Atrial sensing and multiple site stimulation as intervention means for atrial fibrillation

Atrial sensing and stimulation as intervention for atrial fibrillation. The present invention relates to a method of atrial defibrillation. In a variety of protocols varying combinations of conventional and biphasic stimulation are applied at threshold and sub-threshold levels. In a preferred embodiment, the implantable electronic stimulation device of the present invention includes multiple electrodes having stimulating and sensing capabilities. The small size of these electrodes allows for intravenous insertion into the patient.

FIELD OF THE INVENTION
 The present invention relates generally to electronic stimulation devices
 to control the beating of hearts, especially hearts with pathologies that
 interfere with normal rhythmicity, electrical conduction, and/or
 contractility. In particular, the present invention relates to pacemakers
 used to overcome atrial fibrillation by use of 1) atrial sensing; 2)
 electrical test stimulation of the atria; and 3) multiple site stimulation
 in which the various atrial areas are slowly entrained to a common beating
 rate to produce electrical/functional conformity, i.e., cardioversion,
 with each case either eventuating in spontaneous reversion to a normal
 atrial rhythm, or reduced energy requirement for reversion by electrical
 countershock.
 BACKGROUND OF THE INVENTION
 Morbidity associated with malfunctions of the atria, while not immediate,
 is high. Atrial malfunctions of rhythmicity (e.g., atrial fibrillation,
 various atrial arrhythmias, A-V block and other conduction abnormalities,
 etc.) can contribute to thrombosis, emboli, stroke and/or heart failure,
 each of which can place a patient in significant peril.
 Atrial Sensing. A variety of approaches have been developed which use
 pacemakers to counter atrial malfunctions of rhythmicity, as well as
 attendant effects on ventricular function. In addition, sophisticated
 approaches have been developed for pacemaker systems to determine the
 nature of any particular ventricular malfunction, and whether a
 malfunction originates in the atria or in the ventricles. One such
 approach uses ventricular sensing to measure/determine the probability
 density function (pdf) on a moment-to-moment basis. For example, U.S. Pat.
 No. 5,163,429 to Cohen discloses the use of narrow window pdf data as but
 one criterion among several for assessing ventricular cardiac function.
 The use of pdf data to determine ventricular fibrillation also is
 disclosed in Implantable Cardioverter-Defibrillators (N. A. Estes III, A.
 Manolis & P. Wang, ed.). U.S. Pat. No. 5,421,830 to Epstein, et al.
 (discussed further below) also discloses the use of pdf data as one set
 among a variety of data types that collectively are also used to assess
 cardiac function. The use of probability density function data for
 assessing atrial cardiac function has not been disclosed and presents its
 own unique difficulties as will be further discussed.
 Electrical Test Stimulation of Atria. In a few limited cases, pacemaker
 protocols have been employed in which electrical test stimuli are applied
 to the atria, and the physiological responses thereto are monitored to aid
 in the determination of the best or most appropriate protocol to initiate,
 cure, or ameliorate the existing cardiac malfunction. For example, U.S.
 Pat. No. 5,620,471 to Duncan discloses three basic protocols for
 determining whether observed ventricular irregularities are actually
 caused by atrial arrhythmias. One protocol includes atrial electrical test
 stimulation, and all three protocols monitor both atrial and ventricular
 rhythms for three parameters: rates of atrial and ventricular firing,
 stability of firing/beating in atria and ventricles, and whether or not
 ventricular firing tracks atrial firing. In the first protocol, when the
 ventricular firing rate is less than the atrial firing rate (indicating no
 ventricular tracking of atrial beats), and firing rates are stable, then
 ventricular tachycardia is presumed, and ventricular stimulation is
 applied. On the other hand (second protocol), if the ventricular firing
 rate is not stable, then atrial arrhythmia is presumed, and atrial
 stimulation is applied. The third protocol is based on the fact that, when
 the ventricular firing rate equals the atrial firing rate, there may or
 may not be ventricular tracking of atrial firing. Whether or not there is
 ventricular tracking is determined by the presence or not of ventricular
 tracking following premature atrial stimulation by the pacemaker. If there
 is ventricular tracking of atrial firing, the arrhythmic mechanism is
 presumed to be atrial tachycardia. However, if there is no ventricular
 tracking of atrial firing, then ventricular tachycardia is presumed, and
 ventricular stimulation is performed.
