Abstract:
A device for monitoring a heart includes a lead wire having a first end and a second end, the second end in contact with tissue of the heart; a first sensor disposed along the length of the lead wire; and a second sensor disposed at the second end of the lead wire. The first sensor is configured to measure an oxygen content of blood in the heart and the second sensor is configured to measure a fluid pressure in the heart. The device further includes a control module connected to the first end of the lead wire and configured to receive signals related to the measured fluid pressure and the measured oxygen content from the first and second sensors.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority from U.S. Application No. 61/253,599, filed Oct. 21, 2009, the content of which is incorporated herein by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This invention relates to cardiac monitoring. 
       BACKGROUND 
       [0003]    The characteristic of central mixed venous oxygenation (MvO 2 ) represents the blood oxygen concentration in blood returning from its cycle around the body and entering the heart to be re-oxygenated. A reduction in MvO 2  is often the earliest and most specific sign of hemodynamic compromise in a patient with advanced cardiopulmonary disease such as heart failure. Insufficient oxygen availability causes organ perfusion failure, lactic acidosis, and, ultimately, liver or kidney failure. The return of MVO 2  to a normal level is a good indicator of an improvement in combined heart and pulmonary function and of a successful therapeutic intervention. 
         [0004]    The MvO 2  reflects an integrated function of the cardiac pump function, the pulmonary function as measured by oxygen intake, and other peripheral oxygen demands. The MvO 2  indicates the degree to which the net cardiopulmonary function sufficiently supplies the body&#39;s oxygen needs. MvO 2  values below about 30 mmHg suggest that blood returning to the heart is significantly oxygen depleted, an indication of insufficient cardiopulmonary function resulting from a cardiopulmonary disorder such as heart failure or chronic lung disease. 
         [0005]    Blood oxygen content (CO 2 ) represents the total amount of oxygen dissolved in 100 mL of blood and is expressed either as a volume percent or as milliliters of oxygen per deciliter of blood (mL/dL). Blood oxygen content can be measured specifically for arterial blood (CaO 2 ) and venous blood (CvO 2 ). Oxygen in blood exists in two forms: dissolved in plasma and carried by hemoglobin. The amount of oxygen dissolved in plasma is calculated by multiplying the oxygen pressure (PO 2 ) by 0.0031, the solubility coefficient of oxygen in plasma. The amount of oxygen bound to hemoglobin is determined by multiplying 1.38 by the concentration of hemoglobin in the blood by the oxygen saturation in the blood (SO 2 ), where 1 gram of hemoglobin binds 1.38 mL of oxygen. The total blood oxygen content is thus expressed as 
         [0000]    
       
         
           
             
               
                 
                   
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                        
                       bound 
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                         1.38 
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         [0000]    Since 98% of the oxygen in blood binds to hemoglobin, the oxygen dissolved in plasma can be neglected and the total blood oxygen content can be approximated as only the amount of hemoglobin-bound oxygen. Blood oxygen content is thus highly dependent on hemoglobin concentration and oxygen saturation. 
         [0006]    Given the oxygen saturation and hemoglobin concentration, blood oxygen content can be determined. For instance, a normal concentration of hemoglobin is 15 grams per 100 mL of blood. Using the above equation and assuming a normal arterial oxygen saturation (SaO 2 ) of 97%, the arterial blood oxygen content (CaO 2 ) is determined to be 20.1 vol. %. On the venous side, normal venous oxygen saturation (SvO 2 ) is 75%, giving a CvO 2  of 15.5 vol. %. That is, tissues normally use 25% of the oxygen delivered to them and return 75% of the oxygen back to the lungs. The arterial-venous oxygen content difference, or oxygen extraction, is 5 vol. %. 
