WO2003065889A2 - Dynamically optimized multisite cardiac resynchronization device - Google Patents

Dynamically optimized multisite cardiac resynchronization device Download PDF

Info

Publication number
WO2003065889A2
WO2003065889A2 PCT/US2003/003659 US0303659W WO03065889A2 WO 2003065889 A2 WO2003065889 A2 WO 2003065889A2 US 0303659 W US0303659 W US 0303659W WO 03065889 A2 WO03065889 A2 WO 03065889A2
Authority
WO
WIPO (PCT)
Prior art keywords
pacing
regions
hypertrophied
myocardial
determined
Prior art date
Application number
PCT/US2003/003659
Other languages
French (fr)
Other versions
WO2003065889A3 (en
Inventor
Angelo Auricchio
Julio C. Spinelli
Andrew P. Kramer
Original Assignee
Cardiac Pacemakers, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cardiac Pacemakers, Inc. filed Critical Cardiac Pacemakers, Inc.
Priority to EP03737691A priority Critical patent/EP1483021A2/en
Priority to AU2003210894A priority patent/AU2003210894A1/en
Publication of WO2003065889A2 publication Critical patent/WO2003065889A2/en
Publication of WO2003065889A3 publication Critical patent/WO2003065889A3/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362Heart stimulators
    • A61N1/3627Heart stimulators for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362Heart stimulators
    • A61N1/365Heart stimulators controlled by a physiological parameter, e.g. heart potential
    • A61N1/368Heart stimulators controlled by a physiological parameter, e.g. heart potential comprising more than one electrode co-operating with different heart regions
    • A61N1/3684Heart stimulators controlled by a physiological parameter, e.g. heart potential comprising more than one electrode co-operating with different heart regions for stimulating the heart at multiple sites of the ventricle or the atrium
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316Modalities, i.e. specific diagnostic methods
    • A61B5/318Heart-related electrical modalities, e.g. electrocardiography [ECG]
    • A61B5/346Analysis of electrocardiograms
    • A61B5/349Detecting specific parameters of the electrocardiograph cycle
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362Heart stimulators
    • A61N1/365Heart stimulators controlled by a physiological parameter, e.g. heart potential
    • A61N1/368Heart stimulators controlled by a physiological parameter, e.g. heart potential comprising more than one electrode co-operating with different heart regions
    • A61N1/3684Heart stimulators controlled by a physiological parameter, e.g. heart potential comprising more than one electrode co-operating with different heart regions for stimulating the heart at multiple sites of the ventricle or the atrium
    • A61N1/36842Multi-site stimulation in the same chamber
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362Heart stimulators
    • A61N1/365Heart stimulators controlled by a physiological parameter, e.g. heart potential
    • A61N1/368Heart stimulators controlled by a physiological parameter, e.g. heart potential comprising more than one electrode co-operating with different heart regions
    • A61N1/3684Heart stimulators controlled by a physiological parameter, e.g. heart potential comprising more than one electrode co-operating with different heart regions for stimulating the heart at multiple sites of the ventricle or the atrium
    • A61N1/36843Bi-ventricular stimulation

