AU2004201799B2 - Atrial sensing and multiple site stimulation as intervention for atrial fibrillation - Google Patents

Description

Our Ref: 12254271 P/00/011 Regulation 3:2

AUSTRALIA

Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT Applicant(s): The Mower Family CHF Treatment Irrevocable Trust Two East Fayette Street Suite 501 Baltimore Maryland 21202 United States of America Address for Service: Invention Title: DAVIES COLLISON CAVE Patent Trade Mark Attorneys Level 10, 10 Barrack Street Sydney, New South Wales, Australia, 2000 Atrial sensing and multiple site stimulation as intervention for atrial fibrillation The following statement is a full description of this invention, including the best method of performing it known to me:-

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Title: ATRIAL SENSING AND MULTIPLE SITE STIMULATION AS INTERVENTION FOR ATRIAL FIBRILLATION Inventor: Morton M. Mower, M.D.

Field of the Invention 1 The present invention relates generally to electronic stimulation devices to control 2 the beating of hearts, especially hearts with pathologies that interfere with normal 3 rhythmicity, electrical conduction, and/or contractility. In particular, the present invention 4 relates to pacemakers used to overcome atrial fibrillation by use of i) atrial sensing; 2) electrical test stimulation of the atria; and 3) multiple site stimulation in which the various 6 atrial areas are slowly entrained to a common beating rate to produce electrical/functional 7 conformity, cardioversion, with each case either eventuating in spontaneous reversion 8 to a normal atrial rhythm, or reduced energy requirement for reversion by electrical 9 countershock.

11 The present invention also relates generally to a system and method for the 12 stimulation of cardiac muscle tissue. In particular, the embodiments of the present invention provide a system and method for treating cardiac tissue by cooling the 13 cardiac tissue to inhibit the conduction of certain electrical signals in cardiac 14 14 tissue and decrease the duration of tachycardia and enhance the effects of pacing and defibrillation stimuli.

16 17 18 19 21 -2- Background of the Invention 2 Morbidity associated with malfunctions of the atria, while not immediate, is high.

3 Atrial malfunctions of rhythmicity atrial fibrillation, various atrial arrhythmias, A-V 4 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.

6 Atrial Sensing. A variety of approaches have been developed which use 7 pacemakers to counter atrial malfunctions of rhythmicity, as well as attendant effects on 8 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 us ventricular sensing to measure/determine the probability density function (pdf) on a 12 moment-to-moment basis. For example, U.S. Patent No. 5,163,429 to Cohen discloses the 13 14 16 17 18 19 21 22 23 -3- 1 use of narrow window pdf data as but one criterion among several for assessing ventricular 2 cardiac function. The use of pdf data to determine ventricular fibrillation also is disclosed 3 in Implantable Cardioverter-Defibrillators Estes III, A. Manolis P. Wang, ed.).

4 U.S. Patent 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 6 cardiac function. The use of probability density function data for assessing atrial cardiac 7 function has not been disclosed and presents its own unique difficulties as will be further 8 discussed.

9 Electrical Test Stimulation ofAtria. In a few limited cases, pacemaker protocols have been employed in which electrical test stimuli are applied to the atria, and the 11 physiological responses thereto are monitored to aid in the determination of the best or 12 most appropriate protocol to initiate, cure, or ameliorate the existing cardiac malfunction.

13 For example, U.S. Patent No. 5,620,471 to Duncan discloses three basic protocols for 14 determining whether observed ventricular irregularities are actually caused by atrial arrhythmias. One protocol includes atrial electrical test stimulation, and all three protocols 16 monitor both atrial and ventricular rhythms for three parameters: rates of atrial and 17 ventricular firing, stability of firing/beating in atria and ventricles, and whether or not 18 ventricular firing tracks atrial firing. In the first protocol, when the ventricular firing rate 19 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 21 is applied. On the other hand (second protocol), if the ventricular firing rate is not stable, 22 then atrial arrhythmia is presumed, and atrial stimulation is applied. The third protocol is 23 based on the fact that, when the ventricular firing rate equals the atrial firing rate, there -4- 1 may or may not be ventricular tracking of atrial firing. Whether or not there is ventricular 2 tracking is determined by the presence or not of ventricular tracking following premature 3 atrial stimulation by the pacemaker. If there is ventricular tracking of atrial firing, the 4 arrhythmic mechanism is presumed to be atrial tachycardia. However, if there is no ventricular tracking of atrial firing, then ventricular tachycardia is presumed, and 6 ventricular stimulation is performed.

7 U.S. Patent No. 5,421,830 to Epstein. et al. discloses a general means for 8 recording, testing, and analyzing cardiac function based on data from and electrical test 9 stimulation via a patient's pacemaker, as well as data from additional sensors detecting hemodynamic or other body functions. Total intracardiac electrograms (reflecting both 11 atrial and ventricular functional status) or just selected data P-P or R-R intervals, 12 heart rate, arrhythmia duration, slew rate, probability density function, etc.) may be 13 recorded and analyzed. The patient's atrial and ventricular responses to electrical test 14 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 16 specific situation during exercise or exertion) of a given patient.

17 U.S. Patent No. 5,215,083 to Drane. et al. also discloses the use of electrical test 18 stimulation to aid in the fine tuning and evaluation of different possible stimulation 19 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 21 programmed therapies.

22 Multiple Site Atrial Stimulation. The use of multiple site atrial stimulation has 23 been disclosed for various purposes, such as defibrillation, cardioversion, pacing, and dc 1 field production. One example is provided by U.S. Patent No. 5,562,708 to Combs. et al., 2 which discloses the employment of large surface electrodes (each effectively comprising 3 multiple electrodes) that are implanted to one or both atria for providing extended, low 4 energy electrical impulses. The electrical impulses are applied simultaneously at multiple sites over atrial surfaces, and atrial fibrillation is interrupted by gradually entraining 6 greater portions of atrial tissue. These pacemaker electrodes may be used for various 7 purposes in addition to pacing, such as conventional defibrillation and cardioversion.

8 U.S. Patent No. 5,649,966 to Noren. et al. discloses the use of multiple electrodes 9 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.

11 Polarity may also be changed periodically. In one embodiment, four electrodes are 12 positioned within a single plane in the heart, which permits a dipole field in virtually any 13 direction within that plane.

14 U.S. Patent No. 5,411,547 to Causey. Ill discloses the use of sets of complex mesh patch electrodes, in which each electrode comprises an anode patch and a cathode patch, 16 for purposes of cardioversion-defibrillation. Bidirectional cardiac shocking is permitted 17 by these electrodes.

18 U.S. Patent No. 5,391,185 to Kroll discloses the use of multiple electrodes to effect 19 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 21 the QRS phase of the ventricular cycle.

22 U.S. Patent No. 5,181,511 to Nickolls. et al. discloses the use of multiple 23 electrodes in antitachycardia pacing therapy. The electrodes not only each serve an -6- 1 electrical sensing role (to locate the site of an ectopic focus), but also function in concert to 2 create a virtual electrode for stimulating at the site of an ectopic focus.

3 Existing Needs. In the area of atrial malfunctions of rhythmicity what is needed is 4 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.

6 Atrial test stimulation and analysis capability is needed to provide better determination of 7 the nature of the malfunction and the most probable or efficacious corrective therapy to 8 undertake. Furthermore, the use of atrial test stimulation is critically needed for the 9 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 11 stimulation regime, even if that selected stimulation regime would work generally for 12 other cardiac patients. Thus, a trial-and-error testing capability needs to be available for 13 pacemakers whose traditional stimulation regimes do not work for the occasional 14 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.

16 Atrial sensing and use of measurement data are needed to better provide the physician 17 and/or the circuit logic of the pacemaker with information as to the physiological state of 18 the heart; whether there is atrial arrhythmia or fibrillation, where an ectopic focus is 19 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 21 analysis capability, and multiple site stimulation capability.

22 Lastly, a need also exists for a stimulation protocol which can travel more quickly 23 across the myocardium and which provides improved cardiac entrainment along with the P:\WPDOCS\GLF'specnl225427Pg7.doc-29/4fO4 -7- 1 The present invention seeks to provide an electronic stimulation device for 2 stimulating the atria from multiple sites, to sequence the sites to mimic a normal heart beat.

3 The present invention seeks to determine cardiac capture by monitoring cardiac 4 activity and noting when the baseline of such activity is off zero.

The present invention seeks to decrease threshold rises due to a build up of fibrous 6 tissue.

7 The present invention seeks to provide a cardiac pacemaker with a unique 8 constellation of features and capabilities. In particular, a means for entraining multiple 9 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 11 measurement) capability, which, by triangulation, essentially provides the ability to 12 determine the site of any atrial ectopic focus. The multi-site stimulation capability 13 inherently provides a system poised for more efficient entrainment and/or 14 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 16 analysis to determine the best general stimulation protocol, to fine tune a given protocol, or 17 to adjust a protocol in response to changes in the physiological/pathological status of the 18 patient in general and/or the patient's heart in particular.

19 Incorporating the use of biphasic stimulation with the present invention provides the additional benefits of reducing cardiac inflammation damage, reducing or eliminating 21 threshold rises due to the buildup of fibrous tissue and extending battery life of the 22 electrodes.

23 PA\WPDOCSZLF\pM\I2254271 mded.doC-29/04/04 -8- 1 ability to entrain portions of the heart from a greater distance.

2 The function of the cardiovascular system is vital for survival. Through blood 3 circulation, body tissues obtain necessary nutrients and oxygen, and discard waste 4 substances. In the absence of circulation, cells begin to undergo irreversible changes that lead to death. The muscular contractions of the heart are the driving force behind 6 circulation.

7 Each of the heart's contractions, or heartbeats, is triggered by electrical impulses.

8 These electrical impulses are sent from the sinoatrial node (the heart's natural pacemaker), 9 which is located at the top of the upper-right chamber of the heart or right atrium. From there, the electrical impulses travel through the upper chambers of the heart (atria) and to 11 the atrioventricular (AV) node, where they are transmitted to the lower chambers of the 12 heart ventricles via the "bundle branches." Thus, the electrical impulses travel from the 13 sinoatrial node to the ventricles, to trigger and regulate the heartbeat.

14 An arrhythmia is an abnormal heartbeat resulting from any change, deviation or malfunction in the heart's conduction system the system through which normal electrical 16 impulses travel through the heart. Under normal conditions, each of the heart's 17 contractions, or heartbeats, is triggered by electrical impulses. These electrical impulses 18 are sent from the sinoatrial node (the heart's natural pacemaker), which is located at the 19 top of the upper-right chamber of the heart or right atrium. From there, the electrical impulses travel through the upper chambers of the heart (atria) and to the atrioventricular 21 (AV) node, where they are transmitted to the lower chambers of the heart ventricles via the 22 "bundle branches." Thus, the electrical impulses travel from the sinoatrial node to the 23 ventricles, to trigger and regulate the heartbeat.

24 When the electrical "circuits" of the heart do not operate optimally, an arrhythmia may result. An arrhythmia may result in unusually fast (tachycardia) or unusually slow 26 (bradycardia) heartbeats. The cause of an arrhythmia may be related to a previous heart 27 condition previous damage from a heart attack) or to other factors drugs, stress, 28 not getting enough sleep). In the majority of cases, a skipped beat is not medically 29 significant. The most serious arrhythmias, however, contribute to approximately 500,000 deaths in the United States each year according to the American Heart Association. Sudden 31 cardiac death ("cardiac arrest") is responsible for approximately one-half of all deaths due P:\WPDOCS\GLFspd\2254271odd.d-29/4/04 -9- 1 to heart disease, and is the number one cause of death in the US, according to the North 2 American Society of Pacing and Electrophysiology.

3 Almost all clinically important tachyarrhythmias are the result of a propagating 4 impulse that does not die out but continues to propagate and reactivate cardiac tissue (referred to as "reentry"). Such tachyarrhythmias include sinus node reentry, atrial 6 fibrillation, atrial flutter, atrial tychycardia, AV nodal reentry tachycardia, AV reentry 7 (Wolff-Parkinson-White syndrome or concealed accessory AV connection), ventricular 8 tachycardia, and bundled branch reentrant tachycardia.