 U.S. Pat. No. 5,421,830 to Epstein, et al. discloses a general means for
 recording, testing, and analyzing cardiac function based on data from--and
 electrical test stimulation via--a patient's pacemaker, as well as data
 from additional sensors detecting hemodynamic or other body functions.
 Total intracardiac electrograms (reflecting both atrial and ventricular
 functional status) or just selected data (e.g., P-P or R-R intervals,
 heart rate, arrhythmia duration, slew rate, probability density function,
 etc.) may be recorded and analyzed. The patient's atrial and ventricular
 responses to electrical test pulses may also be recorded. In sum, this
 system provides a means to more easily tailor settings for pacemakers to
 achieve optimal settings for the specific patient or for the specific
 situation (e.g., during exercise or exertion) of a given patient.
 U.S. Pat. No. 5,215,083 to Drane, et al. also discloses the use of
 electrical test stimulation to aid in the fine tuning and evaluation of
 different possible stimulation protocols for a patient's heart. In
 particular, electrical test pulses are employed to induce ventricular
 fibrillation or tachycardia for use in evaluating the effectiveness of
 alternative programmed therapies.
 Multiple Site Atrial Stimulation. The use of multiple site atrial
 stimulation has been disclosed for various purposes, such as
 defibrillation, cardioversion, pacing, and dc field production. One
 example is provided by U.S. Pat. No. 5,562,708 to Combs, et al., which
 discloses the employment of large surface electrodes (each effectively
 comprising multiple electrodes) that are implanted to one or both atria
 for providing extended, low energy electrical impulses. The electrical
 impulses are applied simultaneously at multiple sites over atrial
 surfaces, and atrial fibrillation is interrupted by gradually entraining
 greater portions of atrial tissue. These pacemaker electrodes may be used
 for various purposes in addition to pacing, such as conventional
 defibrillation and cardioversion.
 U.S. Pat. No. 5,649,966 to Noren, et al. discloses the use of multiple
 electrodes for the purpose of applying a subthreshold dc field to overcome
 fibrillation. The rate of application of the dc field is sufficiently low
 so that no action potential is triggered. Polarity may also be changed
 periodically. In one embodiment, four electrodes are positioned within a
 single plane in the heart, which permits a dipole field in virtually any
 direction within that plane.
 U.S. Pat. No. 5,411,547 to Causey, III discloses the use of sets of complex
 mesh patch electrodes, in which each electrode comprises an anode patch
 and a cathode patch, for purposes of cardioversion-defibrillation.
 Bidirectional cardiac shocking is permitted by these electrodes.
 U.S. Pat. No. 5,391,185 to Kroll discloses the use of multiple electrodes
 to effect atrial defibrillation. The possibility of inducing ventricular
 fibrillation during the course of atrial defibrillation is greatly reduced
 by synchronizing the atrial stimulation to fall within the QRS phase of
 the ventricular cycle.
 U.S. Pat. No. 5,181,511 to Nickolls, et al. discloses the use of multiple
 electrodes in antitachycardia pacing therapy. The electrodes not only each
 serve an electrical sensing role (to locate the site of an ectopic focus),
 but also function in concert to create a virtual electrode for stimulating
 at the site of an ectopic focus.