Definitions

  • This invention pertains to cardiac rhythm management devices such as pacemakers and implantable monitoring devices.
  • a pacemaker for example, is a cardiac rhythm management device that paces the heart with timed pacing pulses.
  • the most common condition for which pacemakers are used is in the treatment of bradycardia, where the ventricular rate is too slow.
  • Atrio-ventricular conduction defects i.e., AV block
  • AV block Atrio-ventricular conduction defects that are permanent or intermittent and sick sinus syndrome represent the most common causes of bradycardia for which permanent pacing may be indicated. If functioning properly, the pacemaker makes up for the heart's inability to pace itself at an appropriate rhythm in order to meet metabolic demand by enforcing a minimum heart rate.
  • Pacing therapy can also be used in the treatment of heart failure, which refers to a clinical syndrome in which an abnormality of cardiac function causes a below normal cardiac output that can fall below a level adequate to meet the metabolic demand of peripheral tissues.
  • heart failure When uncompensated, it usually presents as congestive heart failure due to the accompanying venous and pulmonary congestion.
  • Heart failure can be due to a variety of etiologies with ischemic heart disease being the most common. It has been shown that some heart failure patients suffer from intraventricular and/or interventricular conduction defects (e.g., bundle branch blocks) such that their cardiac outputs can be increased by improving the synchronization of ventricular contractions with electrical stimulation. Other conduction defects can occur in the atria. Cardiac rhythm management devices have therefore been developed which provide electrical stimulation to the atria and/or ventricles in an attempt to improve the coordination of cardiac contractions, termed cardiac resynchronization therapy.
  • the present invention relates to a method and apparatus for optimally delivering cardiac resynchronization therapy.
  • Hypertrophied regions of the myocardium are identified by placing electrodes at selected myocardial regions and measuring the amplitudes of electrograms from the electrodes during depolarization events.
  • Resynchronization pacing may then be delivered in a manner that pre-excites one or more of the hypertrophied regions in order to subject the region to a lessened preload and afterload.
  • the ventricles may be paced at a selected single electrode site using a conventional bradycardia pacing mode where the paced site is a region identified as hypertrophied.
  • the ventricles may be paced at multiple sites using a multi-site resynchronization pacing mode, where the delivery of paces to multiple ventricular sites during a cardiac cycle is used to not only enforce a minimum ventricular heart rate but also to alter the depolarization patterns of the ventricles during systole and improve the coordination of the ventricular contraction.
  • Multi-site ventricular resynchronization pacing may involve pacing both ventricles or only one ventricle at multiple sites by delivering a pacing pulse to each of the individual electrodes making up a pacing configuration in a specified pulse output sequence.
  • the pulse output sequence can be specified so that one or more hypertrophied regions are paced before other regions during systole and hence mechanically unloaded. By unloading such hypertrophied regions in this way over a period of time, reversal of undesirable ventricular remodeling is effected.
  • Pacing parameters also may be adjusted to increase the frequency of paced beats so that the hypertrophied region is unloaded more often.
  • an implantable pacemaker is configured with sensing/pacing electrodes at a plurality of ventricular locations together with associated sensing and pacing channels for sensing intrinsic cardiac activity and delivering pacing pulses.
  • sensing/pacing electrodes at a plurality of ventricular locations together with associated sensing and pacing channels for sensing intrinsic cardiac activity and delivering pacing pulses.
  • Pacing may then be delivered through one or more selected electrodes in a manner such that a hypertrophied region of the myocardium is pre-excited relative to other regions during systole.
  • Fig. 1 is a block diagram of an exemplary cardiac rhythm management device for practicing the present invention.
  • Fig. 2 shows an exemplary placement of sensing/pacing electrodes.
  • pacing sites for the placement of pacing electrodes and, in the case of multi-site resynchronization pacing, the sequence in which pacing pulses should be output to the multiple pacing sites.
  • One way of selecting a pacing site for resynchronization therapy is to measure the conduction delays of potential pacing sites during an intrinsic systolic contraction.
  • One or more myocardial sites that are demonstrated to be excited later during an intrinsic contraction can then be selected as pacing sites. Pacing the late activated site, or pacing multiple sites in a sequence corresponding to their respective conduction delays, would then supposedly provide the desired resynchronization and a more coordinated contraction.
  • Myocardial regions subjected to the highest levels of mechanical stress during intrinsic contractions may not always be the latest activated regions due to the presence of scar tissue or areas of infarction.
  • resynchronization pacing may be applied to such stressed myocardial regions in a manner that relieves the stress by reducing the preload and afterload to which the region is subjected.
  • Such resynchronization pacing delivered over a period of time then causes reversal of undesirable myocardial remodeling.
  • the present invention provides a means by which a clinician may assess the extent to which particular myocardial regions have undergone hypertrophic remodeling due to increased mechanical stress. This information can then be used to select an optimum pacing configuration for delivering resynchronization pacing therapy in order to mechanically unload the hypertrophied regions. As the therapy is applied over time, the myocardium may undergo further changes due to disease progression or due to the beneficial effects of the resynchronization therapy or other therapies.
  • the invention also allows for the design of a device that monitors these changes so that therapy adjustments can be made.
  • a pacemaker is equipped with multiple sensing and pacing channels and programmed to automatically re- configure itself in accordance with such changes.
  • Conventional cardiac pacing with implanted pacemakers involves excitatory electrical stimulation of the heart by the delivery of pacing pulses to an electrode in electrical contact with the myocardium.
  • the pacemaker is usually implanted subcutaneously on the patient's chest, and is connected to electrodes by leads threaded through the vessels of the upper venous system into the heart.
  • An electrode can be incorporated into a sensing channel that generates an electrogram signal representing cardiac electrical activity at the electrode site and/or incorporated into a pacing channel for delivering pacing pulses to the site.
  • a pacemaker should be taken to mean any cardiac rhythm management device, such as an implantable cardioverter/defibrillator, with a pacing functionality).
  • the controller of the pacemaker is made up of a microprocessor 10 communicating with a memory 12 via a bidirectional data bus, where the memory 12 typically comprises a ROM (read-only memory) for program storage and a RAM (random-access memory) for data storage.
  • the controller could be implemented by other types of logic circuitry (e.g., discrete components or programmable logic arrays) using a state machine type of design, but a microprocessor-based system is preferable.
  • the controller is capable of operating the pacemaker in a number of programmed modes where a programmed mode defines how pacing pulses are output in response to sensed events and expiration of time intervals.
  • a telemetry interface 80 is also provided for communicating with an external programmer.
  • the multiple sensing and pacing channels of the device in Fig. 1 may be configured as either atrial or ventricular channels allowing the device to deliver conventional ventricular single-site pacing with or without atrial tracking, biventricular pacing, or multi-site pacing of a single chamber. Shown in Fig. 1 is a configuration with one atrial sensing/pacing channel and three ventricular sensing/pacing channels.
  • the atrial sensing/pacing chamiel in Fig. 1 comprises ring electrode 53a, tip electrode 53b, sense amplifier 51, pulse generator 52, and an atrial channel interface 50 which communicates bidirectionally with a port of microprocessor 10.
  • the three ventricular sensing/pacing channels that include ring electrodes 23a, 33a, and 43a, tip electrodes 23b, 33b, and 43b, sense amplifiers 21, 31, and 41, pulse generators 22, 32, and 42, and ventricular channel interfaces 20, 30, and 40.
  • a pacing channel is made up of the pulse generator connected to the electrode while a sensing chamiel is made up of the sense amplifier connected to the electrode.
  • the channel interfaces include analog-to-digital converters for digitizing sensing signal inputs from the sensing amplifiers, registers that can be written to for adjusting the gain and threshold values of the sensing amplifiers, and registers for controlling the output of pacing pulses and/or changing the pacing pulse amplitude.
  • bipolar leads that include two electrodes are used for outputting a pacing pulse and/or sensing intrinsic activity.
  • Other embodiments may employ a single electrode for sensing and pacing in each channel, known as a unipolar lead.
  • a MOS switching network 70 controlled by the microprocessor is used to switch the electrodes from the input of a sense amplifier to the output of a pulse generator.
  • the controller 10 controls the overall operation of the device in accordance with programmed instructions stored in memory.
  • the controller 10 interprets electrogram signals from the sensing channels and controls the delivery of paces in accordance with a pacing mode.
  • the sensing circuitry of the pacemaker generates atrial and ventricular electrogram signals from the voltages sensed by the electrodes of a particular channel.
  • an electrogram signal in an atrial or sensing channel exceeds a specified threshold, the controller detects an atrial or ventricular sense, respectively, which pacing algorithms may employ to trigger or inhibit pacing.
  • An electrogram is analogous to a surface ECG and indicates the time course and amplitude of cardiac depolarization that occurs during either an intrinsic or paced beat. As described below, measurement of the amplitudes of electrogram R waves from the different sensing channels allows the device to ascertain regions of relative hypertrophy in the myocardium.
  • Bradycardia pacing modes refer to pacing algorithms used to pace the atria and/or ventricles in a manner that enforces a certain minimum heart rate. Such modes are generally designated by a letter code of three positions where each letter in the code refers to a specific function of the pacemaker. Pacemakers can enforce a minimum heart rate either asynchronously or synchronously. In asynchronous pacing, the heart is paced at a fixed rate irrespective of intrinsic cardiac activity. Because of the risk of inducing an arrhythmia with asynchronous pacing, most pacemakers for treating bradycardia are programmed to operate synchronously in a so-called demand mode where sensed cardiac events occurring within a defined interval either trigger or inhibit a pacing pulse.
  • Inhibited demand pacing modes utilize escape intervals to control pacing in accordance with sensed intrinsic activity.
  • a pacing pulse is delivered to a heart chamber during a cardiac cycle only after expiration of a defined escape interval during which no intrinsic beat by the chamber is detected.
  • a ventricular escape interval can be defined between ventricular events so as to be restarted with each ventricular sense or pace.
  • the inverse of this escape interval is the minimum rate at which the pacemaker will allow the ventricles to beat, sometimes referred to as the lower rate limit (LRL).
  • atrio-ventricular interval In an atrial tracking pacing mode (i.e., VDD or DDD mode), another ventricular escape interval is defined between atrial and ventricular events, referred to as the atrio-ventricular interval (AVI).
  • the atrio-ventricular interval is triggered by an atrial sense or pace and stopped by a ventricular sense or pace.