9 For reentry to occur, there must exist a substrate in the cardiac tissue capable of supporting reentry (the "reentry circuit"). The activation wave front must be able to 11 circulate around a central area of block and encounter a unidirectional block such that it is 12 forced to travel in one direction around the central block. (If the activation wave front is 13 permitted to travel in both directions around the block, the wave fronts will collide and die 14 out.) Of importance is the conductance speed of the circulating wave front. If the conductance speed is too fast, the circulating wave front will arrive at its point of origin 16 before the tissue has repolarized sufficiently to become excitable again. Thus, at least one 17 area of slow conductance is part of the reentry circuit for virtually all clinical reentrant 18 rhythms. Eliminating the slow conductance elements of a reentry circuit destroys the 19 circuit.

Atrial fibrillation (AF) is the most common type of sustained arrhythmia, affecting 21 two million people each year in the United States alone. Both atrial fibrillation and atrial 22 flutter increase the risk of stroke. According to the American Heart Association, they lead 23 to over 54,000 deaths in the United States each year. The risk of developing atrial 24 fibrillation increases dramatically with age. As a result, approximately 70 percent of patients with atrial fibrillation are between the ages of 65 and 85 years old. AF is a rapid, 26 abnormal heart rhythm (arrhythmia) caused by faulty electrical signals from the upper 27 chambers of the heart (atria). Electrical signals should normally be coming only from the 28 sinoatrial node in a steady rhythm about 60 to 100 beats per minute. A heart 29 experiencing AF presents two heart rates an atrial rate and a heart rate. With AF, the atrial rate is 300-400 beats per minute while the heart rate is 100-175 beats per minute.

P:\WPDOCSGLFsplcR225427Iaded.d-29/4/04 1 This heart rate is the result of the AV node blocking out most of the atrial impulses, and 2 allowing only the fewer impulses to emerge to the ventricle.

3 Certain arrhythmias are related to specific electrical problems within the heart. AV 4 nodal reentrant tachycardia is an arrhythmia caused by an extra conducting pathway within the AV node. This allows the heart's electrical activity to "short circuit" or recyle within 6 the AV nodal region.

7 AV reentrant tachycardia results from an extra conducting pathway that allows the 8 electrical impulse to "short circuit" and bypass the AV node altogether. In this mode, the 9 extra "circuit" directly links the atria and ventricles. In most cases, this pathway can only conduct "backwards" from ventricles to atria. This is called a "concealed accessory 11 pathway" since it cannot be diagnosed from a regular electrocardiogram (EKG). These 12 arrhythmias may be treated medically, but can also be cured by catheter ablation. Less 13 often, the extra pathway conducts in the forward direction (from atrium to ventricle) and is 14 evident on the EKG, in which case the condition is called the Wolff-Parkinson-White syndrome (WPW). WPW syndrome may result in extremely rapid heartbeats and could 16 potentially result in death. Symptomatic WPW syndrome generally requires catheter 17 ablation.

18 A quite different (and life threatening) condition is ventricular fibrillation.

19 Ventricular fibrillation involves a quivering of the ventricles instead of the atria. Unlike AF, it is life threatening because it results in 350 beats per minute or higher. The heart 21 cannot keep that rate up for more than a few minutes without treatment with a 22 defibrillator).

23 Under some conditions, arrhythmias may be transient. For example, a patient 24 may be experiencing a particular period of stress, an illness, or a drug (legal or otherwise) reaction. In other cases, more invasive treatments are helpful. For a slow heartbeat 26 (bradycardia), the most common treatment is an electronic (artificial) pacemaker. This 27 device, which is implanted under the skin and permanently attached to the heart, delivers 28 an electrical impulse when a slowing or irregularity of the heart rhythm is detected. For 29 abnormally fast heartbeat rates, an implantable cardioverter defibrillator (ICD) may be implanted. An ICD monitors and, if necessary, corrects an abnormally fast heartbeat.

31 These devices may be lifesaving for patients with ventricular fibrillation or ventricular P:\WPDOCS\GLF\p..2254271m d.do-29/4/04 -11- 1 tachycardia. Another procedure is an electrophysiology study with catheter ablation. This 2 is a procedure in which catheters are introduced into the heart from blood vessels in the 3 legs and/or neck and radio frequency energy is used to very carefully destroy (ablate) the 4 abnormal areas of the heart that are creating the arrhythmias.

In cardiac muscle, the muscle fibers are interconnected in branching networks 6 that spread in all directions through the heart. When any portion of this net is stimulated, a 7 depolarization wave passes to all of its parts and the entire structure contracts as a unit.

8 Before a muscle fiber can be stimulated to contract, its membrane must be polarized. A 9 muscle fiber generally remains polarized until it is stimulated by some change in its environment. A membrane can be stimulated electrically, chemically, mechanically or by 11 temperature change. The minimal stimulation strength needed to elicit a contraction is 12 known as the threshold stimulus. The maximum stimulation amplitude that may be 13 administered without eliciting a contraction is the maximum subthreshold amplitude.

14 Throughout much of the heart are clumps and strands of specialized cardiac muscle tissue. This tissue comprises the cardiac conduction system and serves to initiate 16 and distribute depolarization waves throughout the myocardium. Any interference or block 17 in cardiac impulse conduction may cause an arrhythmia or marked change in the rate or 18 rhythm of the heart.

19 Biphasic either cathodal or anodal current may be used to stimulate the myocardium. However, until the work embodied in USP Nos. 5,871,506 and 6,141,586 21 for example, anodal current was thought not to be useful clinically. Cathodal current 22 comprises electrical pulses of negative polarity. This type of current depolarizes the cell 23 membrane by discharging the membrane capacitor, and directly reduces the membrane 24 potential toward threshold level. Cathodal current, by directly reducing the resting membrane potential toward threshold has a one-half to one-third lower threshold current in 26 late diastole than does anodal current. Anodal current comprises electrical pulses of 27 positive polarity. Presently, virtually all artificial pacemaking is done using stimulating 28 pulses of negative polarity although the utility of anodal pulse has been demonstrated.

29 The typical implantable cardioverter/defibrillator (ICD) delivers an initial electrical countershock within ten to twenty seconds of arrhythmia onset, thereby saving 31 countless lives. Improved devices have antitachycardia pacing capabilities in addition to P:\WPDOCS\GLFpc I\2254271amdd.doc-29/04/04 12- 1 cardioverting/defibrillating functions. These ICDs are capable of different initial responses 2 to one or more tachycardia as well as a programmable sequence of responses to a particular 3 arrhythmia.

4 The output energy level is generally set by a physician in accordance with a patient's capture threshold, determined at the time of heart implantation. This threshold 6 represents the minimum pacing energy required to reliably stimulate a patient's heart.

7 However, due to trauma associated with the stimulation, scar tissue grows at the interface 8 between the implanted cardiac pacer leads and the myocardium. This scar tissue boosts the 9 patient's capture threshold. To insure reliable cardiac capture, the output energy level is thus generally set at a level which is a minimum of two times greater than the initially 11 measured capture threshold. A drawback to such an approach is that the higher stimulation 12 level causes more trauma to the cardiac tissue than would a lower level of stimulation, and 13 hence promotes the formation of scar tissue, thereby boosting the capture threshold. The 14 higher stimulation level also shortens battery life. This is not desirable, as a shorter battery life necessitates more frequent surgery to implant fresh batteries.

16 Another drawback is the potential for patient discomfort associated with this 17 higher stimulation level. This is because the higher stimulation level can stimulate the 18 phrenic or diaphragmatic plexus or cause intercostal muscle pacing. Lastly, the higher 19 stimulation is less effective, due to entry block.

Improvements to pacing technology have resulted in an enhanced conduction of 21 electrical pulses associated with resultant heartbeats for those arrhythmia victims who do 22 not respond to ordinary pacing. For example US Patent No. 6,343,232 B1 entitled 23 "Augmentation of Muscle Contractility by Biphasic Stimulation" was issued to Morton M.

24 Mower M.D. That invention described increasing electrical conduction and contractility by biphasic pacing comprising an initial anodal pulse followed by a cathodal pulse. This 26 technique increased the speed of conduction of the resultant beats by almost 100% over 27 that produced by conventional pacing stimuli. However, this technique did not result in 28 reversion to a sinus rhythm for all victims of cardiac conduction disorder.

29 What would be truly useful is to provide alternative methods of stimulating the myocardium and to inhibit the conduction of certain spurious electrical impulses 31 in the heart as a substitution for, or as an enhancement to, conventional pacing and P:\WPDOCS\GL;pcc 12254271am ded.doc-29/04/04 13- 1 pharmaceutical therapies and/or to use the alternative method in conjunction with 2 conventional pacing and safe pharmaceuticals to provide yet another method for 3 overcoming cardiac conduction problems.

4 Summary of the Invention 6 The present invention seeks to provide a pacemaker that is capable of pacing 7 atria from multiple sites.

8 The present invention seeks to provide a pacemaker that is capable of slowly 9 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 11 heart.

12 The present invention seeks to provide a pacemaker that is capable of 13 detecting the presence of atrial fibrillation and atrial arrhythmias by stimulating the 14 atria and observing and measuring the consequent effects on atrial and ventricular function.

16 The present invention seeks to provide a pacemaker that is capable of 17 obtaining and analyzing probability density function data from atria in order to 18 determine atrial rates of beating and to assess atrial physiological function.

19 The present invention seeks to provide an electronic stimulation device, for stimulating the atria from multiple sites, where the electrodes of the electronic 21 stimulation device can be inserted intravenously.

22 The present invention seeks to provide an electronic stimulation device, for 23 stimulating the atria from multiple sites, where each electrode of the device has an 24 independent generator.

The present invention 'to provide an electronic stimulation device for 26 stimulating the atria from multiple sites, where each site is entrained separately and 27 quickly brought to the same phase.

28 -14- 1 In addition, the ability to conduct trial-and-error testing, including the analysis of 2 the data derived therefrom, permits more thorough and more definitive determination of 3 the physiological status of the heart; this determination can practically approach a 4 moment-to-moment basis when analysis is automated by appropriate software for the purpose.

6 In sum, the present invention provides a cardiac pacemaker that has greater 7 functional capabilities for the patient's atria than current technologies allow. The greater 8 atrial "coverage" from the strategic placement of multiple electrodes permits faster 9 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 11 ectopic focus so as to better apply corrective stimulation procedures. In addition, the 12 ability to apply trial-and-error testing/analytical procedures permits quicker analysis and 13 correction of malfunctions of electrical conduction, cardiac contractility, rhythmicity, etc.

14 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 16 prognosis from the better and faster treatment.

17 The method and apparatus relating to biphasic pacing comprises a first and second 18 stimulation phase, with each stimulation phase having a polarity, amplitude, shape, and 19 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 21 alternative embodiment, the two phases are of differing duration. In a third alternative 22 embodiment, the first phase is in a chopped wave form. In a fourth alternative 23 embodiment, the amplitude of the first phase is ramped. In a fifth alternative embodiment P:\WPDOCS\GLFpcc= 12254271 ammde.do-29/04/04 1 the first phase is administered over 200 milliseconds after completion of a cardiac 2 beating/pumping cycle. In a preferred alternative embodiment, the first phase of 3 stimulation is an anodal pulse at maximum subthreshold amplitude for a long 4 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 6 be combined in differing fashions, It is also noted that these alternative embodiments 7 are intended to be presented by way of example only, and are not limiting.

8 Enhanced myocardial function is obtained through the biphasic stimulation of 9 the present invention. The combination of cathodal with anodal pulses of either a stimulating or conditioning nature, preserves the improved conduction and 11 contractility of anodal stimulation while eliminating the drawback of increased 12 stimulation threshold. The result is a depolarization wave of increased propagation 13 speed. This increased propagation speed results in increased synchronization and 14 reduced heterogenicity of myocardial depolarization resulting in superior blood flow and contraction. Improved stimulation at a lower voltage level also results 16 in:l/reduction in scar tissue buildup thereby reducing the tendency of the capture 17 threshold to rise; 2/reduction in power consumption leading to increased life for 18 pacemaker batteries; and 3/decreased potential for patient discomfort due to 19 stimulation of the phrenic or diaphragmatic plexus or due to intercostal muscle pacing.

21 In one broad form the present invention provides comprises an implantable cardiac 22 treatment/stimulation device designed to inhibit the conduction of certain spurious 23 electrical impulses preferably without pacing. The technique applied in the implantable 24 device comprises a cooling element for cooling cardiac tissue. Optionally, the cooling process may be provided in combination with biphasic stimulation of the cardiac tissue.

26 The present invention seeks to inhibit the conduction of certain spurious electrical 27 impulses in cardiac tissue affected by re-entry circuits.

28 The present invention seeks to inhibit the conduction of certain spurious electrical 29 impulses in the heart by cooling cardiac tissue affected by re-entry circuits.

