Abstract:
A device and method for cardiac pacing is disclosed in which anodal pacing of the left ventricle is provided. Anodal pacing occurs when an anodal surface area is sufficiently small to create an area of hyper-polarization of the myocardial cell membrane. This creates a virtual cathode at a location remote from the anode. The virtual cathode results in depolarization of the heart in a manner similar to the virtual cathode at the true fixed cathode. In addition a device and method for summation anodal pacing is provided in which one anode is common between two or more cathodes. This results in hyperpolarization of a larger segment of the myocardium as compared to non-summation anodal pacing and thereby forms a larger virtual electrode to enable capture of localized, discrete cardiac structures such as the bundle of His or the very proximal portions of the right and left bundles.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part of and claims the benefit of the filing date of co-pending U.S. patent application Ser. No. 12/899,244 filed on Oct. 6, 2010 and entitled “Summation Anodal Pacing to Complement Multisite Stimulation,” which claims priority from U.S. Provisional Patent Application Ser. No. 61/272,563, filed on Oct. 6, 2009, the entire contents of which are hereby expressly incorporated by reference into the present application. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention pertains to the medical field and, more particularly, pertains to uniquely designed pacing circuits to allow stimulation of multiple areas of the heart using anodal as well as cathode current. 
     2. Discussion of the Related Art 
     Traditional pacing of heart chambers is accomplished by delivering electrical current to cardiac tissue at a cathode of a pacing lead. An anode is provided as either a pacemaker/defibrillator casing (unipolar pacing) or as a separate anode positioned on the pacing lead with a large surface area to prevent anodal capture (bipolar pacing). 
     Cardiac pacing has been used for at least 50 years to sustain the heart rhythm in patients with slow or absent innate electrical activation. Conventional pacing uses cathodal capture to excite heart muscle. By delivering a current impulse (electrons) via a conductor, a segment of the myocardial cell membrane is rendered more negative such that the threshold potential is reached. This initiates an action potential, which is propagated to adjacent myocardial cells such that eventually the entire heart muscle is depolarized. More recently, pacing of the left ventricle has been used to synchronize the heart in patients with left bundle branch block, thereby reducing instances of heart failure. 
     Capture of myocardium depends upon current density; a smaller electrode will provide greater current density with the same current than a larger electrode. Traditional theory holds that a certain minimal area of the heart must be captured to allow propagation of the impulse through the heart muscle 
     Capture also depends upon the ease with which current is transferred to underlying viable myocardial tissue. Diseased tissue or poor connection between electrode and myocardium will increase pacing thresholds. Thus, a small electrode surface area and good contact with viable underlying myocardial tissue is required to achieve capture with minimal current expenditure. 
     Recent epi-fluorescence membrane studies have demonstrated that the phenomenon of myocardial capture is much more complicated than previously thought. It appears application of current at the cathode, results in the formation of a “virtual cathode” of “dog bone” shape oriented at a 45 degree angle. Stimulation and propagation depend upon the virtual cathode exciting viable myocardial tissue. 
     Heretofore, anodal capture has been considered undesirable on largely theoretical grounds. In particular, it has been theorized that anodal current may be pro-arrhythmic and may also cause mechanical deterioration of the electrode tip. These theories have now been largely discredited. It has been shown that in left ventricular (LV) pacing, unintended anodal capture occurs frequently and may even have salutary hemodynamic effects. 
     Anodal pacing occurs when the current introduced to the heart at the cathode returns to the pacemaker circuit via the anode. When the anodal surface area is sufficiently small, this creates an area of hyper-polarization of the myocardial cell membrane. In turn, this sets up a “virtual cathode” remote from the anode. The virtual cathode results in depolarization of the heart in a manner similar to the virtual cathode at the true fixed cathode. 
     There are at least two advantages to anodal pacing. First, if the virtual cathode lies in an area of healthy myocardium, the anodal threshold may actually be lower than the true cathodal threshold, especially if the cathode lies in an area of diseased myocardium or has a poor connection to the underlying myocardium. Second, if a considerable distance separates the anode and cathode, the area of the myocardium that can be stimulated will be increased by the formation of virtual cathodes. This may have advantages in allowing rapid depolarization of the myocardium; it may also allow capture of a particular small, specifically located structure, such as the His bundle. 
     The need therefore exists to provide a cardiac pacing apparatus and method including electrical circuits configured to allow for anodal capture. 
