Abstract:
A lead of the present invention comprises an electrode array adapted to be stably anchored at a selected location within the vena cava of a human patient. The electrode array may take various shapes, including helical, annular and linear. The electrode array is connectable to an electrical stimulation means such as an implantable pulse or signal generator. Electrical stimulation applied to a selected region of the vena cava and across the wall of the vein, that is, transvascularly, to the vagus nerve or branches thereof, depolarizes the nerve to thereby effect control of the heart rate.

Description:
FIELD OF THE INVENTION 
   The present invention relates generally to the management of cardiac rhythm, and particularly to an endovascular medical lead for the transvenous electrical stimulation of the vagus nerve for depressing or inhibiting cardiac arrhythmias such as atrial fibrillation and ventricular tachycardia. 
   BACKGROUND OF THE INVENTION 
   The autonomic nervous system controls the involuntary smooth and cardiac muscles and glands throughout the body, serving the vital organ systems such as the heart that function automatically. The two divisions (sympathetic and parasympathetic) of the autonomic nervous system oppose each other in function, thus maintaining balanced activity in the body mechanisms. For example, signals generated in the hypothalamus, cerebral cortex and medulla oblongata within the brain and transmitted via the parasympathetic fibers of the vagus nerve to the sino-atrial node of the heart slow the heart rate while signals along the sympathetic fibers accelerate the heart rate. An imbalance in the relative activity of the sympathetic and parasympathetic divisions of the autonomic nervous system, for example, an increase in the activity of the sympathetic division, can produce abnormal heart rates in the form of tachycardias or fibrillations in either or both chambers (ventricles and/or atria) of the heart. 
   It is well known that the electrical stimulation of the parasympathetic nerves innervating the heart can restore autonomic nervous system balance by counteracting arrhythmias produced by increased sympathetic activity. Thus, electrical stimulation of the right vagus nerve predominantly slows the S-A node rate and thereby reduces heart rate. The vagus nerve, and particularly cardiovagal branches thereof, are found chiefly adjacent to the posterior surface of the vena cava. Accordingly, parasympathetic activity may be increased to restore autonomic balance by electrically stimulating the fibers of the vagus nerve transvenously by means of an endovascular electrode implanted in, for example, the superior vena cava. 
   There remains a need for a suitable endovascular, vagus nerve-stimulating lead for chronic use in the areas of discrimination, rate slowing, termination, prediction and prevention. Such a lead would desirably incorporate an array of electrodes adapted to be arranged along the longitudinal direction of the vena cava, with positionally stable placement or anchoring of the electrode array within the vena cava. 
   SUMMARY OF THE INVENTION 
   Generally, the lead of the present invention comprises an electrode array adapted to be stably anchored at a selected intravascular location, for example, within the vena cava of a human patient. In accordance with certain embodiments of the invention, the electrode array may take various shapes, including helical, annular and linear. The electrode array is electrically connectable to an electrical stimulation means such as an implantable pulse or signal generator. Electrical stimulation applied to a selected region of the vena cava and across the wall of the vein, that is, transvascularly, to the vagus nerve or branches thereof, depolarizes the nerve to thereby effect control of the heart rate. 
   In accordance with one, specific, exemplary embodiment of the present invention, there is provided an intravenous lead adapted to electrically stimulate fibers of the vagus nerve in a human patient. That nerve extends along an outer surface of the vena cava. The lead comprises a lead body having a portion along the length thereof adapted to be placed within the vena cava. That portion of the lead body has a generally helical configuration and carries an electrode array comprising a plurality of electrodes adapted to engage an inner surface of the vena cava. Pursuant to one aspect of the invention, the electrode array comprises a plurality of sets of electrodes. Further, the generally helical portion of the lead body may comprise a plurality of turns, each of the turns carrying one of the electrodes of each of the plurality of sets of electrodes. Preferably, the electrodes of each set of electrodes are adapted to be arranged in substantially longitudinal alignment when the helical portion of the lead body is placed within the vena cava. In one particular embodiment, the electrodes comprising each set of electrodes may be electrically connected to be alternately poled. For example, each set of electrodes may comprise three electrodes electrically connected in double bipolar fashion. Preferably, upon placement of the lead body in the vena cava, the mentioned portion of the lead body is expandable into its generally helical configuration so as to engage the inner surface of the vena cava vein and anchor the lead body portion within the vena cava. According to yet another feature of the invention, there is provided a distal section extending distally from the helical portion of the lead body, the distal section carrying at least one electrode selected from the group consisting of a tip pacing and/or sensing electrode, a ring pacing and/or sensing electrode, a cardioverting electrode and a defibrillating electrode. 