P:\PDOCSZLFq22S4271-dddoc-29/04/M -16- 1 The present invention seeks to selectively apply cold temperature to areas of the 2 cardiac tissue to inhibit the conduction of certain spurious electrical impulses in cardiac 3 tissue affected by re-entry circuits.

4 The present invention seeks to apply cold over large areas of the cardiac tissue to inhibit the conduction of certain spurious electrical impulses in cardiac tissue affected by 6 re-entry circuits.

7 The present invention seeks to affect reentry circuits in a more effective manner 8 than conventional cardiac pacing.

9 The present invention seeks to inhibit the conduction of certain spurious electrical impulses in the heart over large areas of tissue rather than only over small areas of a pacing 11 site.

12 The present invention seeks to provide an implantable stimulation device for 13 automatically applying cold to cardiac tissue affected by re-entry circuits.

14 The present invention seeks to provide a removable device for applying cold to cardiac tissue in operating room settings or trauma settings.

16 The present invention seeks to provide an implantable device that combines cooling 17 of cardiac tissue with stimulation of cardiac tissue through conventional pacing means.

18 The present invention seeks to provide an implantable device that combines cooling 19 of cardiac tissue with stimulation of cardiac tissue through biphasic stimulation.

The present invention seeks to provide an implantable cardiac stimulation device 21 that can sense the onset of fibrillation or other tachyarrhythmias and can selectively apply 22 cooling of cardiac tissue, pacing of cardiac tissue, defibrillation of cardiac tissue or a 23 combination thereof as the situation dictates.

24 In one broad form, the present invention provides for both cooling and biphasic electrical stimulation to be administered to the cardiac muscle. The anodal stimulation 26 component of biphasic electrical stimulation augments cardiac contractility by 27 hyperpolarizing the tissue prior to excitation, leading to faster impulse conduction, more 28 intracellular calcium release, and the resulting superior cardiac contraction. The cathodal 29 stimulation component eliminates the drawbacks of anodal stimulation alone, resulting in P:\WPDOCS\GLFspc 225427l1mOd od.d 2 9 4 /0 4 -17- 1 effective cardiac stimulation at a lower voltage level than would be required with anodal 2 stimulation alone. This in turn, extends pacemaker battery life and reduces tissue damage.

3 In another broad form the present invention provides for cooling to be applied to 4 the cardiac tissue and biphasic electrical stimulation is administered to the cardiac blood pool, that is, the blood entering and surrounding the heart. This enables cardiac 6 stimulation without the necessity of placing electrical leads in intimate contact with cardiac 7 tissue, thereby diminishing the likelihood of damage to this tissue. The stimulation 8 threshold of biphasic stimulation administered via the blood pool is in the same range as 9 standard stimuli delivered directly to the heart muscle. Through the use of biphasic electrical stimulation to the cardiac blood pool it is therefore possible to achieve enhanced 11 cardiac contraction, without skeletal muscle contraction, cardiac muscle damage or adverse 12 effects to the blood pool.

13 In another broad form the present invention comprises an implantable device for 14 automatic treatment of frequently recurring bouts of atrial fibrillation or chronic atrial fibrillation. This embodiment comprises a sensing system which monitors various 16 parameters such as the PDF (probability density function) of the atrium to sense atrial 17 fibrillation. By sensing the PDF of the atrium, this provides a detector for atrial fibrillation 18 that has not been previously considered. Upon sensing the PDF of the atrium and 19 determining that atrial fibrillation is occurring, the implantable device of the present invention initially applies cooling to the cardiac tissue of the atria. This cooling is applied 21 across a broad area via contact device dimensional to cover an extensive area of cardiac 22 tissue. The cold temperature is then applied over the contact device to the cardiac tissue, 23 cooling the cardiac tissue, and thereby inhibiting the conduction of spurious signals 24 through the tissue. This decreased temperature will affect the reentry circuits in an effective fashion. Since the intervention is applied to a large area of tissue rather than a 26 small pacing site, the inhibition of spurious signals can be achieved over a much broader 27 area than a single point of contact as in conventional pacing.

28 Cold is applied to the cardiac tissue for a brief period of time that is programmable 29 and adjustable as sensors detect the need for the application of the cold. The amount of cooling applied and the total temperature of the heart are monitored through a thermostat P:\WPDOCS\GLF1pM12254271 andd.do-29/04/04 -18- 1 function of the apparatus. Cooling can be accomplished by a mechanical hydraulic system 2 for pumping cooled fluid into a bladder on the surface of the atrium.

3 The heart rhythm is monitored and the application of cold temperature is repeated a 4 number of times if initially unsuccessful.

In those cases where the decrease of temperature of this embodiment alone fails to 6 entrain the cardiac tissue, an alternative embodiment comprises both a cooling element in 7 the form of a contact device and more conventional cardiac stimulation elements that apply 8 an electrical pulse to the cardiac tissue in the form of a negative phase, as an anodal pulse 9 followed by a negative pulse, or other stimulation method known in the art.

This combination of cooling of cardiac tissue combined with cardiac stimulation 11 comprises yet another embodiment of the present invention. A processor in the 12 implantable device senses the onset of fibrillation and first applies cold temperature to the 13 cardiac tissue. If this fails to affect the reentry circuits of the heart, a combination of 14 cooling and electrical stimulation and/or electrical stimulation alone could then be applied.

If the combination does not affect the reentry circuit, then individual pacing in the more 16 conventional fashion could be applied. Thus sensing and the application of stimulation of 17 either cold temperature electrical stimulation or a combination thereof are provided by 18 circuitry within the implantable device.

19 The application of the embodiments described above would not require anesthesia and would potentially have a higher effective rate than conventional cardio-version.

21 A further broad form of the present invention involves connecting the implantable 22 device to a communication terminal, preferably wireless, so that an appropriate caregiver 23 can receive notice of a cardiac event. Signals could then be received by the physician 24 indicating the condition. The physician would then have the option to remotely control the stimulation protocol applied by the implantable device of the present invention.

26 Yet another broad form of the present invention involves altering the conductance 27 of the heart by application of cold temperature with other forms of pacing such as rate 28 control, and defibrillation. Pacing includes but is not limited to bipolar, biphasic, unipolar, 29 monophasic, overdrive, atrial alone, atrio-ventricular and sequential pacing.

P:\WPDOCS\GLF~spmcd225427tammded.doc29/4/04 -19- 1 A further broad form of the present invention provides methods for inhibiting the 2 conduction of spurious electrical impulses in cardiac tissue comprising establishing a 3 temperature conducive to inhibited conduction of electrical impulses for a targeted portion 4 of the heart; and applying a temperature decrease to the targeted portion to maintain the established temperature.

6 A further broad form of the present invention provides methods for inhibiting the 7 conduction of spurious electrical impulses in cardiac tissue. The method comprising 8 sensing the onset of arrhythmia, determining the temperature of the cardiac tissue at the 9 time of onset of arrhythmia, and applying a temperature decrease below the present temperature to the cardiac tissue.

11 A further broad form of the present invention provides methods for inhibiting the 12 conduction of spurious electrical impulses in cardiac tissue. A heat-transfer operator is 13 situated at each of one or more targeted portions of the heart. In an embodiment of the 14 present invention, the heat-transfer operator is a Peltier cooler. In another embodiment of the present invention, the heat-transfer operator is a heat sink that is thermally coupled to a 16 Peltier cooler. A symptom associated with an arrhythmia is detected, and, in response to 17 detection of the symptom, the heat is selectively transferred away from the targeted portion 18 in the heart related to arrhythmia by absorbing heat into the heat-transfer operator situated 19 at the targeted portion r.

In a further broad form of the present invention, methods for suppressing 21 arrhythmia in a patient are provided. A heat-transfer operator is implanted at each of one 22 or more targeted portions of a patient's heart. At least one heat-transfer operator is 23 operated to cool at least one targeted portion of the heart, thereby suppressing the 24 arrhythmia.

In a further broad form of the present invention, methods are provided for 26 inhibiting the conduction of spurious electrical impulses in cardiac tissue. The onset of 27 arrhythmia is sensed and the sensed arrhythmia evaluated. The temperature of the cardiac 28 tissue at the time of onset of arrhythmia is also determined. Based on the evaluation of the 29 sensed arrhythmia and cardiac tissue temperature, one or more remedial measures is selected from the group consisting of applying a temperature decrease to the cardiac tissue P.%WPDOCSNTXSSp %122547271 a-Mdod p.c k -py do. -12/I0o O and applying a pacing pulse to the cardiac tissue. The selected remedial measure is applied.

A further broad form of the present invention comprises apparatuses for inhibiting the conduction of spurious electrical impulses in cardiac tissue. A sensing means senses the onset of arrhythmia. A cooling means responsive to the sensing means applies a I cooling stimulus to the cardiac tissue. In yet another embodiment of the present invention, apparatuses are provided or inhibiting the conduction of spurious electrical impulses in cardiac tissue. A sensor detects a symptom associated with an arrhythmia. A heat-transfer operator is situated at each of one or more targeted portions of the heart. In an embodiment of the present invention, the heat-transfer operator is a Peltier cooler. In another embodiment of the present invention, the heat-transfer operator is a heat sink coupled to a Peltier cooler implanted in the torso of the patient. The heat-transfer operator at each of the one or more targeted portions is adapted to respond to the sensor to remove heat from the targeted portion served by that heat-transfer operator.

In a further broad form of the present invention, apparatuses for suppressing arrhythmia in a patient are provided. A sensor detects a symptom associated with an arrhythmia. A heat-transfer operator is implanted at each of one or more targeted portions of a patient's heart. In response to the detection of arrhythmia, the heat-transfer operator at each of the one or more portions is adapted to transfer heat away from the targeted portion served by that heat-transfer operator such that each of the one or more targeted portions is cooled and the arrhythmia is suppressed.

In a further broad form, there is provided a method of atrial defibrillation comprising: sensing atrial fibrillation; recording a baseline of cardiac activity; applying a temperature decrease to a targeted portion of the heart using a cooling process selected from the group consisting of: applying a cooling fluid to the targeted portion, electrically cooling the targeted portion, mechanically cooling the targeted portion, and chemically cooling the targeted portion using an endothermic chemical reaction; P.XWPDOCSXTXS\Spoc12254271I o-dd pogn c- copyd.09/1OAf6

INO

00 stimulating the atrium using a pre-capture stimulation protocol if capture has not been achieved; determining status of capture; and stimulating the atrium using a post-capture stimulation protocol, wherein the precapture stimulation protocol and the post-capture stimulation protocol comprise a Sprocedure and wherein the procedure is selected from the group consisting of precapture stimulation at threshold with post-capture stimulation at threshold, precapture stimulation suat threshold with post-capture stimulation at threshold and pre- 10 capture stimulation atsubthreshold with post-capture stimulation subthreshold and precapture stimulation at threshold with post-capture stimulation subthreshold.

In a further broad form, there is provided an implantable cardiac stimulator to perform atrial defibrillation, the cardiac stimulator comprising: sensor adapted to sense the onset of atrial fibrillation; recorder adapted to record a baseline of cardiac activity; a cooling means adapted to apply a temperature decrease to a targeted portion of the heart, wherein the cooling means is selected from the group consisting of: a means for applying a cooling fluid to the targeted portion, an electrical cooling apparatus, a mechanical cooling apparatus, and means for cooling via an endothermic chemical reaction; a processor adapted to determining whether capture has occurred; and electrodes adapted to stimulate the atrium after the onset of atrial fibrillation has been sensed, wherein, in the event it is determined that capture has not occurred, the atrium is stimulated using a pre-capture stimulation protocol, wherein, in the event it is determined that capture has occurred, the atrium is stimulated using a post-capture stimulation protocol, and wherein the pre-capture stimulation protocol and the post-capture stimulation protocol comprise a procedure, the procedure being selected from the group consisting of: pre-capture stimulation at threshold with post-capture stimulation at P.%WPDDCSTXS1Spca%122342 1 nded pags lwa mpy dow4yNO)6 0 threshold, pre-capture stimulation subthreshold with post-capture stimulation subthreshold, and pre-capture stimulation at threshold with post-capture stimulation subthreshold.

