AU2004201854B2 - Antitachycardial pacing - Google Patents

Description

Our Ref: 12254711 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 Antitachycardial pacing The following statement is a full description of this invention, including the best method of performing it known to me:- 5951 P:\WPDOCS\GLF\spec 12254711pages.doc-03/05/04 -1- 1 Title: ANTITACHYCARDIAL PACING 2 Inventor: Morton M. Mower, M. D.

3 4 Field of the Invention The present invention relates generally to implantable cardioverter/defibrillator 6 with antitachycardial pacing capabilities and/or a method of such pacing.

7 The present invention also relates generally to a system and method for the 8 stimulation of cardiac muscle tissue. In particular, the embodiments of the present 9 invention provide a system and method for treating cardiac tissue by cooling the cardiac tissue to inhibit the conduction of certain electrical signals in cardiac tissue and decrease 11 the duration of tachycardia and enhance the effects of pacing and defibrillation stimuli.

12 13 Background of the Invention 14 The typical implantable cardioverter/defibrillator (ICD) delivers an initial electrical countershock within ten to twenty seconds of arrhythmia onset, thereby saving countless 16 lives. Improved devices have antitachycardia pacing capabilities in addition to 17 cardioverting/defibrillating functions. These ICDs are capable of different initial responses 18 to one or moretachycardia as well as a programmable sequence of responses to a particular 19 arrhythmia.

The output energy level is generally set by a physician in accordance with a 21 patient's capture threshold, determined at the time of heart implantation. This threshold 22 represents the minimum pacing energy required to reliably stimulate a patient's heart.

23 However, due to trauma associated with the stimulation, scar tissue grows at the interface 24 between the implanted cardiac pacer leads and the myocardium. This scar tissue boosts the patient's capture threshold. To insure reliable cardiac capture, the output energy level is 26 thus generally set at a level which is a minimum of two times greater than the initially 27 measured capture threshold. A drawback to such an approach is that the higher stimulation 28 level causes more trauma to the cardiac tissue than would a lower level of stimulation, and 29 hence promotes the formation of scar tissue, thereby boosting the capture threshold.

The higher stimulation level also shortens battery life. This is not desirable, as a 31 PA\WPDOCS\GLPF\spI 225471 l.dc-03/05/04 -2shorter battery life necessitates more frequent surgery to implant fresh batteries.

Another drawback is the potential for patient discomfort associated with this higher stimulation level. This is because the higher stimulation level can stimulate the phrenic or diaphragmatic plexus or cause intercostal muscle pacing.

Lastly, the higher stimulation is less effective, due to entry block.

A need therefore exists for an ICD that can achieve reliable cardiac capture with a lower stimulation level, thereby causing less damage to the heart, extending battery life, causing less pain to the patient and having greater therapeutic effectiveness than currentlCDs. A need also exists for an ICD that can better entrain the heart and can entrain portions of the heart from a greater distance.

The function of the cardiovascular system is vital for survival. Through blood circulation, body tissues obtain necessary nutrients and oxygen, and discard waste 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 circulation.

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

These electrical impulses are sent from the sinoatrial node (the heart's natural pacemaker), 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 the atrioventricular (AV) node, where they are transmitted to the lower chambers of the heart ventricles via the "bundle branches." Thus, the electrical impulses travel from the sinoatrial node to the ventricles, to trigger and regulate the heartbeat.

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 impulses travel through the heart. Under normal conditions, each of the heart's contractions, or heartbeats, is triggered by electrical impulses. These electrical impulses are sent from the sinoatrial node (the heart's natural pacemaker), 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 the atrioventricular (AV) node, where they are transmitted to the lower chambers of the heart ventricles via the P:\WPDOCS\GLF\spWd\1225471 l.doc-03/05104 -3- "bundle branches." Thus, the electrical impulses travel from the sinoatrial node to the ventricles, to trigger and regulate the heartbeat.

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 (bradycardia) heartbeats. The cause of an arrhythmia may be related to a previous heart condition previous damage from a heart attack) or to other factors drugs, stress, not getting enough sleep). In the majority of cases, a skipped beat is not medically 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 cardiac death ("cardiac arrest") is responsible for approximately one-half of all deaths due to heart disease, and is the number one cause of death in the US, according to the North American Society of Pacing and Electrophysiology.

Almost all clinically important tachyarrhythmias are the result of a propagating 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 fibrillation, atrial flutter, atrial tychycardia, AV nodal reentry tachycardia, AV reentry (Wolff-Parkinson-White syndrome or concealed accessory AV connection), ventricular tachycardia, and bundled branch reentrant tachycardia.

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 circulate around a central area of block and encounter a unidirectional block such that it is forced to travel in one direction around the central block. (If the activation wave front is permitted to travel in both directions around the block, the wave fronts will collide and die 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 before the tissue has repolarized sufficiently to become excitable again. Thus, at least one area of slow conductance is part of the reentry circuit for virtually all clinical reentrant rhythms. Eliminating the slow conductance elements of a reentry circuit destroys the circuit.

Th\WPDOCS\GLFspm1225471 I.doc-03/05/04 -4- Atrial fibrillation (AF) is the most common type of sustained arrhythmia, affecting two million people each year in the United States alone. Both atrial fibrillation and atrial flutter increase the risk of stroke. According to the American Heart Association, they lead to over 54,000 deaths in the United States each year. The risk of developing atrial 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, abnormal heart rhythm (arrhythmia) caused by faulty electrical signals from the upper chambers of the heart (atria). Electrical signals should normally be coming only from the sinoatrial node in a steady rhythm about 60 to 100 beats per minute. A heart 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.

This heart rate is the result of the AV node blocking out most of the atrial impulses, and allowing only the fewer impulses to emerge to the ventricle.

Certain arrhythmias are related to specific electrical problems within the heart. AV 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 the AV nodal region.

AV reentrant tachycardia results from an extra conducting pathway that allows the electrical impulse to "short circuit" and bypass the AV node altogether. In this mode, the 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 pathway" since it cannot be diagnosed from a regular electrocardiogram (EKG). These arrhythmias may be treated medically, but can also be cured by catheter ablation. Less often, the extra pathway conducts in the forward direction (from atrium to ventricle) and is 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 potentially result in death. Symptomatic WPW syndrome generally requires catheter ablation.

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

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 P:\WPDOCS\GLFspeI\225471 I.doc-03/05/04 cannot keep that rate up for more than a few minutes without treatment with a defibrillator).

Under some conditions, arrhythmias may be transient. For example, a patient 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 (bradycardia), the most common treatment is an electronic (artificial) pacemaker. This device, which is implanted under the skin and permanently attached to the heart, delivers an electrical impulse when a slowing or irregularity of the heart rhythm is detected. For abnormally fast heartbeat rates, an implantable cardioverter defibrillator (ICD) may be implanted. An ICD monitors and, if necessary, corrects an abnormally fast heartbeat.

These devices may be lifesaving for patients with ventricular fibrillation or ventricular tachycardia. Another procedure is an electrophysiology study with catheter ablation. This is a procedure in which catheters are introduced into the heart from blood vessels in the legs and/or neck and radio frequency energy is used to very carefully destroy (ablate) the abnormal areas of the heart that are creating the arrhythmias.

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

Before a muscle fiber can be stimulated to contract, its membrane must be polarized. A 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 temperature change. The minimal stimulation strength needed to elicit a contraction is known as the threshold stimulus. The maximum stimulation amplitude that may be administered without eliciting a contraction is the maximum subthreshold amplitude.

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 and distribute depolarization waves throughout the myocardium. Any interference or block in cardiac impulse conduction may cause an arrhythmia or marked change in the rate or rhythm of the heart.

P:\WPDOCSGLFsp 225471 l.doc-03/05/04 -6- 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 for example, anodal current was thought not to be useful clinically. Cathodal current comprises electrical pulses of negative polarity. This type of current depolarizes the cell membrane by discharging the membrane capacitor, and directly reduces the membrane 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 late diastole than does anodal current. Anodal current comprises electrical pulses of positive polarity. Presently, virtually all artificial pacemaking is done using stimulating pulses of negative polarity although the utility of anodal pulse has been demonstrated.

The typical implantable cardioverter/defibrillator (ICD) delivers an initial electrical countershock within ten to twenty seconds of arrhythmia onset, thereby saving countless lives. Improved devices have antitachycardia pacing capabilities in addition to cardioverting/defibrillating functions. These ICDs are capable of different initial responses to one or more tachycardia as well as a programmable sequence of responses to a particular arrhythmia.

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 represents the minimum pacing energy required to reliably stimulate a patient's heart.

