Patent Application
20100298901
The present invention relates generally to implantable medical devices and more specifically to cardiac stimulation.
In the early days of implantable cardiac pacing, it was observed that paired pacing (two or more closely spaced pacing pulses delivered at the time-out of an escape interval) and triggered or coupled pacing (one or more pacing pulses delivered following the detection of a P-wave or R-wave terminating an escape interval) with relatively short inter-pulse intervals (150 to 250 milliseconds in dogs and about 300 milliseconds in human subjects) beneficially slowed heart rate and increased cardiac output. The result of the second pulse, applied within the relative refractory period of the first paced or spontaneous depolarization, is to prolong the refractory period and effect a slowing of the heart rate from its spontaneous rhythm without an attendant mechanical myocardial contraction. This slowing effect has been employed since that time in many applications, including the treatment of atrial and ventricular tachycardias, where a single pulse or a burst of pulses are coupled to a spontaneous tachycardia event with a coupling interval that is shorter than and can be set as a fraction of the tachycardia interval as taught, for example, in U.S. Pat. Nos. 3,857,399 and 3,939,844. The slowing of the heart rate by coupled pacing is accompanied by the ability to increase or decrease the rate with subsequent coupled pacing within wide limits.
Paired and coupled stimulation of a heart chamber also cause a potentiation of contractile force effect through a phenomenon known as post-extrasystolic potentiation (PESP) described in detail in commonly assigned U.S. Pat. No. 5,213,098. The force of contraction of the heart is increased during the heart cycle that the paired or coupled stimulation is applied, and the increase persists but gradually diminishes over a number of succeeding heart cycles. Other measurable PESP effects that also persist but gradually decline over a number of heart cycles include changes in the peak systolic blood pressure, the rate of contraction of the ventricular muscle with a resulting increase of the rate of rise of intra-ventricular pressure (dP/dt), an increase in coronary blood flow, and an increase in the oxygen uptake of the heart per beat. Investigators observed that PESP was accompanied by an increase in the myocardial oxygen consumption of 35% to 70% as compared with single pulse stimulation at the same rate and was associated with a significant improvement in ejection fraction. The addition of a third stimulus increased the myocardial oxygen uptake even further without any attendant observed increase in cardiac contractile force. The alterations in coronary flow roughly parallel the oxygen consumption of the heart as observed in such studies.
The marked potentiation effect produced by paired stimulation led certain investigators to speculate that PESP stimulation would be beneficial in treating heart failure in humans and conducted studies using the technique in the treatment of acute heart failure induced in dogs. Improvements in left ventricular performance and cardiac output produced by such paired pacing in these dogs were observed by several investigators. In other studies conducted on relatively normal dogs' hearts, it was confirmed that paired pacing offered no increase in cardiac output, most likely due to reflex compensation. Early investigators conducted a large number of animal and human studies employing paired and coupled stimulation of the atrial and ventricular chambers, and medical devices were made available by Medtronic, Inc. and other companies in an effort to employ the PESP effect. However, it was realized that the application of closely timed paired and coupled pacing pulses, particularly the high energy pacing pulses that were employed at that time in implantable pacemakers, could trigger a tachyarrhythmia in patient's hearts that were susceptible. The efforts to capitalize on the PESP effects were largely abandoned. A history of the investigations and studies conducted is set forth in the above-referenced '098 patent.
A series of PCT publications including, for example, PCT WO 97/25098 describe the application of one or more “non-excitatory” anodal or cathodal stimulation pulses to the heart and maintain that improvements in LV performance may be realized without capturing the heart. In a further commonly assigned U.S. Pat. No. 5,800,464, sub-threshold anodal stimulation is provided to the heart to condition the heart to mechanically respond more vigorously to the conventional cathodal supra-threshold pacing pulses.
