Pacemaker system with inhibition of AV node for rate regulation during atrial fibrillation

There is provided a system for regulating ventricular rate in the presence of abnormally high atrial rates, e.g., during episodes of atrial fibrillation. During such an episode, the system, preferably incorporated into an implantable pacemaker, applies subthreshold bursts of stimulus pulses to or proximate to the patient's AV node so as to inhibit conduction of electrical signals through to the ventricle during the bursts. The bursts are timed in relation to the last conducted ventricular signal, and in terms of burst length, to provide a rate of conducted signals through the AV node which results in a substantially regular and reduced ventricular rate. During the inhibition mode of operation, the system monitors to determine the efficacy of inhibition, by tracking the percentage of ventricular senses that occur during the burst periods. When inhibition is found to be below an acceptable percentage, the system carries out an inhibition test and re-adjusts the burst parameters to provide bursts of optimized stimulation energy.

FIELD OF THE INVENTION
 This invention relates to cardiac pacing systems with the capability of
 responding to episodes of atrial fibrillation and other atrial arrhythmias
 and, in particular, implantable pacing systems which respond to such an
 episode by controllably inhibiting conduction of at least some of the
 atrial signals to the ventricle until the episode terminates naturally.
 BACKGROUND OF THE INVENTION
 Modern cardiac pacing systems have incorporated substantial capability for
 detecting and dealing with various arrhythmias. Of particular importance
 are atrial arrhythmias such as atrial fibrillation (AF), which may lead to
 serious complications. Atrial fibrillation is manifested as an irregular
 disorganized activity of the heart, and in the absence of complete AV
 block, the ventricular response is irregular and random. The irregularity
 of the resulting cardiac rhythm adversely affects the contractile
 performance of the heart. It is a source of considerable morbidity and
 mortality; AF is the leading cause of embolic stroke. As used hereinafter,
 the term atrial fibrillation, or AF, refers broadly to the class of
 dangerous atrial arrhythmias, during episodes of which it is desired to
 inhibit conduction of most of the atrial signals to the ventricles.
 Pacemakers have attempted to deal with such arrhythmias by simply
 switching into an asynchronous mode, such that ventricular pacing does not
 try to track the dangerous atrial excitations. However, with ordinary
 asynchronous ventricular pacing and continued conduction of the atrial
 signals through the AV node, a certain percentage of the atrial signals
 will get through to the ventricle and thus cause chaotic spontaneous
 ventricular contractions and paced contractions, resulting in an
 undesirable cardiac condition. Patients with paroxysmal or chronic AF and
 intact AV conduction who are highly symptomatic and drug refractory are
 presently candidates for His ablation. This is, of course, a procedure
 which stops conduction of all atrial signals to the ventricle permanently.
 The result is that the ventricle needs to be paced permanently even though
 the atrium contracts normally most of the time.
 Another technique that is in use is that of delivering a cardioversion
 shock to the patient's heart. This can be done during general anesthesia,
 which of course is impractical for a patient who has repeated and rather
 long-occurring episodes. Such a patient would also be a candidate for an
 implantable cardioverter device. However, such devices are very expensive,
 and the shocks are not welcome to the patient, i.e., they may be painful.
 Further, if the episodes occur too frequently, these devices have a
 limited lifetime due to the energy expenditure of each shock.
 Another approach known in the literature is to cool the atrium, thereby
 slowing conduction in the atrial tissue to the point of terminating the
 atrial fibrillation. See Abstract, Scaglione et al, E, Vol. 16, p 880,
 April 1993, Part II. In this approach, the entire atrium is cooled by
 introduction of a bolus of cold saline solution. See also U.S. Pat. No.
 5,876,422, issued Mar. 2, 1999, showing a system for Peltier cooling of
 the AV node during which the ventricle must be paced asynchronously for
 the duration of the AF episode.
 Another approach to the problem is for the pacemaker to respond by
 aggressively pacing at a higher, but more stable rate. See, for example,
 U.S. Pat. No. 5,480,413. See also U.S. Pat. No. 5,792,193, which smooths
 the ventricular rate by an algorithm that allows some spontaneous
 ventricular contractions, and delivers some pace pulses which overdrive
 the spontaneous rate.