In a further broad form, there is provided an apparatus for electrical cardiac pacing comprising: I a plurality of electrodes adapted to be disposed proximate atrial tissue; Sa cooling means adapted to apply a temperature decrease to a targeted portion of the heart, C, wherein the cooling means is selected from the group consisting of: a means for applying a cooling fluid to the targeted portion, an electrical cooling apparatus, a mechanical cooling apparatus, and means for cooling via an endothermic chemical reaction; a sense amplifier connected to at least one of the plurality of electrodes to sense atrial fibrillation; a memory in electrical communication with the sense amplifier, for recording a baseline of cardiac activity; an electrical stimulation driver, connected to at least one of the plurality of electrodes, to stimulate atrial tissue; and processor circuitry programmed to determine status of pacing capture; wherein, in the event that atrial fibrillation is sensed, the cooling means applies the temperature decrease to the targeted portion and the electrical stimulation driver uses a precapture stimulation protocol, wherein, in the event that capture status is determined, the electrical stimulation driver uses a post-capture stimulation protocol, and wherein the pre-capture stimulation protocol and the post-capture stimulation protocol comprise a procedure, and wherein the procedure is selected from the group consisting of: pre-capture stimulation at threshold with post-capture stimulation at threshold, pre-capture stimulation subthreshold with post-capture stimulation subthreshold, and pre-capture stimulation at threshold with post-capture stimulation subthreshold.

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,q 0 Typically, the procedure is further selected from the group consisting of 0_ conventional stimulation pre-capture with biphasic stimulation post-capture, biphasic stimulation pre-capture with conventional stimulation post-capture, and biphasic stimulation pre-capture with biphasic stimulation post-capture.

Typically, the method further includes inserting at least two electrodes O intravenously into a patient; and placing the atleast two electrodes in conjunction with cardiac tissue.

0 Typically, the method further includes locating at least one electrode in the right atrial appendage; locating at least one electrode in the right atrial septum; and locating at least one electrode in the coronary sinus.

Typically, the method further includes locating at least one electrode in the left free wall.

Typically, each of the at least two electrodes has an independent generator.

Typically, the method further includes entraining the cardiac tissue in conjunction with each of the at least one electrodes separately; and bringing the cardiac tissue in conjunction with each of the at least one electrodes to the same phase.

Typically, the method further includes sequencing the stimulation of the at least two electrodes to mimic a normal heart beat.

Typically, each of the at least two electrodes comprise sensing circuits and wherein the sensing circuits provide sensing data comprising determining the site of at least one atrial ectopic foci.

Typically, determining the site of at least one atrial ectopic foci comprises triangulating the sensing data.

Typically, determining status of capture comprises establishing a baseline of cardiac activity; and monitoring the baseline for changes.

Typically, the baseline of cardiac activity comprises a template of parameters selected from the group consisting of electrocardiogram data, mechanical motion, and probability density function data.

Typically, biphasic stimulation comprises: defining a first stimulation phase with a first phase polarity, a first phase amplitude, a P. PDOCSNTXS\Spe=sI2254271 .vdd prg, d copy doc2I1m6

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O first phase shape and a first phase duration; 00 defining a second stimulation phase with a polarity opposite to the first phase polarity, a second phase amplitude, a second phase shape and a second phase duration; and 5 applying the first stimulation phase and the second stimulation phase in sequence to cardiac tissue.

Typically, the first phase polarity is positive.

STypically, the first phase amplitude is less than the second phase amplitude.

Typically, the first phase amplitude is ramped from a baseline value to a second value.

Typically, the second value is equal to the second phase amplitude.

Typically, the second value is at a maximum subthreshold amplitude.

Typically, the maximum subthreshold amplitude is about 0.5 to 3.5 volts.

Typically, the first phase duration is at least as long as the second phase duration.

Typically, the first phase duration is about one to nine milliseconds.

Typically, the second phase duration is about 0.2 to 0.9 milliseconds.

Typically, the second phase amplitude is about two volts to twenty volts.

Typically, the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts.

Typically, the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity and duration.

Typically, applying the first stimulation phase further comprises a series of rest periods.

Typically, applying the first stimulation phase further comprises applying a rest period of a baseline amplitude after at least one stimulating pulse.

Typically, the rest period is of equal duration to the stimulating pulse.

Typically, the first phase amplitude is at a maximum subthreshold amplitude.

Typically, the first phase duration is at least as long as the second phase duration.

Typically, the first stimulation phase is initiated greater than 200 milliseconds P XWPDOCSTXSSpcaU225427I1 a-nedd pql acIea vopydoc12/13D6

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O after heart beat.

00 Typically, sensing atrial fibrillation comprises monitoring parameters selected from the group consisting of arterial blood pressure, rate of electrocardiogram deflections, and probability density function of the 5 electrocardiogram.

STypically, electrically cooling the targeted portion comprises transferring heat away from the targeted portion by absorbing heat into a Peltier cooler.

STypically, transferring heat away from the targeted portion by absorbing heat into a Peltier cooler comprises transferring heat away from the targeted portion by absorbing heat into a heat sink located at the targeted portion and thermally coupled to the Peltier cooler enclosed in a housing that is implanted in the patient's torso.

Typically, the Peltier cooler is electrically connected to a power source located within the housing.

Typically, the heat sink is coupled to the Peltier cooler through mechanical contact.

Typically, the heat sink is coupled to the Peltier cooler through a thermal transfer fluid.

Typically, the method further includes: determining the temperature of the targeted portion at the time of onset of atrial fibrillation; monitoring the temperature of the targeted portion; and ceasing applying the temperature decrease to the targeted portion when a preset cooling measure has been achieved.

Typically, the preset cooling measure is selected from the group consisting of a present temperature decrease, a preset temperature, and a preset cooling period.

Brief Description of the Drawings Figure 1 illustrates the location of leads and electrodes in relation to a human heart.

Figure 2 illustrates an alternative location of leads and electrodes in relation to a human heart.

P:\WPDOCS\GLF\specfI2254271amded.doc-2904/04 -21- 1 Figure 2A illustrates a block diagram of the major functional components of 2 the implanted pacemaker.

3 Figure 3 is a schematic representation of leading anodal biphasic stimulation.

4 Figure 4 is a schematic representation of leading cathodal biphasic stimulation.

6 Figure 5 is a schematic representation of leading anodal stimulation of low 7 level and long duration, followed by conventional cathodal stimulation.

8 Figure 6 is a schematic representation of leading anodal stimulation of 9 ramped low level and long duration, followed by conventional cathodal stimulation.

Figure 7 is a schematic representation of leading anodal stimulation of low 11 level and short duration, administered in series followed by conventional cathodal 12 stimulation.

13 Figure 8 illustrates the practice of the present invention.

14 Figure 9 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue according to embodiments of the present invention 16 Figure 10 illustrates a methodology for inhibiting the conduction of spurious 17 electrical impulses in cardiac tissue by application of a temperature decrease to cardiac 18 tissue according to embodiments of the present invention.

19 Figure 11 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue by application of a temperature decrease and at least 21 one pacing pulse to cardiac tissue according to embodiments of the present invention.

22 Figure 12 illustrates a methodology for suppressing arrhythmia by selective 23 application of a temperature decrease to a targeted portion of the heart and pacing pulses to 24 cardiac tissue according to embodiments of the present invention.

Figure 13 illustrates an apparatus for inhibiting the conduction of electrical 26 impulses in cardiac tissue by application of a temperature decrease to a targeted portion of 27 the heart according to embodiments of the present invention.

28 29 Description of the Preferred Embodiments Electrical stimulation is delivered via lead or electrode These leads 31 can be epicardial (external surface of the heart) or endocardial (internal surface of the P:\WPDOCS\GLF\spcil12254271ameded.doc-29/04/04 -22- 1 heart) or any combination of epicardial and endocardial. Leads are well known to 2 those skilled in the art. Lead systems can be unipolar or bipolar. A unipolar lead has 3 one electrode on the lead itself, the cathode. Current flows from the cathode, 4 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 6 each other at the distal end, and both electrodes lie within the heart.

7 Figure 1 illustrates a plan view of implantable electronic stimulation device 8 102 and its associated lead and electrode system, in conjunction with human heart 9 104. As illustrated, the device includes right atrial appendage lead 106, right atrial septal lead 108, 23 1 first coronary sinus lead 110 and second coronary sinus lead 112. Each of these multiple 2 small electrodes can be inserted intravenously and includes an independent generator.

3 Figure 2 illustrates a plan view of implantable electronic stimulation device 102 4 illustrating an alternative location of leads and electrodes in relation to human heart 104.

As illustrated, the device includes right atria appendage lead 106, right atrial septal lead 6 108, first coronary sinus lead 110, second coronary sinus lead 112 and left free wall lead 7 204. Each of these multiple small electrodes can be inserted intravenously and includes an 8 independent generator. Because of the use of independent generators, each electrode can 9 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 septumn to the left side I11 of the heart. The aforementioned placement of leads is for illustration purposes only, and 12 is not intended as a limidtation. It is contemplated that multiple leads placed in a variety of 13 locations could be used.

14 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 16 phase; however, certain situations could require that each site is quickly brought to the 17 same phase. In an alternative embodiment, the sites can be sequenced to mimic a normal 18 heart beat. In addition to allowing multi-site stimulation capability, the sensing circuits of 19 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.

21 Referring to Figure 2A, a block diagram shows the major functional components 22 of the implanted pacemaker 102. Pacing/control circuitry 500, in conjunction with 23 microprocessor 501 detects the occurrence of tachycardia (and/or bradycardia) and in -24- 1 response thereto controls the delivery of the various pacing therapies available via control 2 bus 512. The microprocessor 501 also detects the occurrence ofatrial fibrillation.

3 Detection ofatrial fibrillation may be accomplished by the microprocessor 501 using any 4 of the various detection methodologies known to the art. Generally, atrial fibrillation may be detected in response to an extended series of high rate atrial depolarizations. If greater 6 specificity for atrial fibrillation is desired, analysis of regularity of rate waveform 7 morphology may also be employed. Termination ofatrial fibrillation may be detected in 8 response to a decrease in the rate of atrial depolarizations and/or an increase in their 9 regularity.

The operation of the microprocessor 501 is controlled by programming stored in a 11 read only memory 505 and in a random access memory 503. The operation of the device 12 may be altered by the physician by altering the programming stored in the memory 503, 13 using control and telemetry circuitry conventional in implantable stimulators.

14 Communication to and from the microprocessor 501, the memories 503, 505, and the control logic 500 is accomplished using an address/data bus 507.

16 The atrial sensing circuit 509 can be any conventional cardiac sense amplifier 17 circuits equivalent to any atrial cardiac sensing circuits employed in previous devices 18 known in the art.

19 The implanted pacemaker 102 has a switch matrix 516 that allows selective delivery of pacing pulses from the atrial pacing driver 514 to the electrodes. The matrix 21 516 may be embodied as simply a collection of one or more FET and/or SCR switches 22 activated under control of the pacing/control circuitry 500 to selectively pacing circuitry 23 516 to electrodes 106 and 108, or to electrodes 110 and 112, or other combinations of the 24 electrodes. Thus, atrial anti-tachycardia (or anti-bradycardia pacing) is performed using any combination of the deployed pacing electrodes.

P:\WPDOCS\REQ\bkup 2OO3fl 2003\7626710page13.do-29/0404 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: initiated at threshold and remains at threshold; initiated subthreshold and remains subthreshold; conventional prior to capture and then biphasic biphasic prior to capture and then conventional or 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.

Figures 3 through 7 depict a range of biphasic stimulation protocols. These protocols have been disclosed in United States Patent Application No. 08/699,552 to Mower.

Figure 3 depicts biphasic electrical stimulation wherein a first stimulation phase comprising anodal stimulus 302 is administered having amplitude 304 and duration 306.

-26- 1 This first stimulation phase is immediately followed by a second stimulation phase 2 comprising cathodal stimulation 308 of equal intensity and duration.

3 Figure 4 depicts biphasic electrical stimulation wherein a first stimulation phase 4 comprising cathodal stimulation 402 having amplitude 404 and duration 406 is administered. This first stimulation phase is immediately followed by a second 6 stimulation phase comprising anodal stimulation 408 of equal intensity and duration.