         [0007]    Oxygen transport and delivery (DO 2 ) represents the amount of oxygen delivered to the tissues and is measured in mL or in mL per minute. Oxygen transport is dependent upon two factors: the ability of the heart to maintain an adequate blood flow to the tissues (i.e., cardiac output), and the ability of the lungs to oxygenate blood as the blood passes through the pulmonary capillary network. The latter factor is reflected in the CaO 2  level. Oxygen transport is determined from the following expression: 
         [0000]      O2 transport=Cardiac Output (CO)×Oxygen Content (CO 2 )×10
 
         [0000]    The factor of 10 converts oxygen content to milliliters of oxygen per minute. 
         [0008]    For instance, continuing with the above example, for a normal cardiac output of 5 Liters per minute, arterial oxygen transport (i.e., total oxygen delivery) is 1005 mL of oxygen per minute. Venous oxygen transport, or the amount of unused oxygen returning to the heart, is 775 mL of oxygen per minute. 
         [0009]    When the balance between oxygen supply and oxygen demand is threatened, the body mobilizes its compensatory mechanism to ensure adequate oxygen availability by increasing cardiac output and/or increasing oxygen extraction from the blood. If cardiac output falls (e.g., due to a cardiopulmonary disorder), one of these two compensatory mechanisms is eliminated. If, however, blood oxygen content is reduced due to a decrease in SaO 2  or in hemoglobin concentration, both compensatory mechanisms remain available, albeit less efficient. A patient is thus less able to tolerate a drop in cardiac output than a decrease in SaO 2  or hemoglobin concentration. 
         [0010]    Normal values for the mixed venous oxygen saturation (SvO 2 ) range from 60% to 80%. An SvO 2  value around 50% to 60% indicates a mild decrease in the mixed venous oxygen reserve. For SvO 2  values less than 50%, significant depletion of the mixed venous reserve reduces the patient&#39;s capacity to buffer hypoxic threat. At SvO 2  values less than 32%, a minimum mixed venous saturation has been reached. Anaerobic metabolism and lactic acidosis quickly follow and there is a risk of organ damage and/or circulatory collapse. Low SvO 2  values are generally caused by cardiovascular insufficiency, increased oxygen demand, hypoxemia, anemia, and/or active hemorrhage. The physiologic tolerance of a patient to a fall in SvO 2  and the time to rebound to the patient&#39;s baseline SvO 2  level depend on a variety of factors, including the underlying cause of the decrease, the magnitude of the decrease, the rapidity of institution and the effectiveness of corrective therapies, and the patient&#39;s baseline (i.e., steady state) SvO 2  and cardiac reserves. 
         [0011]    In the opposite direction, SvO 2  values greater than 80% cause decreased cellular oxygen uptake and/or utilization. Causes of a high SvO 2  include intracardial or intravascular shunts (common in sepsis and cirrhosis); increased affinity of hemoglobin for oxygen (due, for instance, to alkalemia, hypocarbia, hypothermia, or administration of a large amount of banked blood); cytotoxicity (e.g., ethanol toxicity, cyanide poisoning, or sepsis); hypometabolism (hypothermia); polycythemia, or muscle paralysis (e.g., due to a neuromuscular blocking agent). 
       SUMMARY 
       [0012]    In a general aspect, a device for monitoring a heart includes a lead wire having a first end and a second end, the second end in contact with tissue of the heart; a first sensor disposed along the length of the lead wire; and a second sensor disposed at the second end of the lead wire. The first sensor is configured to measure an oxygen content of blood in the heart and the second sensor is configured to measure a fluid pressure in the heart. The device further includes a control module connected to the first end of the lead wire and configured to receive signals related to the measured fluid pressure and the measured oxygen content from the first and second sensors. 
         [0013]    Embodiments may include one or more of the following. The first sensor and the second sensor are configured to operate simultaneously. The second sensor is configured to continuously measure the fluid pressure. The first sensor is configured to continuously measure the oxygen content of blood in the heart. 
         [0014]    The first sensor and the second sensor are positioned in a right ventricle of the heart. The second sensor is configured to measure the fluid pressure in the right ventricle and first sensor is configured to measure the oxygen content of blood in the right ventricle. 