However, due to trauma associated with the stimulation, scar tissue grows at the interface between the implanted cardiac pacer leads and the myocardium. This scar tissue boosts the 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 measured capture threshold. A drawback to such an approach is that the higher stimulation level causes more trauma to the cardiac tissue than would a lower level of stimulation, and hence promotes the formation of scar tissue, thereby boosting the capture threshold. The higher stimulation level also shortens battery life. This is not desirable, as a shorter battery life necessitates more frequent surgery to implant fresh batteries.

Another drawback is the potential for patient discomfort associated with this higher stimulation level. This is because the higher stimulation level can stimulate the phrenic or P:\WPDOCSGLFpecI1225471 .dc-03/05/04 -7diaphragmatic plexus or cause intercostal muscle pacing. Lastly, the higher stimulation is less effective, due to entry block.

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

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 technique increased the speed of conduction of the resultant beats by almost 100% over that produced by conventional pacing stimuli. However, this technique did not result in reversion to a sinus rhythm for all victims of cardiac conduction disorder.

What would be truly useful is to provide alternative methods of stimulating the myocardium and to inhibit the conduction of certain spurious electrical impulses in the heart as a substitution for, or as an enhancement to, conventional pacing and pharmaceutical therapies and/or to use the alternative method in conjunction with conventional pacing and safe pharmaceuticals to provide yet another method for overcoming cardiac conduction problems.

Summary of the Invention The present invention seeks to provide an ICD with antitachycardial pacing capabilities, wherein the stimulation is administered with a voltage either at, just above, or just below the diastolic depolarization threshold potential.

The present invention seeks to sense whether cardiac capture has occurred, and if not, to administer additional stimulation.

The present invention seeks to provide the additional stimulation at a slightly higher voltage level than that level of stimulation which resulted in no capture.

The present invention seeks to repeat the stimulation-sensing cycle until cardiac capture has occurred.

The present invention seeks to provide stimulation using a biphasic waveform.

The present invention seeks to provide an implantable cardioverter-defibrillator with a unique constellation of features and capabilities. Protocols disclosed include: P:\WPDOCSGLF'spc=\I22547 lI.do-03105104 -8- 1/ biphasic stimulation administered at, or just above, the diastolic depolarization threshold potential; 2/ biphasic or conventional stimulation initiated at, or just above, the diastolic depolarization threshold potential, reduced, upon capture, to below threshold; and 3/ biphasic or conventional stimulation administered at a level set just below the diastolic depolarization threshold potential.

In one broad form the present invention provides a method of operating an implantable cardiac stimulator to perform cardioverting, the cardiac stimulator having output means for delivering electrical stimulation of a predetermined polarity, amplitude, shape and duration, the method comprising: sensing the onset of tachycardia; applying pulses ofbiphasic pacing stimulation at a first intensity level selected from the group consisting of at the diastolic depolarization threshold, below the diastolic depolarization threshold or above the diastolic depolarization threshold, wherein each pulse ofbiphasic pacing stimulation comprises: a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; and a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration; and determining whether pacing capture has occurred; wherein the first phase amplitude is at a maximum subthreshold amplitude.

In another broad form the present invention provides a cardiac stimulator to perform cardioverting, the cardiac stimulator comprising: sensing means for sensing the onset oftachycardia; output means for delivering, in response to the sensing means, electrical stimulation of a predetermined polarity, amplitude, shape and duration to cause application of pulses of biphasic pacing stimulation at a first intensity level selected from the group consisting of: at the diastolic depolarization threshold, below the diastolic depolarization threshold, and above the diastolic depolarization threshold; and means for determining whether capture has occurred; wherein each pulse ofbiphasic pacing stimulation comprises: PAWPDOCS\GLF\sp.\22547 I .do-03/05/04 -9a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; and a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration; and wherein the first phase amplitude is at a maximum subthreshold amplitude.

As mentioned, the antitachycardial pacing protocols of the present invention can be used in conjunction with biphasic pacing. The method and apparatus relating to biphasic pacing comprises a first and second stimulation phase, with each stimulation phase having a polarity, amplitude, shape, and duration. In a preferred embodiment, the first and second phases have differing polarities. In one alternative embodiment, the two phases are of differing amplitude. In a second alternative embodiment, the two phases are of differing duration. In a third alternative embodiment, the first phase is in a chopped wave form. In a fourth alternative embodiment, the amplitude of the first phase is ramped. In a fifth alternative embodiment the first phase is administered over 200 milliseconds after completion of a cardiac beating/pumping cycle. In a preferred alternative embodiment, the first phase of stimulation is an anodal pulse at maximum subthreshold amplitude for a long duration, and the second phase of stimulation is a cathodal pulse of short duration and high amplitude. It is noted that the aforementioned alternative embodiments can be combined in differing fashions. It is also noted that these alternative embodiments are intended to be presented by way of example only, and are not limiting.

Enhanced myocardial function is obtained through the biphasic pacing of the present invention. The combination of cathodal with anodal pulses of either a stimulating or conditioning nature, preserves the improved conduction and contractility of anodal pacing while eliminating the drawback of increased stimulation threshold. The result is a depolarization wave of increased propagation speed. This increased propagation speed results in superior cardiac contraction leading to an improvement in blood flow and in increased access to reentrant circuits. Improved stimulation at a lower voltage level also results in reduction in scar tissue buildup thereby reducing the tendency of the capture threshold to rise; reduction in power consumption leading to increased life for pacemaker batteries; and decreased pain to the patient.

P:\WPDOCS\GLF 1pcI 225471 l.doc-03/05/04 In one broad from the present invention provides comprises an implantable cardiac treatment/stimulation device designed to inhibit the conduction of certain spurious electrical impulses preferably without pacing. The technique applied in the implantable 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.

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

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

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

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 re-entry circuits.

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

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 site.

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

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

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

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

P:\WPDOCS\GLFspc1225471 I.doc-03/05/04 11 The present invention seeks to provide an implantable cardiac stimulation device that can sense the onset of fibrillation or other tachyarrhythmias and can selectively apply cooling of cardiac tissue, pacing of cardiac tissue, defibrillation of cardiac tissue or a combination thereof as the situation dictates.

In one broad form, the present invention provides both cooling and biphasic electrical stimulation to be administered to the cardiac muscle. The anodal stimulation component of biphasic electrical stimulation augments cardiac contractility by hyperpolarizing the tissue prior to excitation, leading to faster impulse conduction, more intracellular calcium release, and the resulting superior cardiac contraction. The cathodal stimulation component eliminates the drawbacks of anodal stimulation alone, resulting in effective cardiac stimulation at a lower voltage level than would be required with anodal stimulation alone. This in turn, extends pacemaker battery life and reduces tissue damage.

In another broad from the present invention provides for cooling to be applied to 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 stimulation without the necessity of placing electrical leads in intimate contact with cardiac tissue, thereby diminishing the likelihood of damage to this tissue. The stimulation threshold of biphasic stimulation administered via the blood pool is in the same range as 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 cardiac contraction, without skeletal muscle contraction, cardiac muscle damage or adverse effects to the blood pool.

In another broad form the present invention comprises an implantable device for automatic treatment of frequently recurring bouts of atrial fibrillation or chronic atrial fibrillation. This embodiment comprises a sensing system which monitors various parameters such as the PDF (probability density function) of the atrium to sense atrial fibrillation. By sensing the PDF of the atrium, this provides a detector for atrial fibrillation that has not been previously considered. Upon sensing the PDF of the atrium and 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 across a broad area via contact device dimensional to cover an extensive area of cardiac P:\WPDOCSGLF\pc 225471 l.doc-03/05/04 -12tissue. The cold temperature is then applied over the contact device to the cardiac tissue, cooling the cardiac tissue, and thereby inhibiting the conduction of spurious signals 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 small pacing site, the inhibition of spurious signals can be achieved over a much broader area than a single point of contact as in conventional pacing.

Cold is applied to the cardiac tissue for a brief period of time that is programmable 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 function of the apparatus. Cooling can be accomplished by a mechanical hydraulic system for pumping cooled fluid into a bladder on the surface of the atrium.

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

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

This combination of cooling of cardiac tissue combined with cardiac stimulation comprises yet another embodiment of the present invention. A processor in the implantable device senses the onset of fibrillation and first applies cold temperature to the cardiac tissue. If this fails to affect the reentry circuits of the heart, a combination of 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 conventional fashion could be applied. Thus sensing and the application of stimulation of either cold temperature electrical stimulation or a combination thereof are provided by circuitry within the implantable device.

