and an activity monitor for monitoring metabolic demand. 
         [0009]    According to the present invention, at least this object is achieved by an activity monitor for monitoring metabolic demand that has two electrodes that are made of biocompatible materials that have different sensitivities to pH changes. The two electrodes are connected to an activity monitoring unit that is adapted to determine an open-circuit potential difference between said two electrodes and to generate an activity signal derived from said open-circuit potential difference. 
         [0010]    An object of the present invention is further achieved by an implantable leadless pacemaker having a housing and at least two electrodes arranged on said housing. The two electrodes are made of biocompatible materials that have different sensitivities to pH changes. The two electrodes are connected to an activity monitoring unit (i.e., an activity monitor) that is adapted and/or configured to determine an open-circuit potential difference between the two electrodes and to generate an activity signal derived from said open-circuit potential difference. 
         [0011]    Thus, an object of the present invention is achieved by an activity monitor for monitoring metabolic demand and a leadless pacemaker with an activity monitor that utilizes the electrical properties of its electrodes in contact with blood to adapt the pacing rate. 
         [0012]    Changes in metabolic needs, such as, for example, those caused by physical activities or emotional stress, will vary the venous blood pH within a narrow range around 7.35. 
         [0013]    The activity monitoring unit of the activity monitor and the implantable leadless pacemaker of the present invention thus respond to both physical activity and emotional stress. The term “activity” is thus used in broad sense, because it includes both physical activity and emotional stress. 
         [0014]    While pH-based rate-adaptive pacemakers using cardiac leads were proposed and tested in the late 1970s, they did not gain clinical acceptance as the measurement techniques proposed required an Ag/AgCl reference electrode, which is not biocompatible or suitable for long term implantation. 
         [0015]    The activity monitor for monitoring metabolic demand and the leadless pacemaker of the present invention incorporate two electrodes made of biocompatible materials with different sensitivity to pH changes. A first material presents a Nernstian or super-Nernstian behavior with pH, i.e., its open-circuit potential varies with a large negative slope, for example, of about less than −50 mV/pH, and preferably less than −60 mV/pH, and the second material is either insensitive to pH or presents a smaller negative slope (sub-Nernstian behavior), e.g., a slope of more than −40 mV/pH, and preferably more than −30 mV/pH. 
         [0016]    In the implantable pacemaker, the open-circuit potential difference between these two electrodes is periodically measured to allow adjusting the pacing rate. The materials of the present invention are also suitable for electrical stimulation, which allows implementing a rate-adaptive pacemaker with the minimum two electrodes required for pacing. 
         [0017]    The technical advantages of this invention include, but are not limited to: 1) implementing a rate-adaptive leadless pacemaker re-utilizing features already required for pacemaker operation; 2) implementing a rate-adaptive leadless pacemaker with minimum power consumption required for rate adaptation; 3) reduced component count and size (no need for an accelerometer or temperature sensor) saves space; 4) fast response time compared to a temperature-based sensor; 5) rate adaptation using pH is also responsive to emotional stress, which cannot be achieved with an accelerometer or temperature-based activity sensor. 
         [0018]    In a preferred embodiment of the implantable leadless pacemaker, the activity monitoring unit is adapted to periodically determine the open-circuit potential difference between said two electrodes. Preferably, the implantable leadless pacemaker further comprises a control unit (i.e., controller) that is connected to the activity monitoring unit (i.e., activity monitor) and that is adapted to adjust a pacing rate in response to said activity signal generated by said activity monitoring unit. 
         [0019]    In preferred embodiments of the activity monitor or the implantable leadless pacemaker, the sub-Nernstian material is a coating made of or comprising poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). 
         [0020]    In preferred embodiments of the activity monitor or the implantable leadless pacemaker, the super-Nernstian material is a coating made of or comprising iridium oxide (IrO). 
         [0021]    Preferably, the super-Nernstian material is a coating made of or comprising a non-stoichiometric composition of iridium oxide, namely either IrO(2−x) or IrO(2+x), and in particular, IrO(1.5). 
         [0022]    In preferred embodiments, the coating made of or comprising iridium oxide is deposited on the electrode surface using reactive physical vapor deposition (PVD). 
         [0023]    A preferred embodiment of the implantable leadless pacemaker has a housing whereupon the two electrodes are arranged and wherein the activity monitoring unit is adapted to periodically determine the open-circuit potential difference between said two electrodes. The preferred implantable leadless pacemaker further comprises a control unit that is connected to the activity sensor and that is adapted to adjust a pacing rate in response to said activity signal generated by said activity monitoring unit. 