Notwithstanding the above discussed work, there still remains a need for improved treatments for tachycardia, heart failure and hypertension. The present invention provides an apparatus and method to decrease heart rate and blood pressure by focal stimulation of the myocardium. As discussed below, in a healthy heart, the sino-atrial node (SAN) initiates action potentials which propagate to the whole heart via a conductive system. Compared with the ventricles, the SAN, atria and AV node (AVN) are normally excited earlier and to recover earlier in the cardiac cycle than the ventricles. However, due to longer action potential durations associated with the ventricular myocardium, the refractory period of the ventricles continues after the end of the atrial and nodal refractory periods discussed above. Therefore, there is a stimulus time window in the atria, SAN and/or AVN may be excited while the ventricles remain refractory to stimulation.
Excitation of the atria, SAN and/or AVN during the ventricular refractory period resets the atrial cycle (resets the SAN) and starts a new refractory period in the atrial and AV nodal tissue, without triggering a ventricular contraction. The result is that propagation of a depolarization to the ventricles effective to cause a contraction is delayed until the next subsequent depolarization of the SAN. The ventricular rate is thus reduced by up to 50% from the SA nodal rate. The inventors have determined that in conjunction with this reduction in ventricular rate, both the systolic and diastolic blood pressures may be reduced. The degree of reduction in rate and blood pressure varies with the timing of the atrial or nodal excitation stimulus relative to preceding atrial and ventricular depolarizations. The effect of the stimulation can thus be titrated against a desired reduction in rate or blood pressure.
The stimulus pulses may correspond to typical cardiac pacing pulses or may be pulse bursts having burst envelopes corresponding to the duration and/or morphology of normal cardiac pacing pulses. Longer pulse durations, e.g. 10 ms or more may also be employed. The particular form of the pulse is not critical so long as it triggers a depolarization of the desired atrial or nodal tissue. Proper timing of the stimulus pulses within the defined excitation window is important to assure that the desired effect is produced without induction of arrhythmias.
The stimulus time window extends from the point at which the atrial or nodal tissue to be stimulated becomes non-refractory up to the point at which the stimulated atrial or nodal depolarization could propagate to the ventricles to cause a ventricular depolarization. The time window will vary from patient to patient, but generally will fall between the end of the atrial and/or nodal refractory periods and the end of the ventricular refractory period. The window generally thus extends within a time period occurring between about 80 ms to about 200 ms following a normally conducted ventricular depolarization. Refractory period timing and durations may vary with the individual and with the underlying heart rhythm, and thus the duration of the time window will also vary. Timing of the stimulus pulses may be based upon a preceding atrial depolarization, ventricular depolarization, or possibly both. Timing of the stimulus pulses may be predefined by the attending physician and programmed into the device or may be varied by the device in order to achieve a desired reduction in heart rate or blood pressure.
These and other advantages and features of the present invention will be more readily understood from the following detailed description of the preferred embodiments thereof, when considered in conjunction with the drawings, in which like reference numerals indicate identical structures throughout the several views, and wherein:
In the following detailed description, references are made to illustrative embodiments for carrying out the invention. It is understood that other embodiments may be utilized without departing from the scope of the invention.
In
The depolarization impulse that reaches the AV node conducts down the bundle of His in the intra-ventricular septum after a delay of about 120 ms. The depolarization wave reaches the apical region of the heart about 20 ms. later and is then travels superiorly though the Purkinje fiber network over the remaining 40 ms. The aggregate RV and LV depolarization wave and the subsequent T-wave accompanying re-polarization of the depolarized myocardium are referred to as the QRST portion of the PQRST cardiac cycle complex when sensed across external ECG electrodes and displayed. When the amplitude of the QRS ventricular depolarization wave passing between a bipolar or unipolar pace/sense electrode pair located on or adjacent to the RV or LV exceeds a defined threshold amplitude, it is detected as a sensed R-wave. Although the location and spacing of the external ECG electrodes or implanted unipolar ventricular pace/sense electrodes has some influence on R-wave sensing, the normal R-wave duration does not exceed 80 ms. as measured by a high impedance sense amplifier. A normal near field R-wave sensed between closely spaced bipolar pace/sense electrodes and located in or adjacent the RV or the LV typically has a width of no more than 60 ms. as measured by a high impedance sense amplifier.