  • a ventricular pace is delivered upon expiration of the atrio-ventricular interval if no ventricular sense occurs before.
  • Atrial-tracking ventricular pacing attempts to maintain the atrio-ventricular synchrony occurring with physiological beats whereby atrial contractions augment diastolic filling of the ventricles.
  • Atrial-tracking pacing also allows the ventricular pacing rate to be responsive to the metabolic needs of the body.
  • a pacemaker can also be configured to pace the atria on an inhibited demand basis.
  • An atrial escape interval is then defined as the maximum time interval in which an atrial sense must be detected after a ventricular sense or pace before an atrial pace will be delivered.
  • atrial inhibited demand pacing is combined with atrial-triggered ventricular demand pacing (i.e., DDD mode)
  • the lower rate limit interval is then the sum of the atrial escape interval and the atrio- ventricular interval.
  • Cardiac resynchronization therapy is pacing stimulation applied to one or more heart chambers in a manner that restores or maintains synchronized contractions of the atria and/or ventricles and thereby improves pumping efficiency.
  • Ventricular resynchronization pacing is useful in treating heart failure in patients with interventricular or intraventricular conduction defects because, although not directly ionotropic, resynchronization results in a more coordinated contraction of the ventricles with improved pumping efficiency and increased cardiac output.
  • Resynchronization pacing of the atria may also be beneficial in certain patients, particularly for preventing the onset of atrial arrhythmias.
  • Certain patients with conduction abnormalities may experience improved cardiac synchronization with conventional single-chamber or dual-chamber bradycardia pacing as described above because of the way in which depolarization is spread as a result of a pace as opposed to an intrinsic contraction.
  • Resynchronization pacing may also involve delivering paces to multiple sites of either the atria or the ventricles during a cardiac cycle.
  • the multiple pacing sites may be located in a single heart chamber or in both ventricles or both atria, hi multi-site pacing, the atria or ventricles are paced at more than one site in order to effect a spread of excitation that results in a more coordinated contraction.
  • Biventricular resynchonization pacing is one example of multi-site pacing in which both ventricles are paced in order to synchronize their respective contractions. Biventricular resynchronization pacing may be useful in treating certain conduction pathologies such as bundle branch blocks. Multi-site pacing may also be applied to only one chamber. For example, a ventricle may be paced at multiple sites with excitatory stimulation pulses in order to produce multiple waves of depolarization that emanate from the pacing sites. This may produce a more coordinated contraction of the ventricle and thereby compensate for intraventricular conduction defects that may exist.
  • One way to deliver multi-site resynchronization therapy is to pace a site with a synchronous bradycardia pacing mode and then deliver one or more resynchronization paces to one or more additional pacing sites in a defined time relation to one or more selected sensing and pacing events that either reset escape intervals or trigger paces in the bradycardia pacing mode.
  • a primary pacing site is paced with a bradycardia mode, and one or more secondary sites are then paced at specified offset intervals with respect to the pace delivered to the primary site.
  • An offset interval may be zero in order to pace both sites simultaneously, positive in order to pace the primary site after the secondary site, or negative to pace the primary site before the secondary site.
  • Forward failure Inadequate pumping of blood into the arterial system by the heart is sometimes referred to as "forward failure,” with “backward failure” referring to the resulting elevated pressures in the lungs and systemic veins which lead to congestion.
  • Backward failure is the natural consequence of forward failure as blood in the pulmonary and venous systems fails to be pumped out. Forward failure can be caused by impaired contractility of the ventricles or by an increased afterload (i.e., the forces resisting ejection of blood) due to, for example, systemic hypertension or valvular dysfunction.
  • One physiological compensatory mechanism that acts to increase cardiac output is due to backward failure which increases the diastolic filling pressure of the ventricles and thereby increases the preload (i.e., the degree to which the ventricles are stretched by the volume of blood in the ventricles at the end of diastole).
  • An increase in preload causes an increase in stroke volume during systole, a phenomena known as the Frank-Starling principle.
  • heart failure can be at least partially compensated by this mechanism but at the expense of possible pulmonary and/or systemic congestion.
  • the ventricles When the ventricles are stretched due to the increased preload over a period of time, the ventricles become dilated.
  • the enlargement of the ventricular volume causes increased ventricular wall stress at a given systolic pressure. Along with the increased pressure-volume work done by the ventricle, this acts as a stimulus for hypertrophy of the ventricular myocardium which leads to alterations in cellular structure, a process referred to as myocardial remodeling. Hypertrophy can increase systolic pressures but also decreases the compliance of the ventricles and hence increases diastolic filling pressure to result in even more congestion. It also has been shown that the sustained stresses causing hypertrophy may induce apoptosis (i.e., programmed cell death) of cardiac muscle cells and eventual wall thinning which causes further deterioration in cardiac function.
  • apoptosis i.e., programmed cell death
  • ventricular dilation and hypertrophy may at first be compensatory and increase cardiac output, the process ultimately results in both systolic and diastolic dysfunction. It has been shown that the extent of ventricular remodeling is positively correlated with increased mortality in heart failure patients.
  • the degree to which a heart muscle fiber is stretched before it contracts is termed the preload, while the degree of tension or stress on a heart muscle fiber as it contracts is termed the afterload.
  • the maximum tension and velocity of shortening of a muscle fiber increases with increasing preload, and the increase in contractile response of the heart with increasing preload is known as the Frank-Starling principle.
  • the parts of the myocardium that contract earlier in the cycle are subjected to less stress and are less likely to undergo hypertrophic remodeling.
  • This phenomena can be used for effecting reversal of remodeling by delivering paces to one or more ventricular pacing sites in a manner that pre- excites one or more hypertrophied region.
  • the specialized His-Purkinje conduction network of the heart rapidly conducts excitatory impulses from the sino-atrial node to the atrio-ventricular node, and thence to the ventricular myocardium to result in a coordinated contraction of both ventricles.
  • the pre-excitation of a paced site relative to other sites can be used to deliberately change the distribution of wall stress experienced by the ventricle during the cardiac pumping cycle.
  • Such pre-excitation of a remodeled or hypertrophied region relative to other regions unloads the region from mechanical stress by decreasing its afterload and preload, thus allowing reversal of remodeling to occur.
  • Pacing therapy to unload hypertrophied regions may be implemented by pacing the ventricles at a single site or by pacing at multiple ventricular sites where the pulse output sequence to the different electrodes is such that one or more regions are excited earlier than the rest of the myocardium.
  • Paces may be delivered in accordance with an inhibited demand mode or a triggered mode. In the latter case, one or more pre-excitation pacing pulses are applied to a hypertrophied region immediately following the earliest detection of intrinsic activation elsewhere in the ventricle.
  • a wave of depolarization propagating through a hypertrophied myocardial region results in a greater potential being measured by a sensing electrode owing to the greater muscle mass.
  • a depolarization event i.e., either an intrinsic or paced beat
  • an electrogram signal measured from an internal electrode disposed near a relatively hypertrophied region in the heart is therefore of greater amplitude than a signal measured from an electrode near an unhypertrophied region.
  • This phenomena can be used to identify areas of hypertrophy by measuring the amplitudes of electrograms from electrodes placed at locations so as to sense different regions of the myocardium.
  • a pacemaker can then be configured to deliver pacing therapy that pre-excites the region or regions so identified.
  • a pacemaker may be configured to deliver single-site bradycardia pacing to the ventricles where an identified hypertrophic region is selected as the pacing site.
  • a pacemaker may also be configured to deliver multi-site resynchronization pacing to a plurality of pacing sites with a pulse output sequence that specifies the order of the paces to correspond to the regional assessment of myocardial hypertrophy.
  • the pulse output sequence may specify that pacing pulses are delivered to more hypertrophied regions before less hypertrophied or normal regions.
  • a pacemaker may also be equipped with multiple electrodes for disposition at multiple sites where the electrodes are incorporated into sensing channels that allow an electrogram signal to be generated from each individual electrode.
  • the pacemaker may also be programmed to periodically measure and compare the R wave amplitudes from the multiple electrodes in order to monitor changes in the myocardium over time, and trending of the R wave amplitudes may be performed in order to predict future changes.
  • the pacemaker may also be programmed to automatically re-configure itself to deliver resynchronization pacing therapy that pre-excites the stressed regions determined by the measured R wave amplitudes.
  • the pacemaker controller can thus be programmed to select an optimum pacing configuration that defines which of the available implanted electrodes are to be used for pacing and, in the case of multi-site pacing, be further programmed to select a pulse output sequence that specifies the optimum order of the pacing pulses.
  • Fig. 2 depicts an example situation where the left ventricle 200 has epicardial pacing/sensing electrodes disposed at pacing sites 210 and 220. Placement of such electrodes may be accomplished transvenously via the coronary sinus.
  • the myocardium at pacing site 210 is shown as being hypertrophied as compared to the myocardium at pacing site 220 as a result of being subjected to greater stress.
  • a pacemaker such as illustrated in Fig. 1 may incorporate the two electrodes into sensing and pacing channels. By measuring the amplitudes of the electrogram R waves from the two sites, it may be determined that the site 210 is hypertrophied. The pacemaker may then be configured to deliver biventricular pacing with a pulse output sequence specifying that site 210 is paced before site 220.
  • the device of Fig. 1 may be further programmed to automatically adjust the pacing parameters for a given pacing configuration and pulse output sequence in accordance with periodic regional assessments of hypertrophy. For example, if it is determined that regional hypertrophy has increased more than expected, parameters may be adjusted that increase the delay between pre- excitation of the hypertrophied region and excitation of less hypertrophied or normal regions. Conversely, if some of the desired reversal of remodeling has occurred, so that a pre-excited region has become less hypertrophied, the degree of pre-excitation relative to other regions may be decreased by decreasing the delay. Parameters that determine the frequency of pacing may also be adjusted in accordance with periodic regional assessments of hypertrophy.
  • Pacing frequency may be increased by, for example, increasing the LRL and/or decreasing the atrio-ventricular interval. As it is only paced beats that unload the hypertrophied regions, more frequent pacing increases the therapeutic benefit of the therapy in reversing remodeling. It may be desirable, therefore, to increase or decrease the pacing frequency in accordance with the assessment of hypertrophy.

