|Número de publicación||USRE39897 E1|
|Tipo de publicación||Concesión|
|Número de solicitud||US 10/214,474|
|Fecha de publicación||23 Oct 2007|
|Fecha de presentación||8 Ago 2002|
|Fecha de prioridad||23 Ene 1989|
|También publicado como||USRE38119|
|Número de publicación||10214474, 214474, US RE39897 E1, US RE39897E1, US-E1-RE39897, USRE39897 E1, USRE39897E1|
|Inventores||Morton M. Mower|
|Cesionario original||Mirowski Family Ventures, L.L.C.|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (68), Otras citas (99), Citada por (17), Clasificaciones (7)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
This is a continuation of Reissue application No. 08/547,691, filed Oct. 19, 1995 now U.S. Pat. No. RE 38,119 E, which is a continuation of Reissue application No. 07/890,280, filed May 29, 1992 now abandoned, which is a reissue of U.S. Pat. No. 4,928,688, all of which are incorporated herein by reference.
I. Field of the Invention
This invention pertains to medical devices, but more specifically, to a method for increasing the cardiac output of a patient suffering from congestive heart failure by stimulating the heart of the patient at multiple sites simultaneously.
II. Discussion of the Prior Art
Normally, impulses from the SA node affect contraction of the atria and then propagate to the AV node. The AV node, in turn, emits a second nerve impulse which affects contraction of the ventricles. These nerve impulses affect contraction, i.e., depolarization of the tissue of the heart, in a coordinated manner to circulate blood through the body. Cardiac pacers of the type herein described generally are useful for maintaining proper functional operation of a sick heart. Of many cardiac deficiencies which have in the past been diagnosed and treated, conduction difficulties have presented significant problems for which a pacer has been used for treatment. A particular conduction deficiency, known as AV branch block, inhibits the transfer of nerve impulses from the sinoatrial (SA) node to atrial-ventricular (AV) node. When a bundle block occurs, these nerve impulses are not properly transmitted from the SA node to the AV node and ventricles.
When this condition occurs, normal treatment is to employ a pacer which locks onto the rhythmic cycle of a atrial beating signal and supplies to the ventricles a stimulating impulse at a certain time thereafter to effect contraction of the ventricles. The time period between the occurrence of the atrial beat and the normal contraction of the ventricles is known as the A-V delay period. Generally, hemodynamic efficiency is somewhat dependent to the A-V delay period, thus the pacer must emit a stimulating pulse at a time to preserve an optimum A-V delay period.
Other forms of conduction deficiency, such as myocardial scarring and bundle branch block, cause slow conduction of nerve impulses, in which case, nerve impulses are indeed passed from the SA to the AV node, but in a time period which is slower than normal. The Q-R-S complex in this case would manifest itself in being very wide and hemodynamic efficiency also becomes lower than normal.
In each of the above-mentioned cardiac deficiencies, the heart does not contract in coordinated fashion. This uncoordinated movement increases depolarization time and results in more inefficient pumping rather than a more coordinated and simultaneous ventricular depolarization. In essence, such conduction deficiencies result in asynchrony between the left and right ventricle.
Additionally, arrhythmias of the heart produce uncoordinated ventricular contraction that affects the hemodynamic efficiency of the heart. Specifically, the recent paper “Incomplete Filling and Incoordinate Contraction as Mechanisms of Hypotension During Ventricular Tachycardia in Man”, published in Circulation, Vol. 68, No. 5, in 1983, describes that left ventricular function is severely disturbed by the disorganization of wall motion in hearts undergoing ventricular tachycardias. Moreover, it was found that hearts with impaired functions show profound reductions in pumping ability due to incoordinate contraction of the ventricles. It appears reasonable to believe, therefore, that any abnormal functioning heart that requires pacemaking or which has QRS widening will have a better hemodynamic efficiency if both ventricles are paced to contract in coordination with each other. There have been systems developed in the past employing a plurality of electrodes attached to the heart for effecting stimulation of a plurality of regions of the heart. For example, the Funke U.S. Pat. No. 3,937,226 discloses a cardiac electrical stimulation defibrillation system including a plurality of electrode terminals connected in a spaced relation on the heart. The electrodes, which provide stimulating and sensing, are each connected to amplifiers. The amplifiers are connected to electronic control circuit means configured to cause stimulation of all of the electrode terminals simultaneously in response to a sensed depolrization signal on the heart by at least one electrode terminal. In addition, the electronic control circuit is provided with a multivibrator means to synchronize the stimulation signal with the Q-R-S complex. Although Funke does teach the concept of simultaneous stimulation of a plurality of spaced electrodes, he does not disclose its specific use as a method of improving the cardiac output of patients suffering from congestive heart failure, nor does he discuss the specfic placement of the electrodes about the heart.