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

P:\WPDOCS\GLFIspaM225471 l.do -03/05/04 13- A further broad form of the present invention involves connecting the implantable device to a communication terminal, preferably wireless, so that an appropriate caregiver can receive notice of a cardiac event. Signals could then be received by the physician indicating the condition. Thephysician would then have the option to remotely control the stimulation protocol applied by the implantable device of the present invention.

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

A further broad form of the present invention provides methods for inhibiting the conduction of spurious electrical impulses in cardiac tissue comprising 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 maintain the established temperature.

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

A further broad form of the present invention provides methods for inhibiting the conduction of spurious electrical impulses in cardiac tissue. 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 that is thermally coupled to a Peltier cooler. A symptom associated with an arrhythmia is detected, and, in response to detection of the symptom, the heat is selectively transferred away from the targeted portion in the heart related to arrhythmia by absorbing heat into the heat-transfer operator situated at the targeted portion r.

In a further broad form of the present invention, methods for suppressing arrhythmia in a patient are provided. A heat-transfer operator is implanted at each of one P:\VPDOCS\GLftpca\ 225471 ldo-03/05/04 -14or more targeted portions of a patient's heart. At least one heat-transfer operator is operated to cool at least one targeted portion of the heart, thereby suppressing the arrhythmia.

In further broad form of the present invention, methods are provided for inhibiting the conduction of spurious electrical impulses in cardiac tissue. The onset of 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 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 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 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 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 targeted 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.

P AWPDOCSNTXYSpCC.\i22S47J I ladid cli- cupy ID- 14ari In a further broad form, there is provided a method of operating an Simplantable cardiac stimulator to perform cardioverting, the cardiac stimulator having C) Output means for delivering electrical stimulation of a predetermined polarity, amplitude, 0 00 output means for delivering electrical stimulation of a predetermined polarity, amplitude, shape and duration, the method comprising: sensing the onset of tachycardia; In applying a temperature decrease to a targeted portion of the heart using a cooling 00 process selected from the group consisting of: applying a cooling fluid to the targeted (i portion, electrically cooling the targeted portion, mechanically cooling the targeted portion, and chemically cooling the targeted portion using an endothermic chemical reaction; C 10 applying pulses of biphasic pacing stimulation at a first intensity level selected from the group consisting of at the diastolic depolarization threshold, below the diastolic depolarization threshold or above the diastolic depolarization threshold, wherein each pulse of biphasic pacing stimulation comprises: a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; and a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration; and determining whether pacing capture has occurred.

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

Typically, in the event it is determined that capture has occurred, the method further comprising applying a post-capture stimulation protocol selected from the group consisting of: ceasing applying cooling and applying biphasic stimulation for a predetermined period of time; and applying cooling and biphasic stimulation for a predetermined period of time.

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

Typically, 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 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.

PAWPDOCSTXSSp I225471 I =I W ck w mpy doc.I2JLOI/6 ID- 14b- Typically, the heat sink is coupled to the Peltier cooler through a thermal transfer fluid.

0 00 Typically, the method further includes: oO determining the temperature of the targeted portion at the time of onset of tachycardia; V) monitoring the temperature of the targeted portion; and oO 00 ceasing applying the temperature decrease to the targeted portion when a preset Ni cooling measure has been achieved.

Typically, the preset cooling measure is selected from the group consisting of a C 10 preset temperature decrease, a preset temperature, and a preset cooling period.

Typically, in the event it is determined that capture has not occurred, further comprising: continuing to apply cooling to the targeted portion until a maximum cooling limit has been reached.

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

Typically, wherein the first stimulation phase is initiated greater than 200 milliseconds after completion of a cardiac beating cycle.

Typically, the first stimulation phase comprises an anodal stimulus.

Typically, increasing the stimulation intensity level by predefined increments until capture occurs; and upon capture, continuing stimulation selected from the group consisting of biphasic stimulation and conventional stimulation at a second intensity level below the diastolic depolarization threshold.

Typically, in the event it is determined that capture has occurred, the method further comprising: continuing biphasic stimulation for a predetermined period of time.

Typically, in the event it is determined that capture has not occurred, further comprising: increasing the stimulation intensity level by predefined increments until capture occurs.

Typically, the first phase polarity is positive.

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

Typically, the first stimulation phase comprises an anodal stimulus.

P.X\ PDOCS\T=SSp=X\i22547i I a,,,cdod climn, clc= ca~y doc.12110/I)6 IND 14c ri Typically, 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 C0 value.

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

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

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

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

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

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

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

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

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, 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 duration of the stimulating pulse.

In a further broad form, there is provided a cardiac stimulator to perform cardioverting, the cardiac stimulator comprising: sensing means for sensing the onset of tachycardia; 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; PIVPDOCSTXStSpmol2237l I amoded cin ii-ked up doe-1 I A0 INO 14dr output means for delivering, in response to the sensing means, electrical stimulation of a predetermined polarity, amplitude, shape and duration to cause application of pulses of

O

C0 biphasic pacing stimulation at a first intensity level selected from the group consisting of: at the diastolic depolarization threshold, below the diastolic depolarization threshold, and above the diastolic depolarization threshold; and V) means for determining whether capture has occurred; 00 oO wherein each pulse of biphasic pacing stimulation comprises: Sa first stimulation phase with a first phase polarity, a first phase amplitude, a Sfirst phase shape and a first phase duration; and S 10 a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration.

There is further provided an implantable cardiac stimulator device comprising: plural electrodes; sensing circuitry connected to the plural electrodes and adapted to sense the onset of tachycardia; 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; detecting circuitry connected to the sensing circuitry and adapted to detect whether pacing capture has occurred; and pulse generating circuitry connected to the plural electrodes and adapted to generate, in response to the sensing circuitry, electrical pulses of a predetermined polarity, amplitude, shape and duration to cause application of pulses of biphasic pacing stimulation at a first intensity level selected from the group consisting of: at the diastolic depolarization threshold, below the diastolic depolarization threshold, and above the diastolic depolarization threshold; and wherein each pulse of biphasic pacing stimulation comprises: a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; and a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration; P AWPDOCS\TXS'Spca%122547I I ameld chiam markod up doc17/flAY IND W4e wherein, in the event that the detecting circuitry determines that capture has occurred, the pulse generating circuitry continues biphasic stimulation for a predetermined 0 00 P:\WPDOCS\GLFWp=c.225471 I.do-03/05/04 Brief Description of the Drawings Figs. 1A-1C illustrate examples of methodologies for treating arrhythmias.

Fig. 2 illustrates a schematic representation of leading anodal biphasic stimulation.

Fig. 3 illustrates a schematic representation of leading cathodal biphasic stimulation.

Fig. 4 illustrates a schematic representation of leading anodal stimulation of low level and long duration, followed by conventional cathodal stimulation.

Fig. 5 illustrates a schematic representation of leading anodal stimulation of ramped low level and long duration, followed by conventional cathodal stimulation.

Fig. 6 illustrates a schematic representation of leading anodal stimulation of low level and short duration, administered in series followed by conventional cathodal stimulation.

Fig. 7 illustrates an implantable cardioverter/defibrillator useable for implementing embodiments of the present invention.

Fig. 8 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue according to embodiments of the present invention Fig. 9 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue by application of a temperature decrease to cardiac tissue according to embodiments of the present invention.

Fig. 10 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue by application of a temperature decrease and at least one pacing pulse to cardiac tissue according to embodiments of the present invention.

Fig. 11 illustrates a methodology for suppressing arrhythmia by selective application of a temperature decrease to a targeted portion of the heart and pacing pulses to cardiac tissue according to embodiments of the present invention.

Fig. 12 illustrates an apparatus for inhibiting the conduction of electrical impulses in cardiac tissue by application of a temperature decrease to a targeted portion of the heart according to embodiments of the present invention.

P:\WPDOCS\GLF\V

1 ,c\225471 U o-03/05/04 16 Description of the Preferred Embodiments The present invention relates to the use of antitachycardial pacing to break up arrhythmia in the atrium. Figs.1A through IC illustrate examples of methodologies for treating arrhythmias.

17 I Fig. 1A illustrates a first methodology. Hlere, a sensor senses the onset of arrhythmnia 2 102. In a prefer=red embodiment, this sensor comprise an anritachYQArdial Pacing algorithm.

3 Biphasic, stimulation is then administered 104. In varying eMbodiments, this stimnulationt is 4 either at, or just above the diastolic depolarization threshold. The ICD] determnines whether S' capture has occurred 106. If captur has not occurred, then stimulation continues at a slightly 6 higher level 108. This stimulation capture check boost stimulaton cycle contiznes until 7 capture occurs. If capture has occurred, then stimulation is continued for a predetermined 9 period of time 110. In a preferred embodiment, stimulation is administered as long as the 9 arrhythmia persists.