Abstract

A cardiac rhythm management device comprises a plurality of sensing channels (23a, 23b, 33a, 33b, 43a, 43b, 53a, 53b) incorporating electrodes for disposition near different myocardial regions and a controller programmed to measure amplitudes of electrograms from one or more cardiac sites in order to ascertain the extent of hypertrophy. The device may then pace the heart by delivering pacing therapy in a manner that unloads the hypertrophied myocardium to effect reversal of undesirable remodeling.

Description

DYNAMICALLY OPTIMIZED MULTISITE CARDIAC RESYNCHRONIZATION DEVICE
Field of the Invention This invention pertains to cardiac rhythm management devices such as pacemakers and implantable monitoring devices.
Background Cardiac rhythm management devices are implantable devices that provide electrical stimulation to selected chambers of the heart in order to treat disorders of cardiac rhythm. A pacemaker, for example, is a cardiac rhythm management device that paces the heart with timed pacing pulses. The most common condition for which pacemakers are used is in the treatment of bradycardia, where the ventricular rate is too slow. Atrio-ventricular conduction defects (i.e., AV block) that are permanent or intermittent and sick sinus syndrome represent the most common causes of bradycardia for which permanent pacing may be indicated. If functioning properly, the pacemaker makes up for the heart's inability to pace itself at an appropriate rhythm in order to meet metabolic demand by enforcing a minimum heart rate. Pacing therapy can also be used in the treatment of heart failure, which refers to a clinical syndrome in which an abnormality of cardiac function causes a below normal cardiac output that can fall below a level adequate to meet the metabolic demand of peripheral tissues. When uncompensated, it usually presents as congestive heart failure due to the accompanying venous and pulmonary congestion. Heart failure can be due to a variety of etiologies with ischemic heart disease being the most common. It has been shown that some heart failure patients suffer from intraventricular and/or interventricular conduction defects (e.g., bundle branch blocks) such that their cardiac outputs can be increased by improving the synchronization of ventricular contractions with electrical stimulation. Other conduction defects can occur in the atria. Cardiac rhythm management devices have therefore been developed which provide electrical stimulation to the atria and/or ventricles in an attempt to improve the coordination of cardiac contractions, termed cardiac resynchronization therapy.
Summary The present invention relates to a method and apparatus for optimally delivering cardiac resynchronization therapy. Hypertrophied regions of the myocardium are identified by placing electrodes at selected myocardial regions and measuring the amplitudes of electrograms from the electrodes during depolarization events. Resynchronization pacing may then be delivered in a manner that pre-excites one or more of the hypertrophied regions in order to subject the region to a lessened preload and afterload. For example, the ventricles may be paced at a selected single electrode site using a conventional bradycardia pacing mode where the paced site is a region identified as hypertrophied. Alternatively, the ventricles may be paced at multiple sites using a multi-site resynchronization pacing mode, where the delivery of paces to multiple ventricular sites during a cardiac cycle is used to not only enforce a minimum ventricular heart rate but also to alter the depolarization patterns of the ventricles during systole and improve the coordination of the ventricular contraction. Multi-site ventricular resynchronization pacing may involve pacing both ventricles or only one ventricle at multiple sites by delivering a pacing pulse to each of the individual electrodes making up a pacing configuration in a specified pulse output sequence. The pulse output sequence can be specified so that one or more hypertrophied regions are paced before other regions during systole and hence mechanically unloaded. By unloading such hypertrophied regions in this way over a period of time, reversal of undesirable ventricular remodeling is effected. Pacing parameters also may be adjusted to increase the frequency of paced beats so that the hypertrophied region is unloaded more often.
In one particular embodiment of the invention, an implantable pacemaker is configured with sensing/pacing electrodes at a plurality of ventricular locations together with associated sensing and pacing channels for sensing intrinsic cardiac activity and delivering pacing pulses. By measuring the amplitudes of the individual electrogram signals generated at the multiple electrodes during depolarization events, areas of the ventricular myocardium in proximity to an electrode that are hypertrophied can be identified. Pacing may then be delivered through one or more selected electrodes in a manner such that a hypertrophied region of the myocardium is pre-excited relative to other regions during systole.
Brief Description of the Drawings Fig. 1 is a block diagram of an exemplary cardiac rhythm management device for practicing the present invention. Fig. 2 shows an exemplary placement of sensing/pacing electrodes.
Detailed Description Applying cardiac resynchronization therapy in the most efficacious manner requires optimal selection of one or more pacing sites for the placement of pacing electrodes and, in the case of multi-site resynchronization pacing, the sequence in which pacing pulses should be output to the multiple pacing sites. One way of selecting a pacing site for resynchronization therapy is to measure the conduction delays of potential pacing sites during an intrinsic systolic contraction. One or more myocardial sites that are demonstrated to be excited later during an intrinsic contraction can then be selected as pacing sites. Pacing the late activated site, or pacing multiple sites in a sequence corresponding to their respective conduction delays, would then supposedly provide the desired resynchronization and a more coordinated contraction. Myocardial regions subjected to the highest levels of mechanical stress during intrinsic contractions, however, may not always be the latest activated regions due to the presence of scar tissue or areas of infarction. As is explained below, resynchronization pacing may be applied to such stressed myocardial regions in a manner that relieves the stress by reducing the preload and afterload to which the region is subjected. Such resynchronization pacing delivered over a period of time then causes reversal of undesirable myocardial remodeling.
In one of its aspects, the present invention provides a means by which a clinician may assess the extent to which particular myocardial regions have undergone hypertrophic remodeling due to increased mechanical stress. This information can then be used to select an optimum pacing configuration for delivering resynchronization pacing therapy in order to mechanically unload the hypertrophied regions. As the therapy is applied over time, the myocardium may undergo further changes due to disease progression or due to the beneficial effects of the resynchronization therapy or other therapies. The invention also allows for the design of a device that monitors these changes so that therapy adjustments can be made. In one embodiment, a pacemaker is equipped with multiple sensing and pacing channels and programmed to automatically re- configure itself in accordance with such changes.
1. Exemplary device description
Conventional cardiac pacing with implanted pacemakers involves excitatory electrical stimulation of the heart by the delivery of pacing pulses to an electrode in electrical contact with the myocardium. The pacemaker is usually implanted subcutaneously on the patient's chest, and is connected to electrodes by leads threaded through the vessels of the upper venous system into the heart. An electrode can be incorporated into a sensing channel that generates an electrogram signal representing cardiac electrical activity at the electrode site and/or incorporated into a pacing channel for delivering pacing pulses to the site.
A block diagram of a multi-site pacemaker having multiple sensing and pacing channels is shown in Fig. 1. (As the term is used herein, a "pacemaker" should be taken to mean any cardiac rhythm management device, such as an implantable cardioverter/defibrillator, with a pacing functionality). The controller of the pacemaker is made up of a microprocessor 10 communicating with a memory 12 via a bidirectional data bus, where the memory 12 typically comprises a ROM (read-only memory) for program storage and a RAM (random-access memory) for data storage. The controller could be implemented by other types of logic circuitry (e.g., discrete components or programmable logic arrays) using a state machine type of design, but a microprocessor-based system is preferable. The controller is capable of operating the pacemaker in a number of programmed modes where a programmed mode defines how pacing pulses are output in response to sensed events and expiration of time intervals. A telemetry interface 80 is also provided for communicating with an external programmer.
The multiple sensing and pacing channels of the device in Fig. 1 may be configured as either atrial or ventricular channels allowing the device to deliver conventional ventricular single-site pacing with or without atrial tracking, biventricular pacing, or multi-site pacing of a single chamber. Shown in Fig. 1 is a configuration with one atrial sensing/pacing channel and three ventricular sensing/pacing channels. The atrial sensing/pacing chamiel in Fig. 1 comprises ring electrode 53a, tip electrode 53b, sense amplifier 51, pulse generator 52, and an atrial channel interface 50 which communicates bidirectionally with a port of microprocessor 10. The three ventricular sensing/pacing channels that include ring electrodes 23a, 33a, and 43a, tip electrodes 23b, 33b, and 43b, sense amplifiers 21, 31, and 41, pulse generators 22, 32, and 42, and ventricular channel interfaces 20, 30, and 40. A pacing channel is made up of the pulse generator connected to the electrode while a sensing chamiel is made up of the sense amplifier connected to the electrode. The channel interfaces include analog-to-digital converters for digitizing sensing signal inputs from the sensing amplifiers, registers that can be written to for adjusting the gain and threshold values of the sensing amplifiers, and registers for controlling the output of pacing pulses and/or changing the pacing pulse amplitude. For each channel, the same electrode pair is used for both sensing and pacing. In this embodiment, bipolar leads that include two electrodes are used for outputting a pacing pulse and/or sensing intrinsic activity. Other embodiments may employ a single electrode for sensing and pacing in each channel, known as a unipolar lead. A MOS switching network 70 controlled by the microprocessor is used to switch the electrodes from the input of a sense amplifier to the output of a pulse generator.
The controller 10 controls the overall operation of the device in accordance with programmed instructions stored in memory. The controller 10 interprets electrogram signals from the sensing channels and controls the delivery of paces in accordance with a pacing mode. The sensing circuitry of the pacemaker generates atrial and ventricular electrogram signals from the voltages sensed by the electrodes of a particular channel. When an electrogram signal in an atrial or sensing channel exceeds a specified threshold, the controller detects an atrial or ventricular sense, respectively, which pacing algorithms may employ to trigger or inhibit pacing. An electrogram is analogous to a surface ECG and indicates the time course and amplitude of cardiac depolarization that occurs during either an intrinsic or paced beat. As described below, measurement of the amplitudes of electrogram R waves from the different sensing channels allows the device to ascertain regions of relative hypertrophy in the myocardium.
2. Bradycardia pacing modes
Bradycardia pacing modes refer to pacing algorithms used to pace the atria and/or ventricles in a manner that enforces a certain minimum heart rate. Such modes are generally designated by a letter code of three positions where each letter in the code refers to a specific function of the pacemaker. Pacemakers can enforce a minimum heart rate either asynchronously or synchronously. In asynchronous pacing, the heart is paced at a fixed rate irrespective of intrinsic cardiac activity. Because of the risk of inducing an arrhythmia with asynchronous pacing, most pacemakers for treating bradycardia are programmed to operate synchronously in a so-called demand mode where sensed cardiac events occurring within a defined interval either trigger or inhibit a pacing pulse. Inhibited demand pacing modes utilize escape intervals to control pacing in accordance with sensed intrinsic activity. In an inhibited demand mode, a pacing pulse is delivered to a heart chamber during a cardiac cycle only after expiration of a defined escape interval during which no intrinsic beat by the chamber is detected. For example, a ventricular escape interval can be defined between ventricular events so as to be restarted with each ventricular sense or pace. The inverse of this escape interval is the minimum rate at which the pacemaker will allow the ventricles to beat, sometimes referred to as the lower rate limit (LRL). In an atrial tracking pacing mode (i.e., VDD or DDD mode), another ventricular escape interval is defined between atrial and ventricular events, referred to as the atrio-ventricular interval (AVI). The atrio-ventricular interval is triggered by an atrial sense or pace and stopped by a ventricular sense or pace. A ventricular pace is delivered upon expiration of the atrio-ventricular interval if no ventricular sense occurs before. Atrial-tracking ventricular pacing attempts to maintain the atrio-ventricular synchrony occurring with physiological beats whereby atrial contractions augment diastolic filling of the ventricles. If a patient has a physiologically normal atrial rhythm, atrial-tracking pacing also allows the ventricular pacing rate to be responsive to the metabolic needs of the body. A pacemaker can also be configured to pace the atria on an inhibited demand basis. An atrial escape interval is then defined as the maximum time interval in which an atrial sense must be detected after a ventricular sense or pace before an atrial pace will be delivered. When atrial inhibited demand pacing is combined with atrial-triggered ventricular demand pacing (i.e., DDD mode), the lower rate limit interval is then the sum of the atrial escape interval and the atrio- ventricular interval.