     SUMMARY OF THE INVENTION 
     In accordance with a first aspect of the invention, a pacing device is provided for anodal pacing of one or more electrodes in a bipolar or multipolar lead for the left ventricle (LV). In particular, a pacing-enhanced circuit for left-ventricular stimulation may be provided. 
     In a second aspect of the invention, anodal pacing is utilized to capture the His bundle or the very proximal right and left bundles, i.e., His or Para-his pacing. This may be carried out using a bipolar or multipolar lead designed such that multiple poles are in contact with the tricuspid annuls in close proximity to the bundle of His by way of the virtual cathode created by the fixed cathode as well as the virtual cathode created by the anode. 
     In yet another aspect of the invention, anodal pacing may be used in patients requiring bi-atrial pacing. In still another aspect of the invention, the left atrial lead may serve as the anode for the right ventricular pacing lead. 
     Various other features, embodiments and alternatives of the present invention will be made apparent from the following detailed description taken together with the drawings. It should be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration and not limitation. Many changes and modifications could be made within the scope of the present invention without departing from the spirit thereof, and the invention includes all such modifications. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Preferred exemplary embodiments of the invention are illustrated in the accompanying drawings, in which like reference numerals represent like parts throughout, and in which: 
         FIG. 1  is a schematic view of leads of a device, e.g., a biventricular pacemaker or defibrillator, coupled to a heart; 
         FIG. 2  is a schematic view of the leads of the device of  FIG. 1  in which a sub-threshold stimulus is applied and preconditions a left ventricular (LV) anode, which serves as the anode for the right atrium (RA); 
         FIG. 3  is a schematic view of the leads of  FIGS. 1 and 2  and showing the leads coupled to the right ventricle (RV) and left ventricle and demonstrating the concept of summation anodal pacing; 
         FIG. 4  is a schematic view of the leads of  FIGS. 1 and 2  and demonstrating the concept of LV anodal summation as a byproduct of RV stimulation; 
         FIG. 5  is a schematic view of the leads of  FIGS. 1 and 2 , coupled to the heart and demonstrating the concept of summation anodal pacing in which an electrode of the LV multipolar lead serves as a common anode for the RV cathode, LV 1  cathode and LV 6  cathode; 
         FIG. 6  is a partial schematic view of the leads of  FIGS. 1 and 2 , coupled to the right and left ventricles of the heart and demonstrating the concept of summation anodal pacing in a quadripolar LV lead; 
         FIG. 7  is a partial schematic view like that of  FIG. 6  and demonstrating the concept of summation anodal pacing a quadripolar LV lead; 
         FIG. 8  is a schematic view of the leads similar to that of  FIGS. 1 and 2  and showing a bipolar lead in the RA, a bipolar lead in the RV and a bipolar or multipolar lead in the LV; 
         FIG. 9  is a partial schematic view showing the coupling of leads to the LV and RV of the heart and demonstrating the manner in which RV and LV channels in a biventricular pacing device may be configured to stimulate multiple electrodes on the LV lead; 
         FIG. 10  is a schematic view showing the coupling of leads to the heart and showing the leads in the RA, RV, LV and left atrium (LA) introduced through the vein of Marshall; 
         FIG. 11  is a schematic view showing the leads coupled to the heart and demonstrating the concept of four chamber pacing and multipolar LV pacing; 
         FIG. 12  is a schematic view of the leads of the device of the invention coupled to the heart and showing the LA lead as the anode for the RA channel; 
         FIG. 13  is a schematic view showing the leads o coupled to the heart and showing the LA lead as anode for the RV channel; 
         FIG. 14  is a schematic view showing the leads o coupled to the heart and showing the LV lead as the anode for the RV channel; and 
         FIG. 15  is a schematic view of the device according to the invention in which the device is a pacemaker. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     In cardiac pacing, if a single electrode of appropriate size serves as the anode for a single cathode delivering an amount of current represented as X, then an amount of current represented as Y will be delivered to the anode. Summation anodal pacing is a method of cardiac pacing in which if the same anode serves as a common anode for two cathodes and each cathode is delivering an amount of current represented as X, then 2Y current will be delivered to the anode. This results in the hyperpolarization of a larger segment of the myocardium adjacent the anode, and consequently, the creation of a larger virtual electrode. This is likely to reduce the anodal pacing threshold. Further, the larger the virtual electrode, the more likely it is to capture a localized, discrete structure within the heart such as the Bundle of His or the very proximal portions of the right and left bundles. 