   In accordance with another specific, exemplary embodiment of the invention, there is provided an intravenous lead for electrically stimulating fibers of the vagus nerve, the lead comprising a lead body having a proximal end adapted to be electrically connected to a medical device for generating electrical stimulation signals. The lead body further comprises a distal end portion adapted to be placed within a vein having a wall adjacent to the fibers of the vagus nerve. A plurality of electrodes is carried by the distal end portion of the lead body, the plurality of electrodes being deployable within the vein to form a generally annular electrode array in electrical communication with an inner surface of the wall of the vein and lying in a plane substantially perpendicular to the direction of blood flow within the vein, the plurality of electrodes being electrically connected to the proximal end of the lead body. In one form of this embodiment, each of the plurality of electrodes has a circumferential length, and the circumferential lengths of the plurality of electrodes may be substantially the same. Further, the plurality of electrodes may be substantially uniformly spaced apart. In another form of this embodiment, the plurality of electrodes may be connected in a parallel combination, the parallel combination being connected to the proximal end of the lead body with a single electrical conductor. Alternatively, the plurality of electrodes may be grouped into multiple clusters with the electrodes in each of the multiple clusters being connected in a parallel combination, the parallel combination of electrodes in each cluster being connected to the proximal end of the lead body with a single electrical conductor. Pursuant to another aspect of this embodiment, a distal section may be provided that extends distally from the distal end portion of the lead body, the distal section carrying at least one electrode selected from the group consisting of a tip pacing and/or sensing electrode, a ring pacing and/or sensing electrode, a cardioverting electrode and a defibrillating electrode. 
   Pursuant to yet another specific, exemplary embodiment of the invention, there is provided an intravenous lead having a portion along the length thereof for placement within the vena cava vein, the vein having a wall comprising an inner surface and an outer surface, the lead being adapted to electrically stimulate fibers of the vagus nerve disposed adjacent to the outer surface of the wall of the vein. The lead comprises a linear array of electrodes disposed along the mentioned portion of the lead and adapted to be placed adjacent to the inner surface of the wall of the vein in alignment with the direction of blood flow within the vein to stimulate the fibers of the vagus nerve when the electrode array is electrically energized. Preferably, the mentioned portion of the lead has attached thereto an anchoring element adapted to engage the inner surface of the wall of the vein. In one form, the anchoring element comprises an expandable ring adapted to lie in a plane perpendicular to the direction of blood flow and engage the inner surface of the wall of the vein when deployed. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The foregoing and other objects, features and advantages of the invention will become evident to those skilled in the art from the detailed description of the preferred embodiments, below, taken together with the accompanying drawings, in which: 
       FIG. 1  is a diagrammatic, perspective view of the anterior portion of a human heart showing placed therein an endovascular, vagus nerve-stimulating lead in accordance with one specific exemplary embodiment of the invention; 
       FIG. 2  is an enlargement of a part of  FIG. 1  showing, among other things, the details of an electrode array carried by the lead; 
       FIG. 3  is a simplified electrical schematic of the lead of  FIGS. 1 and 2  showing the manner in which the electrodes of the electrode array are interconnected; 
       FIG. 4  is a diagrammatic, perspective view, along the lines of  FIG. 2 , showing a portion of a human heart having placed therein an endovascular, vagus nerve-stimulating lead in accordance with an alternative embodiment of the present invention; and 
       FIG. 5  is a diagrammatic, perspective view, along the lines of  FIG. 2 , showing a portion of a human heart having placed therein an endovascular, vagus nerve-stimulating lead in accordance with another alternative embodiment of the invention. 
   

   DETAILED DESCRIPTION 
   The following description presents preferred embodiments of the invention representing the best mode contemplated for practicing the 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 invention whose scope is defined by the appended claims. 
     FIG. 1  shows in solid lines a passive fixation, dedicated nerve stimulation lead  10  for transvenously stimulating a parasympathetic nerve of a mammalian subject, in particular the vagus nerve and cardiovagal branches thereof in a human subject. 
     FIG. 1  further depicts, in diagrammatic form, the anterior portion of a human heart  12 , specifically showing the superior vena cava (SVC)  14  within which a portion of the lead  10  is placed; the right atrium (RA)  16 ; the right ventricle (RV)  18 ; and the apex  20  of the RV. The SVC  14  comprises a vessel wall  22  having an inner surface  24  and an outer surface  26 . An arrow  28  indicates the direction of venous blood flow toward the RA within the lumen of the SVC. The vagus nerve and its cardiovagal branches, shown diagrammatically in  FIG. 2  and identified therein by the reference numeral  30 , extends along the posterior of the outer surface  26  of the SVC wall  22 . 