The Rockland et al U.S. Pat. No. 4,088,140 discloses a similar system to Funke's although a specific use as a pacemaker is stated in the patent. Rockland, et al discloses a demand anti-arrythmia pacemaker including a plurality of sensing electrodes connected to the heart to sense ventricular depolarizations. Electronic circuitry is provided having two paths of operation. A first path provides stimulation to one area of the heart if depolarization of a naturally occurring heart beat fails to occur within a first predetermined time period. In this first path, it is stated that the circuitry acts as a pacemaker in the event of skipped natural heartbeats. A second path provides stimulation to a plurality of locations on the heart if a depolarization signal is sensed on the heart within a second predetermined time period. In this second path, it is stated that the circuitry acts as a synchronous multiple electrode pacemaker or a synchronous multiple electrode defibrillator. Although, one example of an electrode placed in the intraventricular section and others in a spaced relation on the heart ventricles is given, there are no teachings of the specific placement of the electrodes on the heart nor the improvement of cardiac output from a sick heart. In addition, the electrodes perform either stimulating or sensing, not both, therefore a large number of electrodes is required in this system.
The Tacker, Jr. et al and McCorkle U.S. Pat. Nos. 4,548,203, 4,458,677 and 4,332,259, respectively, disclose the specific placement of an electrode in or around both left and right ventricles of the heart. The Tacker, Jr. et al patent discloses the placement of a catheter having one electrode in the right ventricle and another outside the heart and a third electrode placed on the left ventricle. The catheter electrodes, each being paired with the left ventricular electrode, are pulsed in sequence with a predetermined time separation resulting in uniform current density delivered to the heart. However, this pulsing scheme and configuration is disclosed for use in a ventricular defibrillation device and not for cardiac pacing to improve cardiac output wherein a more precise synchronization of stimulation signals with the Q-R-S complex is required.
The McCorkle, Jr. patents disclose the specific placement of an electrode in the right ventricle and another electrode in the coronary sinus surrounding the left ventricle for connection to a pacemaker. However, there is no specific technique disclose of providing stimulating signals to the electrodes to perform a pacemaking function.
In light of the above difficulties and shortcomings of the prior art, an objective of the present invention is to provide a cardiac pacer for increasing hemodynamic efficiency of a heart experiencing a conduction deficiency.
Another objective of the invention is to ensure a more coordinated and simultaneous ventricular depolarization of both left and right ventricles of the heart.
A yet further objective of this invention is to provide a cardiac pacer suitable for being implanted in a manner so as to impose a minimal surgical risk during implantation thereof.
A further objective of this invention is to provide a method and apparatus of separately sensing and stimulating each ventricle of the heart in order for effecting simultaneous contraction automatically of both ventricles of the heart to narrow the QRS complex of a failing heart and thereby cause an increase in blood pressure and cardiac output.
The method of the present invention involves a procedure for pacing of the heart in a particular way so as to improve its contraction pattern, and thereby augment the movement of blood through the heart. Patients suffering from severe congestive heart failure, which is found not to respond well to conventional drug therapy and to have a conduction defect in the ventricle resulting in a widen Q-R-S complex have been aided by a pacing regimen in which stimulating pulses are simultaneously applied to both ventricles by way of a demand pacemaker or asynchronous pacemaker.
It is theorized that a considerable part of the hemodynamic impairment in refractory congestive heart failure with conduction defects is due to an incoordinate contraction of the heart, so that a part of the heart muscle contracts and balloons out the part that is not contracting. When the latter area of the heart muscle does finally contract, the former has relaxed, so that a large part of the blood volume is merely shunted back and forth within the heart rather than being ejected as would happen with a more coordinate contraction pattern.