The depicted bipolar endocardial RA lead 16 is passed through a vein into the RA chamber of the heart 10, and the distal end of the RA lead 16 is attached to the RA wall by an attachment mechanism 17. In the context of the illustrated embodiment of the present invention, the distal end of the lead 16 is located near the AV node or in the right atrial appendage, although other locations may be substituted in some cases. The bipolar endocardial RA lead 16 is formed with an in-line connector 13 fitting into a bipolar bore of IPG connector block 12 that is coupled to a pair of electrically insulated conductors within lead body 15 and connected with distal tip RA pace/sense electrode 19 and proximal ring RA pace/sense electrode 21. Delivery of atrial pace pulses and sensing of atrial sense events is effected between the distal tip RA pace/sense electrode 19 and proximal ring RA pace/sense electrode 21, wherein the proximal ring RA pace/sense electrode 21 functions as an indifferent electrode (IND_RA). Alternatively, a unipolar endocardial RA lead could be substituted for the depicted bipolar endocardial RA lead 16 and be employed with the IND_CAN electrode 20. Or, one of the distal tip RA pace/sense electrode 19 and proximal ring RA pace/sense electrode 21 can be employed with the IND_CAN electrode 20 for unipolar pacing and/or sensing.
Bipolar, endocardial RV lead 32 is passed through the vein and the RA chamber of the heart 10 and into the RV where its distal ring and tip RV pace/sense electrodes 38 and 40 are fixed in place in the apex by a conventional distal attachment mechanism 41. The RV lead 32 is formed with an in-line connector 34 fitting into a bipolar bore of IPG connector block 12 that is coupled to a pair of electrically insulated conductors within lead body 36 and connected with distal tip RV pace/sense electrode 40 and proximal ring RV pace/sense electrode 38, wherein the proximal ring RV pace/sense electrode 38 functions as an indifferent electrode (IND_RV). Alternatively, a unipolar endocardial RV lead could be substituted for the depicted bipolar endocardial RV lead 32 and be employed with the IND_CAN electrode 20. Or, one of the distal tip RV pace/sense electrode 40 and proximal ring RV pace/sense electrode 38 can be employed with the IND_CAN electrode 20 for unipolar pacing and/or sensing.
In this illustrated embodiment, a unipolar, endocardial LV CS lead 52 is passed through a vein and the RA chamber of the heart 10, into the CS and then inferiorly in a branching vessel of the great vein 48 to extend the distal LV CS pace/sense electrode 50 alongside the LV chamber. The distal end of such LV CS leads is advanced through the superior vena cava, the right atrium, the ostium of the coronary sinus, the coronary sinus, and into a coronary vein descending from the coronary sinus, such as the great vein. The LV CS leads and LA CS leads may employ a deployable fixation mechanism or may instead rely on the close confinement within these vessels to maintain the pace/sense electrode or electrodes at a desired site. The LV CS lead 52 is formed with a small diameter single conductor lead body 56 coupled at the proximal end connector 54 fitting into a bore of IPG connector block 12. A small diameter unipolar lead body 56 is selected in order to lodge the distal LV CS pace/sense electrode 50 deeply in a vein branching inferiority from the great vein 48.
The distal, LV CS active pace/sense electrode 50 may be paired with the proximal ring RV indifferent pace/sense electrode 38 for delivering LV pace pulses across the bulk of the left ventricle and the intra-ventricular septum. The distal LV CS active pace/sense electrode 50 may also be paired with the distal tip RV active pace/sense electrode 40 for sensing across the RV and LV as described further below.
In an embodiment comprising a four chamber pacemaker, LV CS lead 52 could optionally bear a proximal LA CS pace/sense electrode positioned along the lead body and configured to lay in the larger diameter coronary sinus CS adjacent the LA. In that case, the lead body 56 would encase two electrically insulated lead conductors extending proximally from the more proximal LA CS pace/sense electrode(s) and terminating in a bipolar connector 54. The LV CS lead body may be smaller between the proximal LA CS electrode and the distal LV CS active pace/sense electrode 50. In that case, pacing of the RA would be accomplished along the pacing vector between the active proximal LA CS active electrode and the proximal ring RA indifferent pace/sense electrode 21.