         [0015]    The second sensor is further configured to measure a pulse pressure in the heart, an intracardiac electrocardiogram, or an impedance of tissue in the heart. The impedance of tissue in the heart is indicative of the fluid pressure in the heart. The sensor is further configured to measure an impedance of pulmonary tissue. The second sensor includes a pressure sensitive membrane. The pressure sensitive membrane is formed of titanium. The second sensor includes electrodes disposed on an external surface of the sensor. 
         [0016]    The first sensor includes an optical device configured to emit light and to detect an amount of light reflected by the blood in the heart. The optical device is a fiber-optic device. The amount of light reflected by the blood in the heart is indicative of the oxygen content of blood in the heart. 
         [0017]    The device further includes a pacemaker. The second end of the lead wire is a lead of the pacemaker. The second end of the lead wire is mechanically anchored to tissue of a right ventricle of the heart. The device further includes a second lead wire, a first end of the second lead wire connected to the control module. A second end of the second lead wire is a lead of the pacemaker. The second end of the second lead wire is mechanically anchored to tissue of a right atrium of the heart. The control module configured to control the pacemaker in part on the basis of the received signals related to the measured oxygen content. 
         [0018]    The first sensor and the second sensor are configured to remain in the heart for up to 10 years. The control module includes a communication module and a power supply. The communication module is a wireless communication module. 
         [0019]    A cardiac monitoring device as described herein has a number of advantages. As cardiopulmonary disease, such as chronic cardiopulmonary failure, progresses in a patient, monitoring of the volume and hemodynamic status of the patient becomes more challenging due to the wide range of clinical manifestations and patient-driven characteristics associated with the disease. An implantable sensor system that continuously and remotely monitors blood oxygen content and fluid pressure in real time simplifies patient monitoring by enabling early detection of organ perfusion and the degree of compensation or decompensation in a patient. The data collected by the sensor help to guide therapy, triage, and cost-effective long term management of the patient, including when the patient is at a location remote from the medical staff supervising care. 
         [0020]    Continuous, remote SvO 2  and pressure monitoring improves not only the therapeutic effects of treatment, but also the quality of life of the patient. Wireless communication between the sensor and a remote computer means that the patient is not attached to an intravenous (IV) line but rather is allowed move about freely. Monitoring can continue at home rather than in a hospital setting, saving money and reducing inconvenience for the patient. Additionally, with the availability of early indications of worsening of heart failure reflected by dropping MvO 2  levels, treatment can be instituted and/or adjusted, thus preventing further worsening. This treatment allows better health to be maintained and avoids the potentially severe discomfort and disability of worsening cardiopulmonary function. This treatment also significantly reduces the risk of systemic infection that comes with the placement of multiple Swan-Ganz catheters, an intervention that is routinely used today as a last resort to obtain an adequate hemodynamic assessment on patients in heart failure. Many patients with heart failure, pulmonary hypertension, or other types of cardiopulmonary disease are or will become candidates for an implantable therapeutic device, such as a prophylactic implantable cardioverter defibrillator (ICD), a biventricular ICD (BivICD), or a permanent pacemaker (PPM). The integration of a SvO 2  and fluid pressure biosensor with another implanted device is convenient, cost effective, and minimizes invasive medical procedures. Furthermore, the data measured by the sensor can be used to improve the performance of the therapeutic device. For instance, when a SvO 2  and fluid pressure biosensor is incorporated with a PPM or an ICD, the PPM/ICD software is modified to use SvO 2  in an algorithm for setting the pacing rate in order to avoid over-pacing, which can be associated with worsening of patient hemodynamic status and increased morbidity and mortality. The inclusion of SvO 2  readings in the therapeutic algorithm provides additional information to the pacemaker regarding overall patient hemodynamics and increases the accuracy of the therapeutic algorithms. Thus overpacing and use of inappropriate ICD defibrillator shock therapy can be decreased or eliminated. A reduction in such therapies in turn minimizes the deleterious electrophysiologic impact of the pacemaker and will have a major impact in improvement of patient&#39;s quality of life. 