To attain the foregoing and other objectives, the present invention comprises, a bi-ventricular cardiac pacer having detecting and stimulating circuits for effecting substatially simultaneous contraction of both left and right ventricles of the heart. In the preferred embodiment, the bi-ventricular pacer comprises ECG amplifier means for separately processing sensed cardiac signals from each of the right and left ventricles. The amplified sensed signals are used to determined where possible abnormal conduction delays exist on the heart and to activate an electrical stimulator for stimulating the appropriate abnormally functioning part of the heart. More specifically, the stimulator responds to the control circuit to issue stimulating pulses simultaneously to either the left or right ventricle, as appropriate. The stimulator may be of the demand type wherein pacing pulses are only issued in the absence of a normal Q-R-S complex for one or the other of the two ventricles (e.g., occasional bundle branch block or slow conduction), or the nondemand type wherein pacing pulses are always issued (e.g., permanent bundle branch block or slow conduction).
To convey and sense signals to and from the heart, the present invention includes a pacing lead assembly comprising first and second separate electrodes. The first electrode is preferably introduced through the superior vena cava into the right ventricle and the second electrode is introduced through the coronary sinus to the left ventricle. Both lead segments include a sensing and pacing tip electrode which serves to both sense a cardiac depolarization signal or to apply a stimulating pulse from an implanted pulse generator to the ventricle.
Additionally, to preserve a predetermined A-V delay period, additional atrial sensing electrodes may be placed on or around the atrial chambers of the heart and connected to the control circuit. The control circuit responds to the sensed atrial and ventricular depolarization signals to provide simultaneous ventricular contraction signals applied to the left and right ventricles following a preset A-V delay period.
The advantages of the present invention include a more precise and coordinated simultaneous ventricular depolarization of both the right and left ventricular to thereby increase hemodynamic efficiency of a patient experiencing congestive heart failure or weak contractions.
These together with other objects and advantages which will become subsequently apparent reside in the details of construction and operation as more fully hereinafter described and claimed, reference being had to the accompanying drawings forming a part hereof, wherein like numerals refer to like parts throughout.
In operation, the electrodes 13 and 15 are disposed in or about the right and left ventricles, respectively. A preferred surgical procedure for-implanting the lead 12 is to extend it through the superior vena cava 28 so that the sensing stimulating tip 13 thereof lodges in the internal chamber of the right ventricle of the heart 10. A preferred surgical-procedure for implanting lead branch 14 is to extend it through the coronary sinus (not shown) of the heart 10 so that the sensing/stimulating tip 15 thereof lodges directly in or about the coronary sinus and left ventricle. Although it is described that electrodes 13 and 15 perform both sensing and pacing, it is possible for testing and examination, that separate unipolar or bipolar sensing and stimulating electrodes may be used.
When attached to the heart, the electrodes 13 and 15 sense cardiac signals in the form of well-known Q-R-S complex at separate sites within the left and right ventricles. The ECG amplifiers 16 and 17 feed the amplified versions of these signals to the control circuit 20.
The control circuit 20 analyzes the cardiac signals to determine whether an abnormal conduction exists. Specifically, if a cardiac signal is received from the left ventricle but not from the right ventricle, the control circuit 20 provides a control signal to the stimulator 22 to issue a stimulating pacing pulse over conductors 24 and 18 and lead branch 12 to the right ventricle, via the sensing/stimulating tip electrodes 13. Similarly, the control circuit 20 provides a control signal to the stimulator 22 to issue a stimulating pacing pulse over lead branch 14 to the left ventricle, via sensing/stimulating tip electrode 15, if a cardiac depolarization signal is received from the right ventricle, but not from the left ventricle. It is also possible to sense a depolarization signal from only one ventricular chamber and then unconditionally stimulate both ventricular chambers. This is wasteful of power which is a concern only if the stimulator is totally implanted and must rely on an implanted battery power source.
The timing of the stimulating pacing pulse from the stimulator 22 is such that both ventricles will contract substantially simultaneously. Where both ventricles are unconditionally stimulated upon the occurrence of a QRS complex on only one side, the fact that ventricular site which had produced a Q-R-S complex is immediately stimulated along with the other ventricle does not cause a problem since the site producing that complex is still refractory at the time it is stimulated.