 Existing Needs. In the area of atrial malfunctions of rhythmicity what is
 needed is a means to entrain multiple atrial sites, but also in
 combination with an atrial sensing/measurement capability that is coupled
 with atrial test stimulation and analysis capability. Atrial test
 stimulation and analysis capability is needed to provide better
 determination of the nature of the malfunction and the most probable or
 efficacious corrective therapy to undertake. Furthermore, the use of
 atrial test stimulation is critically needed for the fundamental reason
 that the physician cannot know a priori how a given heart (or a given
 heart under a particular medical or pathological condition) will respond
 to a selected stimulation regime, even if that selected stimulation regime
 would work generally for other cardiac patients. Thus, a trial-and-error
 testing capability needs to be available for pacemakers whose traditional
 stimulation regimes do not work for the occasional refractory patient. The
 multiple site stimulation capability is needed in order to more quickly
 and efficiently cardioconvert the atria in the face of arrhythmia,
 fibrillation, etc. Atrial sensing and use of measurement data are needed
 to better provide the physician and/or the circuit logic of the pacemaker
 with information as to the physiological state of the heart; i.e., whether
 there is atrial arrhythmia or fibrillation, where an ectopic focus is
 located, etc. Thus, what is needed is a pacemaker that combines all three
 of these elements: atrial sensing and measurement capability, atrial
 electrical test stimulation and analysis capability, and multiple site
 stimulation capability.
 Lastly, a need also exists for a stimulation protocol which can travel more
 quickly across the myocardium and which provides improved cardiac
 entrainment along with the ability to entrain portions of the heart from a
 greater distance.
 SUMMARY OF THE INVENTION
 It therefore is an object of the present invention to provide a pacemaker
 that is capable of pacing atria from multiple sites.
 It is another object of the present invention to provide a pacemaker that
 is capable of slowly entraining atria by stimulating the atria at multiple
 sites to produce electrical and functional conformity of the atria, with
 resulting increased pumping efficiency of the heart.
 It is yet another object of the present invention to provide a pacemaker
 that is capable of detecting the presence of atrial fibrillation and
 atrial arrhythmias by stimulating the atria and observing and measuring
 the consequent effects on atrial and ventricular function.
 It is a further object of the present invention to provide a pacemaker that
 is capable of obtaining and analyzing probability density function data
 from atria in order to determine atrial rates of beating and to assess
 atrial physiological function.
 It is a further object of the present invention to provide an electronic
 stimulation device, for stimulating the atria from multiple sites, where
 the electrodes of the electronic stimulation device can be inserted
 intravenously.
 It is a further object of the present invention to provide an electronic
 stimulation device, for stimulating the atria from multiple sites, where
 each electrode of the device has an independent generator.
 It is a further object of the present invention to provide an electronic
 stimulation device for stimulating the atria from multiple sites, where
 each site is entrained separately and quickly brought to the same phase.
 It is a further object of the present invention to provide an electronic
 stimulation device for stimulating the atria from multiple sites, to
 sequence the sites to mimic a normal heart beat.
 It is a further object of the present invention to determine cardiac
 capture by monitoring cardiac activity and noting when the baseline of
 such activity is off zero.
 It is a further object of the present invention to decrease threshold rises
 due to a build up of fibrous tissue.
 The present invention accomplishes the above objectives by providing a
 cardiac pacemaker with a unique constellation of features and
 capabilities. In particular, a means for entraining multiple atrial sites
 is provided by the use of multiple electrodes. The multiple electrodes not
 only permit multi-site stimulation capability, but also multi-site sensing
 (including pdf measurement) capability, which, by triangulation,
 essentially provides the ability to determine the site(s) of any atrial
 ectopic focus. The multi-site stimulation capability inherently provides a
 system poised for more efficient entrainment and/or cardioconversion of
 the atria in the face of arrhythmia, fibrillation, etc. Combined with this
 multi-site stimulation/sensing capability is the means to execute
 trial-and-error testing and analysis to determine the best general
 stimulation protocol, to fine tune a given protocol, or to adjust a
 protocol in response to changes in the physiological/pathological status
 of the patient in general and/or the patient's heart in particular.
 Incorporating the use of biphasic stimulation with the present invention
 provides the additional benefits of reducing cardiac inflammation damage,
 reducing or eliminating threshold rises due to the buildup of fibrous
 tissue and extending battery life of the electrodes.
 In addition, the ability to conduct trial-and-error testing, including the
 analysis of the data derived therefrom, permits more thorough and more
 definitive determination of the physiological status of the heart; this
 determination can practically approach a moment-to-moment basis when
 analysis is automated by appropriate software for the purpose.
 In sum, the present invention provides a cardiac pacemaker that has greater
 functional capabilities for the patient's atria than current technologies
 allow. The greater atrial "coverage" from the strategic placement of
 multiple electrodes permits faster correction of atrial arrhythmia,
 fibrillation, etc. Similarly, the use of multi-site electrodes permits
 more accurate sensing, including the capability of locating the site(s) of
 any atrial ectopic focus so as to better apply corrective stimulation
 procedures. In addition, the ability to apply trial-and-error
 testing/analytical procedures permits quicker analysis and correction of
 malfunctions of electrical conduction, cardiac contractility, rhythmicity,
 etc. Thus, the present invention constitutes an advance in cardiac care
 procedures as they relate to atrial pacemakers. The end result for the
 patient is better treatment, and, hence, a better prognosis from the
 better and faster treatment.
 The method and apparatus relating to biphasic pacing comprises a first and
 second stimulation phase, with each stimulation phase having a polarity,
 amplitude, shape, and duration. In a preferred embodiment, the first and
 second phases have differing polarities. In one alternative embodiment,
 the two phases are of differing amplitude. In a second alternative
 embodiment, the two phases are of differing duration. In a third
 alternative embodiment, the first phase is in a chopped wave form. In a
 fourth alternative embodiment, the amplitude of the first phase is ramped.
 In a fifth alternative embodiment the first phase is administered over 200
 milliseconds after completion of a cardiac beating/pumping cycle. In a
 preferred alternative embodiment, the first phase of stimulation is an
 anodal pulse at maximum subthreshold amplitude for a long duration, and
 the second phase of stimulation is a cathodal pulse of short duration and
 high amplitude. It is noted that the aforementioned alternative
 embodiments can be combined in differing fashions. It is also noted that
 these alternative embodiments are intended to be presented by way of
 example only, and are not limiting.
 Enhanced myocardial function is obtained through the biphasic stimulation
 of the present invention. The combination of cathodal with anodal pulses
 of either a stimulating or conditioning nature, preserves the improved
 conduction and contractility of anodal stimulation while eliminating the
 drawback of increased stimulation threshold. The result is a
 depolarization wave of increased propagation speed. This increased
 propagation speed results in increased synchronization and reduced
 heterogenicity of myocardial depolarization resulting in superior blood
 flow and contraction. Improved stimulation at a lower voltage level also
 results in: 1/ reduction in scar tissue buildup thereby reducing the
 tendency of the capture threshold to rise; 2/ reduction in power
 consumption leading to increased life for pacemaker batteries; and 3/
 decreased potential for patient discomfort due to stimulation of the
 phrenic or diaphragmatic plexus or due to intercostal muscle pacing.

DESCRIPTION OF THE PREFERRED EMBODIMENTS
 Electrical stimulation is delivered via lead(s) or electrode(s). These
 leads can be epicardial (external surface of the heart) or endocardial
 (internal surface of the heart) or any combination of epicardial and
 endocardial. Leads are well known to those skilled in the art. Lead
 systems can be unipolar or bipolar. A unipolar lead has one electrode on
 the lead itself, the cathode. Current flows from the cathode, stimulates
 the heart, and returns to the anode on the casing of the pulse generator
 to complete the circuit. A bipolar lead has two poles on the lead a short
 distance from each other at the distal end, and both electrodes lie within
 the heart.
 FIG. 1 illustrates a plan view of implantable electronic stimulation device
 102 and its associated lead and electrode system, in conjunction with
 human heart 104. As illustrated, the device includes right atrial
 appendage lead 106, right atrial septal lead 108, first coronary sinus
 lead 110 and second coronary sinus lead 112. Each of these multiple small
 electrodes can be inserted intravenously and includes an independent
 generator.
 FIG. 2 illustrates a plan view of implantable electronic stimulation device
 102 illustrating an alternative location of leads and electrodes in
 relation to human heart 104. As illustrated, the device includes right
 atrial appendage lead 106, right atrial septal lead 108, first coronary
 sinus lead 110, second coronary sinus lead 112 and left free wall lead
 204. Each of these multiple small electrodes can be inserted intravenously
 and includes an independent generator. Because of the use of independent
 generators, each electrode can be timed differently. In a preferred
 embodiment, left free wall lead 204 is placed by piercing septum 206 and
 passing left free wall lead 204 through the septum to the left side of the
 heart. The aforementioned placement of leads is for illustration purposes
 only, and is not intended as a limitation. It is contemplated that
 multiple leads placed in a variety of locations could be used.