3. Resynchronization pacing modes
Cardiac resynchronization therapy is pacing stimulation applied to one or more heart chambers in a manner that restores or maintains synchronized contractions of the atria and/or ventricles and thereby improves pumping efficiency. Ventricular resynchronization pacing is useful in treating heart failure in patients with interventricular or intraventricular conduction defects because, although not directly ionotropic, resynchronization results in a more coordinated contraction of the ventricles with improved pumping efficiency and increased cardiac output. Resynchronization pacing of the atria may also be beneficial in certain patients, particularly for preventing the onset of atrial arrhythmias.
Certain patients with conduction abnormalities may experience improved cardiac synchronization with conventional single-chamber or dual-chamber bradycardia pacing as described above because of the way in which depolarization is spread as a result of a pace as opposed to an intrinsic contraction. Resynchronization pacing, however, may also involve delivering paces to multiple sites of either the atria or the ventricles during a cardiac cycle. The multiple pacing sites may be located in a single heart chamber or in both ventricles or both atria, hi multi-site pacing, the atria or ventricles are paced at more than one site in order to effect a spread of excitation that results in a more coordinated contraction. Biventricular resynchonization pacing is one example of multi-site pacing in which both ventricles are paced in order to synchronize their respective contractions. Biventricular resynchronization pacing may be useful in treating certain conduction pathologies such as bundle branch blocks. Multi-site pacing may also be applied to only one chamber. For example, a ventricle may be paced at multiple sites with excitatory stimulation pulses in order to produce multiple waves of depolarization that emanate from the pacing sites. This may produce a more coordinated contraction of the ventricle and thereby compensate for intraventricular conduction defects that may exist.
One way to deliver multi-site resynchronization therapy is to pace a site with a synchronous bradycardia pacing mode and then deliver one or more resynchronization paces to one or more additional pacing sites in a defined time relation to one or more selected sensing and pacing events that either reset escape intervals or trigger paces in the bradycardia pacing mode. For example, in an offset resynchronization pacing mode, a primary pacing site is paced with a bradycardia mode, and one or more secondary sites are then paced at specified offset intervals with respect to the pace delivered to the primary site. An offset interval may be zero in order to pace both sites simultaneously, positive in order to pace the primary site after the secondary site, or negative to pace the primary site before the secondary site.
4. Heart failure and myocardial remodeling
Inadequate pumping of blood into the arterial system by the heart is sometimes referred to as "forward failure," with "backward failure" referring to the resulting elevated pressures in the lungs and systemic veins which lead to congestion. Backward failure is the natural consequence of forward failure as blood in the pulmonary and venous systems fails to be pumped out. Forward failure can be caused by impaired contractility of the ventricles or by an increased afterload (i.e., the forces resisting ejection of blood) due to, for example, systemic hypertension or valvular dysfunction. One physiological compensatory mechanism that acts to increase cardiac output is due to backward failure which increases the diastolic filling pressure of the ventricles and thereby increases the preload (i.e., the degree to which the ventricles are stretched by the volume of blood in the ventricles at the end of diastole). An increase in preload causes an increase in stroke volume during systole, a phenomena known as the Frank-Starling principle. Thus, heart failure can be at least partially compensated by this mechanism but at the expense of possible pulmonary and/or systemic congestion. When the ventricles are stretched due to the increased preload over a period of time, the ventricles become dilated. The enlargement of the ventricular volume causes increased ventricular wall stress at a given systolic pressure. Along with the increased pressure-volume work done by the ventricle, this acts as a stimulus for hypertrophy of the ventricular myocardium which leads to alterations in cellular structure, a process referred to as myocardial remodeling. Hypertrophy can increase systolic pressures but also decreases the compliance of the ventricles and hence increases diastolic filling pressure to result in even more congestion. It also has been shown that the sustained stresses causing hypertrophy may induce apoptosis (i.e., programmed cell death) of cardiac muscle cells and eventual wall thinning which causes further deterioration in cardiac function. Thus, although ventricular dilation and hypertrophy may at first be compensatory and increase cardiac output, the process ultimately results in both systolic and diastolic dysfunction. It has been shown that the extent of ventricular remodeling is positively correlated with increased mortality in heart failure patients.
The degree to which a heart muscle fiber is stretched before it contracts is termed the preload, while the degree of tension or stress on a heart muscle fiber as it contracts is termed the afterload. The maximum tension and velocity of shortening of a muscle fiber increases with increasing preload, and the increase in contractile response of the heart with increasing preload is known as the Frank-Starling principle. When a myocardial region contracts late relative to other regions, the contraction of those other regions stretches the later contracting region and increases its preloading, thus causing an increase in the contractile force generated by the region. Because pressure within the ventricles rises rapidly from a diastolic to a systolic value as blood is pumped out into the aorta and pulmonary arteries, the parts of the ventricles that contract later during systole do so against a higher afterload than do parts of the ventricles contracting earlier. Thus a ventricular region that contracts later than other regions is subjected to both an increased preload and afterload, both of which act to increase the mechanical stress experienced by the region relative to other regions. This situation is created frequently by the ventricular conduction delays associated with heart failure and ventricular dysfunction. The heart's initial physiological response to the uneven stress resulting from an increased preload and afterload is compensatory hypertrophy in those later contracting regions of the ventricular myocardium. In the later stages of remodeling, the regions may undergo atrophic changes with wall thinning due to continuing of the increased stress.
5. Reversal of remodeling with resynchronization therapy
The parts of the myocardium that contract earlier in the cycle, on the other hand, are subjected to less stress and are less likely to undergo hypertrophic remodeling. This phenomena can be used for effecting reversal of remodeling by delivering paces to one or more ventricular pacing sites in a manner that pre- excites one or more hypertrophied region. In a normal heartbeat, the specialized His-Purkinje conduction network of the heart rapidly conducts excitatory impulses from the sino-atrial node to the atrio-ventricular node, and thence to the ventricular myocardium to result in a coordinated contraction of both ventricles. Artificial pacing with an electrode fixed into an area of the myocardium does not take advantage of the heart's normal specialized conduction system for conducting excitation throughout the ventricles because the specialized conduction system can only be entered by impulses emanating from the atrio- ventricular node. Thus the spread of excitation from a ventricular pacing site must proceed only via the much slower conducting ventricular muscle fibers, resulting in the part of the ventricular myocardium stimulated by the pacing electrode contracting well before parts of the ventricle located more distally to the electrode.
The pre-excitation of a paced site relative to other sites can be used to deliberately change the distribution of wall stress experienced by the ventricle during the cardiac pumping cycle. Such pre-excitation of a remodeled or hypertrophied region relative to other regions unloads the region from mechanical stress by decreasing its afterload and preload, thus allowing reversal of remodeling to occur. Pacing therapy to unload hypertrophied regions may be implemented by pacing the ventricles at a single site or by pacing at multiple ventricular sites where the pulse output sequence to the different electrodes is such that one or more regions are excited earlier than the rest of the myocardium. Paces may be delivered in accordance with an inhibited demand mode or a triggered mode. In the latter case, one or more pre-excitation pacing pulses are applied to a hypertrophied region immediately following the earliest detection of intrinsic activation elsewhere in the ventricle.
6. Identification of hypertrophied regions and optimization of resynclironization pacing
A wave of depolarization propagating through a hypertrophied myocardial region results in a greater potential being measured by a sensing electrode owing to the greater muscle mass. During a depolarization event (i.e., either an intrinsic or paced beat), an electrogram signal measured from an internal electrode disposed near a relatively hypertrophied region in the heart is therefore of greater amplitude than a signal measured from an electrode near an unhypertrophied region. This phenomena can be used to identify areas of hypertrophy by measuring the amplitudes of electrograms from electrodes placed at locations so as to sense different regions of the myocardium. A pacemaker can then be configured to deliver pacing therapy that pre-excites the region or regions so identified. For example, a pacemaker may be configured to deliver single-site bradycardia pacing to the ventricles where an identified hypertrophic region is selected as the pacing site. A pacemaker may also be configured to deliver multi-site resynchronization pacing to a plurality of pacing sites with a pulse output sequence that specifies the order of the paces to correspond to the regional assessment of myocardial hypertrophy. For example, the pulse output sequence may specify that pacing pulses are delivered to more hypertrophied regions before less hypertrophied or normal regions. As illustrated in Fig. 1, a pacemaker may also be equipped with multiple electrodes for disposition at multiple sites where the electrodes are incorporated into sensing channels that allow an electrogram signal to be generated from each individual electrode. By measuring the amplitudes of the electrograms from the multiple electrodes during systole (i.e., the amplitude of an R wave in the case of a ventricular electrogram), the extent of hypertrophy at each of the electrode sites can be assessed. This information can then be used to select one or more of the available electrodes for delivering pacing pulses to the heart in a manner that redistributes stress during systole and causes reversal of the hypertrophy. The pacemaker may also be programmed to periodically measure and compare the R wave amplitudes from the multiple electrodes in order to monitor changes in the myocardium over time, and trending of the R wave amplitudes may be performed in order to predict future changes. The pacemaker may also be programmed to automatically re-configure itself to deliver resynchronization pacing therapy that pre-excites the stressed regions determined by the measured R wave amplitudes. The pacemaker controller can thus be programmed to select an optimum pacing configuration that defines which of the available implanted electrodes are to be used for pacing and, in the case of multi-site pacing, be further programmed to select a pulse output sequence that specifies the optimum order of the pacing pulses. Fig. 2 depicts an example situation where the left ventricle 200 has epicardial pacing/sensing electrodes disposed at pacing sites 210 and 220. Placement of such electrodes may be accomplished transvenously via the coronary sinus. The myocardium at pacing site 210 is shown as being hypertrophied as compared to the myocardium at pacing site 220 as a result of being subjected to greater stress. A pacemaker such as illustrated in Fig. 1 may incorporate the two electrodes into sensing and pacing channels. By measuring the amplitudes of the electrogram R waves from the two sites, it may be determined that the site 210 is hypertrophied. The pacemaker may then be configured to deliver biventricular pacing with a pulse output sequence specifying that site 210 is paced before site 220.
The device of Fig. 1 may be further programmed to automatically adjust the pacing parameters for a given pacing configuration and pulse output sequence in accordance with periodic regional assessments of hypertrophy. For example, if it is determined that regional hypertrophy has increased more than expected, parameters may be adjusted that increase the delay between pre- excitation of the hypertrophied region and excitation of less hypertrophied or normal regions. Conversely, if some of the desired reversal of remodeling has occurred, so that a pre-excited region has become less hypertrophied, the degree of pre-excitation relative to other regions may be decreased by decreasing the delay. Parameters that determine the frequency of pacing may also be adjusted in accordance with periodic regional assessments of hypertrophy. Pacing frequency may be increased by, for example, increasing the LRL and/or decreasing the atrio-ventricular interval. As it is only paced beats that unload the hypertrophied regions, more frequent pacing increases the therapeutic benefit of the therapy in reversing remodeling. It may be desirable, therefore, to increase or decrease the pacing frequency in accordance with the assessment of hypertrophy. Although the invention has been described in conjunction with the foregoing specific embodiments, many alternatives, variations, and modifications will be apparent to those of ordinary skill in the art. Other such alternatives, variations, and modifications are intended to fall within the scope of the following appended claims.