         [0021]    Other features and advantages of the invention are apparent from the following description and from the claims. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0022]      FIG. 1  is a schematic diagram of a cardiac sensor system implanted in the right ventricle of a heart. 
           [0023]      FIG. 2  is a block diagram of the control module of the cardiac sensor system of  FIG. 1 . 
           [0024]      FIG. 3  is a schematic diagram of a cardiac sensor system integrated with a pacemaker. 
           [0025]      FIG. 4  is a block diagram of the pulse generator associated with the sensor system and pacemaker of  FIG. 3 . 
       
    
    
     DETAILED DESCRIPTION 
       [0026]    Referring to  FIG. 1 , a sensor system  1  implanted in a right ventricle  102  of a heart  104  continuously monitors physiological parameters of a patient. An oxygen sensor  100  measures the central mixed venous oxygen level (MvO 2 ) or the central mixed venous oxygen saturation (SvO 2 ) and the percent oxygen saturation in right ventricular blood. Simultaneously, a pressure sensor  101  measures the central venous fluid pressure and pulse pressure in the right ventricle and the maximum positive and negative rate of change of the pressure during the cardiac cycle (dP/dt). In some embodiments, pressure sensor  101  also measures an intracardiac electrocardiogram and an impedance of heart and lung tissue. In other embodiments, only oxygen sensor  100  is used. The use of an oxygen sensor alone is useful, for instance, for monitoring patients with pulmonary hypertension. 
         [0027]    These physiological parameters provide data that can be used to identify and monitor organ perfusion, congestion in the chest cavity, and the degree of compensation or decompensation in patients with chronic cardiopulmonary failure or other types of cardiopulmonary disease. When coupled with cardiac output measurements, these data enable the calculation of oxygen transport and oxygen consumption; early identification of impending or actual global tissue hypoxia; a determination of the cause of a hypoxic episode; an assessment of the response of a patient to a treatment of hypoxia; and a prediction of patient survival based on an underlying cause of a hypoxia episode and on the patient&#39;s response to the hypoxia treatment. 
         [0028]    Oxygen sensor  100  is approximately less than 1 cm in diameter and is positioned along the length of a lead  106  that passes through a right atrium  108  and a superior vena cava  110  at about 3-4 cm above the tip of the lead. Pressure sensor  101  is positioned toward the end of lead  106 , embedded in the wall of the right ventricle towards the apical septum  102 . Lead  106  and sensor  100  are inserted intravenously into the right ventricle through the subclavian or cephalic vein of the patient. Lead  106  connects to a control module  112  positioned in a subcutaneous device pocket in the subclavicular region of the patient, which pocket is formed by a small cutaneous incision, as in currently performed during the implantation of a pacemaker. Lead  106  is between 5-7 mm thick, and is typically about 5 mm thick. 
         [0029]    A tip of  114  of lead  106  is anchored in the myocardium of heart  104  by soft tines or a tiny screw (not shown). A steroid elutes from tip  114  to decrease inflammation at the tip-myocardium interface, thus improving the chronicity of sensor system  1 . As a result, the sensor system  1  is able to remain implanted for long periods of time, allowing long term monitoring of physiological parameters. 
         [0030]    Measurement data are transmitted from oxygen sensor  100  and pressure sensor  101  to control module  112  along lead  106 . Control module  112  includes a wireless communication module  115 , such as an antenna coil. Communication module  115  wirelessly communicates the measurement data to a remote computer  116  for display, storage, or processing. Computer  116  may be, for instance, a clinician&#39;s computer, a patient&#39;s computer, or a handheld computing device. Communication between control module  108  and computer  112  may be periodic or upon request by computer  112 . For instance, computer  112  may calculate both a continuous SvO 2  level and an average SvO 2  level at a preselected timing interval. Also, once a baseline SvO 2  of the patient is obtained, an alarm setting can be programmed that will be activated at pretermined levels of SVO 2 , thus allowing early recognition of a decline or a decompensated status. 