7 Figure 5 depicts a preferred embodiment ofbiphasic stimulation wherein a first 8 stimulation phase, comprising low level, long duration anodal stimulation 502 having 9 amplitude 504 and duration 506, is administered. This first stimulation phase is immediately followed by a second stimulation phase comprising cathodal stimulation 508 11 of conventional intensity and duration. In differing alternative embodiments, anodal 12 stimulation 502 is: 1) at maximum subthreshold amplitude; 2) less than three volts; 3) of a 13 duration of approximately two to eight milliseconds; and/or 4) administered over 200 14 milliseconds post heart beat. Maximum subthreshold amplitude is defined for purposes of this application as the maximum stimulation amplitude that can be administered without 16 eliciting a contraction. In a preferred embodiment, anodal stimulation is approximately 17 two volts for approximately three milliseconds duration. In differing alternative 18 embodiments, cathodal stimulation 508 is: 1) of a short duration; 2) approximately 0.3 to 19 1.5 milliseconds; 3) of a high amplitude; 4) in the approximaie range of three to twenty volts; and/or 5) of a duration less than 0.3 millisecond and at a voltage greater than twenty 21 volts. In a preferred embodiment, cathodal stimulation is approximately six volts 22 administered for approximately 0.4 millisecond. In the manner disclosed by these 23 embodiments, as well as those alterations and modifications which can become obvious -27- 1 upon the reading of this specification, a maximum membrane potential without activation 2 is achieved in the first phase of stimulation.

3 Figure 6 depicts an alternative preferred embodiment of biphasic stimulation 4 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 6 linear or non-linear, and the slope can vary. This anodal stimulation is immediately 7 followed by a second stimulation phase comprising cathodal stimulation 608 of 8 conventional intensity and duration. In alternative embodiments, anodal stimulation 602: 9 rises to a maximum subthreshold amplitude less than three volts; is of a duration of approximately two to eight milliseconds; and/or is administered over 200 milliseconds 11 post heart beat. In yet other alternative embodiments, cathodal stimulation 608 is: of a 12 short duration; approximately 0.3 to 1.5 milliseconds; of a high amplitude; in 13 the approximate range of three to twenty volts; and/or of a duration less than 0.3 14 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 16 upon the reading of this specification, a maximum membrane potential without activation 17 is achieved in the first phase of stimulation.

18 Figure 7 depicts biphasic electrical stimulation wherein a first stimulation phase, 19 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 21 administered at baseline amplitude. In an alternative embodiment, rest period 706 is of a 22 differing duration than stimulation period 708, and is administered at baseline amplitude.

23 Rest period 706 occurs after each stimulation period 708, with the exception that a second -28- 1 stimulation phase, comprising cathodal stimulation 710 of conventional intensity and 2 duration, immediately follows the completion of series 702. In alternative embodiments: 3 the total charge transferred through series 702 of anodal stimulation is at the maximum 4 subthreshold level; and/or the first stimulation pulse of series 702 is administered over 200 milliseconds post heart beat. In yet other alternative embodiments, cathodal 6 stimulation 710 is: of a short duration; approximately 0.3 to 1.5 milliseconds; of 7 a high amplitude; in the approximate range of three to twenty volts, and/or of a 8 duration less than 0.3 milliseconds and at a voltage greater than twenty volts.

9 Figure 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 11 example, direct sensing can be based on data from multiple atrial sensing electrodes. The 12 sensing electrodes sense the cardiac activity as depicted by electrical signals. For example, 13 as is known in the art, R-waves occur upon the depolarization of ventricular tissue and P- 14 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 16 heart beat, and thereby determine whether the heart is undergoing arrhythmia. This 17 determination can be made by determining the rate of the sensed R-waves and/or P-waves 18 and comparing this determined rate against various reference rates.

19 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 21 heart rate. When applying the primary rate criteria, if the heart rate should exceed a 22 predefined level, then treatment is begun. Sensing electronics set to sudden onset criteria 23 ignore those changes which occur slowly, and initiate treatment when there is a sudden -29- 1 change such as immediate paroxysmal arrhythmia. This type of criteria would thus 2 discriminate against sinus tachycardia. Stability of rate can also be an important criteria.

3 For example, treatment with a ventricular device would not be warranted for a fast rate 4 that varies, here treatment with an atrial device would be indicated.

In alternative embodiments, sensing can be indirect. Indirect sensing can be based 6 on any of various functional parameters such as arterial blood pressure, rate of the 7 electrocardiogram deflections or the probability density function (pdf) of the 8 electrocardiogram. While it has been known'in the art to apply pdf to the global 9 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 11 electrodes are specific to the atrium and data related to the R wave is canceled out. Thus, 12 whether or not to administer treatment can also be affected by pdf monitoring of the time 13 the signal spends around the baseline.

14 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 16 rhythm. For example, in a ventricular rhythm, an atrial test impulse can capture the 17 atrium, but the ventricular rhythm will continue unchanged afterwards. In an atrial 18 rhythm, (or Sinus rhythm), if the atrial test pulse captures, the timing of all subsequent 19 beats is changed. To determine ifa 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 21 so, the beat can be inferred to have captured. In addition, the pdf pattem of the rhythm can 22 be shown to have changed, inferring capture.

23 Thus, in a preferred embodiment, sensing electronics are based upon multiple 1 criteria. In addition, the present invention envisions devices working in more than one 2 chamber such that appropriate treatment can be administered to either the atrium or the 3 ventricle in response to sensing electronics based upon a variety of criteria, including those 4 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 6 recorded 804. The template can be based on parameters such as electrocardiogram data, 7 mechanical motion and/or probability density function data. in an alternative embod iment, 8 the template is established after capture has occurred.

9 Pacing is initiated 806. In a preferred embodiment, stimulation is administered at threshold until capture has occurr-ed, at which time stimulation is adm-inistered at a I11 subthreshold level. In alternative embodiments, stimulation is: initiated at threshold 12 and remains at threshold; initiated subthreshold and remains subthreshold; (3) 13 conventional prior to capture and then biphasic; bipliasic prior to capture and then 14 conventional or biphasic throughout The atrium is monitored throughout this initial pacing period to determine the 16 status of capture 808. Capture can be determined by multiple means. First, capture or the 17 loss thereof, can be determined by monitoring cardiac rhythm. Loss of capture can result 18 in a change in timing of the heart beat.

19 Second, capture or the loss thereof, can be determined through monitoring the previously described template. Where the template is established pre-stimulation, a 21 change in the baseline signifies capture. Where the template is established after capture 22 has occurred, a change in the template characteristics signifies loss of captu.re. The 23 templates can be established and/or updated at any time.

1 One cptue ocur tu ~aian -31 I One cptue ocursthesfuulaionprokocol of the. entrained sites is adjuste 810.

2 In a first embodiment the Stimulation rates of the entrained sites are slowed 3 simultaneously 1 and then stopped. [n a second emnbodirneat, the spread of conduction is 4 slowed. In a third embodiment, the stimulation speed is increaged anid stimulation is then stopped- In addition to-adjusting stimulation razes upon the occurrence of capture, the 6 stimulation protocol can also be adjusted such that if stimunlation of a conventional 7 nature was administered prior to caprure, biphasic stimulation is administered posta capture, if biplbasic stimulation was administered prior to capture, conventional 9 stimulation is admuinistered post-capture or if bipbasic stimulation was administered prior to capture, biphasic, stimulation continnes to be administeed post-capure.

I1I Having thus described the basic concept of the inventon, it will be readily apparent 12 to those Silled ini the art that the foregoing detailed disclosure is intended to be presented 13 by way of example only, and is not limiting. Various alterations, improvements and 14 modifications will ocour and are intended to those sicifled in the art, but are not expressly is stated herein. These modifications, alteraions and improvements are intended to be 16 suggested hereby, and within the scope of the invention. Further, the pacing pulses 17 described in this specification are well within the capabilities of existing pacemaker 18 electronics with appTopl ale programming. Accordingly, thc invention is limited only by 19 the Molowing claims.

P:\WPDOCS\REQ\bxkup 203\Do 2003\7626710plge13.dm29O4/04 32 1 An embodiment of the present invention comprises an implantable cardiac 2 treatment/stimulation device designed to inhibit the conduction of spurious electrical 3 signals in cardiac tissue without pacing. The technique applied in the implantable device 4 comprises a cooling element for cooling cardiac tissue. Optionally, one or both of the cooling embodiments may be provided in combination with cathodal-only or biphasic 6 stimulation of the cardiac tissue.

7 An embodiment of the present invention provides a method for inhibiting the 8 conduction of spurious electrical impulses in cardiac tissue. The method comprises 9 establishing a temperature conducive to inhibited conduction of electrical impulses for a targeted portion of the heart; and applying a temperature decrease to the targeted portion to 11 maintain the established temperature. The temperature of the targeted portion is sensed. If 12 the targeted portion has reached the established temperature, the application of the 13 temperature decrease is ceased. If the targeted portion has not achieved the established 14 temperature, application of the temperature decrease to the targeted portion continues.

The decrease in temperature of the cardiac tissue may be achieved through various 16 means, including by way of example and not as a limitation, applying a cooling fluid to the 17 cardiac tissue, electrically cooling the cardiac tissue, and mechanically cooling the cardiac 18 tissue.

19 Another embodiment of the present invention provides methods for inhibiting the conduction of spurious electrical impulses in cardiac tissue. The method comprises 21 sensing the onset of arrhythmia, determining the temperature of the cardiac tissue at the 22 time of onset of arrhythmia, and applying a temperature decrease to the cardiac tissue. In 23 another method, the functioning of the cardiac tissue is sensed. If the cardiac tissue reverts 24 to sinus rhythm, the application of the temperature decrease is ceased. If the cardiac tissue has not reverted to sinus rhythm, the application of the temperature decrease to the cardiac 26 tissue is continued.

27 The decrease in temperature of the cardiac tissue may be achieved through various 28 means, including by way of example and not as a limitation, applying a cooling fluid to the 29 cardiac tissue, electrically cooling the cardiac tissue, mechanically cooling the cardiac tissue, and cooling the cardiac tissue via an endothermic chemical reaction. Examples of P:\WPDOCS\REQ\bwckp 2003\Dmv 2003\7626710pagc1.doc-29/04/04 33 1 cooling devices suitable for use in practicing the present invention are evaporative coolers, 2 radiative coolers, chillers, thermal holdover devices (such as thermal storage units, with or 3 without utilization of phase change phenomena), and gas expansion coolers. Cooling may 4 be accomplished via a heat exchanger structure or via direct contact.

In another embodiment of the present invention, sensing the onset of arrhythmia 6 comprises sensing a symptom indicative of arrhythmia. Various symptoms indicative of 7 arrhythmia may be sense, including by way of example and not as a limitation an electrical 8 change within the heart, and a change in a measure of heart function.

9 In another embodiment of the present invention, a method for inhibiting the conduction of spurious electrical impulses in cardiac tissue further comprising applying a 11 pacing pulse to cardiac tissue. Pacing may be accomplished by one or more electrodes in 12 contact with cardiac tissue, or electrodes located in the blood pool of one or more of the 13 heart chambers. In either method, the pacing pulse is applied to the one or more electrodes.

14 The pacing pulse may be a cathodal electrical waveform or a biphasic electrical waveform comprising cathodal and anodal elements.

16 Another embodiment of the present invention provides methods for inhibiting the 17 conduction of spurious electrical impulses in cardiac tissue. One or more portions of the 18 .heart affected by one or more reentry circuits is targeted. In an embodiment of the present 19 invention, each of the one or more targeted portions is selected from the group consisting of a right anterior-lateral atrial surface, a left anterior-lateral atrial surface, a right postero- 21 lateral atrial surfaces, and a left postero-lateral atrial surface. A heat-transfer operator is 22 situated at each of one or more targeted portions of the heart. In an embodiment of the 23 present invention, the heat-transfer operator is a Peltier cooler. The Peltier cooler may be 24 electrically connected to a power source implanted in the patient's torso. In another embodiment of the present invention, the heat-transfer operator is a heat sink that is 26 thermally coupled to a Peltier cooler implanted in a patient's torso. Optionally, the heat 27 sink is thermally couple using a mechanical contact or a thermal transfer fluid.

28 A symptom associated with an arrhythmia is detected, and, in response to detection 29 of the symptom, the heat is selectively transferred away from the targeted portion in the P:\WPDOCSREQ\bwkup 2003\De 2003\7626710pag3.do-29/04/04 -34- 1 heart related to arrhythmia by absorbing heat into the heat-transfer operator situated at the 2 targeted portion.

3 The symptom may be detected within the heart. The heat-transfer operator is 4 activated in response to the detection of arrhythmia. Various symptoms may be detected, including by way of example and not as a limitation, an electrical change within the heart 6 and a change in a measure of heart function.

7 Another method comprises sensing the functioning of the heart and, in the event the 8 symptom associated with arrhythmia is not detected, ceasing transferring heat away from 9 at least one of the targeted portions.