 However, there remains a substantial need for an improved system and
 technique for effectively regulating the ventricular rate until the atrium
 can return on its own to a normal sinus rhythm, and without requiring a
 high ventricular rate so that the ventricle be paced asynchronously.
 SUMMARY OF THE INVENTION
 It is an object of this invention to provide a stimulating system,
 preferably an implantable system such as a pacemaker system, which is
 responsive to atrial fibrillation by regulating the rate of atrial signals
 which are conducted through the AV node, thereby regulating the rate of
 ventricular contractions. The invention is thus aimed at cardiac patients
 who have normal AV conduction but are susceptible to episodes of atrial
 fibrillation, and provides for limiting the ventricular rate by allowing
 passage of enough signals through to the ventricle to maintain at least a
 predetermined rate, and for inhibiting passage of other atrially generated
 excitation signals through the AV node. In this manner, the ventricle
 contracts synchronously with some of the atrial beats, but does not
 receive others, resulting in synchronous ventricular beats at a regulated
 rate.
 The above object is achieved by responding to an episode of atrial
 fibrillation by generating and delivering subthreshold bursts of pulses to
 the patient's AV node, the bursts being controlled in energy level and
 frequency to inhibit conduction of signals through the node while they are
 being applied. Each burst is timed relative to a last sensed ventricular
 contraction so as to inhibit AV conduction for a period that is related to
 a desired V--V interval, or ventricular rate. The start of the burst, and
 the end of the burst are automatically adjusted to provide a desired burst
 duration; and the energy level of the burst is also automatically adjusted
 to ensure inhibition while minimizing energy expenditure. Inhibition
 threshold is tested by determining the percentage of ventricular
 contractions that occur at intervals shorter than that which corresponds
 to the predetermined regulation rate; when the percentage is too high,
 pulse level and/or frequency of pulses within the burst are adjusted to
 regain optimum inhibition. When the AF episode stops of its own accord,
 the system returns to a normal mode of pacing.

DESCRIPTION OF THE PREFERRED EMBODIMENTS
 Referring first to FIG. 1A, there is shown a diagram of a pacing system in
 accordance with this invention. Pacemaker 30 is suitably a dual chamber
 pacemaker, providing pacing pulses at least for delivery to the patient's
 ventricle, and preferably also providing for atrial pacing pulses. The
 pacemaker is encased in a pacemaker "can" 30-C, of conventional material.
 Ventricular pacing pulses are delivered from pacemaker 30 on lead 32,
 which is illustrated as being positioned with its distal end at about the
 apex of the right ventricle. Lead 32 may be unipolar or bipolar, and has
 at least one electrode, shown at 33, substantially at the distal tip, and
 may have a second ring electrode shown diagrammatically at 34. A second
 lead 31 is an atrial lead, for positioning against the inner wall of the
 atrium, as shown. This lead has a distal tip electrode 36, and suitably
 may also have a ring electrode 38 indicated as being displaced proximally
 from the distal end. It also carries at least one electrode 37, having a
 surface positioned for placement in proximity to the AV node, as
 indicated. Electrode 37 can be positioned on or proximate to the AV node,
 and the term "proximate" as used herein also refers to a position
 sufficiently close to the His, which enables inhibition of the excitation
 signal as it exits the AV node. It is important that the lead be fixed
 permanently proximate to the AV node, which can be done best by placing it
 in the triangle of Koch. It is known that in this area it is difficult to
 attach leads passively, and accordingly in the preferred embodiment a
 screw-in lead is used, as illustrated in FIG. 1C. Screwing a helical tip
 element into the AV node itself may or may not prove to be desirable; a
 safe procedure is for the physician to manipulate the separate atrial lead
 31 into position so as to screw the tip end into the heart wall just
 proximate to the AV node or the His. As used hereinafter, reference to the
 AV node includes the exit area of the heart proximate to the AV node.
 Referring now to FIG. 1B, there is shown a more detailed diagrammatic
 sketch of an atrial lead in accordance with this invention, carrying AV
 electrode 37. It is to be understood that FIG. 1B is illustrative only of
 electrode placement, and that the screw-in embodiment of FIG. 1C is
 presently a preferred embodiment. FIG. 1B shows details of the distal end
 of lead 31, which otherwise has a conventional outer casing and has a
 proximal end (not shown) for attachment to pacemaker 30 in a known manner.
 The AV electrode 37 is connected electrically to the pacemaker by
 conductor 43, and is positioned adjacent to distal end of the lead 31 so
 that it is in good contact with the AV node when the lead is fixed within
 the atrium. The burst may be delivered in unipolar fashion, i.e., between
 electrode 37 and the pacemaker can, or in a bipolar arrangement, in which
 case two AV ring electrodes are used. Also, as shown in FIG. 1B, conductor
 41 connects to tip electrode 36, providing for delivery of pacing pulses
 from the pacemaker and delivery of sensed signals from the atrium back to
 the pacemaker, in a known fashion.
 Referring to FIG. 1C, there is shown diagrammatically a preferred
 embodiment of lead 31, having a distally carried screw element 49 which
 can be pushed out from the distal tip for fixation into or around the AV
 node. The lead has a first ring electrode 37B at the tip end, and a second
 ring electrode 38 positioned about 10 mm proximal from the tip. Screw
 element 49 is held within the lead casing during introduction, and can be
 extended axially outward in a known manner; both ring electrodes and the
 screw element are connected by conductors to the pacemaker, or stimulator
 device. The physician may search the vicinity of the AV node to find the
 optimal position for fixating the lead in order to inhibit the AV node, at
 which time the screw is then pushed out and fixated. Stimulation can be
 performed with any desired combination of the 3 electrode elements.
 Additionally, for dual chamber pacemaker operation, any combination of one
 or more of the lead electrodes, as well as the pacemaker can, can be used
 for delivering pacing pulses and sensing atrial signals.
 Referring now to FIG. 2, there is shown a block diagram of a pacemaker
 system in accordance with this invention. A generator 15 is provided for
 generating ventricular pace pulses, under control of control block 20. The
 ventricular pace pulses are delivered on lead 32 to one or more
 ventricular electrodes 33, 34. Likewise, generator 18 is provided for
 generating atrial pulses, which are delivered by lead 31 to atrial
 electrodes 37, 38 (or 49). Both generators 15 and 18 are controlled by
 control block 20, which preferably incorporates a microprocessor, for
 control of timing, amplitude, pulse width, etc. in a known manner. Memory
 21 is interconnected with control block 20, for providing software for
 logic control, as well as pacing parameters and other data. Programmer
 receiver 29 is used to receive downloaded program data from an external
 programmer in a known fashion, and such received data is connected through
 control block 20 to storage in memory 21. A sensor 28 may be employed for
 obtaining one or more rate-indicating parameters, in a known manner.
 Signals sensed from ventricular electrodes 33, 34 are connected through to
 QRS sense block 24, for appropriate signal processing and delivery to
 control block 20. Although not shown, the pacemaker may also sense T wave
 portions of the signals received from the ventricular electrodes.
 Likewise, signals from the atrial electrodes 37, 38, 49 are connected
 through to P wave sense block 25, for appropriate processing and
 connection through to control block 20.
 Of specific importance to the pacemaker system of this invention, burst
 generator 26 is controlled by block 20 to provide inhibiting bursts of
 subthreshold pulses to the AV node, in the event of an atrial arrhythmia.
 The bursts are delivered on conductor 43 to AV electrode 37 (or 49). The
 electrical parameters of the bursts, and the control of burst generation,
 are discussed in detail in connection with FIGS. 3-6B. Referring now to
 FIG. 3, there is shown a timing diagram illustrating the timing of an
 inhibiting burst relative to a ventricular sense (VS) and the ventricular
 refractory period. A burst is shown having a duration which extends from a
 start time (BST) to an end time (BET). The BST is timed to occur after an
 atrial signal is conducted through the AV node and produces a ventricular
 contraction, which is sensed (VS) by the device. Note that following a QRS
 there is a ventricular refractory interval, and BST is suitably timed to
 occur just before the end of this refractory period. As shown, after BET
 another atrial, or AF signal can be conducted through the AV node,
 producing a next VS. In this situation, the V--V interval is greater than
 the burst duration by the patient's natural AV interval plus the time from
 the prior VS to BST, showing that the patient ventricular rate can be
 controlled by controlling time of BST and BET, i.e., the burst duration
 and its timing relative to the last VS. This control can be achieved by
 adjusting the timing of both BST and BET.
 If the monitored V--V interval is shorter than expected based on the burst
 duration and the AV delay, the BST may need adaptation; it may be that AF
 signals are slipping through between the end of the ventricular refractory
 period and BST. In a preferred embodiment, BST is caused to continually
 drift (e.g., in 10 microsecond steps) towards BET, in order to decrease
 the burst duration; but if BST is found to be too late it is set back with
 a much larger step (e.g., 10 ms). Drifting away from the VS stops when BST
 reaches a maximum programmable start time, and adaptation towards the VS
 stops at a programmable minimum. Alternately, BST can be set relative to
 the T wave, which is an indicator of the end of the ventricular refractory
 period. The value of BET depends on the desired ventricular interval,
 which may be programmed: by increasing the burst length, the AV node is
 inhibited longer, and ventricular rate is decreased. As is seen from the
 timing diagram, the first AF wave that is no longer inhibited is conducted
 to the ventricle with the AV delay. Assuming the atrial rate is very high
 compared to the V--V rate, BET is determined by the equation:
 BET=VV_int-AV_int, where BET is timed from the prior VS. The patient's
 AV_int can be determined, and thus BET can be set. Burst duration is then
 adjusted by adjusting BST, as is discussed further in connection with FIG.
 5.
 In a preferred embodiment, the available energy levels and frequencies of
 the burst pulses are programmable. Typical values are:
 voltage-from 0.1 V to 5.0 V, in steps of 0.1V;
 pulse width-from 0.1 ms to 10.0 ms, in steps of 0.1 ms;
 current-from 0.5 mA to 5.0 mA, in steps of 0.1 mA; and
 pulse interval-from 10 to 200 ms, in steps of 0.5 ms.
 Referring now to FIG. 4A, there is shown a simplified flow diagram showing
 the relationship of the AF therapy algorithm of this invention to the
 normal handling routine of a cardiac pacemaker. It is to be noted that the
 preferred environment of the invention is that of being incorporated into
 a pacemaker. However, it can likewise be used in other stimulating
 systems, e.g., as part of a pacemaker-cardioverter-defibrillator, or any
 other system dedicated to treatment of cardiac arrhythmias. In FIG. 4A,
 the normal pacemaker event detection and handling is illustrated at 50.
 Each cardiac cycle, the system tests for AF, as indicated at 51. Assuming
 no AF, the system remains in a conventional pacemaker mode. However if AF
 is detected, the system goes to the AF main flow 52, and regulates
 conduction of atrial signals to the ventricles. As long as AF continues,
 the system stays in this flow; if AF ceases, the system returns to the
 normal mode of operation.
 Referring now to FIG. 4B, there is illustrated a flow diagram showing the
 primary routines carried out in the main flow 52. Starting at the top of
 the diagram, the Tune Burst Duration routine 54 is entered after a VS.
 This determines the start and end times of the burst with respect to the
 conducted VS. Next, at 55, the system carries out the Determine Inhibition
 Threshold routine. This controls the output pulse characteristics and
 frequency of the burst, to insure that AV conduction is inhibited during
 the burst. After this, at 56, the BST timer is started, to time out the
 start of the burst. BST may be timed out relative to the just sensed VS,
 or relative to the T wave, as discussed above. After this, the flow goes
 to the Event Detection routine, shown at 57. The next event can be time
 out of the BST timer; a VS; or an AS. The T wave may also be detected
 here, for use in setting the BST timer. If there is BST time out, the flow
 goes to routine 58, and controls generation and delivery of the burst from
 burst gen 26. After this, the next event is awaited at 57. When a VS
 occurs, it is interpreted at 62. Operations such as distinguishing
 ventricular extra systoles can be done here. The VV interval is saved. If
 the event detected at 57 is an atrial sense, it is interpreted at 59. The
 AA interval is saved, and it is determined whether AF has terminated. If
 there is no longer AF, the main flow is exited.