     Referring now to the drawings, and initially  FIG. 1 , a schematic illustration of a heart is provided. The heart includes four chambers, namely: a right atrium RA, left atrium LA, right ventricle RV, and left ventricle LV. The coronary sinus CS is shown in the groove between the left atrium and left ventricle on the posterior surface of the heart. Referring now to  FIGS. 1 and 8 , the positions of a number of leads of a device  10  (see  FIG. 15 ) according to the invention are shown. The device  10  may be, for example, a biventricular pacemaker or a defibrillator. Device  10  includes a housing  12  for carrying and protecting the circuitry of the device  10 . Housing  12  is configured for mounting within a cavity of a patient as is generally understood. One or more lead wires  14  are operably coupled with device  10  and extend from the housing  12 . Device  10  may be powered by a battery  16  of the kind generally known in the art. The embodiment of the invention illustrated in  FIGS. 1 and 8  shows a bipolar lead  18  in the RA, a bipolar lead  20  in the RV, and a bipolar or multipolar lead  22  in the LV are shown. 
     A pacing enhanced circuit for left ventricular stimulation according to an embodiment of the present invention may include a biventricular pacemaker having a battery capable of powering at least three pacing circuits. The three pacing circuits are provided to pace the RA, RV endocardium and the LV epicardium via a branch of the coronary vein. In addition, device  10  may include one or more sensing circuits that may sense intrinsic electrical activity from any or all of the three locations. 
     The RA pacing circuit usually incorporates a bipolar lead in which a tip electrode serves as the cathode, and a proximal ring electrode serves as the anode. Capture of the myocardium may occur from the cathode as the electrical current (electrons) generated by the cathode by the pacing circuit depolarizes the cell membranes of a critical mass of myocardium. A local action potential is thereby initiated that subsequently propagates through the myocardium. There are several factors which determine whether successful “capture” of the myocardium occurs. The factors include the (i) amount of the current applied, (ii) duration of application, (iii) lead and tissue impedance, and (iv) electrode surface area. These factors serve to define a resultant current density, and the current density at the electrode tissue interface determines successful depolarization of the cell membranes and propagation of the action potential. 
     Referring now to  FIG. 2 , the effect of a sub-threshold stimulus on the LV anode is shown. In particular, the sub-threshold stimulus preconditions the LV anode and the LV anode serves as the anode for the RA. This is schematically demonstrated in  FIG. 2  by way of the presence of a number of arrows demonstrating the current flow from the RA to the LV, wherein current emanates from electrode RA 1  and flows into electrode LV 2 . 
     If the right atrial pacing circuit is configured such that the anode is one of the (selected) electrodes of the LV lead, anodal stimulation can occur. Normally, this is not desirable as the LV stimulation should occur at least 70 msec after the atrial stimulus. However, if the right atrial cathodal stimulus is relatively small, sub-threshold stimulation of the chosen LV electrode will occur. This has been shown to decrease the threshold for a subsequent LV anodal stimulus, as demonstrated by, e.g.  FIG. 2 . 
     With respect to biatrial pacing in a CRT device, it is possible to pace the left atrium via leads introduced into the proximal coronary sinus and into the obtuse vein of Marshall or by direct fixation onto the epicardial surface of the LA. In particular, a left atrial lead  24  may be provided. It is theorized that this may improve LA-LV synchrony. The LA may be paced using the RA channel in a unipolar fashion; the LA electrode would then serve as the cathode; while the RA electrode serves as the anode as shown in  FIG. 12 . 
     With respect to  FIG. 13 , in certain circumstances, it may be desirable to pace the LA and RA at different times with each timed to its respective ventricle. This would require an additional channel, i.e., the LA channel, in the pacing CRT device. As there is a delay of at least 70 milliseconds between RA pacing and RV pacing, it is conceivable that the RV channel could be used to anodally pace the LA as there is prolonged intra-atrial conduction time when the RA is paced from the RA appendage. The average time delay in such situations is approximately 70 milliseconds. Of course alternative delay times are within the scope of the present invention. 
     In pacemakers, the RV pacing circuit is usually connected to a bipolar lead with the tip electrode serving as the cathode. The proximal electrode on the RV lead usually functions as the anode. As in atrial circuits, the size of the proximal electrode is at least 7 times that of the tip electrode to minimize the chances of anodal capture of the right ventricle. Anodal capture of the right ventricle has traditionally been thought to be deleterious to the patient, and this pacing modality is avoided in the ventricles by increasing the size of the anode to reduce current density and avoid anodal capture. 