In a preferred embodiment, stimulation pulses awe adminitrd at 80 to 100 percent of I1I the intinic rate with an approximately one to two second pause betwee each set of 12 stimulation pulses. Then either the number of pulses increases, or the timing betoeen pulses 13 is adjusted. For example, in a preferred embodiment, the first pulse sequence can be at 14 percent of the intrinsic heart rare, the second pulse sequence at 82 percent, the third pulse sequence at 84 percent, and so on. In a preferred embodiment a plurality of feedback loops 16 provide data such that the voltage can be adjusted to constantly skirt the captur threshold.

17 Stimulation is continued until the rhythm reverts.

13 Fig. 13 illustrates a second methodology. Here. a sensor senses the onset of 19 arrhythmia 112. In varying embodiments of the second method, biphasic, stimulation is then administered 114. This stimulation level is set at or just above the diastolic depolarization 21 threshold potential. The 1CD determines-whether capture has occurred 116. If captue has 22 not occurred, then stimulation continues at a slightly higher level 118. This stimuilation 23 capture check boost stimulation cycle continues until capture occurs. If captue has 24 occurred, then stimulation is gradually and continuously reduced to 18 1 below threshold, and continued 120. Then, if capture is lost, the stimulation is raised to a 2 slightly higher level and is again gradually and continuously reduced. This entire sequence is 3 repeated, such that the stimulation level hovers as close as possible to the lowest stimulation 4 level which provides capture. Stimulation continues until the rhythm reverts, for example, when the antitachycardial pacing algorithm determines that pacing is no longer necessary.

6 Fig. IC illustrates a third methodology. Here, a sensor senses the onset of arrhythmia 7 122. In varying embodiments of the third method, either biphasic or conventional stimulation 8 is then administered 124. This stimulation level is set just below the diastolic depolarization 9 threshold potential. The ICD determines whether capture has occurred 126. If capture has not occurred, then stimulation continues at a slightly higher level 128. This stimulation 11 capture check boost stimulation cycle continues until capture occurs. If capture has 12 occurred, then stimulation is continued at below threshold level 130. If capture is lost then 13 the stimulation is raised to a slightly higher level and is gradually and continuously reduced.

14 This entire sequence is repeated, such that the stimulation level hovers as close as possible to the lowest stimulation level which provides capture. Stimulation continues until the rhythm 16 reverts, for example, when the antitachycardial pacing algorithm determines that pacing is no 17 longer necessary.

18 Sensinp, 19 Sensing can be direct or indirect. For example, direct sensing can be based on data from sensing electrodes. The ICD of the present invention includes sensing 21 circuits/electronics to sense an arrhythmia through one or more sensing and/or stimulating 22 electrodes. The sensing electronics sense the cardiac activity as depicted by electrical signals.

23 For example, as is known in the art, R-waves occur upon the depolarization of ventricular 24 tissue and P-waves occur upon the depolarization of atria] tissue. By monitoring these 19 1 electrical signals the control/timing circuit of the ICD can determine the rate and regularity of .2 the patient's heart beat, and thereby determnine whether the heart is undergoing arrhythmia.

3 This determination can be made by determining the rate of the sensed R-waves and/or P- 4 waves and comparing this determined rate against various reference rates.

Direct sensing can be based upon varying criteria; such as, but not limited to, primary 6 rate, sudden onset, and stability. The sole criteria of a primary rate sensor is the heart rate.

7 When applying the primary rate criteria, if the heart rate should exceed a predefined level, 8 then treatment is begun. Sensing electronics set to sudden onset criteria ignore those changes 9 which occur slowly, and initiate treatment when ther e is a sudden change such as immediate paroxysmal arrhythmia. This type of criteria would thus discriminate against sinus I1I tachycardia. Stability of rate can also be an important criteria. For example, treatment with a 12 ventricular device would not be warranted for a fast rate that varies, here treatment with an 13 atrial device would be indicated.

14 In alternative embodiments, sensing can be indirect. Indirect sensing can be based on any of various functional parameters such as arterial blood pressure, rate of the 16 electrocardiogram deflections or the probability density function (pdf) of the 17 electrocardiogram. For example, whether or not to administer treatment can also be affected 18 by pdf monitoring of the time the signal spends around the baseline.

19 Sensing can also be augmented by stimulating the atria and observing and measuring the consequent effects on atrial and ventricular function.

21 Thus, in a preferred embodiment, sensing electronics are based upon multiple criteria.

22 In addition, the present invention envisions devices working in more than one chamber such 23 that appropriate treatment can be administered to either the atrium or the ventricle in response 24 to sensing electronics based upon a variety of criteria, including those described above as well 1 as other criteria known to those skilled in the art.

.2 Stimulation 3 Electrical stimulation is delivered via lead(s) or electrode(s). These leads can be 4 epicardial (external surface of the heart) or endocardial (internal surface of the heart) or any combination of epicardial and endocardial. Leads are well known to those skilled in the art; 6 see, for example, United States Patent Nos. 4662377 to Heilman et al., 4481953 to Gold et 7 al., and 4010758 to Rockland et al., each of which is herein incorporated by reference in its 8 entirety.

9 Lead systems can be unipolar or bipolar. A unipolar lead has one electrode on the lead itself, the cathode. Current flows from the cathode, stimulates the heart, and returns to 11 the anode on the casing of the pulse generator to complete the circuit. A bipolar lead has two 12 poles on the lead a short distance from each other at the distal end, and both electrodes lie 13 within the heart.

14 With the reference to Fig. 7, an exemplary system by which the present invention may be embodied is illustrated. An automatic implantable cardioverter/defibrillator 2 is implanted 16 within the body of the patient and has a pair of output terminals, an anode 4 and a cathode 6.

17 The ICD 2 is coupled to a flexible catheter electrode arrangement 8 having a distal electrode 18 10 and a proximal electrode 12, each associated with the patient's heart. Other electrode 19 configurations may be employed, such as ring-type electrodes. As for external electrodes, an anodal electrode 24 may be employed. The automatic ICD 2 includes sensing and detecting 21 circuitry, as well as pulse generating circuitry, the output of the latter being coupled to the 22 implantable electrodes 10, 12. The ICD 2 senses an arrhythmic condition of the heart and, in 23 response thereto, issues or emits cardioverting or defibrillating pulses to the heart, through the 24 implantable electrodes 10, 12.

21 1 The catheter electrde 8 is inserted intravenously to a Pouitiorn such that the distal 2 lectodc 10 is positioned in The right ventricular Wxe 14 of the heart and t proXimal 3 electrode 12 is positioned in the superior vena cava region 16 of the heart. It should be 4 appreciated that, as the term is used herein, the superior vena cava 16 may also include portions of the right atrium 18.

6 Conventional stimulationl is well known to those skilled in the art and comprises 7 monophasic waveforms (cathodal or anodal) as well as multiphasic waveforms wherein the 3 nonstimulatiflg pulses mr of a minimal magitude and are used, for example, to dissipate a 9 residual charge on an electrode.

Figs. 2 througb 6 depict a range of biphasic stimulation protocols. These protocols I1I have been disclosed in United States Patent No. 5,871,506 to Mower, Wbich is herein 12 incorporated by referencee in its enitirety.

13 Fig. 2 depicts biphasic- electrical stimiulation wherein a first stimulation phase 14 comprisn anoda stimulus 102 is administered havisg amplitude 104 and duration 106 is This first stimulation phase is immediately followed by a seconid stimulation phase 16 comprising cathodal stimulation 101 of equal intensity and duration.

17 Fig. 3 depicts biphasiC electrical stimulation wherein a first stimulation phase is comprising cathodal stimulation 202 having amplitude 204 and duration 206 is administerd.

19 This first stimulation phase is immediately followed by a second stimulation phase comprising anodal stimulation 208 of equal intensity and duration.

21 Fig. 4 depicts a preferred embodiment of biphasic stimulation wherein a first 22 stimulation phase, comprising low level, long duration anodal stimulation 302 having 23 amplitude 304 and duration 306, is administered. This first stimulation phase is immediately 22 1 followed by a second stimulation phase comprising cathodal stimulation 308 of conventional -2 intensity and duration. In differing alternative embodiments, anodal stimulation 302 is: 1) at 3 maximum subthreshold amplitude; 2) less than three volts; 3) of a duration of 4 approximately two to eight milliseconds; and/or 4) administered over 200 milliseconds post heart beat. Maximum subthreshold amplitude is understood to mean the maximum 6 stimulation amplitude that can be administered without eliciting a contraction, In a preferred 7 embodiment, anodal stimulation is approximately two volts for approximately three 8 milliseconds duration. In differing alternative embodiments, cathodal stimulation 308 is: 1) 9 of a short duration;, 2) approximately 0.3 to 1.5 milliseconds; 3) of a high amplitude; 4) in the approximate range of three to twenty volts; and/or 5) of a duration less than 0.3 11 millisecond and at a voltage greater than twenty volts. In a preferred embodiment, cathodal 12 stimulation is approximately six volts administered for approximately 0.4 millisecond. In the 13 manner disclosed by these embodiments, as well as those alterations and modifications which 14 can become obvious upon the reading of this specification, a maximum membrane potential without activation is achieved in the first phase of stimulation.

16 Fig. 5 depicts an alternative preferred embodiment of biphasic stimulation wherein a 17 first stimulation phase, comprising anodal stimulation 402, is administered over period 404 18 with rising intensity level 406. The ramp of rising intensity level 406 can be linear or non- 19 linear, and the slope can vary. This anodal stimulation is immediately followed by a second stimulation phase compriging cathodal stimulation 408 of conventional intensity and duration.

21 In alternative embodiments, anodal stimulation 402: rises to a maximum subthreshold 22 amplitude less than three volts; is of a duration of approximately two to eight 23 milliseconds; and/or is administered over 200 milliseconds post heart beat. In yet other 24 alternative embodiments, cathodal stimulation 408 is: of a short duration; (2) 23 1 approximately 0.3 to 1.5 milliseconds; of a high amplitude; in the approximate range .2 of three to twenty volts; and/or of a duration less than 0.3 milliseconds and at a voltage 3 greater than twenty volts. In the manner disclosed by these embodiments, as well as those 4 alterations and modifications which can become obvious upon the reading of this specification, a maximum membrane potential without activation is achieved in the first 6 phase of stimulation.

7 Fig. 6 depicts biphasic electrical stimulation wherein a first stimulation phase, 8 comprising series 502 of anodal pulses, is administered at amplitude: 504. In one 9 embodiment, rest period 506 is of equal duration to stimulation period 508, and is administered at baseline amplitude. In an alternative embodiment, rest period 506 is of a I1I differing duration than stimulation period 508, and is administered at baseline amplit ude.

12 Rest period 506 occurs after each stimulation period 508, with the exception that a second 13 stimulation phase, comprising cathodal stimulation 510 of conventional intensity and 14 duration, immediately follows the completion of series 502. In alternative embodiments: (1) the total charge transferred through series 502 of anodal stimulation is at the maximum 16 subthreshold level; and/or the first stimulation pulse of series 502 is administered over 17 200 milliseconds post heart beat. In yet other alternative embodiments, cathodal stimulation 18 510 is: of a short duration; approximately 0.3 to 1.5 milliseconds; of a high 19 amplitude; in the approximate range of three to twenty volts, and/or of a duration less than 0.3 milliseconds and at a voltage greater than twenty volts.

21 Determininiz Cardiac Cature 22 Capture can be determined by multiple means. First, capture or the loss thereof, can 23 be determined by monitoring cardiac rhythm. Loss of capture can result in a change in timing 24 of the heart beat.

P:\WPDOCSGLF'sp=dA225471 I.doc-03/05/04 -24- Second, capture can be monitored through the development of a template. The template can be based on parameters such as electrocardiogram data, mechanical motionand/or probability density function data. Where the template is established prestimulation, a change in the baseline signifies capture. Where the template is established after capture has occurred, a change in the template characteristics signifies loss of capture.

The templates can be established and/or updated at any time.

Once capture occurs the stimulation protocol of the entrained sites is adjusted as illustrated by Figs.1 A throughl C.

Having thus described the basic concept of the invention, it will be readily apparent to those skilled in the art that the foregoing detailed disclosure is intended to be presented by way of example only, and is not limiting. Various alterations, improvements and modifications will occur and are intended to those skilled in the art, but are not expressly stated herein. These modifications, alterations and improvements are intended to be suggested hereby, and within the scope of the invention. Further, the pacing pulses described in this specification are well within the capabilities of existing pacemaker electronics with appropriate programming. Accordingly, the invention is limited only by the following claims and equivalents thereto.

An embodiment of the present invention comprises an implantable cardiac treatment/stimulation device designed to inhibit the conduction of spurious electrical signals in cardiac tissue without pacing. The technique applied in the implantable device 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 stimulation of the cardiac tissue.

An embodiment of the present invention provides a method for inhibiting the conduction of spurious electrical impulses in cardiac tissue. The method comprises 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 maintain the established temperature. The temperature of the targeted portion is sensed. If the targeted portion has reached the established temperature, the application of the temperature decrease is ceased. If the targeted portion has not achieved the established temperature, application of the temperature decrease to the targeted portion continues.

PAWPDOCSGLF'spW*\I225471 I.doc-1O35/04 25 The decrease in temperature of the cardiac tissue may be achieved through various means, including by way of example and not as a limitation, applying a cooling fluid to the cardiac tissue, electrically cooling the cardiac tissue, and mechanically cooling the cardiac tissue.

Another embodiment of the present invention provides methods for inhibiting the conduction of spurious electrical impulses in cardiac tissue. The method comprises sensing the onset of arrhythmia, determining the temperature of the cardiac tissue at the time of onset of arrhythmia, and applying a temperature decrease to the cardiac tissue. In another method, the functioning of the cardiac tissue is sensed. If the cardiac tissue reverts 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 tissue is continued.

The decrease in temperature of the cardiac tissue may be achieved through various means, including by way of example and not as a limitation, applying a cooling fluid to the cardiac tissue, electrically cooling the cardiac tissue, mechanically cooling the cardiac tissue, and cooling the cardiac tissue via an endothermic chemical reaction. Examples of cooling devices suitable for use in practicing the present invention are evaporative coolers, radiative coolers, chillers, thermal holdover devices (such as thermal storage units, with or without utilization of phase change phenomena), and gas expansion coolers. Cooling may be accomplished via a heat exchanger structure or via direct contact.

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

In another embodiment of the present invention, a method for inhibiting the conduction of spurious electrical impulses in cardiac tissue further comprising applying a pacing 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 chambers. In either method, the pacing pulse is applied to the one or more electrodes.

P:\WPDOCS\GLFpec\l225471 I.do-03/05104 26 The pacing pulse may be a cathodal electrical waveform or a biphasic electrical waveform comprising cathodal and anodal elements.

Another embodiment of the present invention provides methods for inhibiting the conduction of spurious electrical impulses in cardiac tissue. One or more portions of the heart affected by one or more reentry circuits is targeted. In an embodiment of the present 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 posterolateral atrial surfaces, and a left postero-lateral atrial surface. 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. The Peltier cooler may be 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 thermally coupled to a Peltier cooler implanted in a patient's torso. Optionally, the heat sink is thermally couple using a mechanical contact or a thermal transfer fluid.

A symptom associated with an arrhythmia is detected, and, in response to detection of the symptom, the heat is selectively transferred away from the targeted portion in the heart related to arrhythmia by absorbing heat into the heat-transfer operator situated at the targeted portion.

The symptom may be detected within the heart. The heat-transfer operator is 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 and a change in a measure of heart function.

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

In another embodiment of the present invention, a method for inhibiting the conduction of spurious electrical impulses in cardiac tissue further comprising applying a pacing 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 chambers. In either method, the pacing pulse is applied to the one or more electrodes.

P:\WPDOCS\GLFV'p\I225471 I.do-03/05/04 -27- The pacing pulse may be a cathodal electrical waveform or a biphasic electrical waveform comprising cathodal and anodal elements.

In another embodiment of the present invention, a method for inhibiting the conduction of spurious electrical impulses in cardiac tissue comprises applying a pacing 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 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 comprising cathodal and anodal elements.

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 each of one or more targeted portions of a patient's heart. At least one heat-transfer operator is operated to cool at least one targeted portion of the heart, thereby suppressing the arrhythmia. In an embodiment of the present invention, the heat-transfer operator is a 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 right postero-lateral atrial surfaces, and a left postero-lateral atrial surface. The Peltier cooler may be 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 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 posterolateral atrial surfaces, and a left postero-lateral atrial surface that is thermally coupled to a Peltier cooler implanted in a patient's torso. Optionally, the heat sink is thermally couple using a mechanical contact or a thermal transfer fluid.

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 sensing-contact to a power source that supplies power for the operation of the heat-transfer operator upon the sensing of a symptom. Various symptoms may be sensed, including by way of illustration and not as a limitation, an electrical change within the heart, and a measure of heart function.