         [0031]    Control module  108  also includes control circuitry  118  that controls the operation of sensor  100  and communication module  115 . A lithium battery  120  in control module   112  supplies power to control circuitry  118 , communication module  115 , and sensor  100 . The lifetime of battery  120  is typically in the range of 5-10 years and depends on factors such as the output voltage of control module  112 , the resistance of lead  106  and sensor   100 , and the frequency and duration of use of the battery. The components in control module  108  are enclosed in a biocompatible casing  122 . 
         [0032]    Referring to  FIG. 2 , oxygen sensor  100  and pressure sensor  101  are hermetically sealed devices made of titanium, iridium, or another biocompatible material that is pharmacologically inert, nontoxic, sterilizable, and able to function in the environmental conditions of the body. Ideally the material is not affected by stress cracking or metal ion oxidation. Circuitry  200  in sensor  100  and circuitry  201  in sensor  101  control the operation of measurement devices housed in sensors  100  and  101  and control the communication between the sensors and control module  112 . 
         [0033]    A light emission module  206  in oxygen sensor  100  includes a red (660 nm) and/or infrared (880 nm) light emitting diode (LED) hermetically sealed in a sapphire capsule. The LED emits light which illuminates blood in the right ventricle. The amount of light reflected by the blood, which is indicative of the oxygen saturation (i.e., the SvO 2 ) is detected by a photodetector  208 . 
         [0034]    A titanium pressure sensing membrane  204  mounted on pressure sensor  101  measures fluid pressure and pulse pressure in the right ventricle or right atrium. 
         [0035]    A set of electrodes  214  mounted on the external surface of pressure sensor  101  measures the impedance of tissue in the chest cavity, such as cardiac tissue and pulmonary tissue, at a digital rate of 128 Hz. Impedance measurements allow for portioned analysis of contractile cardiac function and pulmonary ventilation function. Average pulmonary impedance, e.g., averaged over a period of 72 hours or more, provides a baseline value against which an instantaneous impedance measurement can be compared. Signal processing of the impedance data allows deviations from baseline impedance values to be detected. For instance, a decrease in lung impedance is indicative of increasing fluid content and congestion in the lungs, which can lead to congestive heart failure. 
         [0036]    In some embodiments, the sensor system is integrated with another implantable diagnostic or therapeutic device, such as a prophylactic implantable cardioverter defibrillator (ICD), a biventricular ICD, or a permanent pacemaker (PPM). In general, when the sensor system is integrated with another implantable device, certain structures (e.g., lead  106  in  FIG. 1 ) may be shared between either or both of sensor  100  or sensor  101  and the other implantable device. 
         [0037]    Referring to  FIG. 3 , a sensor system  300  is combined with a pacemaker and implanted in a heart  300 . Oxygen sensor  100  is positioned along a ventricular lead  302  of the pacemaker; pressure sensor  101  is positioned at the end of the lead  302 . Ventricular lead  302  is anchored in the myocardium of a right ventricle  304  by an anchor   303 . An atrial lead  306  of the pacemaker is anchored in the myocardium of a right atrium towards the right interatrial septum  308  by an anchor  307 . In some instances, a sensor system such as that shown in  FIG. 1  is later upgraded to include a pacemaker (i.e., to become sensor system  300 ) if a patient&#39;s illness evolves to indicate the use of a pacemaker. In other instances, an existing pacemaker is upgraded to include sensors  100  and  101 . 