     In one embodiment, a selected electrode of the multipolar LV lead would serve as the anode. Thus, anodal capture at the selected LV electrode could be achieved along with cathodal capture from another selected LV pole via the LV channel. If the RV and LV are paced simultaneously, such an arrangement would have the advantage of allowing anodal stimulation of an additional LV electrode without expending additional battery energy. This would be possible if the anodal threshold in the selected LV electrode were to be less than the anodal current delivered by the RV channel. 
     Referring now to  FIGS. 3-6 , in some situations, the selected LV electrode may not have an anodal threshold appropriate for anodal stimulation via the RV channel. In that case, another LV electrode could be used as the LV anode, or the selected anode could serve as the common anode of the RV cathode and the LV cathode(s), which would increase current density and allow anodal capture at the selected LV electrode without expending additional battery energy. 
     Referring now to  FIG. 3  in particular, the LV multipolar lead  22  has five electrodes, which may be denoted as electrodes  1 - 5  (LV 1 , LV 2 , LV 3 , LV 4 , and LV 5 ) starting at the tip with LV 1  and moving proximally therefrom in succession. In this configuration, LV 1  and LV 2  are paced as cathodes through the LV channel. The RV tip electrode (RV 1 ) is paced as the cathode. LV 3  serves as the anode for the LV 1 , LV 4  serves as the common anode for the RV cathode and the LV 2  cathode, and LV 5  serves as the anode for the RV cathode. A sixth electrode LV 6  (not shown) may be provided and serve as a cathode, and a seventh electrode LV 7  (not shown) may be provided and serve as the common anode for RV cathode as well as LV 6 . 
     Turning to  FIG. 4 , LV anodal stimulation is demonstrated as a byproduct of RV stimulation. In particular, a multipolar lead is positioned in the LV, and LV 3  thereof serves as the anode for the RV channel cathode. With respect to  FIG. 5 , LV 3  multipolar lead  22  serves as the common anode for the RV cathode, LV 1  cathode, and LV 6  cathode. 
     Turning now to  FIGS. 6 and 7 , there are situations when some electrodes of a multipolar lead need to be stimulated earlier or later than the RV cathode. For example, in a quadripolar lead with widely spaced electrodes pacing different areas of the LV, it may be preferential to stimulate some electrodes earlier than others. In this situation, using LV offset, cathodal stimulation of electrodes  1  and  2  could be performed earlier than anodal stimulation of, e.g., LV  3  or LV 4 . Either or both of the LV 3  and LV 4  could be stimulated anodally using the RV channel. 
     With reference again to  FIG. 8 , the LV pacing channel may be used to simulate one or more cathodes in a multipolar lead, stimulate other LV electrodes by making them the anodes for the LV cathodes as in  FIG. 5 , and some LV electrodes may be stimulated by making them common anodes between the RV and LV channels as shown in  FIG. 6 . 
     In patients with atrial fibrillations (AF), the atrial channel is not used. As is demonstrated in  FIG. 9 , the atrial channel may be connected to another LV lead (multi-lead, multi-site LV stimulation, or MMLVS). This allows the opportunity for summation anodal pacing of multiple sites using two multipolar leads. In particular, the atrial, RV, and LV channels in a biventricular pacing device may be configured to stimulate multiple electrodes on the LV lead. LV 1  serves as the cathode for the LV channel, LV 2  serves as a cathode for the RA channel, and LV 3  serves as a common anode, i.e., anodal summation capturing anode for LV 1  and RV channels. Meanwhile, LV 4  serves as the anode for LV 2  (RA channel). 
     With reference now to  FIG. 10 , in one embodiment, the leads in the RA, RV, multipolar lead in the LV, and a LA lead are introduced via the vein of Marshall. With respect to  FIG. 11 , four chamber pacing and multipolar LV pacing are shown. LV 1 , LV 4 , and LV 6  are paced by the LV channel. LV 2  is the anode for LV 1 , and LV 3  is the anode for RV. LA is the anode for the RA channel. 
     As noted previously, anodal pacing may be used to capture the His bundle or the very proximal right and left bundles, that is, His or Para-His pacing. By using a bipolar or multipolar lead, designed such that multiple poles are in contact with the tricuspid annulus in close proximity to the bundle of His, it should be possible to pace the selected structure (e.g. His Bundle) using the virtual cathode created by the fixed cathode; as well as the virtual cathode created by the anode(s). In this aspect of the invention, it will be important for the electrodes to be in close contact with the RV septum/TV annulus area. 