Claims

What is claimed is:
1. A cardiac rhythm management device, comprising: a plurality of sensing channels incorporating electrodes for disposition near different myocardial regions; a controller programmed to measure the amplitudes of electrograms generated by the plurality of sensing channels during a depolarization event and thereby determine the extent to which the different myocardial regions are hypertrophied.
2. The device of claim 1 further comprising: a plurality of pacing channels incorporating the electrodes; wherein the controller is programmed to deliver pacing therapy in accordance with a programmed pacing mode and with a pacing configuration that pre-excites at least one myocardial region determined to be hypertrophied.
3. The device of claim 2 wherein the controller is programmed to deliver multi-site resynchronization pacing with a pacing configuration and pulse output sequence that specifies the order of the pacing pulses delivered to the different myocardial regions in accordance with the extent to which the different myocardial regions are determined to be hypertrophied.
4. The device of claim 2 wherein the controller is programmed to periodically determine the extent to which the different myocardial regions are hypertrophied by measurement of electrogram amplitudes and automatically reconfigure itself to deliver pacing therapy with a pacing configuration that pre- excites a myocardial region determined to be most hypertrophied.
5. The device of claim 4 wherein the controller is programmed to periodically determine the extent to which the different myocardial regions are hypertrophied by measurement of electrogram amplitudes and automatically reconfigure itself to deliver multi-site resynchronization pacing with a pacing configuration and pulse output sequence that specifies the order of the pacing pulses delivered to the different myocardial regions in accordance with the extent to which the different myocardial regions are determined to be hypertrophied.
6. The device of claim 4 wherein the controller is programmed to adjust a pacing parameter that increases the frequency of pacing if it is determined that the hypertrophy of a myocardial region has increased.
7. The device of claim 4 wherein the controller is programmed to adjust a pacing parameter that increases the delay between pre-excitation of a hypertrophied myocardial region and excitation of other regions if it is determined that the hypertrophy has increased.
8. The device of claim 4 wherein the controller is programmed to adjust a pacing parameter that decreases the delay between pre-excitation of a hypertrophied myocardial region and excitation of other regions if it is determined that the hypertrophy has decreased.
9. The device of claim 1 wherein the controller is programmed to compute a trend for the measured electrogram amplitudes.
10. The device of claim 1 wherein the depolarization event during which an electrogram amplitude is measured is an intrinsic beat.
11. The device of claim 1 wherein the depolarization event during which an electrogram amplitude is measured is a paced beat.
12. The device of claim 2 wherein sensing and pacing channels are configured to sense and pace ventricular regions.
13. A method for operating a cardiac rhythm management device, comprising: disposing electrodes incorporated into a plurality of sensing channels near different myocardial regions; measuring the amplitudes of electrograms generated by the plurality of sensing channels during a depolarization event to thereby determine the extent to which the different myocardial regions are hypertrophied.
14. The method of claim 13 further comprising: delivering pacing therapy in accordance with a programmed pacing mode and with a pacing configuration that pre-excites at least one myocardial region determined to be hypertrophied.
15. The method of claim 14 further comprising delivering multi-site resynchronization pacing with a pacing configuration and pulse output sequence that specifies the order of the pacing pulses delivered to the different myocardial regions in accordance with the extent to which the different myocardial regions are determined to be hypertrophied.
16. The method of claim 14 further comprising periodically determining the extent to which the different myocardial regions are hypertrophied by measurement of electrogram amplitudes and automatically reconfiguring itself to deliver pacing therapy with a pacing configuration that pre-excites a myocardial region determined to be most hypertrophied.
17. The method of claim 14 further comprising periodically determining the extent to which the different myocardial regions are hypertrophied by measurement of electrogram amplitudes and automatically reconfiguring itself to deliver multi-site resynchronization pacing with a pacing configuration and pulse output sequence that specifies the order of the pacing pulses delivered to the different myocardial regions in accordance with the extent to which the different myocardial regions are determined to be hypertrophied.
18. The method of claim 16 further comprising adjusting a pacing parameter that increases the frequency of pacing if it is determined that the hypertrophy of a myocardial region has increased.
19. The method of claim 16 further comprising adjusting a pacing parameter that increases the delay between pre-excitation of a hypertrophied myocardial region and excitation of other regions if it is determined that the hypertrophy has increased.
20. The method of claim 16 further comprising adjusting a pacing parameter that decreases the delay between pre-excitation of a hypertrophied myocardial region and excitation of other regions if it is determined that the hypertrophy has decreased.
21. The method of claim 13 further comprising computing a trend for the measured electrogram amplitudes.
22. The method of claim 13 wherein the depolarization event during which an electrogram amplitude is measured is an intrinsic beat.
23. The method of claim 13 wherein the depolarization event during which an electrogram amplitude is measured is a paced beat.
24. The method of claim 14 wherein the sensed and paced myocardial regions are ventricular regions.
PCT/US2003/003659 2002-02-08 2003-02-06 Dynamically optimized multisite cardiac resynchronization device WO2003065889A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP03737691A EP1483021A2 (en) 2002-02-08 2003-02-06 Dynamically optimized multisite cardiac resynchronization device
AU2003210894A AU2003210894A1 (en) 2002-02-08 2003-02-06 Dynamically optimized multisite cardiac resynchronization device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/071,875 2002-02-08
US10/071,875 US6915160B2 (en) 2002-02-08 2002-02-08 Dynamically optimized multisite cardiac resynchronization device

Publications (2)

Publication Number Publication Date
WO2003065889A2 true WO2003065889A2 (en) 2003-08-14
WO2003065889A3 WO2003065889A3 (en) 2003-10-02

Family

ID=27659343

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/003659 WO2003065889A2 (en) 2002-02-08 2003-02-06 Dynamically optimized multisite cardiac resynchronization device

Country Status (4)

Country Link
US (2) US6915160B2 (en)
EP (1) EP1483021A2 (en)
AU (1) AU2003210894A1 (en)
WO (1) WO2003065889A2 (en)