It is also possible that no cardiac signals are sensed from either ventricle, possibly resulting from complete conduction failure between the sinoatrial node and the atrialventricular node. In this case, the control circuit 20 will again activate the stimulator 22 to provide stimulating signals to both ventricles simultaneously.
In an alternative embodiment of the invention, the issuance of pacing pulses to the ventricles is time-coupled to the rhythmic cycle of the atrial beat of the heart to preserve a preset atrial-ventricular delay period of about 120 to 200 milliseconds. Additional atrial sensing is accomplished, via lead 23 and a sense electrode 25 similar to the ventricular leads 12 and 14, but disposed in or about the right atrial chamber and connected to the control circuit 20, via atrial sense amplifier 27. The control circuit 20 may be configured to respond to the sensed atrial and ventricular signals to activate the stimulator for providing appropriate simultaneous stimulating signals to the ventricles as described above in accordance with the predetermined A-V delay period.
In the case where the conduction of the natural stimulating signal originating at the sinoatrial node of the heart 10 is only partially blocked or slowed, the ventricles may partially or incompletely contract, in which case hemodynamic efficiency is reduced. Under these circumstances, provision is made in the control circuit 20 for determining whether a Q-R-S cardiac signal, although present, is weak or slow, and if so, to activate the stimulator 22 to stimulate the ventricles of the heart by passing pacing pulses simultaneously thereto.
To accomplish bi-ventricular pacing, activity is sensed in both the left and the right ventricle. When a ventricular contraction is sensed in either ventricle, a timer is initiated. If within a time window established by said timer, the contraction is sensed in the other ventricle, all pacing is inhibited because the natural contractions are deemed to be simultaneous. On the other hand, if ventricular contractions are not sensed in both ventricles within a period of coincidence defined by the time delay, at the end of this delay, the pacing pulse will be emitted, but only to the ventricle for which a QRS complex has not been sensed. Generally, ventricular contractions which occur within 5-10 milliseconds of each other result in sufficient hemodynamic efficiency so as to not require treatment. Hence, the delay window may be of this order of magnitude. As used herein, the term “substantially simultaneous contraction” includes the occurrence of natural contractions of both ventricles within the window period or an evoked contraction of one or both ventricles immediately following the expiration of the window period.
Operation of the circuit of
Let if first be assumed that a left ventricle contraction procedes that of the right. In this case, an R-wave signal propagates through amplifier 16 to set the Set-Reset type flip-flop 30. a logical “1” signal passes through OR gate 32 to clock D-type of flop 34 to the “set” state which, in turn, initiates the aforementioned delay timing. Window register 36 is loaded with a digital count value which is representative of the desired delay window, e.g., 5-10 ms. This may be either a fixed, hard-wired register or, alternatively, a programmable register which may be set by telemetry means in a known manner. When the preset enable input (PE) in high, counter 38 is held at a digital count corresponding to the value held in window register 36. When flip-flop 34 is set, the PE on counter 38 is removed, allowing the counter to be decremented with each clock pulse provided on clock line 40. At the end of the preprogrammed window delay interval, counter 38 is decremented to zero, causing the zero detect (ZD) line 42 to go high. The leading edge of the zero detect pulse is used to trigger a ventricle pacing pulse from pulse generator 44, via gates 54 and 56, as required. The pulse generator circuitry 44 converts this leading edge trigger to a pulse of the proper amplitube and duration for effective stimulation of the right ventricle. Note that, since under the assumed conditions flip-flop 30 has been set, AND gate 48 is disabled and, therefore, pulse generator 50 is inhibited from generating a left ventricle pacing pulse.
Next to be considered is the case where a right ventricle contraction has not been sensed within the prescribed window interval. In this case, flip-flop 52 remains reset and AND gate 54 is enabled which allows the zero detect pulse ZD to propagate through OR gate 56 to trigger pulse generator 44, thus stimulating the right ventricle. If, however, a right ventricle contraction has been detected, flip-flop 52 would have been set prior to the generation of the ZD pulse and, in this case, both AND gates 48 and 54 are disabled and no pacing pulse in either ventricle is generated.
It can be seen from the symmetry of the circuit that the operation is identical if the right ventricle contraction precedes the left ventricle contraction by more than the preprogrammed delay interval. In either case, the setting of either flip-flop 30 or 52 causes 52 causes the initiation of the timing window delay interval. When one of these flip-flop sets, the other must set within the window period, otherwise a pacing pulse will be generated in the unsensed ventricle.
The bi-ventriclar pacing control circuitry may be combined with other well-known pacer control circuitry such that the bi-ventriclar mode can be realized in combination with any other pacing mode, such as VVI, DDD, VOO. Line 58 is the logical OR of either of left ventricle event or a right ventricle event. It may be connected to other pacing control circuitry 62 in place of the signal which is normally responsive to only activity in the left ventricle. A sensed ventricle event thus inhibits the generation of a pacing trigger from another pacing circuitry and leaves the control of pacing in the alternate ventricle, as required, to the circuitry of FIG. 1. If line 58 is not activated within the escape interval of the other pacing control circuitry, a paced ventricle trigger signal on line 60 is produced which propagates through both OR gate 62 and OR gate 56 to trigger pacing pulses in both ventricles.
It is also contemplated that when a ventricular depolarization signal is sensed in one or the other of the ventricles, that a stimulating pulse may also be immediately delivered, on an unconditional basis, to both ventricles, via the implanted leads 13 and 15, thus resulting in a coordinated contraction of both ventricles.
The foregoing illustrate preferred arrangements for carrying out the objectives of this invention. Modifications and variations can obviously be made by those skilled in the art without departing from the true spirit and scope of the invention. For instance, the circuit may be employed to simultaneously pace the auricles, instead of ventricles, if such is required to improve pumping efficiency. The arrangement may also be employed as an improvement of conventional pacers thereby to improve their performance. As stated herein, the inventive arrangement can be used in an implanted device or in an external treating, diagnostic or testing device. Accordingly, the invention is limited only by the scope of the appended claims rather than by what is shown and described. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention.
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|14||Brief for Plaintiff-Appellant Medtronic, Inc. filed Oct. 28, 2005 in Medtronic, Inc. v. Guidant Corp., No. 05-1515 (Fed. Cir.).|
|15||Brief for St. Jude Medical, Inc., as Amicus Curiae Supporting Appellant filed Nov. 8, 2005 in Medtronic, Inc. v. Guidant Corp., No. 05-1515 (Fed. Cir.).|
|16||Brief of Defendants-Appellees Guidant Corporation, Guidant Sales Corporation, Eli Lilly & Company, and Mirowski Family Ventures LLC filed Jan. 11, 2006 in Medtronic, Inc. v. Guidant Corp., No. 05-1515 (Fed. Cir.).|
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|18||Burkoff, D, et al., "Influence of Pacing Site on Canine Left Ventricular Contraction," Am. J. Physiol. (Heart Circ. Physiol.), 1986:20:H428-H435.|
|19||Case Docket for Medtronic, Inc. v. Guidant Corp., No. 05-1515 (Fed. Cir.) appealed from Medtronic, Inc. v.Guidant Corp., No. 03-848-SLR (D. Del.).|
|20||Castellanos, A, et al., "A New Instrument for Automatic Monitoring and Tape Recording in Infants and Children," Boletin de la Associacion Medica de Puerto Rico, vol. 58, No. 7, Jul. 1966, pp. 355-359.|
|21||Castellanos, A, et al., "A Study of Arrival of Excitation at Selected Ventricular Sites during Human Bundle Branch Block Using Close Bipolar Catheter Electrodes," CHEST, vol. 63, No. 2, Feb. 1973, pp. 208-213.|
|22||Castellanos, A, et al., "An Electrical Digitalis Tolerance Test," Am. J. of Medical Sciences, Nov. 1967, pp. 159-168.|
|23||Castellanos, A, et al., "Atrial Demand and AV Sequential Pacemakers," Pacemaker Therapy, L. Dreifus, ed., 1983, pp. 149-164.|
|24||Castellanos, A, et al., "Cardiac Pacemakers," Cardiac Surgery 2, vol. 3, No. 2, D. Harken, ed., 1971, pp. 32-44.|
|25||Castellanos, A, et al., "Effects of Pacemaker Impulses on Latent Arrhythmias Produced by Intramyocardial Chemical Stimulation," Cardiologia, vol. 51, No. 6, 1967, pp. 340-348.|
|26||Castellanos, A, et al., "Electronic Pacemaker Models of Parasystole: With Special Reference to Artificial Intermittent Parasystole With Phase 3 and Phase 4 Protection and to Parasystolic Modulation," PACE, vol. 5, No. 4, Jul. 1982, pp. 537-545.|
|27||Castellanos, A, et al., "Evaluacion Clinica De Los Marcapasos Implantados, " Boletin de la Associacion Medica de Puerto Rico, vol. 73, No. 12, Dec. 1981, pp. 644-653.|
|28||Castellanos, A, et al., "His Bundle Recordings in Atrioventricular Nodal Alternating Wenckebach Periods Ending in 5:1 Atrioventricular Block Coexisting with Paroxysmal Atrioventricular Nodal Block," CHEST, vol. 74, No. 3, Sep. 1978, pp. 274-279.|
|29||Castellanos, A, et al., "Implantable Demand Pacemaker," Brit. Heart J., vol. 30, 1968, pp. 29-33.|
|30||Castellanos, A, et al., "Implantable Pacemakers for Cardiac Tachyarrhythmias," Cardiac Arrythmias: Mechanisms and Management, A. Castellanos, ed., 1980, pp. 159-173.|
|31||Castellanos, A, et al., "Pacemaker Vectorcardiography," Am. Heart J., vol. 75, No. 1, Jan. 1968, pp. 6-18.|
|32||Castellanos, A, et al., "Pacing in Acute Myocardial Infarction: A Programmed Introduction," CHEST, vol. 58, No. 2, Aug. 1970, pp. 152-163.|
|33||Castellanos, A, et al., "Preliminary Studies With an Implantable Multimodal A-V Pacemaker for Reciprocating Atrioventricular Tachycardias," PACE, vol. 3, No. 3, May 1980, pp. 257-265.|
|34||Castellanos, A, et al., "Repetitive Firing Occurring During Synchronized Electrical Stimulation of the Heart," J. of Thoracic Cardiovascular Surgery, vol. 51, No. 3, Mar. 1966, pp. 334-340.|
|35||Castellanos, A, et al., "Sextapolar Catheter Electrode for Temporary Sequential Atrioventricular Pacing," Cardiovascular Research, vol. 8, No. 5, Sep. 1974, pp. 712-714.|
|36||Castellanos, A, et al., "Significance of Multiple Responses Produced by Electrical Depolarization of the Heart," Acta Cardiologica, vol. 21, No. 2, 1966, pp. 157-166.|
|37||Castellanos, A, et al., "St-qR Pattern: New Sign for Diagnosis of Anterior Myocardial Infarction During Right Ventricular Pacing," Br. Heart J., vol. 35, Oct. 1973, pp. 1161-1165.|
|38||Castellanos, A, et al., "The Electrocardiogram and Vectorcardiogram of Ectopic Ventricular Beats," Acta Cardiologica, vol. 28, No. 6, 1973, pp. 562-575.|
|39||Castellanos, A, et al., "The Use of the Demand Pacemaker in Auriculo-Ventricular Conduction Disturbances," J. of Cardiovascular Surgery, vol. 7, No. 2, Mar.-Apr. 1966, pp. 92-96.|
|40||Castellanos, A, et al., "The Wedensky Effect in the Human Heart," Brit. Heart J., vol. 28, 1966, pp. 276-283.|
|41||Castellanos, A, et al., "Ventricular-triggered Pacemaker Arrhythmias," Brit. Heart J., vol. 31, 1969, pp. 546-552.|
|42||Castellanos, A., et al., "Pacemaker-Induced Cardiac Rhythm Disturbances," Annals of New York Academy of Sciences, vol. 167, No. 2, Oct. 1969, pp. 903-910.|
|43||Castellanos, A., et al., "Simultaneous Biventricular Stimulation for Ventricular Arrhythmias," Am. J. Cardiol, vol. 88, Nov. 15, 2001, pp. 1217-1218.|
|44||Castillo, C, et al., "Bifocal Demand Pacing," CHEST, vol. 59, No. 4, Apr. 1971, pp. 360-364.|
|45||Cazeau S, et al., "Effects of Multisite Biventricular Pacing in Patients With Heart Failure and Intraventricular Conduction Delay," N. Engl. J. Med., vol. 344, 2001, pp.: 873-880.|
|46||Chamorro, JL, et. al., "Ejection VAVE; EF and Phase Histogram to Evaluate a Correct Programation of AV Delay in DDD Pacemakers," European Journal of Nuclear Medicine, vol. 8, No. 5, 1983, Abstract P96.|
|47||Chamorro, JL, et. al., "Quantification of Experimental Myocardial Infarction with 99TcGlucogeptonate," European Journal of Nuclear Medicine, vol. 8, No. 5, 1983, Abstract P104.|
|48||Curriculum Vitae of Dr. Morton M. Mower (Exhibit 90 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|49||D'Ajutolo, R, and Posse, R, Tratamiento de Las Arritmias Cardiacas, Buenos Aires 1968 and English-language translaton of Chapter 10.|
|50||De Teresa, E., Grandes Temas de la Medicina: Marcapasos, Nueva Lente, Madrid 1987.|
|51||De Teresa, et al., "Haemodynamics of Ventricular Depolarization Sequence During Permanent Cardiac Pacing," Cardio Stimolazione, vol. 2, No. 3, 1984, p. 225.|
|52||Defendants' (St. Jude et al.) Opposition to Plaintiffs' (Guidant et al.) Motion for Leave to File a Surreply from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|53||Defendants' (St. Jude et al.) Request for Oral Argument from Guidant Corp. v. St. Jude Medical,Inc. , No. 04-0067-SLR (D. Del.).|
|54||Defendants' (St. Jude et al.) Supplemental Initial Disclosures (Documents) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|55||Defendants' (St. Jude et al.) Supplemental Response to Plaintiffs' (Guidant et al.) Fourth Set of Interrogatories (No. 19) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|56||Diotallevi, P, et al., "Rescuing Failed Biventricular Implants Using Right Ventricular Bifocal Pacing to Assure Cardiac Resynchronization Benefits to Heart Failure Patients," Heart Rhythm, vol. 3, No. 5, May Supplement 2006, Abstract No. AB48-2.|
|57||Document bearing bates Nos. A0095-108 (Exhibit 133 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|58||Document dated Jul. 20, 1988 and bearing bates Nos. GDT2800-02 (Exhibit 146 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|59||Document entitled "Bibliography 35. What's New?" (Exhibit 94 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|60||Document entitled "New Idea" (Exhibit 103 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|61||Document showing Biventricular Pacer of American Optical Co. (Exhibit 143 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|62||Dreifus, L, et al., "Effects of AV Sequential Versus Asynchronous AV Pacing on Pulmonary Hemodynamics," PACE, vol. 9, No. 2, Mar.-Apr. 1986, pp. 171-177.|
|63||Email from J. Spinelli to A. Kadish dated Aug. 2, 2005 (Ex. 222 of the Deposition of Julio Spinelli, taken Nov. 10, 2005).|
|64||Expert Report of Eduardo De Teresa Galván (Expert for St. Jude, et al.) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.) With Accompanying Exhibits A-B).|
|65||Expert Report of Harry F. Manbeck, Jr. (Expert for St. Jude, et al.) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.) (With Accompanying Exhibits A-D).|
|66||Expert Report of Kimberly A. Moore (Expert for St. Jude, et al.) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.) (With Accompanying Exhibit A).|
|67||Fax from J. Heemels to J. Spinelli dated Feb. 21, 1992 (Exhibit 109 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|68||Fax from M. Mower to J. Millerhagen (Exhibit 110 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|69||Letter from M. Mower to S. Barold (Exhibit 95 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|70||Letter from R. Cohn to T. Nikolai dated Aug. 23, 1988 (Exhibit 105 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|71||Letter from S. Rickerson to T. Nikolai dated Oct. 30, 1987 (Exhibit 102 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|72||Letter from T. Nikolai to M. Mower dated Aug. 31, 1988 (Exhibit 106 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|73||Letter from T. Nikolai to M. Mower dated Dec. 3, 1987 (Exhibit 104 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|74||Materials related to the Mirowski Symposium (Exhibit 93 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005.|