P:\WPDOCS\GLF1spi\l225471 I.doc-03/05/04 -28- In another embodiment of the present invention, the method for suppressing arrhythmia in a patient further comprises applying a pacing 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 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 comprising cathodal and anodal elements.

In still another embodiment of the present invention, methods are provided for inhibiting the conduction of spurious electrical impulses in cardiac tissue. The onset of 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 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 and applying a pacing pulse to the cardiac tissue. The selected remedial measure is applied. Optionally, the cardiac tissue function is sensed and if the cardiac tissue reverts to sinus rhythm, the application of the remedial measure ceases. Similarly, if the cardiac tissue does not revert to sinus rhythm, application of the remedial measure continues.

In still other embodiments of the present invention, apparatuses for inhibiting the 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 responsive to the sensing means for applying a cooling stimulus to the cardiac tissue. An apparatus further comprises logic means for sensing when a sinus rhythm has been reestablished in the cardiac tissue and for halting the cooling stimulus in the event a sinus rhythm has been reestablished. Additional means are provided to continue the cooling stimulus in the event a sinus rhythm has not been reestablished.

Cooling means include, by way of illustration and not as a limitation, means for applying a cooling fluid to the cardiac tissue, an electrical cooling apparatus, and a mechanical cooling apparatus. Additionally, the sensing means may be adapted to sense a 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.

P:\WPDOCS\GLFp.1225471 l.doc-03/05/04 -29- Another apparatus of the present invention further comprises a cardiac stimulation generator and one or more electrodes in contact with cardiac tissue. 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 caridiac tissue. In an alternative embodiment of the present invention, the electrodes are in contact with the cardiac blood pool. Optionally, the cardiac stimulation generator is responsive to the sensing means.

Yet another apparatus of the present invention for inhibiting the conduction of 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 may be an electrical change within the heart, a measure of heart function, and a change indicative of an arrhythmia. A heat-transfer operator is situated at each of one or more targeted portions in the heart. In an embodiment of the present invention, the heat-transfer 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, the heat-transfer operator is a heat sink that is thermally coupled to a Peltier cooler implanted in a patient's torso. Optionally, the heat sink is thermally couple using a mechanical contact or a thermal transfer fluid.

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. The sensor may be located on the heat-transfer operator.

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

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 operator upon detection of a symptom. Optionally, the power source stores sufficient 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 P:\WPDOCS\GLFspec 1225471 l.dc-03/05/04 one or more targeted portions are sufficiently cooled. In an embodiment of the present invention, the one or more targeted portions are sufficiently cooled when there is a subsidence of the symptom as detected by the sensing-contact. Alternatively, the one or more targeted portions are sufficiently cooled when each targeted portion reaches a predetermined temperature as measured by a thermacouple. In yet another alternative embodiment, the one or more targeted portions are sufficiently cooled when heat is transferred away from the one or more targeted portions for a programmed period of time.

In an embodiment of the present 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-lateral atrial surfaces, and a left postero-lateral atrial surface.

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

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 caridiac tissue. In an alternative embodiment of the present invention, the electrodes are in contact with the cardiac blood pool. Optionally, the cardiac stimulation generator is responsive to the sensing means.

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.

By way of illustration and not as a limitation, the symptom may be an electrical change within the heart, a measure of heart function, and a change indicative of an arrhythmia. A heat-transfer operator is situated at each of one or more targeted portions in the heart, In 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 that heat-transfer operator. As result, each of the one or more targeted portions is cooled and the arrhythmia is suppressed.

In an embodiment of the present invention, the heat-transfer operator is a Peltier 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 PAWPD0CS\GLF\sp.h22471 I.dc-03/05/04 -31 activate the heat-transfer operator upon the detection of a symptom. In another embodiment of the present invention, the heat-transfer operator is a heat sink that is thermally coupled to a Peltier cooler implanted in a patient's torso. Optionally, the heat 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 portions is each 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 posterolateral atrial surface.

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 operator upon detection of a symptom.

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

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 caridiac tissue. In an alternative embodiment of the present invention, the electrodes are in contact with the cardiac blood pool. Optionally, the cardiac stimulation generator is responsive to the sensor.

Figure 8 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue according to embodiments of the present invention.

Referring to Figure 8, a temperature conducive to inhibited conduction of electrical impulses is established for a targeted portion of the heart 100. A temperature decrease is applied to the targeted portion to maintain the established temperature 110. The 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 portion has reached the established temperature, the application of the temperature decrease is ceased 125. If the targeted portion has not achieved the established temperature, application of the temperature decrease to the targeted portion continues 130.

While Figure 8 illustrates a single targeted portion, the present invention is not so limited.

P:\WPDOCS\GLF spcm12254711 doc-03/05/04 -32- One or more targeted portions may be identified and associated with an established temperature 120 without departing from the scope of the present invention.

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

Figure 9 illustrates a methodology for inhibiting the conduction of electrical spurious electrical impulses in cardiac tissue by application of a temperature decrease to cardiac tissue according to embodiments of the present invention. Referring to Figure 9, 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 whether the cardiac tissue has reverted to sinus rhythm 220. If the cardiac tissue has reverted to sinus rhythm, the application of a temperature decrease to the cardiac tissue is ceased 225. If the cardiac tissue has not reverted to sinus rhythm, the application of a temperature decrease to the cardiac tissue is continued 230.

Figure 10 illustrates a methodology for inhibiting the conduction of spurious electrical impulses in cardiac tissue by application of a temperature decrease and at least one pacing pulse to cardiac tissue according to embodiments of the present invention.

Referring to Figure 10, 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 cardiac tissue is sensed 315 and a determination is made as to whether the cardiac tissue has reverted to sinus rhythm 320. If the cardiac tissue has reverted to sinus rhythm, the application of the at least one pacing pulse and a temperature decrease to the cardiac tissue 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 described, a pacing pulse may be cathodal or biphasic and may be applied to the cardiac tissue through electrodes in contact with the blood pool of the heart or in contact with the cardiac tissue.

Figure 11 illustrates a methodology for suppressing arrhythmia by selective application of a temperature decrease to a targeted portion of the heart and pacing pulses to P:\WPDOCS"LFp=A1225471 Ldoe-03/05/04 -33 cardiac tissue according to embodiments of the present invention. Referring to Figure 11, the onset of arrhythmia is sensed 400. The arrhythmia is evaluated and the temperature of the cardiac tissue is determined 405. Based on the evaluation of the 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 and applying a pacing pulse to the cardiac tissue 410. The selected remedial measure(s) is (are) applied to the cardiac tissue 415. The selective application of heart cooling and pacing pulses is determined by logic incorporated into a computer processor. In an embodiment of the 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 yet another embodiment of the present invention, the processor is a separate device. The functioning of the cardiac tissue is sensed 420 and a determination is made as to whether the cardiac tissue has reverted to sinus rhythm 425. If the cardiac tissue has reverted to 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 measure(s) continues 435. In an alternate embodiment, the temperature of the cardiac tissue and the arrhythmia are re-evaluated and one or more remedial measures are again selected.

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

Figure 12 illustrates an apparatus for inhibiting the conduction of spurious electrical impulses in cardiac tissue by application of a temperature decrease to a targeted portion of the heart according to embodiments of the present invention. Referring to Figure 12, 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 senses the onset of arrhythmia. In response to the heart sensing means 510, cooling is applied to the heart via heart cooling means 515. Logic 520 senses when a sinus rhythm has been reestablished in the cardiac tissue. If a sinus rhythm has been reestablished in the cardiac tissue, logic 520 halts the cooling stimulus to cooling means 515. If a sinus rhythm PAFPDOCS\GLFsp=A1225471 ldo-03/05/04 -34has not been reestablished in the cardiac tissue, logic 520 continues the cooling stimulus to cooling means 515.

In an embodiment of the present invention, heart cooling means 515 comprises a Peltier cooler. Such heat-transfer operators pass electricity through junctions between 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 passed through the metals, the electrons of the metal with the lower energy level pass the first step as they flow to the metal with the higher energy level. In order to pass this step and continue the circuit, the electrons must absorb heat energy that causes the metal at the 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 at that junction.

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

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 through convection of fluids or conduction. Alternatively, cooling may be accomplished by a mechanical hydraulic system for pumping cooled fluid into a bladder on the surface of the atrium. The amount of cooling applied and the total temperature of the heart may be monitored through a "thermostat" function of the apparatus.

In another embodiment of the present invention, heart cooling means further comprises a heat sink thermally coupled to a heat-transfer operator, such as a Peltier cooler. The heat-transfer operator is electrically connected to a power source that supplies a current through the heat-transfer operator to affect heat transfer. The power source 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 DC current to the heat-transfer operator that will, in turn, activate heat transfer from the targeted portion through the temperature-contact to the cold junction of the heat-transfer operator.