In another embodiment of the present invention, a method for inhibiting the 11 conduction of spurious electrical impulses in cardiac tissue further comprising applying a 12 pacing pulse to cardiac tissue. Pacing may be accomplished by one or more electrodes in 13 contact with cardiac tissue, or electrodes located in tthe blood pool of one or more of the 14 heart chambers. In either method, the pacing pulse is applied to the one or more electrodes.

The pacing pulse may be a cathodal electrical waveform or a biphasic electrical waveform 16 comprising cathodal and anodal elements.

17 In another embodiment of the present invention, a method for inhibiting the 18 conduction of spurious electrical impulses in cardiac tissue comprises applying a pacing 19 pulse to cardiac tissue. Pacing may be accomplished by one or more electrodes in contact with cardiac tissue, or electrodes located in the blood pool of one or more of the heart 21 chambers. In either method, the pacing pulse is applied to the one or more electrodes. The 22 pacing pulse may be a cathodal electrical waveform or a biphasic electrical waveform 23 comprising cathodal and anodal elements.

24 In another exemplary embodiment of the present invention, a method for suppressing arrhythmia in a patient is provided. A heat-transfer operator is implanted at 26 each of one or more targeted portions of a patient's heart. At least one heat-transfer 27 operator is operated to cool at least one targeted portion of the heart, thereby suppressing 28 the arrhythmia. In an embodiment of the present invention, the heat-transfer operator is a 29 Peltier cooler implanted on one or more targeted portions each selected from the group consisting of a right anterior-lateral atrial surface, a left anterior-lateral atrial surface, a P:\WPDOCS\REQ\bwkup 2003\Dw 2003\7626710pagc.doc-29104/D4 1 right postero-lateral atrial surfaces, and a left postero-lateral atrial surface. The Peltier 2 cooler may be electrically connected to a power source implanted in the patient's torso. In 3 another embodiment of the present invention, the heat-transfer operator is a heat sink 4 implanted on one or more targeted portions each selected from the group consisting of a right anterior-lateral atrial surface, a left anterior-lateral atrial surface, a right postero- 6 lateral atrial surfaces, and a left postero-lateral atrial surface that is thermally coupled to a 7 Peltier cooler implanted in a patient's torso. Optionally, the heat sink is thermally couple 8 using a mechanical contact or a thermal transfer fluid..

9 Another method for suppressing arrhythmia in a patient comprises implanting in the patient's heart at least one sensing-contact for sensing a symptom and connecting the 11 sensing-contact to a power source that supplies power for the operation of the heat-transfer 12 operator upon the sensing of a symptom. Various symptoms may be sensed, including by 13 way of illustration and not as a limitation, an electrical change within the heart, and a 14 measure of heart function.

In another embodiment of the present invention, the method for suppressing 16 arrhythmia in a patient further comprises applying a pacing pulse to cardiac tissue. Pacing 17 may be accomplished by one or more electrodes in contact with cardiac tissue, or 18 electrodes located in the blood pool of one or more of the heart chambers. In either 19 method, the pacing pulse is applied to the one or more electrodes. The pacing pulse may be a cathodal electrical waveform or a biphasic electrical waveform comprising cathodal 21 and anodal elements.

22 In still another embodiment of the present invention, methods are provided for 23 inhibiting the conduction of spurious electrical impulses in cardiac tissue. The onset of 24 arrhythmia is sensed and the sensed arrhythmia evaluated. The temperature of the cardiac tissue at the time of onset of arrhythmia is also determined. Based on the evaluation of the 26 sensed arrhythmia and cardiac tissue temperature, one or more remedial measures is 27 selected from the group consisting of applying a temperature decrease to the cardiac tissue 28 and applying a pacing pulse to the cardiac tissue. The selected remedial measure is 29 applied. Optionally, the cardiac tissue function is sensed and if the cardiac tissue reverts to P:\WPDOCS\REQ\bakcp 2003\D=c 2003\7626710pgc3.doc-29/04/G4 -36- 1 sinus rhythm, the application of the remedial measure ceases. Similarly, if the cardiac 2 tissue does not revert to sinus rhythm, application of the remedial measure continues.

3 In still other embodiments of the present invention, apparatuses for inhibiting the 4 conduction of spurious electrical impulses in cardiac tissue are provided. An apparatus comprises a sensing means for sensing the onset of arrhythmia and a cooling means 6 responsive to the sensing means for applying a cooling stimulus to the cardiac tissue. An 7 apparatus further comprises logic means for sensing when a sinus rhythm has been 8 reestablished in the cardiac tissue and for halting the cooling stimulus in the event a sinus 9 rhythm has been reestablished. Additional means are provided to continue the cooling stimulus in the event a sinus rhythm has not been reestablished.

11 Cooling means include, by way of illustration and not as a limitation, means for 12 applying a cooling fluid to the cardiac tissue, an electrical cooling apparatus, and a 13 mechanical cooling apparatus. Additionally, the sensing means may be adapted to sense a 14 symptom associated with an arrhythmia. By way of illustration and not as a limitation, the symptom may be an electrical change within the heart and a measure of heart function.

16 Another apparatus of the present invention further comprises a cardiac stimulation 17 generator and one or more electrodes in contact with cardiac tissue. The electrodes are 18 connected to the cardiac stimulation generator, which is adapted to apply a pacing pulse as 19 a cathodal electrical waveform or a biphasic waveform to the caridiac tissue. In an alternative embodiment of the present invention, the electrodes are in contact with the 21 cardiac blood pool. Optionally, the cardiac stimulation generator is responsive to the 22 sensing means.

23 Yet another apparatus of the present invention for inhibiting the conduction of 24 spurious electrical impulses in cardiac tissue comprises a sensor for detecting a symptom associated with an arrhythmia. By way of illustration and not as a limitation, the symptom 26 may be an electrical change within the heart, a measure of heart function, and a change 27 indicative of an arrhythmia. A heat-transfer operator is situated at each of one or more 28 targeted portions in the heart. In an embodiment of the present invention, the heat-transfer 29 operator is a Peltier cooler. The Peltier cooler may be electrically connected to a power source implanted in the patient's torso. In another embodiment of the present invention, P:\WPDOCS\REQ\b kp 2003\De 2003\7626710pagI3ldo-29/4/04 -37- 1 the heat-transfer operator is a heat sink that is thermally coupled to a Peltier cooler 2 implanted in a patient's torso. Optionally, the heat sink is thermally couple using a 3 mechanical contact or a thermal transfer fluid.

4 The heat-transfer operator at each of the one or more targeted portions is adapted to respond to the sensor to remove heat from the targeted portion served by that heat-transfer 6 operator. The sensor may be located on the heat-transfer operator.

7 An apparatus further comprises logic means for sensing when a sinus rhythm has 8 been reestablished in the cardiac tissue and for halting the cooling stimulus in the event a 9 sinus rhythm has been reestablished. Additional means are provided to continue the cooling stimulus in the event a sinus rhythm has not been reestablished.

11 In another embodiment of the present invention, the apparatus further comprises a 12 power source adapted to apply power to the sensor and to activate the heat-transfer 13 operator upon detection of a symptom. Optionally, the power source stores sufficient 14 energy to suppress arrhythmia in a patient for an extended period of time. Additionally, the power source automatically ceases to apply power to the heat-transfer operator after the 16 one or more targeted portions are sufficiently cooled. In an embodiment of the present 17 invention, the one or more targeted portions are sufficiently cooled when there is a 18 subsidence of the symptom as detected by the sensing-contact. Alternatively, the one or 19 more targeted portions are sufficiently cooled when each targeted portion reaches a predetermined temperature as measured by a thermacouple. In yet another alternative 21 embodiment, the one or more targeted portions are sufficiently cooled when heat is 22 transferred away from the one or more targeted portions for a programmed period of time.

23 In an embodiment of the present invention, each of the one or more targeted 24 portions is selected from the group consisting of a right anterior-lateral atrial surface, a left anterior-lateral atrial surface, a right postero-lateral atrial surfaces, and a left postero-lateral 26 atrial surface.

27 In another embodiment of present invention, the apparatus further comprises a 28 cardiac stimulation generator and one or more electrodes in contact with cardiac tissue.

29 The electrodes are connected to the cardiac stimulation generator, which is adapted to apply a pacing pulse as a cathodal electrical waveform or a biphasic waveform to the P:\WPDOCS\REQ\backup 203\Dc 2003\7626710pagI3ldoc-29/O4/O4 -38- 1 caridiac tissue. In an alternative embodiment of the present invention, the electrodes are in 2 contact with the cardiac blood pool. Optionally, the cardiac stimulation generator is 3 responsive to the sensing means.

4 Yet another apparatus of the present invention suppresses arrhythmia in a patient.

The apparatus comprises a sensor for detecting a symptom associated with an arrhythmia.

6 By way of illustration and not as a limitation, the symptom may be an electrical change 7 within the heart, a measure of heart function, and a change indicative of an arrhythmia. A 8 heat-transfer operator is situated at each of one or more targeted portions in the heart, In 9 response to the detection of arrhythmia, the heat-transfer operator at each of the one or more targeted portions is adapted to transfer heat away from the targeted portion served by 11 that heat-transfer operator. As result, each of the one or more targeted portions is cooled 12 and the arrhythmia is suppressed.

13 In an embodiment of the present invention, the heat-transfer operator is a Peltier 14 cooler. The Peltier cooler may be electrically connected to a power source implanted in the patient's torso. The power source is adapted to apply power to the sensor and to 16 activate the heat-transfer operator upon the detection of a symptom. In another 17 embodiment of the present invention, the heat-transfer operator is a heat sink that is 18 thermally coupled to a Peltier cooler implanted in a patient's torso. Optionally, the heat 19 sink is thermally couple using a mechanical contact or a thermal transfer fluid.

In yet another embodiment of the present invention, the one or more targeted 21 portions is each selected from the group consisting of a right anterior-lateral atrial surface, 22 a left anterior-lateral atrial surface, a right postero-lateral atrial surfaces, and a left postero- 23 lateral atrial surface.

24 In another embodiment of the present invention, the apparatus further comprises a power source adapted to apply power to the sensor and to activate the heat-transfer 26 operator upon detection of a symptom.

27 In another embodiment of present invention, the apparatus further comprises a 28 cardiac stimulation generator and one or more electrodes in contact with cardiac tissue.

29 The electrodes are connected to the cardiac stimulation generator, which is adapted to apply a pacing pulse as a cathodal electrical waveform or a biphasic waveform to the P:\WPDOCS\REQ\b.Lkp 2003\D. 2003\7626710pagc13.dm-29/04/04 -39- 1 caridiac tissue. In an alternative embodiment of the present invention, the electrodes are in 2 contact with the cardiac blood pool. Optionally, the cardiac stimulation generator is 3 responsive to the sensor.

4 Figure 9 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue according to embodiments of the present invention.

6 Referring to Figure 9, a temperature conducive to inhibited conduction of electrical 7 impulses is established for a targeted portion of the heart 100. A temperature decrease is 8 applied to the targeted portion to maintain the established temperature 110. The 9 temperature of the targeted portion is sensed 115 and a determination is made as to whether the targeted portion has reached the established temperature 120. If the targeted 11 portion has reached the established temperature, the application of the temperature 12 decrease is ceased 125. If the targeted portion has not achieved the established 13 temperature, application of the temperature decrease to the targeted portion continues 130.

14 While Figure 1 illustrates a single targeted portion, the present invention is not so limited.

One or more targeted portions may be identified and associated with an established 16 temperature 120 without departing from the scope of the present invention.

17 The decrease in temperature of the cardiac tissue may be achieved through various 18 means, including by way of example and not as a limitation, applying a cooling fluid to the 19 cardiac tissue, electrically cooling the cardiac tissue, and mechanically cooling the cardiac tissue.

21 Figure 10 illustrates a methodology for inhibiting the conduction of electrical 22 spurious electrical impulses in cardiac tissue by application of a temperature decrease to 23 cardiac tissue according to embodiments of the present invention. Referring to Figure 24 the onset of arrhythmia is sensed 200 and a temperature decrease applied to cardiac tissue 210. The functioning of the cardiac tissue is sensed 215 and a determination is made as to 26 whether the cardiac tissue has reverted to sinus rhythm 220. If the cardiac tissue has 27 reverted to sinus rhythm, the application of a temperature decrease to the cardiac tissue is 28 ceased 225. If the cardiac tissue has not reverted to sinus rhythm, the application of a 29 temperature decrease to the cardiac tissue is continued 230.

P:\WPDOCS\REQ\bukup 2003\Dev 2003\7626710page3.doc-29/04/04 1 Figure 11 illustrates a methodology for inhibiting the conduction of spurious 2 electrical impulses in cardiac tissue by application of a temperature decrease and at least 3 one pacing pulse to cardiac tissue according to embodiments of the present invention.