|75||Memorandum Opinion dated Jan. 6, 2006 denying Defendants' (St. Jude et al.) Motion for Summary Judgment of Invalidity Based on Reissue Recapture issued in Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|76||Motion of St. Jude Medical, Inc. For Leave to File Brief as Amicus Curiae filed Nov. 8, 2005 in Medtronic, Inc. v. Guidant Corp., No. 05-1515 (Fed. Cir.).|
|77||Plaintiffs' (Guidant et al.) Additional Supplemental Responses to Defendants' (St. Jude et al.) First, Second, and Third Sets of Interrogatories (1-35).|
|78||Plaintiffs' (Guidant et al.) Motion for Leave to File a Surreply from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|79||Plaintiffs' (Guidant et al.) Opposition to St. Jude's Request for Oral Argument from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|80||Plaintiffs' (Guidant et al.) Reply to St. Jude's Opposition to Plaintiffs' (Guidant et al.) Motion for Leave to File a Surreply from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|81||Plaintiffs' (Guidant et al.) Responses to Defendants' (St. Jude et al.) Fourth Set of Interrogatories (36-40) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|82||Plaintiffs' (Guidant et al.) Responses to Defendants' (St. Jude et al.) Second Set of Requests for Admissions (27-38) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|83||Plaintiffs' (Guidant et al.) Third Supplemental Response to Defendants' (St. Jude et al.) Interrogatory No. 1 from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|84||Presentation bearing bates Nos. MM0013-79 (Exhibit 126 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|85||Presentation bearing bates Nos. MM0247-51 (Exhibit 124 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|86||Presentation bearing bates Nos. MM0278-342 (Exhibit 125 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|87||Presentation bearing bates Nos. MM0343-401 (Exhibit 129 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|88||Presentation bearing bates Nos. MM0508-692 (Exhibit 131 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|89||Presentation entitled "A History of ICD & Related Therapies" and bearing bates Nos. MM0087-139 (Exhibit 127 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|90||Presentation entitled "Cardiac Resynchronization Therapy (CRT) Reduces Hospitalizations, and CRT with Implantable Defibrillator (CRT-D) Reduces Mortality in Chronic Heart Failure: The Companion Trial" and bearing bates Nos. MM0257-77 (Exhibit 128 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|91||Presentation entitled "Evolution of Cardiac Rhythm Management Systems: A History of Automatic Implantable Cardioverter-Defibrillator (AICD)" and bearing bates Nos. MM0402-454 (Exhibit 130 of the Deposition of Dr. Morton M. Mower, M.D., taken Oct. 17-18, 2005).|
|92||Reply Brief for Plaintiff-Appellant Medtronic, Inc. filed Feb. 8, 2006 in Medtronic, Inc. v. Guidant Corp., No. 05-1515 (Fed. Cir.).|
|93||Summary of Expected Testimony of David G. Benditt, MD, FACC, FRCP(C), FHRS, (Expert for St. Jude, et al.) from Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.) (With Accompanying Exhibits A-C).|
|94||Transcript of the Deposition of Dr. Barouh V. Berkovits, taken Dec. 7, 2005 in Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|95||Transcript of the Deposition of Julio Spinelli, taken Nov. 10, 2005 in Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|96||Transcript of the Deposition of Morton M. Mower, M.D., taken Oct. 17, 2005 in Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|97||Transcript of the Deposition of Morton M. Mower, M.D., taken Oct. 18, 2005 in Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|98||Updated Case Docket for Guidant Corp. v. St. Jude Medical, Inc., No. 04-0067-SLR (D. Del.).|
|99||Updated Case Docket for Medtronic, Inc. v. Guidant Corp., No. 03-848-SLR (D. Del.)|
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|Clasificación de EE.UU.||607/9|
|Clasificación internacional||A61N1/368, A61N1/362|
|Clasificación cooperativa||A61N1/3627, A61N1/368, A61N1/3684|