         [0024]    Preferably, the activity monitoring unit or the control unit, or both, are configured to generate an activity signal indicating an increase of pacing rate or increasing the pacing rate, respectively, only when a sudden decrease of pH is determined. 
         [0025]    It is further preferred when the activity monitoring unit or the control unit or both are configured to determine or to respond to the activity signal during diastole only. 
         [0026]    Similarly, it is further preferred when the activity monitoring unit or the control unit, or both, are configured evaluate the activity signal so as to determine a contact with an inner heart wall and thus to monitor cardiac contraction during systole. 
         [0027]    The implantable leadless pacemaker may further comprise impedance determination circuitry and a third electrode made of or comprising iridium oxide, which is connected to said impedance determination circuitry. In such embodiment, in which preferably the first and/or the second electrodes are also connected to the impedance circuitry, the impedance determination circuitry is configured to determine a tissue-electrode capacitance or changes thereof. The third electrode preferably has a smaller surface than the first and second electrode. 
         [0028]    In preferred embodiments of both, the activity monitor for monitoring metabolic demand or the implantable leadless pacemaker itself are configured to perform long-term monitoring of pH. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0029]    The above and other aspects, features, object, advantages and possible applications of the present invention will be more apparent from the following more particular description thereof presented in conjunction with the following drawings, and the appended claims, wherein: 
           [0030]      FIG. 1  is an external view of a leadless implantable pacemaker; 
           [0031]      FIG. 2  is a schematic block diagram of some internal components of the pacemaker of  FIG. 1 ; and 
           [0032]      FIG. 3  is a schematic block diagram of some internal components of an alternative embodiment of a pacemaker according to the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0033]    The following description is of the best mode presently contemplated for carrying out the present invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles of the present invention. The scope of the present invention should be determined with reference to the claims, which should be given their full breadth. 
         [0034]      FIG. 1  shows an implantable leadless pacemaker with an elongate housing  100  and two electrodes  101  and  102 . Each electrode is arranged at a respective longitudinal end of the housing  100 . 
         [0035]    Electrode  102  is a return electrode for pacing purposes. Electrode  101  is coated with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (also known as PEDOT:PSS), a biocompatible conductive polymer with a linear sub-Nernstian response in the pH range considered. Electrode  102 , on the other hand, is coated with iridium oxide deposited with a state of oxidation that provides at least a linear Nernstian behavior with pH. 
         [0036]    As shown in  FIGS. 2-3 , the electrodes  101  and  102  are connected to the inputs of an amplifier  104  contained within the housing  100  capable of measuring such varying open-circuit potentials difference. The measured potential is fed to an activity monitoring unit  105  (i.e., activity monitor) that generates an activity signal for a pacing control unit  106  (i.e., pacing controller). Pacing control unit  106  is connected to a stimulation unit  107  (i.e., stimulator) and a sensing unit  108  (i.e., sensor). Pacing control unit  106  is further connected to a memory  109  and a communication unit  110 . By means of stimulation unit  107  and sensing unit  108 , control unit  106  can apply demand pacing of a heart chamber through electrodes  101  and  102  in a manner known per se. By means of the activity signal provided by the activity monitoring unit  105 , pacing can be rate-adaptive, that is, a respective pacing rate can be adapted to the metabolic demand of a respective person. In another embodiment, the sensing unit  108  is adapted to implement the tasks of  104  thus reducing the circuitry required for rate adaptation. Further, control unit  106  can interact with the electrodes  101  and  102  by means of the communication unit  110 . 
         [0037]    The implantable leadless pacemaker determines a metabolic demand by means of blood pH changes. Metabolic needs, including emotional stress, will vary the pH in the range of 7.35 to 7.29. Hence, with a resulting slope of −30 mV/pH, this translates into a full-range voltage variation of 1.8 mV. Sixteen steps of rate adaptation imply a resolution of approximately 112 μVN, which can be implemented with very low-power consumption. 
         [0038]    The two electrodes  101  and  102  are made of biocompatible materials with different sensitivity to pH changes. A first material presents a Nernstian or super-Nernstian behavior with pH, i.e. its open-circuit potential varies with a large negative slope, for example of about −60 mV/pH, and the second material is either insensitive to pH or presents a smaller negative slope (sub-Nernstian behavior), e.g. a slope of −30 mV/pH. 
         [0039]    Since pacing affects the ionic concentrations of the immediate layer next to an electrode, activity monitoring unit  105  and/or control unit  106  are configured to perform measurements for rate adaptation during diastole. 