4 Referring to Figure 11, the onset of arrhythmia is sensed 300. At least one pacing pulse and a temperature decrease are applied to cardiac tissue 310. The functioning of the 6 cardiac tissue is sensed 315 and a determination is made as to whether the cardiac tissue 7 has reverted to sinus rhythm 320. If the cardiac tissue has reverted to sinus rhythm, the 8 application of the at least one pacing pulse and a temperature decrease to the cardiac tissue 9 is ceased 325. If the cardiac tissue has not reverted to sinus rhythm, the application of the at least one pacing pulse and a temperature decrease is continued 330. As previously 11 described, a pacing pulse may be cathodal or biphasic and may be applied to the cardiac 12 tissue through electrodes in contact with the blood pool of the heart or in contact with the 13 cardiac tissue.

14 Figure 12 illustrates a methodology for suppressing arrhythmia by selective application of a temperature decrease to a targeted portion of the heart and pacing pulses to 16 cardiac tissue according to embodiments of the present invention. Referring to Figure 12, 17 the onset of arrhythmia is sensed 400. The arrhythmia is evaluated and the temperature of 18 the cardiac tissue is determined 405. Based on the evaluation of the sensed arrhythmia and 19 cardiac tissue temperature, one or more remedial measures is selected from the group consisting of applying a temperature decrease to the cardiac tissue and applying a pacing 21 pulse to the cardiac tissue 410. The selected remedial measure(s) is (are) applied to the 22 cardiac tissue 415. The selective application of heart cooling and pacing pulses is 23 determined by logic incorporated into a computer processor. In an embodiment of the 24 present invention, the processor is located in the means that provides the pacing pulse.

Alternatively, the processor is located in the means that provides the cooling function. In 26 yet another embodiment of the present invention, the processor is a separate device. The 27 functioning of the cardiac tissue is sensed 420 and a determination is made as to whether 28 the cardiac tissue has reverted to sinus rhythm 425. If the cardiac tissue has reverted to 29 sinus rhythm, the application of the selected remedial measure(s) ceases 430. If the cardiac tissue has not reverted to sinus rhythm, the application of the selected remedial 31 measure(s) continues 435. In an alternate embodiment, the temperature of the cardiac P:\WPDOCS\REQ\bakp 2OO3\D. 2003\7626710pl3.doc-29/04/04 -41- 1 tissue and the arrhythmia are re-evaluated and one or more remedial measures are again 2 selected.

3 As previously described, the pacing pulse may be cathodal or biphasic and may be 4 applied to the cardiac tissue through electrodes in contact with the blood pool of the heart or in contact with the cardiac tissue.

6 Figure 13 illustrates an apparatus for inhibiting the conduction of spurious 7 electrical impulses in cardiac tissue by application of a temperature decrease to a targeted 8 portion of the heart according to embodiments of the present invention. Referring to 9 Figure 13, a heart sensing means 510 and a heart cooling means 515 are applied to a heart 505 in a patient 500. In an embodiment of the present invention, heart sensing means 510 11 senses the onset of arrhythmia. In response to the heart sensing means 510, cooling is 12 applied to the heart via heart cooling means 515. Logic 520 senses when a sinus rhythm 13 has been reestablished in the cardiac tissue. If a sinus rhythm has been reestablished in the 14 cardiac tissue, logic 520 halts the cooling stimulus to cooling means 515. If a sinus rhythm has not been reestablished in the cardiac tissue, logic 520 continues the cooling stimulus to 16 cooling means 515.

17 In an embodiment of the present invention, heart cooling means 515 comprises a 18 Peltier cooler. Such heat-transfer operators pass electricity through junctions between 19 dissimilar metals. The atoms of the dissimilar metals have a difference in energy levels that results in a step between energy levels at each of the metals' junctions. As electricity is 21 passed through the metals, the electrons of the metal with the lower energy level pass the 22 first step as they flow to the metal with the higher energy level. In order to pass this step 23 and continue the circuit, the electrons must absorb heat energy that causes the metal at the 24 first junction to cool. At the opposite junction, where electrons travel from a high energy level to a low energy level they give off energy which results in an increase in temperature 26 at that junction.

27 As will be appreciated by those skilled in the art, other cooling means may be 28 utilized to perform the functions of the present invention without departing from its scope.

29 By way of illustration and not as a limitation, heart cooling means 515 may be another device or system that absorbs heat from a specific area and accomplishes heat transfer P:\WPDOCS\REQ\bwkup 2003\Dcc 2003\76267cpagcl3.doc.29/04/4 42 1 through convection of fluids or conduction. Alternatively, cooling may be accomplished by 2 a mechanical hydraulic system for pumping cooled fluid into a bladder on the surface of 3 the atrium. The amount of cooling applied and the total temperature of the heart may be 4 monitored through a "thermostat" function of the apparatus.

In another embodiment of the present invention, heart cooling means further 6 comprises a heat sink thermally coupled to a heat-transfer operator, such as a Peltier 7 cooler. The heat-transfer operator is electrically connected to a power source that supplies 8 a current through the heat-transfer operator to affect heat transfer. The power source 9 operates efficiently by powering off the heat-transfer operator supply when heat transfer is not needed. When heat transfer is desired, the power source can be activated to supply a 11 DC current to the heat-transfer operator that will, in turn, activate heat transfer from the 12 targeted portion through the temperature-contact to the cold junction of the heat-transfer 13 operator.

14 In another embodiment of the present invention, the heat-transfer operator is responsive to the heart sensing means 510, which detects a symptom of arrhythmia. The 16 symptoms detected by the heart sensing means may be electrical or physiological measures 17 indicative of arrhythmia.

18 In yet another embodiment of the present invention, logic 520 determines a time for 19 sufficient cooling the heart. The time necessary for sufficient cooling may be programmed into logic 520 or may be calculated by logic 520 based on information obtained from heart 21 sensing means 510.

22 Referring again to Figure 13, in another embodiment of the present invention, a 23 cardiac stimulation generator 530 applies a pacing pulse to the cardiac tissue via electrode 24 525. While Figure 13 illustrates a single electrode, the present invention is not so limited.

As will be appreciated by those skilled in the art, multiple electrodes may be utilized 26 without departing from the scope of the present invention. Additionally, electrode 525 27 may be placed in contact with the cardiac tissue or be located within a blood pool of the 28 heart. Cardiac stimulation generator 530 is responsive to heart sensing means 510. The 29 pacing pulse generated by cardiac stimulation generator 530 may be a cathodal electrical waveform or a biphasic electrical waveform comprising cathodal and anodal elements.

P:\WPDOCS\REQ\backp 2003\Dc 2003\7626710pagc13.doc29104104 43 1 While the embodiments of the present invention have been directed to cooling 2 cardiac tissue for the purpose of inhibiting the conduction of spurious electrical impulses, 3 the present invention is not so limited. Spurious electrical signals affect other parts of the 4 human body the brain, skeletal muscles, pain receptors) that can be inhibited by cooling. As would be apparent to those skilled in the art, the embodiments of the present 6 invention may be applied to inhibit spurious electrical signals of other parts of the body 7 without departing from the scope of the present invention.

8 Systems and methods for inhibiting the conduction of spurious electrical impulses 9 in cardiac tissue have been described. It will be understood by those skilled in the art of the present invention may be embodied in other specific forms without departing from the 11 scope of the invention disclosed and that the examples and embodiments described herein 12 are in all respects illustrative and not restrictive. Those skilled in the art of the present 13 invention will recognize that other embodiments using the concepts described herein are 14 also possible.

The reference to any prior art in this specification is not, and should not be taken 16 as, an acknowledgment or any form of suggestion that that prior art forms part of the 17 common general knowledge in Australia.

18 Throughout this specification and the claims which follow, unless the context 19 requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or step or group 21 of integers or steps but not the exclusion of any other integer or step or group of integers or 22 steps.

23 24

Claims (84)

1. A method of atrial defibrillation comprising: sensing atrial fibrillation; recording a baseline of cardiac activity; applying a temperature decrease to a targeted portion of the heart using a cooling process selected from the group consisting of: applying a cooling fluid to the targeted portion, electrically cooling the targeted portion, mechanically cooling the targeted portion, and chemically cooling the targeted portion using an endothermic chemical reaction; determining status of capture; stimulating the atrium using a pre-capture stimulation protocol if capture has not been achieved; determining status of capture; and stimulating the atrium using a post-capture stimulation protocol, wherein the pre-capture stimulation protocol and the post-capture stimulation protocol comprise a procedure and wherein the procedure is selected from the group consisting of pre-capture stimulation at threshold with post-capture stimulation at threshold, pre-capture stimulation subthreshold with post-capture stimulation subthreshold and pre-capture stimulation at threshold with post-capture stimulation subthreshold.

2. The method of atrial defibrillation of claim 1, wherein the procedure is further selected from the group consisting of conventional stimulation pre-capture with biphasic stimulation post-capture, biphasic stimulation pre-capture with conventional stimulation post-capture, and biphasic stimulation pre-capture with biphasic stimulation post-capture.

3. The method of atrial defibrillation of claim 2, comprising: inserting at least two electrodes intravenously into a patient; and placing the at least two electrodes in conjunction with cardiac tissue.

4. The method of atrial defibrillation of claim 3 comprising: locating at least one electrode in the right atrial appendage; locating at least one electrode in the right atrial septum; and locating at least one electrode in the coronary sinus. The method of atrial defibrillation of claim 4 comprising: locating at least one electrode in the left free wall.

6. The method of atrial defibrillation of claim 3 wherein each of the at least two electrodes has an independent generator.

7. The method of atrial defibrillation of claim 3 comprising: entraining the cardiac tissue in conjunction with each of the at least one electrodes separately; and bringing the cardiac tissue in conjunction with each of the at least one electrodes to the same phase.

8. The method of atrial defibrillation of claim 3 comprising: sequencing the stimulation of the at least two electrodes to mimic a normal heart beat.

9. The method of atrial defibrillation of claim 3, wherein each of the at least two electrodes comprise sensing circuits and wherein the sensing circuits provide sensing data comprising: determining the site of at least one atrial ectopic foci. The method of atrial defibrillation of claim 9 wherein determining the site of at least one atrial ectopic foci comprises: triangulating the sensing data.

11. The method of atrial defibrillation of claim 2 wherein determining status of capture comprises: establishing a baseline of cardiac activity; and monitoring the baseline for changes.

12. The method of atrial defibrillation of claim 2 wherein the baseline of cardiac activity comprises a template of parameters selected from the group consisting of electrocardiogram data, mechanical motion, and probability density function data. -46-

13. The method of atrial defibrillation of claim 2 wherein biphasic stimulation comprises: defining a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phaseduration; defining a second stimulation phase with a polarity opposite to the first phase polarity, a second phase amplitude, a second phase shape and a second phase duration; and applying the first stimulation phase and the second stimulation phase in sequence to cardiac tissue.

14. The method of atrial defibrillation of claim 13 wherein the first phase polarity is positive.

15. The method of atrial defibrillation of claim 13 wherein the first phase amplitude is less than the second phase amplitude.

16. The method of atrial defibrillation of claim 13 wherein the first phase amplitude is ramped from a baseline value to a second value.

17. The method of atrial defibrillation of claim 16 wherein the second value is equal to the second phase amplitude.

18. The method of atrial defibrillation of claim 16 wherein the second value is at a maximum subthreshold amplitude.

19. The method of atrial defibrillation of claim 18 wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts.

20. The method of atrial defibrillation of claim 16 wherein the first phase duration is at least as long as the second phase duration.

21. The method of atrial defibrillation of claim 16 wherein the first phase duration is about one to nine milliseconds.

22. The method of atrial defibrillation of claim 16 wherein the second phase duration is about 0.2 to 0.9 milliseconds.

23. The method of atrial defibrillation of claim 16 wherein the second phase amplitude is about two volts to twenty volts. -47- -24. The method of atrial defibrillation of claim 16 wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts. The method of atrial defibrillation of claim 13 wherein the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity and duration.

26. The method of atrial defibrillation of claim 25 wherein the first stimulation phase further comprises a series of rest periods. C 27. The method of atrial defibrillation of claim 26 wherein applying the first stimulation phase further comprises applying a rest period of a baseline amplitude after at least one stimulating pulse.

28. The method of atrial defibrillation of claim 27 wherein the rest period is of equal duration to the stimulating pulse.