 After VS interpretation at 62, the flow goes to a diagnostics block shown
 at 64. The diagnostics that are particularly important for this invention
 are those that indicate the efficacy of the therapy. For example,
 ventricular stability from beat to beat is important. The number of
 conducted ventricular senses (Vses) during the inhibition phase (i.e.,
 conducted atrial signals during and despite the burst) is stored,
 preferably as a function of the burst output characteristics in histogram
 form. Also, test results when tuning and adjusting the burst can be
 stored. This data can be downloaded to a programmer for analysis by the
 physician, who then can re-program the burst control accordingly. Finally,
 at 65, various miscellaneous operations are performed, and the flow
 returns to block 54.
 Referring now to FIG. 5, there is shown a flow diagram for the tune burst
 duration routine 54. At 70, the VV_int is compared to BST+AV_int. If it is
 less, this means that an AF signal got started through the AV node before
 the burst was initiated at BST, such that BST needs to be shortened. At 71
 it is determined whether BST is greater than the programmed minimum BST
 value. If no, this means that it is already at the minimum value, and the
 routine exits. If yes, at 72 BST is moved to the left (as seen in FIG. 3),
 or shortened, by a programmable decrement. Returning to block 70, if the
 answer is no, the routine goes to 75, and determines whether BST is less
 than the programmable maximum value. If no, meaning that it is already at
 the maximum, the routine exits; if yes, then at 76 BST is moved to the
 right (extended), i.e., BST drifts to minimize energy expenditure.
 Referring now to FIG. 6A, there is shown a routine for determining when an
 inhibition threshold test should be undertaken, and for placing the
 pacemaker into a test phase. The object is to monitor the efficacy of the
 inhibition bursts, and if too many VS events are found, adjust the burst
 output level required to inhibit conduction through the AV node during the
 burst delivery. At 80, it is determined whether the latest VV_int was less
 than the value of BET+AV_int. If yes, this indicates that an atrial signal
 slipped through the AV node during the last burst. In this case, the
 routine goes to 81 and increments a YES counter, tallying the number of
 such failures to inhibit. If no, then the NO buffer is incremented, as
 shown at 82. At 84, the buffer is evaluated, e.g., the percentage of YES
 events is determined. At 85, the test status is determined, i.e., whether
 the test_phase flag is set FALSE. If no, the routine branches directly to
 the test phase, which is illustrated in FIG. 6B. However, if the test
 phase flag is FALSE, the routine goes to block 86 and determines whether
 the percentage of YES events is greater than a predetermined percentage T.
 If no, the routine exits. But if Yes, then the conclusion is that too many
 early VSs are occurring, i.e., the inhibition rate is unacceptably low,
 and threshold should be tested and the burst parameters reset. The object
 of the test is to tune the burst output so as to achieve a reliably high
 inhibition efficacy rate, without raising output too greatly, which would
 result in wasted energy and possibly raising the pulse level above the AV
 node excitation threshold.
 The pacemaker prepares for the test by setting certain flags, as seen at
 91; the purpose of these flags is discussed in connection with FIG. 6B. At
 92, the burst pulse amplitude is set to its lowest available level, and
 the burst pulse frequency to the highest value. A VS_test_counter is set
 to zero at 93, to enable counting of VS events. The pacemaker then goes to
 the test phase, illustrated in FIG. 6B.
 At 94, the VS_test counter is compared with predetermined criteria, to see
 if enough VS events have taken place to test the burst parameters. If not,
 the routine goes to block 95 and increments the counter. When the count
 reaches the predetermined number, the counter is reset to zero at 96. At
 97, it is determined whether the amplitude flag is set to TRUE. If yes,
 this means that the test is to proceed with adjustment of burst pulse
 amplitude. The routine goes to 98 where it checks to see if there is a
 reference percentage to compare to (save 2% means save percentage for the
 second test cycle). If yes, the routine branches to block 103; but if no,
 the routine goes to block 99 and determines whether the current % Yes is
 greater than the previously calculated %. If no, this means that amplitude
 is still below excitation threshold, and the pacemaker can try to raise
 it. At 103, the burst frequency and burst amplitude are saved, and then at
 104 the burst amplitude is raised one step. At 106 the save 2% flag is set
 FALSE (meaning that there is no reference set), and at 107 the value of
 previous % is set equal to % Yes. At 108 the burst amplitude is compared
 to a programmed maximum value. If the amplitude has been raised to this
 max value, this means that maximum allowable amplitude has been reached
 without finding inhibition threshold, in which case the therapy must be
 stopped. The Error flag is set TRUE, and the routine exits. But, assuming
 that max amplitude has not been reached, the routine exits.
 At the next pacemaker cycle, the pacemaker enters the routine of FIG. 6A at
 80, and updates the % yes at 81. Since test phase is now TRUE, the
 pacemaker proceeds to the test phase of FIG. 6B, and runs another loop to
 determine if the increase in amplitude has raised % Yes greater than the
 previous % Yes (at 99). When the answer becomes yes, this means that
 amplitude has been raised too high; the bursts have an energy level above
 the AV node threshold, and are conducted through to the ventricle. The
 routine branches to block 100, and restores the previous burst frequency
 and burst amplitude (which had been saved at 103, before amplitude was
 increased one step). Then, at 101 the burst frequency is decreased one
 step, to start the test of looking to see how much the burst energy can be
 reduced without making the burst energy too low to achieve inhibition. At
 102, the Amplitude flag is set false, and the routine exits.
 During the next cycles, the required number of VS events are collected,
 until the VS_test counter reaches the required number at 94. The test
 branches at 97, and goes to the right as seen in the flow, to test for the
 desired frequency. At 112, the % Yes is compared to previous % Yes.
 Assuming it is not greater, at 115 the values of burst frequency and
 amplitude are saved, and at 116 frequency is decreased by one step. At
 117, the value of prev % Yes is set equal to the current % Yes. At 118,
 the burst frequency is checked to see if it has been reduced to the
 minimum value. If yes, the frequency can not be lowered any more, so the
 test phase flag is set FALSE, and the routine exits. But if frequency
 remains above the programmed minimum value, the routine exits directly,
 and runs the test again at the decreased frequency. When the % Yes becomes
 greater than prev % Yes at 112, the routine branches to 114 and restores
 the burst parameters that had been previously saved at 115. Test phase or
 status is set FALSE at 120, and the test is over.
 Referring now to FIG. 6C, there is shown a state transition diagram which
 further illustrates the inventive feature of determining inhibition
 threshold. The disclosure of FIG. 6C augments that of FIGS. 6A and 6B. As
 seen, after monitoring of VS, the percentage of early VS events is
 determined at 126. If there are too many such VS events, the burst
 amplitude is tested at 127. When a valid higher percentage is determined
 at 128, the pacemaker then goes into a state of testing frequency, at 129.
 When the frequency test produces an increased percentage, the settings are
 restored, and the test is concluded.
 There is thus disclosed a system and method for intermittently inhibiting
 the AV node by stimulating it with subthreshold bursts of pulses. The
 system monitors to determine whether the inhibition efficacy rate has
 decreased to an unacceptable level, and when this is found to be the case,
 an inhibition threshold test is carried out to readjust the pulse
 parameters so as to restore reliable inhibition. As seen, the pulses of
 the bursts can be adjusted in terms of both energy level and frequency.
 Although the invention has been illustrated by showing amplitude
 adjustment, it is to be understood that pulse width can also be adjusted.
 Further, while bursts of pulses are the preferred way of providing the
 inhibiting stimulation, other waveforms can be used in an equal manner.
 Thus, the term "burst" as used in claiming the invention embraces other
 waveforms than that used in illustrating the preferred embodiment, e.g.,
 continuous and aperiodic waveforms.