 Each site (area of lead placement) can be entrained separately, and then
 brought to the same phase. In a preferred embodiment each site is
 gradually brought to the same phase; however, certain situations could
 require that each site is quickly brought to the same phase. In an
 alternative embodiment, the sites can be sequenced to mimic a normal heart
 beat. In addition to allowing multi-site stimulation capability, the
 sensing circuits of each electrode also allow for multi-site sensing.
 Through triangulation the multi-site sensing provides a means for
 determining the site(s) of any atrial ectopic focus.
 In a preferred embodiment, stimulation is administered at threshold until
 capture has occurred, at which time stimulation is administered at a
 subthreshold level. In alternative embodiments, stimulation is: (1)
 initiated at threshold and remains at threshold; (2) initiated
 subthreshold and remains subthreshold; (3) conventional prior to capture
 and then biphasic; (4) biphasic prior to capture and then conventional or
 (5) biphasic throughout.
 Threshold refers to the minimum voltage level (or pulse width using a fixed
 voltage) which succeeds in stimulating (capturing) the myocardium. To
 capture is to produce a driven beat because of the stimulus given. Thus,
 in the absence of the pulse, the beat would not have been produced. Pulses
 which do not capture are subthreshold, (even though they may be shown to
 perturb the membrane potential somewhat, and transiently). Subthreshold
 pulses thus may affect subsequent conduction, but not by the mechanism of
 initiating a driven beat. Generally, to determine threshold, voltage (or
 pulse width) is varied (upward or downward) until capture is gained or
 lost.
 Conventional stimulation is well known to those skilled in the art and
 comprises monophasic waveforms (cathodal or anodal) as well as multiphasic
 waveforms wherein the nonstimulating pulses are of a minimal magnitude and
 are used, for example, to dissipate a residual charge on an electrode.
 FIGS. 3 through 7 depict a range of biphasic stimulation protocols. These
 protocols have been disclosed in U.S. patent application Ser. No.
 08/699,552 to Mower, which is herein incorporated by reference in its
 entirety.
 FIG. 3 depicts biphasic electrical stimulation wherein a first stimulation
 phase comprising anodal stimulus 302 is administered having amplitude 304
 and duration 306. This first stimulation phase is immediately followed by
 a second stimulation phase comprising cathodal stimulation 308 of equal
 intensity and duration.
 FIG. 4 depicts biphasic electrical stimulation wherein a first stimulation
 phase comprising cathodal stimulation 402 having amplitude 404 and
 duration 406 is administered. This first stimulation phase is immediately
 followed by a second stimulation phase comprising anodal stimulation 408
 of equal intensity and duration.
 FIG. 5 depicts a preferred embodiment of biphasic stimulation wherein a
 first stimulation phase, comprising low level, long duration anodal
 stimulation 502 having amplitude 504 and duration 506, is administered.
 This first stimulation phase is immediately followed by a second
 stimulation phase comprising cathodal stimulation 508 of conventional
 intensity and duration. In differing alternative embodiments, anodal
 stimulation 502 is: 1) at maximum subthreshold amplitude; 2) less than
 three volts; 3) of a duration of approximately two to eight milliseconds;
 and/or 4) administered over 200 milliseconds post heart beat. Maximum
 subthreshold amplitude is defined for purposes of this application as the
 maximum stimulation amplitude that can be administered without eliciting a
 contraction. In a preferred embodiment, anodal stimulation is
 approximately two volts for approximately three milliseconds duration. In
 differing alternative embodiments, cathodal stimulation 508 is: 1) of a
 short duration; 2) approximately 0.3 to 1.5 milliseconds; 3) of a high
 amplitude; 4) in the approximate range of three to twenty volts; and/or 5)
 of a duration less than 0.3 millisecond and at a voltage greater than
 twenty volts. In a preferred embodiment, cathodal stimulation is
 approximately six volts administered for approximately 0.4 millisecond. In
 the manner disclosed by these embodiments, as well as those alterations
 and modifications which can become obvious upon the reading of this
 specification, a maximum membrane potential without activation is achieved
 in the first phase of stimulation.
 FIG. 6 depicts an alternative preferred embodiment of biphasic stimulation
 wherein a first stimulation phase, comprising anodal stimulation 602, is
 administered over period 604 with rising intensity level 606. The ramp of
 rising intensity level 606 can be linear or non-linear, and the slope can
 vary. This anodal stimulation is immediately followed by a second
 stimulation phase comprising cathodal stimulation 608 of conventional
 intensity and duration. In alternative embodiments, anodal stimulation
 602: (1) rises to a maximum subthreshold amplitude less than three volts;
 (2) is of a duration of approximately two to eight milliseconds; and/or
 (3) is administered over 200 milliseconds post heart beat. In yet other
 alternative embodiments, cathodal stimulation 608 is: (1) of a short
 duration; (2) approximately 0.3 to 1.5 milliseconds; (3) of a high
 amplitude; (4) in the approximate range of three to twenty volts; and/or
 (5) of a duration less than 0.3 milliseconds and at a voltage greater than
 twenty volts. In the manner disclosed by these embodiments, as well as
 those alterations and modifications which can become obvious upon the
 reading of this specification, a maximum membrane potential without
 activation is achieved in the first phase of stimulation.
 FIG. 7 depicts biphasic electrical stimulation wherein a first stimulation
 phase, comprising series 702 of anodal pulses, is administered at
 amplitude 704. In one embodiment, rest period 706 is of equal duration to
 stimulation period 708, and is administered at baseline amplitude. In an
 alternative embodiment, rest period 706 is of a differing duration than
 stimulation period 708, and is administered at baseline amplitude. Rest
 period 706 occurs after each stimulation period 708, with the exception
 that a second stimulation phase, comprising cathodal stimulation 710 of
 conventional intensity and duration, immediately follows the completion of
 series 702. In alternative embodiments: (1) the total charge transferred
 through series 702 of anodal stimulation is at the maximum subthreshold
 level; and/or (2) the first stimulation pulse of series 702 is
 administered over 200 milliseconds post heart beat. In yet other
 alternative embodiments, cathodal stimulation 710 is: (1) of a short
 duration; (2) approximately 0.3 to 1.5 milliseconds; (3) of a high
 amplitude; (4) in the approximate range of three to twenty volts, and/or
 (5) of a duration less than 0.3 milliseconds and at a voltage greater than
 twenty volts.
 FIG. 8 illustrates the practice of the present invention. Sensing is used
 to determine the existence of atrial fibrillation 802. Sensing can be
 direct or indirect. For example, direct sensing can be based on data from
 multiple atrial sensing electrodes. The sensing electrodes sense the
 cardiac activity as depicted by electrical signals. For example, as is
 known in the art, R-waves occur upon the depolarization of ventricular
 tissue and P-waves occur upon the depolarization of atrial tissue. By
 monitoring these electrical signals the control/timing circuit of the ICD
 can determine the rate and regularity of the patient's heart beat, and
 thereby determine whether the heart is undergoing arrhythmia. This
 determination can be made by determining the rate of the sensed R-waves
 and/or P-waves and comparing this determined rate against various
 reference rates.
 Direct sensing can be based upon varying criteria; such as, but not limited
 to, primary rate, sudden onset, and stability. The sole criteria of a
 primary rate sensor is the heart rate. When applying the primary rate
 criteria, if the heart rate should exceed a predefined level, then
 treatment is begun. Sensing electronics set to sudden onset criteria
 ignore those changes which occur slowly, and initiate treatment when there
 is a sudden change such as immediate paroxysmal arrhythmia. This type of
 criteria would thus discriminate against sinus tachycardia. Stability of
 rate can also be an important criteria. For example, treatment with a
 ventricular device would not be warranted for a fast rate that varies,
 here treatment with an atrial device would be indicated.