29. The method of atrial defibrillation of claim 13 wherein the first phase amplitude is at a maximum subthreshold amplitude.

30. The method of atrial defibrillation of claim 29 wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts.

31. The method of atrial defibrillation of claim 13 wherein the first phase duration is at least as long as the second phase duration.

32. The method of atrial defibrillation of claim 13 wherein the first phase duration is about one to nine milliseconds.

33. The method of atrial defibrillation of claim 13 wherein the second phase duration is about 0.2 to 0.9 milliseconds.

34. The method of atrial defibrillation of claim 13 wherein the second phase amplitude is about two volts to twenty volts.

35. The method of atrial defibrillation of claim 13 wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts.

36. The method of atrial defibrillation of claim 13 wherein the first stimulation phase is initiated greater than 200 milliseconds after heart beat. -48-

37. The method of atrial defibrillation of claim 2 wherein sensing atrial fibrillation comprises: monitoring parameters selected from the group consisting of arterial blood pressure, rate of electrocardiogram deflections, and probability density function of the electrocardiogram.

38. The method of atrial defibrillation of claim 1, wherein electrically cooling the targeted portion comprises transferring heat away from the targeted portion by absorbing heat into a Peltier cooler.

39. The method of atrial defibrillation of claim 38, wherein transferring heat away from the targeted portion by absorbing heat into a Peltier cooler comprises transferring heat away from the targeted portion by absorbing heat into a heat sink located at the targeted portion and thermally coupled to the Peltier cooler enclosed in a housing that is implanted in the patient's torso. The method of atrial defibrillation of claim 39, wherein the Peltier cooler is electrically connected to a power source located within the housing.

41. The method of atrial defibrillation of claim 39, wherein the heat sink is coupled to the Peltier cooler through mechanical contact.

42. The method of atrial defibrillation of claim 39, wherein the heat sink is coupled to the Peltier cooler through a thermal transfer fluid.

43. The method of atrial defibrillation of claim 1 further comprising: determining the temperature of the targeted portion at the time of onset of atrial fibrillation; monitoring the temperature of the targeted portion; ceasing applying the temperature decrease to the targeted portion when a preset cooling measure has been achieved.

44. The method of atrial defibrillation of claim 43 wherein the preset cooling measure is selected from the group consisting of a preset temperature decrease, a preset temperature, and a preset cooling period. An implantable cardiac stimulator to perform atrial defibrillation, the cardiac stimulator comprising: -49- sensor adapted to sense the onset of atrial fibrillation; recorder adapted to record a baseline of cardiac activity; a cooling means adapted to apply a temperature decrease to a targeted portion of the heart, wherein the cooling means is selected from the group consisting of: a means for applying a cooling fluid to the targeted portion, an electrical cooling apparatus, a mechanical cooling apparatus, and means for cooling via an endothermic chemical reaction; a processor adapted to determining whether capture has occurred; and electrodes adapted to stimulate the atrium after the onset of atrial fibrillation has been sensed, wherein, in the event it is determined that capture has not occurred, the atrium is stimulated using a pre-capture stimulation protocol, wherein, in the event it is determined that capture has occurred, the atrium is stimulated using a post-capture stimulation protocol, and wherein the pre-capture stimulation protocol and the post-capture stimulation protocol comprise a procedure, the procedure being selected from the group consisting of: pre- capture stimulation at threshold with post-capture stimulation at threshold, pre-capture stimulation subthreshold with post-capture stimulation subthreshold, and pre-capture stimulation at threshold with post-capture stimulation subthreshold.

46. The implantable cardiac stimulator of claim 45, wherein the procedure utilizes biphasic stimulation pre-capture with biphasic stimulation post-capture.

47. The implantable cardiac stimulator of claim 46, where at least two of the electrodes are adapted to be inserted intravenously into a patient, and at least two of the electrodes are adapted to be placed in conjunction with cardiac tissue.

48. The implantable cardiac stimulator of claim 47, wherein at least one of the electrodes is adapted to be located in the right atrial appendage, at least one of the electrodes is adapted to be located in the right atrial septum, and at least one of the electrodes is adapted to be located in the coronary sinus.

49. The implantable cardiac stimulator of claim 48, wherein at least one of the electrodes is adapted to be located in the left free wall. The implantable cardiac stimulator of claim 47, wherein each of the electrodes has an independent generator.

51. The implantable cardiac stimulator of claim 47, wherein the stimulation of the electrodes is sequenced so as to mimic a normal heart beat.

52. The implantable cardiac stimulator of claim 46, wherein the processor determines status of capture by monitoring for changes in the baseline of cardiac activity established by the recorder.

53. The implantable cardiac stimulator of claim 46, wherein the baseline of cardiac activity comprises a template of parameters selected from the group consisting of: electrocardiogram data, mechanical motion, and probability density function data.

54. The implantable cardiac stimulator of claim 46, wherein biphasic stimulation comprises: defining a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; defining a second stimulation phase with a polarity opposite to the first phase polarity, a second phase amplitude, a second phase shape and a second phase duration; and applying the first stimulation phase and the second stimulation phase in sequence to cardiac tissue. The implantable cardiac stimulator of claim 54, wherein the first phase polarity is positive.

56. The implantable cardiac stimulator of claim 54, wherein the first phase amplitude is less than the second phase amplitude.

57. The implantable cardiac stimulator of claim 54, wherein the first phase amplitude is ramped from a baseline value to a second value.

58. The implantable cardiac stimulator of claim 57, wherein the second value is equal to the second phase amplitude.

59. The implantable cardiac stimulator of claim 57, wherein the second value is at a maximum subthreshold amplitude. -51 The implantable cardiac stimulator of claim 59, wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts.

61. The implantable cardiac stimulator of claim 57, wherein the first phase duration is at least as long as the second phase duration.

62. The implantable cardiac stimulator of claim 57, wherein the first phase duration is about one to nine milliseconds.

63. The implantable cardiac stimulator of claim 57, wherein the second phase duration is about 0.2 to 0.9 milliseconds.

64. The implantable cardiac stimulator of claim 57, wherein the second phase amplitude is about two volts to twenty volts. The implantable cardiac stimulator of claim 57, wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts.

66. The implantable cardiac stimulator of claim 54, wherein the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity and duration.

67. The implantable cardiac stimulator of claim 66, wherein the first stimulation phase further comprises a series of rest periods.

68. The implantable cardiac stimulator of claim 67, wherein applying the first stimulation phase further comprises applying a rest period of a baseline amplitude after at least one stimulating pulse.

69. The implantable cardiac stimulator of claim 68, wherein the rest period is of equal duration to the stimulating pulse. The implantable cardiac stimulator of claim 54, wherein the first phase amplitude is at a maximum subthreshold amplitude.

71. The implantable cardiac stimulator of claim 70, wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts.

72. The implantable cardiac stimulator of claim 54, wherein the first phase duration is at least as long as the second phase duration. -52-

73. The implantable cardiac stimulator of claim 54, wherein the first phase duration is about one to nine milliseconds.

74. The implantable cardiac stimulator of claim 54, wherein the second phase duration is about 0.2 to 0.9 milliseconds.

75. The implantable cardiac stimulator of claim 54, wherein the second phase amplitude is about two volts to twenty volts.

76. The implantable cardiac stimulator of claim 54, wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts.

77. The implantable cardiac stimulator of claim 54, wherein the first stimulation phase is initiated greater than 200 milliseconds after heart beat.

78. The implantable cardiac stimulator of claim 54, wherein the first stimulation phase comprises anodal stimulation.

79. The implantable cardiac stimulator of claim 46, wherein the sensor senses atrial fibrillation by monitoring parameters selected from the group consisting of: arterial blood pressure, rate of electrocardiogram deflections, and probability density function of the electrocardiogram. The implantable cardiac stimulator of claim 46, further comprising: sensing circuits, each of the sensing circuits being connected to a respective one of the electrodes and being adapted to provide sensing data concerning the site of one or more atrial ectopic foci.

81. The implantable cardiac stimulator of claim 80, wherein the processor is connected to receive the sensing data from the sensing circuits and determines the site of one or more atrial ectopic foci by triangulating the sensing data.

82. The implantable cardiac stimulator of claim 45, wherein the electrical cooling apparatus comprises a Peltier cooler.

83. The implantable cardiac stimulator of claim 82, wherein electrical cooling apparatus further comprises a heat sink located at the targeted portion and thermally coupled to the Peltier cooler enclosed in a housing that is implanted in the patient's torso. -53

84. The implantable cardiac stimulator of claim 83, wherein the Peltier cooler is electrically connected to a power source located within the housing. The implantable cardiac stimulator of claim 83, wherein the heat sink is coupled to the Peltier cooler through mechanical contact.

86. The implantable cardiac stimulator of claim 83, wherein the heat sink is coupled to the Peltier cooler through a thermal transfer fluid.

87. The implantable cardiac stimulator of claim 45 further comprising: a temperature sensor adapted for: determining the temperature of the targeted portion at the time of onset of atrial fibrillation; and monitoring the temperature of the targeted portion; wherein the processor is further adapted for ceasing applying the temperature decrease to the targeted portion when a preset cooling measure has been achieved.

88. The implantable cardiac stimulator of claim 87, wherein the preset cooling measure is selected from the group consisting of a preset temperature decrease, a preset temperature, and a preset cooling period.

89. An apparatus for electrical cardiac pacing comprising: a plurality of electrodes adapted to be disposed proximate atrial tissue; a cooling means adapted to apply a temperature decrease to a targeted portion of the heart, wherein the cooling means is selected from the group consisting of: a means for applying a cooling fluid to the targeted portion, an electrical cooling apparatus, a mechanical cooling apparatus, and means for cooling via an endothermic chemical reaction; a sense amplifier connected to at least one of the plurality of electrodes to sense atrial fibrillation; a memory in electrical communication with the sense amplifier, for recording a baseline of cardiac activity; an electrical stimulation driver, connected to at least one of the plurality of electrodes, to stimulate atrial tissue; and -54- processor circuitry programmed to determine status of pacing capture; wherein, in the event that atrial fibrillation is sensed, the cooling means applies the temperature decrease to the targeted portion and the electrical stimulation driver uses a pre- capture stimulation protocol, wherein, in the event that capture status is determined, the electrical stimulation driver uses a post-capture stimulation protocol, and wherein the pre-capture stimulation protocol and the post-capture stimulation protocol comprise a procedure, and wherein the procedure is selected from the group consisting of: pre-capture stimulation at threshold with post-capture stimulation at threshold, pre-capture stimulation subthreshold with post-capture stimulation subthreshold, and pre-capture stimulation at threshold with post-capture stimulation subthreshold. The apparatus for electrical cardiac pacing of claim 89, wherein the procedure uses biphasic stimulation post-capture.

91. The apparatus for electrical cardiac pacing of claim 90, wherein the biphasic stimulation has a first phase that comprises anodal stimulation.

92. The apparatus for electrical cardiac pacing of claim 89, wherein the procedure uses biphasic stimulation pre-capture.

93. The apparatus for electrical cardiac pacing of claim 92, wherein the biphasic stimulation has a first phase that comprises anodal stimulation.

94. The apparatus for electrical cardiac pacing of claim 89, wherein the procedure uses biphasic stimulation pre-capture with biphasic stimulation post-capture. The apparatus for electrical cardiac pacing of claim 94, wherein the biphasic stimulation has a first phase that comprises anodal stimulation.

96. The apparatus for electrical cardiac pacing of claim 89 further comprising: a temperature sensor adapted for: determining the temperature of the targeted portion at the time of onset of atrial fibrillation; and monitoring the temperature of the targeted portion; PA\ PDOCSTXS Sp %1225421 nm-dd pgsm cIm opy doc.16110A)6 NO O wherein the processor circuitry is further programmed for ceasing applying the temperature decrease to the targeted portion when a preset cooling measure has been achieved.

97. The apparatus for electrical cardiac pacing of claim 96, wherein the preset 5 cooling measure is selected from the group consisting of a preset temperature O decrease, a preset temperature, and a preset cooling period.

98. A method of atrial defibrillation, the method being substantially as herein Sbefore described with reference to the accompanying figures.

99. An implantable cardiac stimulator to perform atrial defibrillation, the stimulator being substantially as herein before described with reference to the accompanying figures.

100. An apparatus for electrical cardiac pacing, the apparatus being substantially as herein before described with reference to the accompanying figures. The Mower Family CHF Treatment Irrevocable Trust By Its Patent Attorneys DAVIES COLLISON CAVE