P:\WPDOCS\GLF\pA1225471 I.doc-03/0504 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 symptoms detected by the heart sensing means may be electrical or physiological measures indicative of arrhythmia.

In yet another embodiment of the present invention, logic 520 determines a time for 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 sensing means 510.

Referring again to Figure 12, in another embodiment of the present invention, a cardiac stimulation generator 530 applies a pacing pulse to the cardiac tissue via electrode 525. While Figure 12 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 without departing from the scope of the present invention. Additionally, electrode 525 may be placed in contact with the cardiac tissue or be located within a blood pool of the heart. Cardiac Stimulation generator 530 is responsive to heart sensing means 510. The pacing pulse generated by cardiac stimulation generator 530 may be a cathodal electrical waveform or a biphasic electrical waveform comprising cathodal and anodal elements.

While the embodiments of the present invention have been directed to cooling cardiac tissue for the purpose of inhibiting the conduction of spurious electrical impulses, the present invention is not so limited. Spurious electrical signals affect other parts of the 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 invention may be applied to inhibit spurious electrical signals of other parts of the body without departing from the scope of the present invention.

Systems and methods for inhibiting the conduction of spurious electrical impulses 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 scope of the invention disclosed and that the examples and embodiments described herein are in all respects illustrative and not restrictive. Those skilled in the art of the present P:\WPDOCS\GLF\pshl\225471 I.doc-03/0104 -36invention will recognize that other embodiments using the concepts described herein are also possible.

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

Throughout this specification and the claims which follow, unless the context 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 of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

Claims (63)