 In alternative embodiments, sensing can be indirect. Indirect sensing can
 be based on any of various functional parameters such as arterial blood
 pressure, rate of the electrocardiogram deflections or the probability
 density function (pdf) of the electrocardiogram. While it has been known
 in the art to apply pdf to the global electrocardiogram and/or to the R
 wave, it has been unexpectedly discovered that pdf of the baseline is also
 indicated for the determination of atrial abnormalities. Here, the
 electrodes are specific to the atrium and data related to the R wave is
 canceled out. Thus, whether or not to administer treatment can also be
 affected by pdf monitoring of the time the signal spends around the
 baseline.
 Lastly, to determine whether an arrhythmia comes from the atria or the
 ventricles, a test impulse(s) can be given to one chamber to see if
 capture occurs and perturbs the rhythm. For example, in a ventricular
 rhythm, an atrial test impulse can capture the atrium, but the ventricular
 rhythm will continue unchanged afterwards. In an atrial rhythm, (or Sinus
 rhythm), if the atrial test pulse captures, the timing of all subsequent
 beats is changed. To determine if a pulse captures, the baseline
 immediately after the beat can be examined to determine if it is different
 from zero (or from a baseline template). If so, the beat can be inferred
 to have captured. In addition, the pdf pattern of the rhythm can be shown
 to have changed, inferring capture.
 Thus, in a preferred embodiment, sensing electronics are based upon
 multiple criteria. In addition, the present invention envisions devices
 working in more than one chamber such that appropriate treatment can be
 administered to either the atrium or the ventricle in response to sensing
 electronics based upon a variety of criteria, including those described
 above as well as other criteria known to those skilled in the art.
 If atrial fibrillation occurs, a baseline of cardiac activity or a template
 can be recorded 804. The template can be based on parameters such as
 electrocardiogram data, mechanical motion and/or probability density
 function data. In an alternative embodiment, the template is established
 after capture has occurred.
 Pacing is initiated 806. In a preferred embodiment, stimulation is
 administered at threshold until capture has occurred, at which time
 stimulation is administered at a subthreshold level. In alternative
 embodiments, stimulation is: (1) initiated at threshold and remains at
 threshold; (2) initiated subthreshold and remains subthreshold; (3)
 conventional prior to capture and then biphasic; (4) biphasic prior to
 capture and then conventional or (5) biphasic throughout.
 The atrium is monitored throughout this initial pacing period to determine
 the status of capture 808. Capture can be determined by multiple means.
 First, capture or the loss thereof, can be determined by monitoring
 cardiac rhythm. Loss of capture can result in a change in timing of the
 heart beat.
 Second, capture or the loss thereof, can be determined through monitoring
 the previously described template. Where the template is established
 pre-stimulation, a change in the baseline signifies capture. Where the
 template is established after capture has occurred, a change in the
 template characteristics signifies loss of capture. The templates can be
 established and/or updated at any time.
 Once capture occurs the stimulation protocol of the entrained sites is
 adjusted 810. In a first embodiment, the stimulation rates of the
 entrained sites are slowed simultaneously, and then stopped. In a second
 embodiment, the spread of conduction is slowed. In a third embodiment, the
 stimulation speed is increased and stimulation is then stopped. In
 addition to adjusting stimulation rates upon the occurrence of capture,
 the stimulation protocol can also be adjusted such that (1) if stimulation
 of a conventional nature was administered prior to capture, biphasic
 stimulation is administered post-capture; (2) if biphasic stimulation was
 administered prior to capture, conventional stimulation is administered
 post-capture or (3) if biphasic stimulation was administered prior to
 capture, biphasic stimulation continues to be administered post-capture.
 Having thus described the basic concept of the invention, it will be
 readily apparent to those skilled in the art that the foregoing detailed
 disclosure is intended to be presented by way of example only, and is not
 limiting. Various alterations, improvements and modifications will occur
 and are intended to those skilled in the art, but are not expressly stated
 herein. These modifications, alterations and improvements are intended to
 be suggested hereby, and within the scope of the invention. Further, the
 pacing pulses described in this specification are well within the
 capabilities of existing pacemaker electronics with appropriate
 programming. Accordingly, the invention is limited only by the following
 claims and equivalents thereto.