     A number of different embodiments are contemplated with respect to this aspect of the present invention. For instance, in one embodiment, a bipolar lead with an anode closely applied to the RV septum by a preformed bend or a screw may be utilized. In this case, if either the cathode or the anode lies in close proximity with the His bundle, capture by the virtual cathodes generated by the cathode and/or anode is likely to occur. If a large His potential is recorded between the cathode and the anode, His capture is likely. 
     In another embodiment, a multipolar lead with closely spaced electrodes, some of which may be fixated to the RV septum may be used. In this case, these may be paced in different configurations. That is, for example, the pacing may utilize some cathodes, some anodes, or summation anodes between the His cathodes, LV cathodes, and/or RV cathodes. 
     Anodal pacing may additional be used in patients requiring biatrial pacing. Such patients may have left atrial leads inserted transvenously via the obtuse vein of Marshall, surgically implanted, or introduced to the left atrium via different means. The right atrial lead would be placed in the right atrium in the conventional fashion. One of the leads&#39; terminal electrodes would function as the cathode while the other would function as an anode. In another aspect of the invention, the left atrial lead serves as the anode for the RV pacing lead: Tthe RV is paced at least 70 msec after the RA; and a similar timing has been suggested for the LA ( FIG. 13 ). 
     Studies have confirmed that an application having a common anode for more than one cathode has a lower stimulation threshold than a corresponding application having a single anode for each cathode. The study involved six human subjects undergoing pacemaker or defibrillator implantation. The inter-operative determination of the anodal threshold at a 0.5 millisecond pulse width was determined. The anodal threshold of each of the cathodes “a” and “b” were determined using a single anode for each of the cathodes and using the same anode for both cathodes. 
     The study confirmed that an anode serving as a common anode for two cathodes has a capture threshold that is half the sum of the anodal threshold obtained from each cathode alone. 
     This is particularly significant from a clinical standpoint. When multiple sites are paced simultaneously using multiple cathodes, an anode common to two or more cathodes will capture at lower cathodal pacing thresholds than an anode for a single cathode. As a result, the anodal current that would otherwise be wasted by returning to the device or to a lead anode not configured to provide pacing can be directed to an anode that can be used to pace another chamber or another segment of the same chamber. 
     In another study, a population of 100 patients undergoing biventricular ICD or pacemaker implantation was studied. The mean age of the 100 patients was 66+/−12 years. The study included 44 female patients. The mean left ventricular ejection fraction was 26+/−16%. The thresholds were measured in a number of configurations including bipolar, unipolar cathodal, and unipolar anodal. In the bipolar configuration, the thresholds were measured from the LV tip to the LV ring and the LV ring to the LV tip at varying impedances. In the unipolar, cathodal configuration, the thresholds were measured from the LV tip to the RV coil, the LV tip to the case, the LV ring to the RV coil, the LV ring to the case, the LV tip to the RA ring, and the LV ring to the RA ring. In the unipolar anodal configuration, the threshold was measured from the case to the LV tip, from the case to the LV ring, from the RV coil to the LV tip, and from the RV coil to the LV ring. 
     The mean measured LV threshold unipolar, cathodal from the LV tip was 1.7+/−1.7 while unipolar, anodal was 2.4+/−2.1. From the LV ring electrode, the unipolar cathodal threshold was 1.6+/−1.2 and the unipolar anodal threshold was 3.4+/−1.8. During single cathode LV pacing, anodal thresholds of &lt;2.5 were obtained in ⅔ of patients using the tip electrode and in ⅓ of all patients using the ring electrode. The proportion of patients with adequate thresholds is expected to be considerably higher in summation anodal pacing. Thus, it is feasible to use the anodal current generated as a byproduct of cathodal pacing and use it for pacing another site in the left ventricle in &gt;⅔ patients. This proportion is also expected to increase in using summation anodal pacing. 
     Although the best mode contemplated by the inventor of carrying out the present invention is disclosed above, practice of the present invention is not limited thereto. It will be manifest that various additions, modifications and rearrangements of the aspects and features of the present invention may be made in addition to those described above without deviating from the spirit and scope of the underlying inventive concept. The scope of some of these changes is discussed above. The scope of other changes to the described embodiments that fall within the present invention but that are not specifically discussed above will become apparent from the appended claims and other attachments.