Families Citing this family (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6317615B1 (en) * 1999-04-19 2001-11-13 Cardiac Pacemakers, Inc. Method and system for reducing arterial restenosis in the presence of an intravascular stent
US6640135B1 (en) * 2000-04-06 2003-10-28 Cardiac Pacemakers, Inc. Apparatus and method for spatially and temporally distributing cardiac electrical stimulation
US7181285B2 (en) * 2000-12-26 2007-02-20 Cardiac Pacemakers, Inc. Expert system and method
US6628988B2 (en) * 2001-04-27 2003-09-30 Cardiac Pacemakers, Inc. Apparatus and method for reversal of myocardial remodeling with electrical stimulation
US7493162B2 (en) * 2001-06-15 2009-02-17 Cardiac Pacemakers, Inc. Pulmonary vein stent for treating atrial fibrillation
US6973349B2 (en) * 2001-12-05 2005-12-06 Cardiac Pacemakers, Inc. Method and apparatus for minimizing post-infarct ventricular remodeling
US6915160B2 (en) * 2002-02-08 2005-07-05 Cardiac Pacemakers, Inc. Dynamically optimized multisite cardiac resynchronization device
US7236821B2 (en) * 2002-02-19 2007-06-26 Cardiac Pacemakers, Inc. Chronically-implanted device for sensing and therapy
US7039462B2 (en) * 2002-06-14 2006-05-02 Cardiac Pacemakers, Inc. Method and apparatus for detecting oscillations in cardiac rhythm
US7113825B2 (en) * 2002-05-03 2006-09-26 Cardiac Pacemakers, Inc. Method and apparatus for detecting acoustic oscillations in cardiac rhythm
US6965797B2 (en) * 2002-09-13 2005-11-15 Cardiac Pacemakers, Inc. Method and apparatus for assessing and treating myocardial wall stress
US7065405B2 (en) * 2002-11-15 2006-06-20 Cardiac Pacemakers, Inc. Stress reduction pacing mode for arrhythmia prevention
US8712549B2 (en) 2002-12-11 2014-04-29 Proteus Digital Health, Inc. Method and system for monitoring and treating hemodynamic parameters
US7136707B2 (en) 2003-01-21 2006-11-14 Cardiac Pacemakers, Inc. Recordable macros for pacemaker follow-up
EP1585441A4 (en) * 2003-01-24 2008-05-21 Proteus Biomedical Inc Methods and systems for measuring cardiac parameters
US7267649B2 (en) * 2003-01-24 2007-09-11 Proteus Biomedical, Inc. Method and system for remote hemodynamic monitoring
US7200439B2 (en) 2003-01-24 2007-04-03 Proteus Biomedical, Inc. Method and apparatus for enhancing cardiac pacing
US7320675B2 (en) 2003-08-21 2008-01-22 Cardiac Pacemakers, Inc. Method and apparatus for modulating cellular metabolism during post-ischemia or heart failure
US7392084B2 (en) 2003-09-23 2008-06-24 Cardiac Pacemakers, Inc. Demand-based cardiac function therapy
US7572226B2 (en) 2003-10-28 2009-08-11 Cardiac Pacemakers, Inc. System and method for monitoring autonomic balance and physical activity
US20060247693A1 (en) 2005-04-28 2006-11-02 Yanting Dong Non-captured intrinsic discrimination in cardiac pacing response classification
US7774064B2 (en) 2003-12-12 2010-08-10 Cardiac Pacemakers, Inc. Cardiac response classification using retriggerable classification windows
US7840263B2 (en) 2004-02-27 2010-11-23 Cardiac Pacemakers, Inc. Method and apparatus for device controlled gene expression
US7764995B2 (en) * 2004-06-07 2010-07-27 Cardiac Pacemakers, Inc. Method and apparatus to modulate cellular regeneration post myocardial infarct
US7209786B2 (en) 2004-06-10 2007-04-24 Cardiac Pacemakers, Inc. Method and apparatus for optimization of cardiac resynchronization therapy using heart sounds
US7729761B2 (en) * 2004-07-14 2010-06-01 Cardiac Pacemakers, Inc. Method and apparatus for controlled gene or protein delivery
US7828711B2 (en) 2004-08-16 2010-11-09 Cardiac Pacemakers, Inc. Method and apparatus for modulating cellular growth and regeneration using ventricular assist device
US7567841B2 (en) * 2004-08-20 2009-07-28 Cardiac Pacemakers, Inc. Method and apparatus for delivering combined electrical and drug therapies
WO2006029090A2 (en) * 2004-09-02 2006-03-16 Proteus Biomedical, Inc. Methods and apparatus for tissue activation and monitoring
US7647108B2 (en) * 2004-09-30 2010-01-12 Cardiac Pacemakers, Inc. Methods and systems for selection of cardiac pacing electrode configurations
US8060219B2 (en) 2004-12-20 2011-11-15 Cardiac Pacemakers, Inc. Epicardial patch including isolated extracellular matrix with pacing electrodes
US7981065B2 (en) 2004-12-20 2011-07-19 Cardiac Pacemakers, Inc. Lead electrode incorporating extracellular matrix
US7662104B2 (en) 2005-01-18 2010-02-16 Cardiac Pacemakers, Inc. Method for correction of posture dependence on heart sounds
US7366567B2 (en) * 2005-03-23 2008-04-29 Cardiac Pacemakers, Inc. Method for treating myocardial infarction
US8036743B2 (en) 2005-03-31 2011-10-11 Proteus Biomedical, Inc. Automated optimization of multi-electrode pacing for cardiac resynchronization
US7392086B2 (en) 2005-04-26 2008-06-24 Cardiac Pacemakers, Inc. Implantable cardiac device and method for reduced phrenic nerve stimulation
US7366568B2 (en) 2005-05-06 2008-04-29 Cardiac Pacemakers, Inc. Controlled delivery of intermittent stress augmentation pacing for cardioprotective effect
US7894896B2 (en) * 2005-05-13 2011-02-22 Cardiac Pacemakers, Inc. Method and apparatus for initiating and delivering cardiac protection pacing
US7526338B1 (en) 2005-05-23 2009-04-28 Pacesetter, Inc. Implantable cardiac device for monitoring diastolic heart failure and method of operation and use thereof
US7922669B2 (en) 2005-06-08 2011-04-12 Cardiac Pacemakers, Inc. Ischemia detection using a heart sound sensor
WO2007021804A2 (en) 2005-08-12 2007-02-22 Proteus Biomedical, Inc. Evaluation of depolarization wave conduction velocity
US20070043412A1 (en) * 2005-08-18 2007-02-22 Herve Janssens Cardiac electrode assembly
US7774057B2 (en) 2005-09-06 2010-08-10 Cardiac Pacemakers, Inc. Method and apparatus for device controlled gene expression for cardiac protection
US7616990B2 (en) 2005-10-24 2009-11-10 Cardiac Pacemakers, Inc. Implantable and rechargeable neural stimulator
US8108034B2 (en) 2005-11-28 2012-01-31 Cardiac Pacemakers, Inc. Systems and methods for valvular regurgitation detection
US7780606B2 (en) 2006-03-29 2010-08-24 Cardiac Pacemakers, Inc. Hemodynamic stability assessment based on heart sounds
US9295845B2 (en) * 2006-06-29 2016-03-29 Cardiac Pacemakers, Inc. Post-MI pacing with autocapture function
US8620430B2 (en) 2006-06-30 2013-12-31 Cardiac Pacemakers, Inc. Selection of pacing sites to enhance cardiac performance
US8209013B2 (en) 2006-09-14 2012-06-26 Cardiac Pacemakers, Inc. Therapeutic electrical stimulation that avoids undesirable activation
US8948867B2 (en) 2006-09-14 2015-02-03 Cardiac Pacemakers, Inc. Capture detection with cross chamber backup pacing
US8219210B2 (en) * 2006-10-02 2012-07-10 Cardiac Pacemakers, Inc. Method and apparatus for identification of ischemic/infarcted regions and therapy optimization
US8019416B2 (en) * 2006-11-13 2011-09-13 Cardiac Pacemakers, Inc. Reduction of AV delay for treatment of cardiac disease
US7941216B2 (en) * 2006-11-17 2011-05-10 Cardiac Pacemakers, Inc. Method and device for treating myocardial ischemia
US8725255B2 (en) * 2006-11-17 2014-05-13 Cardiac Pacemakers, Inc. Cardiac resynchronization therapy optimization using cardiac activation sequence information
US8600499B2 (en) * 2006-12-05 2013-12-03 Cardiac Pacemakers, Inc. Method and device for cardiac vasoactive therapy
US8265736B2 (en) 2007-08-07 2012-09-11 Cardiac Pacemakers, Inc. Method and apparatus to perform electrode combination selection
US9037239B2 (en) 2007-08-07 2015-05-19 Cardiac Pacemakers, Inc. Method and apparatus to perform electrode combination selection
CN101939051B (en) 2008-02-14 2013-07-10 心脏起搏器公司 Method and apparatus for phrenic stimulation detection
US8473069B2 (en) 2008-02-28 2013-06-25 Proteus Digital Health, Inc. Integrated circuit implementation and fault control system, device, and method
US8380309B2 (en) * 2008-09-30 2013-02-19 Medtronic, Inc. Method and apparatus to optimize pacing heart rate
US8423141B2 (en) * 2009-01-30 2013-04-16 Medtronic, Inc. Pre-excitation stimulus timing based on mechanical event
EP2424588A4 (en) 2009-04-29 2013-05-22 Proteus Digital Health Inc Methods and apparatus for leads for implantable devices
US8786049B2 (en) 2009-07-23 2014-07-22 Proteus Digital Health, Inc. Solid-state thin-film capacitor
US9393429B2 (en) 2010-05-12 2016-07-19 Cardiac Pacemakers, Inc. Programming ambulatory optimization systems and methods for cardiac rhythm management
US8588910B2 (en) 2010-07-02 2013-11-19 Cardiac Pacemakers, Inc. Non-linear dynamic AV delay
US8600504B2 (en) 2010-07-02 2013-12-03 Cardiac Pacemakers, Inc. Physiologic demand driven pacing
US8718770B2 (en) 2010-10-21 2014-05-06 Medtronic, Inc. Capture threshold measurement for selection of pacing vector
EP2654885B1 (en) 2010-12-20 2016-02-24 Cardiac Pacemakers, Inc. Left ventricle-only and right ventricular safety pacing
AU2011349642B2 (en) * 2010-12-20 2015-07-02 Cardiac Pacemakers, Inc. Refractory and blanking intervals for multi-site ventricular pacing
JP5788525B2 (en) 2010-12-20 2015-09-30 カーディアック ペースメイカーズ, インコーポレイテッド Biventricular triggered pacing for multi-site ventricular pacing
WO2012087758A2 (en) 2010-12-20 2012-06-28 Cardiac Pacemakers, Inc. Left ventricular pacing protection for multi-site left ventricular pacing
US10052488B2 (en) 2010-12-20 2018-08-21 Cardiac Pacemakers, Inc. Refractory and blanking intervals in the context of multi-site left ventricular pacing
US8355784B2 (en) 2011-05-13 2013-01-15 Medtronic, Inc. Dynamic representation of multipolar leads in a programmer interface
DE102018221635B8 (en) * 2018-12-13 2020-08-06 Heraeus Deutschland GmbH & Co. KG Contacting procedure and system

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5534016A (en) * 1995-02-21 1996-07-09 Vitatron Medical, B.V. Dual chamber pacing system and method utilizing detection of ventricular fusion for adjustment of the atrial-ventricular delay as therapy for hypertrophic obstructive cardiomyopathy
US5824019A (en) * 1996-10-11 1998-10-20 Medtronic, Inc. Pacing system with physiologically timed ventricular pacing
WO1999010042A1 (en) * 1997-08-27 1999-03-04 Pacesetter, Inc. Dual chamber implantable pacemaker having negative av/pv hysteresis and ectopic discrimination
WO2001076689A2 (en) * 2000-04-06 2001-10-18 Cardiac Pacemakers, Inc. System for spatially and temporally distributing cardiac stimulation
US20020002389A1 (en) * 2000-05-15 2002-01-03 Kerry Bradley Cardiac stimulation devices and methods for measuring impedances associated with the left side of the heart
WO2002087694A1 (en) * 2001-04-27 2002-11-07 Cardiac Pacemakers, Inc. Apparatus and method for reversal of myocardial remodeling with electrical stimulation