Typically, in pacing systems of the type illustrated in
In addition, as described further below, each of the leads could carry a pressure sensor for developing systolic and diastolic pressures and a series of spaced apart impedance sensing leads for developing volumetric measurements of the expansion and contraction of the RA, LA, RV and LV.
The multi-chamber pacemaker 100 also typically includes patient interface circuitry 104 for receiving signals from sensors and pace/sense electrodes located at specific sites of the patient's heart chambers and/or delivering stimulation to derive heart failure parameters or a pacing therapy to the heart chambers. The patient interface circuitry 104 therefore comprises a stimulation delivery system 106 optionally including pacing and other stimulation therapies and a physiologic input signal processing circuit 108 for processing the blood pressure and volumetric signals output by sensors. For purposes of illustration of the possible uses of the invention, a set of lead connections are depicted for making electrical connections between the therapy delivery system 106 and the input signal processing circuit 108 and sets of pace/sense electrodes located in operative relation to the RA, LA, RV and LV.
The therapy delivery system 106 can also optionally be configured to include circuitry for delivering cardioversion/defibrillation shocks and/or cardiac pacing pulses delivered to the heart or cardiomyostimulation to a skeletal muscle wrapped about the heart. The therapy delivery system 106 can also optionally be configured as a drug pump for delivering drugs into the heart to alleviate heart failure or to operate an implantable heart assist device or pump implanted in patients awaiting a heart transplant operation.
A battery provides a source of electrical energy to power the multi-chamber pacemaker operating system including the circuitry of multi-chamber pacemaker 100 and to power any electromechanical devices, e.g., valves, pumps, etc. of a substance delivery multi-chamber pacemaker, or to provide electrical stimulation energy of an ICD shock generator, cardiac pacing pulse generator, or other electrical stimulation generator. The typical energy source is a high energy density, low voltage battery 136 coupled with a power supply/POR circuit 126 having power-on-reset (POR) capability. The power supply/POR circuit 126 provides one or more low voltage power Vlo, the POR signal, one or more VREF sources, current sources, an elective replacement indicator (ERI) signal, and, in the case of an ICD, high voltage power Vhi to the therapy delivery system 106. Not all of the conventional interconnections of these voltages and signals are shown in
In addition, in certain multi-chamber pacemakers, an audible patient alert warning or message is generated by a transducer 128 when driven by a patient alert driver 118 to advise of device operations, battery power level or a monitored patient condition. In ids, the patient may be warned of the detection of a malignant tachyarrhythmia and the imminent delivery of a cardioversion/defibrillation shock to enable the patient to assume a resting position prior to delivery.
Virtually all current electronic multi-chamber pacemaker circuitry employs clocked CMOS digital logic ICs that require a clock signal CLK provided by a piezoelectric crystal 132 and system clock 122 coupled thereto as well as discrete components, e.g., inductors, capacitors, transformers, high voltage protection diodes, and the like that are mounted with the ICs to one or more substrate or printed circuit board. In
The RAM registers may be used for storing data compiled from sensed cardiac activity and/or relating to device operating history or sensed physiologic parameters for uplink telemetry transmission on receipt of a retrieval or interrogation instruction via a downlink telemetry transmission. The criteria for triggering data storage can also be programmed in via downlink telemetry transmitted instructions and parameter values The data storage is either triggered on a periodic basis or by detection logic within the physiologic input signal processing circuit 108 upon satisfaction of certain programmed-in event detection criteria. In some cases, the multi-chamber pacemaker 100 includes a magnetic field sensitive switch 130 that closes in response to a magnetic field, and the closure causes a magnetic switch circuit to issue a switch closed (SC) signal to control and timing system 102 which responds in a magnet mode. For example, the patient may be provided with a magnet 116 that can be applied over the subcutaneously implanted multi-chamber pacemaker 100 to close switch 130 and prompt the control and timing system to deliver a therapy and/or store physiologic episode data when the patient experiences certain symptoms. In either case, event related data, e.g., the date and time, may be stored along with the stored periodically collected or patient initiated physiologic data for uplink telemetry in a later interrogation session.