   The lead  10  comprises a lead body  40  having a longitudinal axis  42  and an outer, tubular sheath or housing  44  of a suitable flexible, insulating, biocompatible, biostable material such as, for example, silicone rubber or polyurethane. By way of illustration and not restriction, the lead body  40  may have a diameter ranging from about 0.026 inch (2F) to about 0.156 inch (12F) with a diameter of 0.091 inch (7F) being preferred. The tubular lead body housing  44  may comprise a multilumen member defining, for example, two or more axially or longitudinally extending parallel passages or lumens for carrying electrical conductors and one lumen providing access for a stylet used during lead placement. 
   The lead body  40  has a proximal end  46  carrying a conventional connector assembly  48  details of which have been omitted but which is configured to be received by one or more receptacles  50  formed in a signal or pulse generator such as an implantable electrical medical device  52 . As is known in the art, the connector assembly  48  may comprise a single coaxial component or a multiple branch assembly such as one that is bifurcated or trifurcated. The lead body  40  further comprises a distal end portion  60  having a preformed, generally helical configuration extending about the longitudinal axis  42  of the lead body. 
   Referring now also to  FIG. 3 , the helical distal end portion  60  of the lead body carries an electrode array  62  adapted to be placed within the vena cava, and preferably within the SVC  14 , of the heart in engagement with the inner surface  24  thereof so as to positionally stabilize or anchor the distal end portion  60 . In the embodiment shown, the electrode array  62  may comprise eight electrode sets  71 - 78  each set comprising three electrodes for a total of twenty-four electrodes. Thus, the electrode set  71  comprises electrodes  71   a ,  71   b  and  71   c , the electrode set  72  comprises electrodes  72   a ,  72   b  and  72   c , and so forth. The helical distal end portion  60  of the lead body carrying the electrode array  62  comprises, in the specific embodiment shown, three turns  81 - 83 , each turn carrying eight electrodes, one from each set. Thus, the first helical turn  81  carries electrodes  71   a - 78   a , the second helical turn  82  carries electrodes  71   b - 78   b , and the third helical turn  83  carries electrodes  71   c - 78   c . It will be seen that the electrode set  74 , comprising electrodes  74   a ,  74   b  and  74   c  on the successive turns  81 - 83  of the helical lead body lie along a longitudinal line  84  extending along the length of the vein in the direction of blood flow; similarly, the electrode set  78  comprising electrodes  78   a ,  78   b  and  78   c  lie along a longitudinal line  86  also aligned with the direction of blood flow within the vein, and so forth, for the remaining electrode sets  71 - 73  and  75 - 77 . 
   In one embodiment, each of the electrode sets  71 - 78  may be connected to form a double bipolar stimulation channel with corresponding electrodes of the various sets being electrically connected in parallel. By way of example, as best seen in  FIG. 3 , by way of illustration, the electrodes  71   a - 78   a  along the first turn  81  of the helical portion  60  are electrically connected in parallel to a first anodal contact  88  on the connector assembly  48  on the proximal end of the lead body, the electrodes  71   b - 78   b  along the second turn  82  of the helical portion  60  are electrically connected in a parallel to a cathodal contact  90  on the connector assembly  48  and the electrodes  71   c - 78   c  on the third turn  83  of the helical portion  60  are electrically connected to a second anodal contact  92  on the connector assembly  48 . The polarities of the connector assembly contacts  88 ,  90   92  and therefore the polarities of the electrodes to which they are connected may, of course, be reversed so that the first and third contacts  88  and  92  are cathodal and the intermediate contact  90  is anodal. Further, all of the electrodes of all of the sets may be connected in parallel to provide a “unipolar” arrangement in which, for example, the electrodes are unipolar cathodal while the pulse generator casing or can comprises a common, electrode of complementary, anodal polarity. 
   It will be evident that electrodes along a given turn of the helical distal portion  60  of the lead body  40  may be equally spaced apart (45° for eight electrodes) or unequally spaced apart. Still further, the number of electrode sets may be greater or less than eight. For example, ten sets of electrodes may be provided with the electrodes along each turn of the helical distal portion appropriately spaced apart, for example, equiangulary at 36° intervals. Further yet, the helical distal portion  60  of the lead body  40  may comprise more or less than three full turns. Although not intended to limit the scope of the invention, at least three turns is preferred since a larger number of stimulation sites arranged generally linearly along the inner surface of the vena cava adjacent to and in alignment with the vagus nerve is generally more effective to improve the likelihood of stimulating parasympathetic cardiovagal branches of the vagus nerve to counteract arrhythmias and thereby restore autonomic nervous system balance. 