         [0038]    In some embodiments, pressure sensor  101  is positioned at the end of atrial lead   306 . In some instances, atrial lead  306  is directed toward the base of the inter-atrial septum (not shown) such that pressure sensor  101  is embedded in the wall of the right atrium. The measurements of the right atrial pressure provided by the pressure sensor located on the right atrial lead generally are more accurate than measurements of the right ventricular pressure provided by a pressure sensor located on a right ventricular lead (e.g., sensor  101  in  FIG. 1 ). The placement of both an atrial lead and a ventricular lead is a more invasive procedure (such as a transseptal puncture) than the placement of only a ventricular lead. However, when the sensor system is used in conjunction with a pacemaker (e.g., a dual chamber pacemaker, a PPM/ICD, or a BivICD), an atrial lead and a ventricular lead are already used and thus no additional intervention occurs. Referring to  FIGS. 3 and 4 , a pulse generator  310  is implanted in a subcutaneous device pocket in the subcutaneous region of a patient and connects to ventricular lead  302  and atrial lead  306 . Pulse generator  310  includes a sensor module  312 , a pacemaker module  314 , and a lithium battery  316 . Sensor module  312  controls the operation of sensors  100  and  101  and receives measurement data from sensors  100  and  101  via lead  302 . Sensor module   312  includes a wireless communication module  318  that communicates the measurement data to a remote computer. Pacemaker module  314  sends electrical pacing signals along ventricular lead  302  and atrial lead  306 . Pacemaker module  314  controls the pacing of the pacemaker according to a predetermined algorithm that takes into account physiological parameters including heart rate, QRS duration and morphology, PR intervals, and SvO 2  levels. Battery  316  provides power to sensor module  312 , pacemaker module  314 , communication module  318 , and sensors  100  and  101 . The lifetime of battery  316  is typically 5-10 years and depends on factors such as the output voltage of sensor module  312  and pacemaker module  314 , the resistance of leads  302  and  306  and sensor  100 , the pacing rate, and the frequency and duration of use of the battery. 
         [0039]    In some embodiments, a sensor system that performs continuous SvO 2  and pressure monitoring is used in conjunction with diagnostic and/or treatment algorithms that enable more accurate monitoring, diagnosis and treatment. In some instances, algorithms incorporated into the control module enable remote management of patients. When the sensor system is incorporated with a pacemaker, the algorithms also enable more accurate and efficient pacing. Such systems can be used for a variety of applications, including the following:
       Guiding outpatient treatment and monitoring of chronic cardiac, pulmonary, or muscle failure   Facilitating the early identification of patients with acute cardiopulmonary decompensation that will benefit from early hospitalization and/or treatment modification   Enabling follow up to medical therapy and observation of a patient&#39;s response to changes in therapy in both inpatient and outpatient settings   Guiding treatment and titration of continuous-inotrope-based home treatment on patients waiting for cardiac, lung or combined lung cardiac transplant   Guiding treatment of advanced cardiomyopathy, advanced pulmonary disease, or end-stage muscular disease   Guiding treatment of moderate to severe primary or secondary pulmonary hypertension   Monitoring of a patient with chronic pulmonary hypertension undergoing treatment with continuous IV vasodilator, prostaglandin or immune-modulating agent therapy   Monitoring and guiding treatment of advanced pulmonary fibrosis, emphysema, or interstitial lung and bronchospastic disease   Guiding the management of a patient on mechanical ventilation or the weaning of a patient from mechanical ventilation, including patients for whom weaning by other methods has failed   Facilitating acute post-surgical care   Monitoring high-risk surgical anesthesia and post-surgical care   Guiding the assessment and/or adjustment of therapy and routine nursing care   Guiding the management of a patient having intra-aortic balloon counterpulsation   Guiding the management of a patient with a left, right, or biventricular assisted device to ensure hemodynamic stability   Facilitating the identification of patients who have life-threatening arrhythmias with major hemodynamic manifestations   Guiding the management of a patient after an acute cerebrovascular accident or seizure   Guiding the early identification of vegetative patients that could potentially become donors for organ transplantation       
 
         [0057]    It is to be understood that the foregoing description is intended to illustrate and not to limit the scope of the invention, which is defined by the scope of the appended claims. Other embodiments are within the scope of the following claims.