In the multi-chamber pacemaker 100, uplink and downlink telemetry capabilities are provided to enable communication with either a remotely located external medical device or a more proximal medical device on the patient's body or another multi-chamber pacemaker in the patient's body as described above with respect to
The physiologic input signal processing circuit 108 therefore includes at least one electrical signal amplifier circuit for amplifying, processing and in some cases detecting sense events from characteristics of the electrical sense signal or sensor output signal.
The physiologic input signal processing circuit 108 in multi-chamber pacemakers providing dual chamber or multi-site or multi-chamber monitoring and/or pacing functions includes a plurality of cardiac signal sense channels for sensing and processing cardiac signals from sense electrodes located in relation to a heart chamber. Each such channel typically includes a sense amplifier circuit for detecting specific cardiac events and an EGM amplifier circuit for providing an EGM signal to the control and timing system 102 for sampling, digitizing and storing or transmitting in an uplink transmission. Atrial and ventricular sense amplifiers include signal processing stages for detecting the occurrence of a P-wave or R-wave, respectively and providing an ASENSE or VSENSE event signal to the control and timing system 102. Timing and control system 102 responds in accordance with its particular operating system to deliver or modify a pacing therapy, if appropriate, or to accumulate data for uplink telemetry transmission or to provide a Marker Channel® signal in a variety of ways known in the art.
In addition, the input signal processing circuit 108 includes at least one physiologic sensor signal processing channel for sensing and processing a sensor derived signal from a physiologic sensor located in relation to a heart chamber or elsewhere in the body.
In the context of the present invention, the described pacemaker provides the inventive stimulation therapy to the atrial electrodes at defined time intervals during the defined time window discussed above, following a normally conducted ventricular depolarization. For purposes of the present application, a normally conducted ventricular depolarization should be understood to be a ventricular depolarization preceded by an atrial depolarization at an interval corresponding to a normal A-V conduction interval (i.e. not a premature ventricular depolarization (PVC)). The ventricular depolarization may be sensed, paced or some combination of both, (e.g. during delivery of ventricular resynchronization therapy).
In some embodiments of the invention, delivery of the stimulus may be triggered at a defined interval following the ventricular depolarization. Such embodiments are believed to reflect the simplest form of the invention and to be easiest to implement. It is desirable, however, that the preceding occurrence of an atrial depolarization, paced or sensed, is verified as a precondition of delivery of the stimulation therapy provided by the present invention. In more complex embodiments, the timing of both the atrial and ventricular depolarizations (paced or sensed) may be employed to determine the stimulus delivery time or the permitted range of delivery times (i.e., the stimulation time window).
The defined intervals chosen for delivery of the stimulus pulses may be pre-programmed by the attending physician based upon an electrophysiological study of the patient. Alternatively, the pacemaker itself may determine the optimal stimulus delivery times by varying the stimulus times within the time window and adjusting the defined stimulation intervals to produce the desired result. The desired result may be, for example, a defined degree of lowering of heart rate or blood pressure or the lowest achievable blood pressure or heart rate.
Activation of the stimulation therapy of the present invention may be triggered by the device, for example in response to an excessive heart rate or blood pressure and the stimulation therapy may be deactivated responsive to the heart rate or blood pressure returning to acceptable ranges. The determination of whether the heart rate or blood pressure is excessive may be made by comparing the values of these parameters to pre-defined threshold values. Alternatively, activation and deactivation of the stimulation therapy of the present invention may be triggered by the patient or attending physician by means of an associated programmer or activator.
In most embodiments, it is anticipated that the parameters of the individual stimulation pulses (width, amplitude, etc.) will be determined at implant and programmed into the pacemaker's memory by the attending physician. However, in some embodiments mechanism for optimizing these parameters analogous to the mechanism described above in conjunction with
This application claims the benefit of U.S. Provisional Application No. 61/179,452, filed on May 19, 2009. The disclosure of the above application is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 61179452 | May 2009 | US |