   The electrical conductors connecting the electrodes with the contacts on the connector assembly may comprise conventional multi-strand/multi-filar cable conductors or coil conductors each occupying a lumen of the preferred multilumen housing. The interconnection configuration of the electrodes is preferably such that the number of electrical conductors coupling the electrode array and the connector assembly is minimized so as to minimize the diameter of the lead body. For example, three electrical conductors  94 ,  96  and  98  are required in the double bipolar interconnection arrangement of  FIG. 3 . In a unipolar arrangement, with all of the electrodes connected in parallel to a single contact on the connector assembly, only one electrical conductor running the length of the lead body would be needed. 
   The process for placing the helical distal end portion  60  of the lead body  40  within the SVC  14  follows conventional practice. The lead body is very flexible and its housing may have, as already explained, a lumen for receiving a stylet or guidewire that may be used by the implanting physician to maneuver the electrode-bearing portion of the lead body into position within the vena cava under fluoroscopy or other lead body position monitoring technique. When inserted into the lead body  40 , the stylet or guidewire will tend to straighten the helical distal end portion  60  to facilitate advancement and placement of the electrode array  62  within the vein. Once the lead body has been placed at the target location within the vein, the stylet or guidewire is withdrawn allowing the helical portion of the lead body to expand to its preformed configuration in which the helical portion frictionally engages the inner surface  24  of the wall  22  of the vein to anchor that portion. 
   In one embodiment, the electrodes of the array  62  may be hard-wired to predetermine the stimulation configuration. For example, the electrodes may be hard-wired in sets of three along the lines described above. In another embodiment, the electrodes would be neither hard-wired nor grouped into predetermined sets of electrodes but instead a combination of electrodes would be selected for optimal vagal stimulation, as further explained below. 
   As shown in broken lines in  FIG. 1 , the lead body  40  may further comprise a lead body section  100  extending distally from the distal end portion  60 . The optional distal section  100 , comprising an extension of the tubular housing  44 , may carry a conventional complement of cardiac stimulating and/or sensing electrodes. For example, in the exemplary embodiment depicted in  FIG. 1 , the distal section  100  carries, in a bipolar arrangement, a tip pacing and/or sensing electrode  102  preferably in electrical communication with the apex  20  of the RV, a ring pacing and/or sensing electrode  104  disposed proximally of the tip electrode, and a pair of spaced-apart cardioverting and/or defibrillating electrodes  106  and  108  proximally of the ring electrode  102 . The electrodes  106  and  108  may be placed within the RV  18  and the RA  16 , respectively. The tubular housing along the distal section  100  of the lead body may include a plurality of outwardly projecting tines  110  positioned proximally of the ring electrode. As is well known in the art, these tines function to become interlocked in the trabeculi within the heart to inhibit displacement of the distal section once the lead is implanted. It will be understood that projecting fins, a screw-in helix (electrically active or inactive), or some other suitable anchoring means may be used instead of, or in addition to, the tines  110 . 
     FIG. 4  shows an alternative embodiment of the present invention comprising a lead  120  connectable to a pulse generator in the form of, for example, an implantable medical device  122  for delivering electrical stimulation signals to the vagus nerve  123 . The lead  120  comprises a lead body  124  having a proximal end  126  carrying a connector assembly  128  receivable by the implantable medical device. Attached to a distal end  130  of the lead body  124  is a deployable annular member  132  that, when deployed within the SVC  134 , lies generally in a plane perpendicular to the longitudinal direction of the vein, that is, the direction  136  of venous blood flow. The annular member  132  carries an electrode array  138  comprising a plurality of spaced-apart stimulating electrodes  140 . The electrodes  140  may be equally spaced about the circumference of the annular member  132  or may be grouped into clusters or sets. By way of illustration, not restriction, a total of sixteen electrodes  140  equally spaced at 22.5° intervals may be provided. Alternatively, the sixteen electrodes may be grouped into four clusters of four electrodes each, the groups being spaced apart at 90° with the electrodes within each cluster being spaced 10° apart, and with the electrodes of each cluster being connected in parallel to a contact on the connector assembly  128  with a single electrical conductor. 
   It will be evident that the electrode array  138  may comprise more or less than sixteen electrodes; for example, the number of electrodes may be increased to thirty two or sixty four. The electrodes  140  may be electrically connected in a wide variety of ways. For example, all of the electrodes  140  may have the same polarity, anodal or cathodal, or the electrode polarities may alternate for bipolar operation. The electrodes may all have the same circumferential length and spaced apart by the same interelectrode gap, for example 5 mm long with a gap of 5 mm between adjacent electrodes. Alternatively, the electrode lengths and interelectrode gaps may vary. 
   As before, a distal section  142 , carrying one or more stimulating and/or sensing electrodes for placement in the RA and/or RV, may extend distally from the distal end  130  of the lead body  124 . Further, the lead body and optional distal section may comprise an insulating, outer, tubular sheath or housing  144 , preferably multilumen, for containing electrical conductors connecting the electrodes  140  with corresponding contacts on the connector assembly  128 . 
   A stylet-like tool may be used to steer the annular member  132  into position within the SVC under fluoroscopic observation. Once in position within the SVC, the stylet-like tool expands the member  132  so that its outer periphery engages the inner surface of the SVC wall to anchor the annular member and thus the lead body in place after which the stylet is withdrawn. During an implant of the lead body, the electrodes  140  may be energized in succession and heart activity monitored to determine which electrodes or combination of electrodes in the electrode array best capture the vagus nerve. The system may be arranged to be reprogrammable to maintain optimal stimulation during the life of the implant. 
   In a third specific, exemplary embodiment shown in  FIG. 5 , there is provided a lead  150  comprising a lead body  152  having an outer, insulating, preferably multilumen tubular housing  153  and a distal end portion  154  carrying a linear electrode array  156  comprising a plurality of electrodes  158 , in this case, eight in number. The electrodes  158  are electrically connected to a signal generator such as an implantable pulse generator  160  for providing controlled electrical stimulation energy to the vagus nerve  161  via the plurality of electrodes  158  which are spaced apart along the length of the distal end portion  154  of the lead body  152 . The electrodes  158  may have the same length, for example, 5 mm, with the same interelectrode gap between adjacent electrodes of, for example, 5 mm. Alternatively, the electrodes may have different lengths, may be non-uniformly spaced-apart, and may be grouped, for example, in pairs. 
   The distal end portion  154  of the lead body  152  is anchored in place within the SVC  162  by means of a deployable anchoring ring  164  that lies generally in a plane perpendicular to the direction of venous blood flow. The ring  164 , which is secured to the lead body&#39;s distal end portion  154 , preferably at a point  166  approximately midway between the ends of the portion  154 , is expandable when deployed to engage the inner wall surface of the SVC  162 . When fully expanded, the ring  164  urges the distal end portion  154  and the electrode array carried thereby into engagement with the inner wall of the SVC, preferably along the posterior thereof, opposite to, and in alignment with, the vagus nerve  161 . The ring  164  may of the kind well-known for anchoring a stent deployed within a blood vessel. 
   Again, a distal section  168 , carrying one or more stimulating and/or sensing electrodes for placement in the RA and/or RV, may extend distally from the distal end portion  154  of the lead body  152 . 
   During placement of the leads of the various embodiments described herein, after the distal end or distal end portion has been positioned in the vein, the most suitable electrode combination that can capture the nerve is found in the following manner. Stimulus voltage is gradually increased and electrode pairs or triplets are sequentially selected. The intrinsic PR interval and ventricular rate are monitored continuously during this process. When a significant prolongation of the PR interval or reduction in ventricular rate is observed, the electrode combination providing that result is selected and programmed for stimulation. With lead systems depicted in  FIGS. 1-4 , the device may be made capable of re-evaluating the best electrode combination at a later time, automatically and periodically, to achieve most optimal stimulation site. This feature will enable the device to respond to slight changes in lead position over time so as to achieve successful stimulation at all times. 
   The vagal stimulation unit of the device can either be triggered by a prevention unit, a prediction trigger, a therapy trigger, or a discrimination algorithm. In the case of vagal stimulation for prevention, prediction, termination, and rate slowing, the stimulation may be turned on for a programmable interval or for a programmable number of short bursts that are triggered by each atrial activation. In the case of discrimination, there will be very low level stimulation applied to the nerve only to lengthen the PR interval without a need for high voltage levels to get complete AV block. The device is then able to determine whether a fast arrhythmia is being originated in the upper chambers and conducted through the AV node to the lower chambers or the arrhythmia is being originated in the lower chambers and there is no correlation with beats in the upper chambers. 
   While several illustrative embodiments of the invention have been shown and described, numerous variations and alternate embodiments will occur to those skilled in the art. Such variations and alternate embodiments are contemplated, and can be made without departing from the spirit and scope of the invention as defined in the appended claims.