         [0040]    The control unit  106  is configured to increase the pacing rate only when sudden pH decreases are detected. This avoids runaway pacing rate changes that can occur from long-term pH changes in the body due to medication or other systemic effects. 
         [0041]    In an alternative embodiment, electrodes  101  and  102  are coated with iridium oxide and PE-DOT:PSS, respectively. 
         [0042]      FIG. 3  illustrates yet another embodiment, wherein the leadless pacemaker includes a third iridium oxide electrode  111  of much smaller area compared with the other iridium oxide electrode  102 . pH variations will result in changes of the tissue-electrode capacitance, which can be detected by impedance measurements or other type of AC measurements. Accordingly, the activity monitoring unit  105 ′ of the embodiment illustrated in  FIG. 3  further comprises impedance determination circuitry including an AC current source  112  and a voltmeter  113 . 
         [0043]    In another embodiment, the pH sensor is used for long-term monitoring of blood pH. Changes in blood pH may occur due to medication, and monitoring the pH may help the physician to titrate the proper dosage of medication. pH also may change due to sleep apnea or other metabolic disease states that cause alkalosis or acidosis. The monitor would allow for a physician to monitor the pH trend of the patient and prescribe long-term treatment accordingly. 
         [0044]    In yet another embodiment, the mechanical motion of the heart chamber is sensed by measuring the potential of the dissimilar electrode materials in response to contact with the inner heart wall. When the heart wall contacts the electrodes, the thin layer of electrons is perturbed, thereby changing the measured potential. The force of the cardiac contraction will alter the potential change on the electrodes. Measurement of the cardiac contraction would occur during systole. Therefore, constant monitoring of the electrode potential during systole and diastole allows for cardiac contractile force measurement as well as venous pH measurements. 
         [0045]    For pH sensors, it is preferred to identify materials that undergo a reversible reduction-oxidation reaction when in solution, such that the ratio of activation energies maximizes the resulting cell potential as predicted by the Nernst equation. In the case of iridium oxide, this ratio is facilitated by the transition of Ir from a 4+ to a 3+ charge state (in the form of IrO2 and Ir2O3, respectively). Since the ratio of activation energies is dependent on the molar concentrations of the ions in solutions (and therefore driven by pH), one can see that the voltage sensitivity of the redox reaction can be changed by altering the amount of molar concentration of highly active constituents. In this regard, a preferred iridium oxide coating may actually be a non-stoichiometric composition, meaning that the deposited coating is either IrO(2−x) or IrO(2+x). In this regard, it is possible to tailor the Nernst potential in such a way that it matches specific device and/or sensor requirements. 
         [0046]    In a preferred embodiment, the IrOx is deposited on the surface of the device or device component using reactive physical vapor deposition (PVD), although chemical vapor deposition (CVD), or related techniques (PE-CVD, ion beam, etc.) may be used. In reactive PVD, the stoichiometry of the resulting IrOx coating is dependent on the amount of oxygen gas injected into the carrier gas (typically Ar), and the amount of iridium sputtered from a pure target. In this manner, it is possible to create a variety of iridium oxide compositions; the most preferred stoichiometry would be IrO(1.5). 
         [0047]    In a preferred embodiment, an IrOx coating is developed such that it exhibits Nernstian or super-Nernstian behavior, and is paired with a counter electrode that provides sub-Nernstian behavior. It is possible that this counter electrode could be a different IrOx composition, as well as PEDOT, bare metal, or other materials. 
         [0048]    Although an exemplary embodiment of the present invention has been shown and described, it should be apparent to those of ordinary skill that a number of changes and modifications to the invention may be made without departing from the spirit and scope of the present invention. In particular, it is possible to integrate the activity monitor according to the present invention in devices other than pacemakers. This invention can readily be adapted to a number of different kinds of medical devices by following the present teachings. All such changes, modifications and alterations should therefore be recognized as falling within the scope of the present invention. 
         [0049]    It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teachings of the disclosure. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention, which is to be given the full breadth thereof. 
         [0050]    Additionally, the disclosure of a range of values is a disclosure of every numerical value within that range. 
       LIST OF REFERENCE NUMERALS 
       [0051]      100  (elongate) housing 
         [0052]      101 ,  102  electrodes 
         [0053]      104  amplifier 
         [0054]      105 ,  105 ′ activity monitoring unit 
         [0055]      106  pacing control unit 
         [0056]      107  stimulation unit 
         [0057]      108  sensing unit 
         [0058]      109  memory 
         [0059]      110  communication unit 
         [0060]      111  iridium oxide electrode 
         [0061]      112  AC current source 
         [0062]      113  voltmeter