1. 2. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first phase amplitude is at a maximum subthreshold amplitude.
2. 3. The method of operating an implantable cardiac stimulator as in claim 1, wherein in the event it is determined that capture has occurred, the method further comprising applying a post-capture stimulation protocol selected from the group consisting of: ceasing applying cooling and applying biphasic stimulation for a predetermined period of time; and applying cooling and biphasic stimulation for a predetermined period of time.
3. 4. The method of operating an implantable cardiac stimulator as in claim 1, wherein electrically cooling the targeted portion comprises transferring heat away from the targeted portion by absorbing heat into a Peltier cooler. P lWPDOCSTXSSpc' 2254111 amcnded cIamu cke copy dOc-I2J106 INO -38- The method of operating an implantable cardiac stimulator as in claim 3, O wherein transferring heat away from the targeted portion by absorbing heat into a Peltier 0 C cooler comprises transferring heat away from the targeted portion by absorbing heat into 00 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. V) 00
4. 6. The method of operating an implantable cardiac stimulator as in claim N wherein the Peltier cooler is electrically connected to a power source located within the Shousing.
5. 7. The method of operating an implantable cardiac stimulator as in claim wherein the heat sink is coupled to the Peltier cooler through mechanical contact.
6. 8. The method of operating an implantable cardiac stimulator as in claim wherein the heat sink is coupled to the Peltier cooler through a thermal transfer fluid.
7. 9. The method of operating an implantable cardiac stimulator as in claim 1 further comprising: determining the temperature of the targeted portion at the time of onset of tachycardia; 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.
8. 10. The method of operating an implantable cardiac stimulator as in claim 9 wherein the preset cooling measure is selected from the group consisting of a preset temperature decrease, a preset temperature, and a preset cooling period.
9. 11. The method of operating an implantable cardiac stimulator as in claim 1, wherein in the event it is determined that capture has not occurred, further comprising: continuing to apply cooling to the targeted portion until a maximum cooling limit has been reached. PAWPDOCSMTXS\SpeUl22547 I. ff-doj dw~c c copy doe-I2110/06 INO -39- i 12. The method of operating an implantable cardiac stimulator as in claim 2, O wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts. O 00
10. 13. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first stimulation phase is initiated greater than 200 milliseconds after V) completion of a cardiac beating cycle. 00 i 14. The method of operating an implantable cardiac stimulator as in claim 13, Swherein the first stimulation phase comprises an anodal stimulus. I The method of operating an implantable cardiac stimulator as in claim 1, increasing the stimulation intensity level by predefined increments until capture occurs; and upon capture, continuing stimulation selected from the group consisting of biphasic stimulation and conventional stimulation at a second intensity level below the diastolic depolarization threshold.
11. 16. The method of operating an implantable cardiac stimulator as in claim 1, wherein in the event it is determined that capture has occurred, the method further comprising: continuing biphasic stimulation for a predetermined period of time.
12. 17. The method of operating an implantable cardiac stimulator as in claim 1, wherein in the event it is determined that capture has not occurred, further comprising: increasing the stimulation intensity level by predefined increments until capture occurs.
13. 18. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first phase polarity is positive.
14. 19. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first phase duration is at least as long as the second phase duration. P MWPDOCSTXS SpWI225471 I amend caim a clem cop.doc-II2IOO6 INO O oO
15. 20. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first stimulation phase comprises an anodal stimulus. C) 0 00
16. 21. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first phase amplitude is less than the second phase amplitude. 00
17. 22. The method of operating an implantable cardiac stimulator as in claim 1, riwherein the first phase amplitude is ramped from a baseline value to a second value.
18. 23. The method of operating an implantable cardiac stimulator as in claim 22, wherein the second value is equalto the second phase amplitude.
19. 24. The method of operating an implantable cardiac stimulator as in claim 22, wherein the second value is at the maximum subthreshold amplitude. The method of operating an implantable cardiac stimulator as in claim 24, wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts.
20. 26. The method of operating an implantable cardiac stimulator as in claim 22, wherein the first phase duration is at least as long as the second phase duration.
21. 27. The method of operating an implantable cardiac stimulator as in claim 22, wherein the first phase duration is about one to nine milliseconds.
22. 28. The method of operating an implantable cardiac stimulator as in claim 22, wherein the second phase amplitude is about two volts to twenty volts.
23. 29. The method of operating an implantable cardiac stimulator as in claim 22, wherein the second phase duration is about 0.2 to 0.9 milliseconds. The method of operating an implantable cardiac stimulator as in claim 22, wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts. P \WPDOCS\TXSSpmU225471 I am-dcd cbn cm COpy do.121IO6 INO -41- S31. The method of operating an implantable cardiac stimulator as in claim 1, O C wherein the first phase duration is about one to nine milliseconds. oO
24. 32. The method of operating an implantable cardiac stimulator as in claim 1, Swherein the second phase duration is about 0.2 to 0.9 milliseconds. 00 S33. The method of operating an implantable cardiac stimulator as in claim 1, Swherein the second phase amplitude is about two volts to twenty volts. S
25. 34. The method of operating an implantable cardiac stimulator as in claim 1, wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts.
26. 35. The method of operating an implantable cardiac stimulator as in claim 1, wherein the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity and duration.
27. 36. The method of operating an implantable cardiac stimulator as in claim wherein the first stimulation phase further comprises a series of rest periods.
28. 37. The method of operating an implantable cardiac stimulator as in claim 36, wherein applying the first stimulation phase further comprises applying a rest period of a baseline amplitude after at least one stimulating pulse.
29. 38. The method of operating an implantable cardiac stimulator as in claim 37, wherein the rest period is of equal duration to the duration of the stimulating pulse.
30. 39. A cardiac stimulator to perform cardioverting, the cardiac stimulator comprising: sensing means for sensing the onset of tachycardia; 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 P, WPDOCSU4S3Sp 7111bol,\ 225-471 pp 4 2 43 47 Cla i 1nndn4doe.29/212(16 3 42- N applying a cooling fluid to the targeted portion, an electrical cooling apparatus, a C mechanical cooling apparatus, and means for cooling via an endothermic chemical Sreaction; output means for delivering, in response to the sensing means, electrical stimulation of a predetermined polarity, amplitude, shape and duration to cause application of pulses of 00 biphasic pacing stimulation at a first intensity level selected from the group consisting of: at the diastolic depolarization threshold, below the diastolic depolarization threshold, and above the diastolic depolarization threshold; and means for determining whether capture has occurred; wherein each pulse of biphasic pacing stimulation comprises: a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; and a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration. The cardiac stimulator as in claim 39, wherein the first phase amplitude is at a maximum subthreshold amplitude.
31. 41. The cardiac stimulator as in claim 39, wherein the electrical cooling apparatus comprises a Peltier cooler.
32. 42. The cardiac stimulator as in claim 41, 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.
33. 43. The cardiac stimulator as in claim 42, wherein the Peltier cooler is electrically connected to a power source located within the housing.
34. 44. The cardiac stimulator as in claim 42, wherein the heat sink is coupled to the Peltier cooler through mechanical contact. The cardiac stimulator as in claim 42, wherein the heat sink is coupled to the Peltier cooler through a thermal transfer fluid. P 3WPDOCSU4S\Spfkluions\ 22547 1 pp 42 43 47 claim a~nmdnmna doc-29I1212106 43- S46. The cardiac stimulator as in claim 39 further comprising: c a processor; Cc a temperature sensor adapted for: determining the temperature of the targeted portion at the time of onset of tachycardia; and oO monitoring the temperature of the targeted portion; wherein the processor is adapted for ceasing applying the temperature decrease to the targeted portion when a preset cooling measure has been achieved.
35. 47. The cardiac stimulator as in claim 46, wherein the preset cooling measure is selected from the group consisting of a preset temperature decrease, a preset temperature, and a preset cooling period.
36. 48. The cardiac stimulator as in claim 39 further comprising a processor, wherein in the event that the means for determining determines that capture has not occurred, the processor is adapted for continuing to apply cooling to the targeted portion until a maximum cooling limit has been reached.
37. 49. The cardiac stimulator as in claim 39 further comprising a processor, wherein in the event that the means for determining determines that capture has occurred the processor is adapted for applying a post-capture stimulation protocol selected from the group consisting of: ceasing applying cooling and applying biphasic stimulation for a predetermined period of time; and applying cooling and biphasic stimulation for a predetermined period of time. The cardiac stimulator as in claim 39, wherein the maximum subthreshold amplitude is about 0.5 to 3.5 volts.
38. 51. The cardiac stimulator to perform cardioverting of claim 39, wherein the first phase duration is about one to nine milliseconds.
39. 52. The cardiac stimulator to perform cardioverting of claim 39, wherein the second phase duration is about 0.2 to 0.9 milliseconds. \WPDOCSTXS'SpUl2254711 camf d cln anpcdoc16110/06 OD -44- O O S53. The cardiac stimulator to perform cardioverting of claim 39, wherein the O second phase amplitude is about two volts to twenty volts. 00
40. 54. The cardiac stimulator to perform cardioverting of claim 39, wherein the n) second phase duration is less than 0.3 milliseconds and the second phase amplitude is 00 OO Sgreater than 20 volts. The cardiac stimulator to perform cardioverting of claim 39, wherein the C 10 first stimulation phase is initiated greater than 200 milliseconds after completion of a cardiac beating cycle.
41. 56. The cardiac stimulator to perform cardioverting of claim 39, wherein in the event that the means for determining determines that capture has occurred, the output means continues biphasic stimulation for a predetermined period of time.
42. 57. The cardiac stimulator as in claim 39, wherein in the event that the means for determining determines that capture has not occurred, the output means increases the stimulation intensity level by predefined increments until capture occurs.
43. 58. The cardiac stimulator as in claim 39, wherein the first stimulation phase comprises an anodal stimulus.
44. 59. The cardiac stimulator as in claim 39, wherein the first phase duration is at least as long as the second phase duration. The cardiac stimulator to perform cardioverting of claim 39, wherein the first phase amplitude is less than the second phase amplitude.
45. 61. The cardiac stimulator to perform cardioverting of claim 39, wherein the first phase amplitude is ramped from a baseline value to a second value. PXWPDOCSMThSlSp=cl 225411 cbmS cdaimc copy dc16110A16 IN C 62. The cardiac stimulator as in claim 61, wherein the second value is equal to the second phase amplitude. 0 00
46. 63. The cardiac stimulator as in claim 61, wherein the second value is at the maximum subthreshold amplitude. 00 oO
47. 64. The cardiac stimulator as in claim 63, wherein the maximum subthreshold (i amplitude is about 0.5 to 3.5 volts. 10 65. The cardiac stimulator as in claim 61, wherein the first phase duration is at least as long as the second phase duration.
48. 66. The cardiac stimulator as in claim 61, wherein the first phase duration is about one to nine milliseconds.
49. 67. The cardiac stimulator as in claim 61, wherein the second phase duration is about 0.2 to 0.9 milliseconds.
50. 68. The cardiac stimulator as in claim 61, wherein the second phase amplitude is about two volts to twenty volts.
51. 69. The cardiac stimulator as in claim 61, wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than 20 volts.
52. 70. The cardiac stimulator to perform cardioverting of claim 39, wherein the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity and duration.
53. 71. The cardiac stimulator as in claim 70, wherein the first stimulation phase further comprises a series of rest periods. PA\WPDOCTXSpcW 711U I .mdcd eldCW ckW OPy dcc.IVI/Oi6 IN -46- ,i 72. The cardiac stimulator as in claim 71, wherein applying the first stimulation phase further comprises applying a rest period of a baseline amplitude after at least one O C0 stimulating pulse. 00
54. 73. The cardiac stimulator as in claim 71, wherein the rest period is of equal V) duration to the duration of the stimulating pulse. 00 S74. The implantable cardiac stimulator device comprising: Splural electrodes; S 10 sensing circuitry connected to the plural electrodes and adapted to sense the onset of tachycardia; 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; detecting circuitry connected to the sensing circuitry and adapted to detect whether pacing capture has occurred; and pulse generating circuitry connected to the plural electrodes and adapted to generate, in response to the sensing circuitry, electrical pulses of a predetermined polarity, amplitude, shape and duration to cause application of pulses of biphasic pacing stimulation at a first intensity level selected from the group consisting of: at the diastolic depolarization threshold, below the diastolic depolarization threshold, and above the diastolic depolarization threshold; and wherein each pulse of biphasic pacing stimulation comprises: a first stimulation phase with a first phase polarity, a first phase amplitude, a first phase shape and a first phase duration; and a second stimulation phase with a second phase polarity, a second phase amplitude, a second phase shape and a second phase duration; wherein, in the event that the detecting circuitry determines that capture has occurred, the pulse generating circuitry continues biphasic stimulation for a predetermined period of time. P PDOCS\HSSpeCfkationsI225471 I pg2 43 47 clam i-cndnu dow-29/122OD6 -47- The implantable cardiac stimulator device as in claim 74, wherein the first c phase amplitude is at a maximum subthreshold.
55. 76. The implantable cardiac stimulator device as in claim 74, wherein the electrical cooling apparatus comprises a Peltier cooler. 00
56. 77. The implantable cardiac stimulator device as in claim 76, 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.
57. 78. The implantable cardiac stimulator device as in claim 77, wherein the Peltier cooler is electrically connected to a power source located within the housing.
58. 79. The implantable cardiac stimulator device as in claim 77, wherein the heat sink is coupled to the Peltier cooler through mechanical contact. The implantable cardiac stimulator device as in claim 77, wherein the heat sink is coupled to the Peltier cooler through a thermal transfer fluid.
59. 81. The implantable cardiac stimulator device as in claim 74 further comprising: a processor; a temperature sensor adapted for: determining the temperature of the targeted portion at the time of onset of tachycardia; and monitoring the temperature of the targeted portion; wherein the processor is adapted for ceasing applying the temperature decrease to the targeted portion when a preset cooling measure has been achieved.
60. 82. The implantable cardiac stimulator device as in claim 81, wherein the preset cooling measure is selected from the group consisting of a preset temperature decrease, a preset temperature, and a preset cooling period. P:%WPDCSTXSZp=c\122547j I aMooded d Cc Copy do.12J130/6 \D -48- O O S83. The implantable cardiac stimulator device as in claim 74 further comprising O a processor, wherein, in the event that the detecting circuitry determines that capture has 00 not occurred, the processor is adapted for applying cooling to the targeted portion until a maximum cooling limit has been reached. oO 00
61. 84. The implantable cardiac stimulator device as in claim 74 further comprising C a processor, wherein, in the event that the detecting circuitry determines that capture has 0 occurred the processor is adapted for applying a post-capture stimulation protocol selected 10 from the group consisting of: ceasing applying cooling and applying biphasic stimulation for a predetermined period of time; and applying cooling and biphasic stimulation for a predetermined period of time. A method of operating an implantable cardiac stimulator to perform cardioverting, the method being substantially as herein before described with reference to the accompanying figures.
62. 86. A cardiac stimulator to perform cardioverting, the cardiac stimulator being substantially as herein before described with reference to the accompanying figures.
63. 87. An implantable cardiac stimulator device, the device being substantially as herein before described with reference to the accompanying figures. DATED this 30th day of October 2006 The Mower Family CHF Treatment Irrevocable Trust By its Patent Attorneys DAVIES COLLISON CAVE