Family Cites Families (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4939796B1 (en) * 1968-05-20 1974-10-29
US4354497A (en) * 1977-05-23 1982-10-19 Medtronic, Inc. Cardiac depolarization detection apparatus
US4686987A (en) 1981-06-18 1987-08-18 Cardiac Pacemakers, Inc. Biomedical method and apparatus for controlling the administration of therapy to a patient in response to changes in physiologic demand
US4554922A (en) * 1982-09-30 1985-11-26 Prystowsky Eric N Method of inhibiting cardiac arrhythmias
US4549548A (en) * 1983-09-14 1985-10-29 Vitafin N.V. Pacemaker system with automatic event-programmed switching between unipolar and bipolar operation
US4628934A (en) * 1984-08-07 1986-12-16 Cordis Corporation Method and means of electrode selection for pacemaker with multielectrode leads
US4872459A (en) * 1985-08-12 1989-10-10 Intermedics, Inc. Pacemaker for detecting and terminating a tachycardia
CA1290813C (en) * 1985-08-12 1991-10-15 Michael B. Sweeney Pacemaker for detecting and terminating a tachycardia
US4674518A (en) * 1985-09-06 1987-06-23 Cardiac Pacemakers, Inc. Method and apparatus for measuring ventricular volume
US5003975A (en) 1988-04-19 1991-04-02 Siemens-Pacesetter, Inc. Automatic electrode configuration of an implantable pacemaker
US4928688A (en) * 1989-01-23 1990-05-29 Mieczyslaw Mirowski Method and apparatus for treating hemodynamic disfunction
CS275292B2 (en) * 1989-02-22 1992-02-19 Cvut Fakulta Elektrotechnick Private rehabilitation apparatus with ion transcutaneous acceleration
US5156149A (en) * 1990-08-10 1992-10-20 Medtronic, Inc. Sensor for detecting cardiac depolarizations particularly adapted for use in a cardiac pacemaker
US5233985A (en) * 1990-08-10 1993-08-10 Medtronic, Inc. Cardiac pacemaker with operational amplifier output circuit
US5370665A (en) 1990-08-10 1994-12-06 Medtronic, Inc. Medical stimulator with multiple operational amplifier output stimulation circuits
US5267560A (en) 1990-09-07 1993-12-07 Cohen Fred M Methods for control of the ventricular activation sequence
US5174289A (en) * 1990-09-07 1992-12-29 Cohen Fred M Pacing systems and methods for control of the ventricular activation sequence
WO1994008657A1 (en) * 1992-10-20 1994-04-28 Noel Desmond Gray A heart pacemaker
US5209229A (en) 1991-05-20 1993-05-11 Telectronics Pacing Systems, Inc. Apparatus and method employing plural electrode configurations for cardioversion of atrial fibrillation in an arrhythmia control system
US5340361A (en) 1992-11-13 1994-08-23 Siemens Pacesetter, Inc. Implantable pacemaker having adaptive AV interval adoptively shortened to assure ventricular pacing
US5496362A (en) * 1992-11-24 1996-03-05 Cardiac Pacemakers, Inc. Implantable conformal coil patch electrode with multiple conductive elements for cardioversion and defibrillation
US6285898B1 (en) * 1993-07-20 2001-09-04 Biosense, Inc. Cardiac electromechanics
US5738096A (en) 1993-07-20 1998-04-14 Biosense, Inc. Cardiac electromechanics
US5507782A (en) 1994-03-17 1996-04-16 Medtronic, Inc. Method and apparatus for dual chamber cardiac pacing
FR2718036B1 (en) * 1994-04-05 1996-08-30 Ela Medical Sa Method for controlling a triple atrial pacemaker of the triple chamber type.
FR2718035B1 (en) * 1994-04-05 1996-08-30 Ela Medical Sa Method for controlling a double atrial pacemaker of the triple chamber type programmable in fallback mode.
US5626620A (en) 1995-02-21 1997-05-06 Medtronic, Inc. Dual chamber pacing system and method with continual adjustment of the AV escape interval so as to maintain optimized ventricular pacing for treating cardiomyopathy
CN1168511C (en) 1996-01-08 2004-09-29 伊帕斯动力公司 Electrical muscle controller
IL125424A0 (en) 1998-07-20 1999-03-12 New Technologies Sa Ysy Ltd Pacing with hemodynamic enhancement
US6363279B1 (en) * 1996-01-08 2002-03-26 Impulse Dynamics N.V. Electrical muscle controller
US5797970A (en) * 1996-09-04 1998-08-25 Medtronic, Inc. System, adaptor and method to provide medical electrical stimulation
US5800464A (en) 1996-10-03 1998-09-01 Medtronic, Inc. System for providing hyperpolarization of cardiac to enhance cardiac function
US5935160A (en) * 1997-01-24 1999-08-10 Cardiac Pacemakers, Inc. Left ventricular access lead for heart failure pacing
FR2760369B1 (en) * 1997-03-07 1999-04-30 Ela Medical Sa MULTI-SITE HEART STIMULATOR FOR THE TREATMENT OF HEART FAILURE BY STIMULATION
US5978707A (en) * 1997-04-30 1999-11-02 Cardiac Pacemakers, Inc. Apparatus and method for treating ventricular tachyarrhythmias
US6112117A (en) * 1997-05-06 2000-08-29 Cardiac Pacemakers, Inc. Method and apparatus for treating cardiac arrhythmia using electrogram features
US5792203A (en) * 1997-08-18 1998-08-11 Sulzer Intermedics Inc. Universal programmable cardiac stimulation device
US5995871A (en) * 1997-10-29 1999-11-30 Uab Research Foundation System and method for cardioversion using scan stimulation
US6070100A (en) * 1997-12-15 2000-05-30 Medtronic Inc. Pacing system for optimizing cardiac output and determining heart condition
US6314322B1 (en) * 1998-03-02 2001-11-06 Abiomed, Inc. System and method for treating dilated cardiomyopathy using end diastolic volume (EDV) sensing
CA2340911A1 (en) 1998-08-17 2000-02-24 Medtronic, Inc. Method and apparatus for prevention of atrial tachyarrhythmias
US6044298A (en) * 1998-10-13 2000-03-28 Cardiac Pacemakers, Inc. Optimization of pacing parameters based on measurement of integrated acoustic noise
US6292693B1 (en) 1998-11-06 2001-09-18 Impulse Dynamics N.V. Contractility enhancement using excitable tissue control and multi-site pacing
US6496730B1 (en) 1998-12-29 2002-12-17 Medtronic, Inc. Multi-site cardiac pacing system having conditional refractory period
US6868287B1 (en) 1999-02-12 2005-03-15 The Trustees Of Columbia University In The City Of New York Cardiac remodeling
US6112116A (en) * 1999-02-22 2000-08-29 Cathco, Inc. Implantable responsive system for sensing and treating acute myocardial infarction
US6556872B2 (en) * 1999-08-24 2003-04-29 Ev Vascular, Inc. Therapeutic device and method for treating diseases of cardiac muscle
US6418343B1 (en) * 1999-10-01 2002-07-09 Cardiac Pacemakers, Inc. Method and apparatus for adjusting the sensing threshold of a cardiac rhythm management device
WO2001030445A1 (en) 1999-10-25 2001-05-03 Impulse Dynamics N.V. Cardiac contractility modulation device having anti-arrhythmic capabilities and a method of operating thereof
US6507756B1 (en) 2000-04-03 2003-01-14 Medtronic, Inc. Dual chamber pacing system having time-adaptive AV delay
US7346397B2 (en) 2000-06-30 2008-03-18 Cochlear Limited Cochlear implant
US20020115081A1 (en) * 2000-08-22 2002-08-22 Lee Richard T. Diagnosis and treatment of cardiovascular conditions
US6564094B2 (en) * 2000-12-22 2003-05-13 Acorn Cardiovascular, Inc. Cardiac disease treatment and device
US7346394B2 (en) 2001-04-27 2008-03-18 Cardiac Pacemakers, Inc. Cardiac stimulation at high ventricular wall stress areas
US6973349B2 (en) 2001-12-05 2005-12-06 Cardiac Pacemakers, Inc. Method and apparatus for minimizing post-infarct ventricular remodeling
US6915160B2 (en) 2002-02-08 2005-07-05 Cardiac Pacemakers, Inc. Dynamically optimized multisite cardiac resynchronization device
US6970743B2 (en) 2002-08-30 2005-11-29 Pacesetter, Inc. System and method for treating abnormal ventricular activation-recovery time
US6965797B2 (en) * 2002-09-13 2005-11-15 Cardiac Pacemakers, Inc. Method and apparatus for assessing and treating myocardial wall stress
US7065405B2 (en) 2002-11-15 2006-06-20 Cardiac Pacemakers, Inc. Stress reduction pacing mode for arrhythmia prevention
US7215997B2 (en) 2003-12-22 2007-05-08 Cardiac Pacemakers, Inc. Dynamic device therapy control for treating post myocardial infarction patients
US7295874B2 (en) 2005-01-06 2007-11-13 Cardiac Pacemakers, Inc. Intermittent stress augmentation pacing for cardioprotective effect

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5534016A (en) * 1995-02-21 1996-07-09 Vitatron Medical, B.V. Dual chamber pacing system and method utilizing detection of ventricular fusion for adjustment of the atrial-ventricular delay as therapy for hypertrophic obstructive cardiomyopathy
US5824019A (en) * 1996-10-11 1998-10-20 Medtronic, Inc. Pacing system with physiologically timed ventricular pacing
WO1999010042A1 (en) * 1997-08-27 1999-03-04 Pacesetter, Inc. Dual chamber implantable pacemaker having negative av/pv hysteresis and ectopic discrimination
WO2001076689A2 (en) * 2000-04-06 2001-10-18 Cardiac Pacemakers, Inc. System for spatially and temporally distributing cardiac stimulation
US20020002389A1 (en) * 2000-05-15 2002-01-03 Kerry Bradley Cardiac stimulation devices and methods for measuring impedances associated with the left side of the heart
WO2002087694A1 (en) * 2001-04-27 2002-11-07 Cardiac Pacemakers, Inc. Apparatus and method for reversal of myocardial remodeling with electrical stimulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1483021A2 *

Also Published As

Publication number Publication date
US6915160B2 (en) 2005-07-05
WO2003065889A3 (en) 2003-10-02
US20050216066A1 (en) 2005-09-29
US7676259B2 (en) 2010-03-09
US20030153952A1 (en) 2003-08-14
EP1483021A2 (en) 2004-12-08
AU2003210894A1 (en) 2003-09-02
AU2003210894A8 (en) 2003-09-02

Similar Documents

Publication Publication Date Title
US6915160B2 (en) Dynamically optimized multisite cardiac resynchronization device
US7206634B2 (en) Method and apparatus for optimizing cardiac pumping performance
US7257443B2 (en) Method and apparatus for detecting oscillations in cardiac rhythm with electrogram signals
US7013176B2 (en) Method and apparatus for setting pacing parameters in cardiac resynchronization therapy
US8489204B2 (en) Method and apparatus for identification of ischemic/infarcted regions and therapy optimization
US8504155B2 (en) Dynamic device therapy control for treating post myocardial infarction patients
US7389141B2 (en) Biatrial pacing optimization for biventricular pacing
US8311630B2 (en) Reduction of AV delay for treatment of cardiac disease
EP1885439B1 (en) Apparatus for treatment of prolonged inter-atrial delay
EP1536859A1 (en) System for detection and treatment of myocardial wall stress
US8406878B2 (en) Method for treating myocardial infarction
US7194307B2 (en) Pacing method and device for preserving native conduction system
US8731666B2 (en) Minimizing hemodynamic compromise during post-MI remodeling control pacing

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2003737691

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2003737691

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP