Cardiac resynchronization via left ventricular pacing

The invention is directed to techniques for providing cardiac resynchronization therapy by synchronizing delivery of pacing pulses to the left ventricle with intrinsic right ventricular depolarizations. An implantable medical device measures an interval between an atrial depolarization and an intrinsic ventricular depolarization is measured. In various embodiments, the intrinsic ventricular depolarization may be an intrinsic right or left ventricular depolarization. The implantable medical device delivers pacing pulses to the left ventricle to test a plurality of pacing intervals. The pacing intervals tested may be within a range around the measured interval between the atrial depolarization and the intrinsic ventricular depolarization. One of the pacing intervals is selected based on a measured characteristic of an electrogram that indicates ventricular synchrony. For example, the pacing interval may be selected based on measured QRS complex widths and/or Q-T intervals. The implantable medical device paces the left ventricle based on the selected pacing interval.

FIELD OF THE INVENTION

The invention relates to medical devices and, more particularly, to implantable medical devices used for cardiac pacing.

BACKGROUND OF THE INVENTION

Many patients that suffer from congestive heart failure (CHF) develop a wide QRS complex resulting from a delayed activation of one of the ventricles in the heart, and inter- and/or intraventricular electrical-mechanical dysynchrony. This ventricular “dysynchrony” may be caused by dilation of the heart, which disrupts the conductive pathways and interferes with depolarization sequences. Ventricular dysynchrony may worsen heart failure symptoms.

In a classic case of ventricular dysynchrony, the right ventricle of the heart activates first, and the left ventricle activates at a later time. Delayed activation of the left ventricle may be caused by a particular disruption of the conductive pathways of the heart, referred to as a left bundle branch block (LBBB). A patient who has LBBB often experiences a reduction in cardiac output because of dysynchronous ventricular contraction. Moreover, in the case of LBBB, different regions within the left ventricle may not contract together in a coordinated fashion, further reducing cardiac output.

Patients having a wide QRS complex or having inter- and/or intraventricular electrical-mechanical dysynchrony often are treated with an implanted medical device, such as a pacemaker, that paces both ventricles. The implanted medical device senses or paces atrial contractions, waits a predetermined time (or atrioventricular (AV) delay) after each sensed or paced atrial contraction, and then paces both ventricles. The ventricles may be paced simultaneously, or one ventricle may be paced before another. This biventricular pacing is often referred to as cardiac resynchronization.

BRIEF SUMMARY OF THE INVENTION

The invention is directed to techniques for cardiac resynchronization. In particular, the invention is directed to techniques for synchronizing delivery of pacing pulses to the left ventricle with intrinsic right ventricular depolarizations. One exemplary situation in which the invention may be applied is the provision of cardiac resynchronization therapy to patients with left bundle branch block (LBBB) who have adequate atrial-right ventricular conduction. Implantable medical devices employing these techniques may provide a more physiological interval between atrial and ventricular contractions, in the sense that the interval between the atrial and ventricular contractions is a function of an intrinsic, rather than paced, depolarization of the right ventricle. Further, implantable medical device employing this technique may consume less power than conventional devices that provide cardiac resynchronization therapy by delivering pacing pulses to both the right and left ventricles.

In order to determine the proper timing for delivery of pacing pulses to the left ventricle, an implantable medical device according to the invention measures an interval between an intrinsic or paced atrial depolarization and an intrinsic ventricular depolarization. The intrinsic ventricular depolarization may be an intrinsic right or left ventricular depolarization. The implantable medical device delivers pacing pulses to the left ventricle to test a plurality of pacing intervals determined based on the measured interval. A pacing interval is the interval between an atrial depolarization and delivery of a pacing pulse to the left ventricle. The pacing intervals tested may be within a range around the measured interval.

One of the pacing intervals is selected based on a measured characteristic of an electrogram that indicates ventricular synchrony. For example, the pacing interval may be selected based on measured QRS complex widths and/or Q-T intervals. The pacing interval selected may be the tested pacing interval that provides the shortest QRS complex width or the longest Q-T interval. In some embodiments, the selected pacing interval may be an average of the interval that provides the shortest QRS complex width and the pacing interval that provides the longest Q-T interval.

The implantable medical device paces the left ventricle based on the selected pacing interval. The implantable medical device may determine a difference between the selected pacing interval and the measured interval between the atrial depolarization and the intrinsic ventricular depolarization, and pace the left ventricle based on the difference. For example, the intrinsic ventricular depolarization may be a right ventricular depolarization, and where the pacing interval is equal to the measured interval, i.e., the left ventricular pace should be delivered at the same time as the intrinsic right ventricular depolarization, the implantable medical device may pace the left ventricle upon detection of subsequent intrinsic right ventricular contractions.

Where the pacing interval is greater than the measured interval, i.e., the left ventricular pace should be delivered after the intrinsic right ventricular depolarization, the implantable medical device may pace the left ventricle based on a determined difference between pacing interval and the measured interval. In particular, the implantable medical device paces the left ventricle upon expiration of an interval that is initiated upon detection of subsequent intrinsic right ventricular depolarizations. The interval is equal to the determined difference between the selected pacing interval and the measured interval. Pacing the left ventricle based on the determined difference may allow an implantable medical device to maintain ventricular synchrony despite beat-to-beat changes in the interval between atrial depolarizations and intrinsic right ventricular depolarizations due to changes in patient activity level, medication, or the like.

Where the pacing interval is less than the measured interval, i.e., the left ventricular pace should be delivered before the intrinsic right ventricular depolarization, the implantable medical device may, in order to maintain ventricular synchrony despite beat-to-beat changes in the interval between atrial depolarizations and intrinsic right ventricular depolarizations, periodically determine a current interval between an atrial depolarization and an intrinsic right ventricular depolarization. The implantable medical device may then determine a current pacing interval based on the current measured interval. The current pacing interval may be the difference between the current measured interval and the previously determined difference between the previously determined pacing interval and the previous measured interval. The implantable medical device paces the left ventricle upon expiration of the current pacing interval, which is initiated upon detection of subsequent paced or sensed atrial depolarizations.

In some embodiments, an implantable medical device according to the invention may include electrodes capable of sensing electrical activity within and delivering pacing pulses to an atrium, a right ventricle, and a left ventricle of a heart. In some embodiments, an implantable medical device may not include or may not use electrodes in the right ventricle. In such embodiments, the implantable medical device may detect an interval between an atrial depolarization and an intrinsic left ventricular depolarization, test pacing intervals around the measured interval, and select a pacing interval based on QRS complex widths and/or Q-T intervals. In such embodiments, the implantable medical device may determine a difference between the measured interval and the selected pacing interval, periodically measure a current interval between an atrial depolarization and an intrinsic left ventricular depolarization, determine a current pacing interval based on the current measure interval and the difference, and pace according to the current pacing interval.

In one embodiment, the invention provides an implantable medical device to provide cardiac resynchronization therapy. The implantable medical device includes electrodes to detect electrical signals within and deliver pacing pulses to a heart of a patient and a processor. The processor measures an interval between an atrial depolarization of the heart and an intrinsic ventricular depolarization of the heart based on the detected signals. The processor controls delivery of pacing pulses to a left ventricle of the heart via the electrodes at pacing intervals determined based on the interval between the atrial depolarization and the intrinsic ventricular depolarization. The processor selects one of the pacing intervals based on an electrogram signal representing signals detected by the electrodes. The processor may control delivery of pacing pulses to the left ventricle based on the selected one of the pacing intervals.

In another embodiment, the invention is directed to a method for providing cardiac resynchronization therapy in which an interval between an atrial depolarization and an intrinsic ventricular depolarization is measured. Pacing pulses are delivered to a left ventricle of a heart at pacing intervals determined based on the interval between the atrial depolarization and the intrinsic ventricular depolarization. One of the pacing intervals is selected based on an electrogram signal that represents signals within the heart. Pacing pulses may be delivered to the left ventricle based on the selected one of the pacing intervals.

In still another embodiment, the invention provides a computer-readable medium that comprises program instructions. The program instructions cause a programmable processor to measure an interval between an atrial depolarization and an intrinsic ventricular depolarization. The instructions also cause a processor to control delivery of pacing pulses to a left ventricle of a heart at pacing intervals determined based on the interval between the atrial depolarization and the intrinsic ventricular depolarization. The instructions further cause a processor to select one of the pacing intervals based on an electrogram representing signals within the heart. The instructions may cause the processor to control delivery of pacing pulses to the left ventricle based on the selected one of the pacing intervals.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1is a conceptual diagram illustrating an exemplary implantable medical device (IMD)10implanted in a patient12. IMD10may, as shown inFIG. 1, take the form of a multi-chamber cardiac pacemaker. In the exemplary embodiment illustrated inFIG. 1, IMD10is coupled to leads14A,14B and14C (collectively “leads14”) that extend into the heart16of patient12

More particularly, right ventricular (RV) lead14A may extend through one or more veins (not shown), the superior vena cava (not shown), and right atrium24, and into right ventricle18. Left ventricular (LV) coronary sinus lead14B may extend through the veins, the vena cava, right atrium24, and into the coronary sinus20to a point adjacent to the free wall of left ventricle22of heart16. Right atrial (RA) lead14C extends through the veins and vena cava, and into the right atrium24of heart16.

Each of leads14includes electrodes (not shown), which IMD10may use to sense electrical signals attendant to the depolarization and repolarization of heart16, and to provide pacing pulses to heart16. In some embodiments, IMD10may also provide cardioversion or defibrillation pulses via electrodes located on leads14. The electrodes located on leads14may be unipolar or bipolar, as is well known in the art.

IMD10delivers cardiac resynchronization therapy to patient12via leads14. In particular, as will be described in greater detail below, IMD10delivers pacing pulses to left ventricle22via lead14B to synchronize contractions of left ventricle22with contractions of right ventricle18resulting from intrinsic depolarizations of right ventricle18. One exemplary situation in which IMD10may be used is where patient12has left bundle branch block (LBBB), but has adequate physiological atrial-right ventricular conduction. By synchronizing contraction of ventricles18and22through pacing of left ventricle22alone, IMD10may provide a more physiological interval between atrial and ventricular contractions in the sense that the interval between the atrial and ventricular contractions is a function of an intrinsic, rather than paced, depolarization of the right ventricle. In addition, by pacing left ventricle22alone, IMD10may consume less power than conventional devices that provide cardiac resynchronization therapy by delivering pacing pulses to both the right ventricle18and left ventricle22.

IMD10determines the timing of delivery of pacing pulses to left ventricle22based on one or more measured characteristics of an electrogram signal detected via one or more of leads14that represents electrical activity within heart16. The measured characteristics indicate synchrony of contractions of ventricles18and22. For example, wider QRS complex width indicates less synchronous contraction of ventricles18and22. As another example, short Q-T intervals indicate increased sympathetic drive resulting from inadequate cardiac output, which in turn indicates dysynchrony of contraction of ventricles18and22. Therefore, IMD10may, for example, select the left ventricular pace timing that results in the smallest QRS complex width, the largest Q-T interval, or the best combination of QRS complex width and Q-T interval.

The configuration of IMD10and leads14illustrated inFIG. 1is merely exemplary. IMD10may be coupled to any number of leads14that extend to a variety of positions within or outside of heart16. For example, in some embodiments, IMD10may not be coupled to a right ventricular lead14A. Further, lead14C may extend to the left atrium of heart16.

Some of leads14may be epicardial leads. Some electrodes used by IMD10to sense electrical activity of heart16need not be carried by leads14at all, but may instead be integral with a housing of IMD10(not shown). Further, IMD10need not be implanted within patient12, but may instead be coupled with subcutaneous leads14that extend through the skin of patient12to a variety of positions within or outside of heart16.

FIG. 2is conceptual diagram further illustrating IMD10and heart16of patient12. Each of leads14may include an elongated insulative lead body carrying a number of concentric coiled conductors separated from one another by tubular insulative sheaths. Located adjacent distal end of leads14A,14B and14C are bipolar electrodes30and32,34and36, and38and40respectively. Electrodes30,34and38may take the form of ring electrodes, and electrodes32,36and40may take the form of extendable helix tip electrodes mounted retractably within insulative electrode heads42,44and46, respectively. Each of the electrodes30-40is coupled to one of the coiled conductors within the lead body of its associated lead14.

Sense/pace electrodes30,32,34,36,38and40sense electrical signals attendant to the depolarization and repolarization of heart16. The electrical signals are conducted to IMD10via leads14. Sense/pace electrodes30,32,34,36,38and40further may deliver pacing to cause depolarization of cardiac tissue in the vicinity thereof. IMD10may also include one or more indifferent housing electrodes, such as housing electrode48, formed integral with an outer surface of the hermetically sealed housing50of IMD10. Any of electrodes30,32,34,36,38and40may be used for unipolar sensing or pacing in combination with housing electrode48.

Leads14A,14B and14C may also, as shown inFIG. 2, include elongated coil electrodes52,54and56, respectively. IMD10may deliver defibrillation or cardioversion shocks to heart16via defibrillation electrodes52-56. Defibrillation electrodes52-56may be fabricated from platinum, platinum alloy or other materials known to be usable in implantable defibrillation electrodes, and may be about 5 cm in length.

FIG. 3is a functional block diagram of IMD10. As shown inFIG. 3, IMD10may take the form of a multi-chamber pacemaker-cardioverter-defibrillator (PCD) having a microprocessor-based architecture. However, this diagram should be taken as exemplary of the type of device in which various embodiments of the present invention may be embodied, and not as limiting, as it is believed that the invention may be practiced in a wide variety of device implementations, including devices that provide cardiac resynchronization pacing therapies but do not provide cardioverter and/or defibrillator functionality.

IMD10includes a microprocessor60. Microprocessor60may execute program instructions stored in a memory, e.g., a computer-readable medium, such as a ROM (not shown), EEPROM (not shown), and/or RAM62. Program instruction stored in a computer-readable medium and executed by microprocessor60control microprocessor60to perform the functions ascribed to microprocessor60herein. Microprocessor60may be coupled to, e.g., to communicate with and/or control, various other components of IMD10via an address/data bus64.

IMD10senses electrical activity within heart16. Electrodes30and32are coupled to amplifier66, which may take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured R-wave amplitude. A signal is generated on RV out line68whenever the signal sensed between electrodes30and32exceeds the present sensing threshold. Thus electrodes30and32and amplifier66may be used to detect intrinsic right ventricular depolarizations.

Electrodes34and36are coupled to amplifier70, which also may take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of measured R-wave amplitude. A signal is generated on LV out line72whenever the signal sensed between electrodes34and36exceeds the present sensing threshold. Thus, electrodes34and36and amplifier70may be used to detect intrinsic left ventricular depolarizations.

Electrodes38and40are coupled to amplifier74, which may take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured P-wave amplitude. A signal is generated on RA out line76whenever the signal between electrodes38and40exceeds the present sensing threshold. Thus, electrodes38and40and amplifier74may be used to detect intrinsic atrial depolarizations.

IMD10paces heart16. Pacer timing/control circuitry78preferably includes programmable digital counters which control the basic time intervals associated with modes of pacing. Circuitry78also preferably controls escape intervals associated with pacing. For example, IMD10may pace right atrium24via timing/control circuitry78triggering generation of pacing pulses by pacer output circuit84, which is coupled to electrodes38and40. Pacer timing/control circuitry78may trigger generation of pacing pulses for right atrium24upon expiration of an atrial escape interval.

As mentioned above, IMD10delivers pacing pulses to left ventricle22to synchronize contractions of left ventricle22with contractions of right ventricle18resulting from intrinsic depolarizations of right ventricle18. Pacer timing/control circuitry78triggers generation of pacing pulses for left ventricle22by pacer output circuit82, which is coupled to electrodes34and36. As will be described in greater detail below, circuitry78triggers generation of pacing pulses delivered to left ventricle22upon expiration of an interval that may be timed from detection of either an atrial or intrinsic right ventricular depolarization.

IMD10may also provide biventricular modes of cardiac resynchronization therapy, or non-resynchronization pacing modalities that require delivery of pacing pulses to right ventricle18, and may switch from a left ventricular cardiac resynchronization mode as described herein to one of these additional modes. Pacer timing/control circuitry78triggers generation of pacing pulses for right ventricle18by pacer output circuit80, which is coupled to electrodes30and32. Pacer timing/control circuitry78may trigger generation of pacing pulses for right ventricle18upon expiration of an A-V or V-V escape interval, depending on the pacing mode.

Output circuits80,82and84may be pulse generation circuits known in the art, which include capacitors and switches for the storage and delivery of energy as a pulse. Pacer timing/control circuitry78resets escape interval counters upon detection of R-waves or P-waves, or generation of pacing pulses, and thereby controls the basic timing of cardiac pacing functions. Intervals defined by pacing circuitry78may also include refractory periods during which sensed R-waves and P-waves are ineffective to restart timing of escape intervals, and the pulse widths of the pacing pulses. The durations of these intervals are determined by microprocessor60in response to data stored in RAM62, and are communicated to circuitry78via address/data bus64. Pacer timing/control circuitry78also determines the amplitude of the cardiac pacing pulses under control of microprocessor60.

Microprocessor60may operate as an interrupt driven device, and is responsive to interrupts from pacer timing/control circuitry78corresponding to the occurrence of sensed P-waves and R-waves and corresponding to the generation of cardiac pacing pulses. Those interrupts are provided via data/address bus66. Any necessary mathematical calculations to be performed by microprocessor60and any updating of the values or intervals controlled by pacer timing/control circuitry78take place following such interrupts.

Microprocessor60determines the timing of delivery of pacing pulses to left ventricle22, i.e., the intervals used to pacer timing/control circuit78to trigger generation of pacing pulses by output circuit82, based on one or more measured characteristics, e.g., QRS complex width or Q-T interval, of one or more electrogram signals that represent electrical activity within heart16. IMD10receives signals that represent electrical activity within heart16, and may digitally process the signals to measure characteristics of the signals. Switch matrix92is used to select which of the available electrodes30-40and48are coupled to wide band (0.5-200 Hz) amplifier94for use in digital signal analysis. As will be described in greater detail below, any of a number of potential combinations of these electrodes may be used, so long as the signal provided by the combination allows for identification and measurement of the desired characteristic. Selection of electrodes is controlled by microprocessor60via data/address bus66, and the selections may be varied as desired.

The analog signals derived from the selected electrodes and amplified by amplifier94are provided to multiplexer96, and thereafter converted to a multi-bit digital signal by A/D converter98. A digital signal processor (DSP)100may process the multi-bit digital signals to measure QRS complex widths and/or Q-T intervals, as will be described in greater detail below. In some embodiments, the digital signal may be stored in RAM62under control of direct memory access circuit102for later analysis by DSP100.

Although IMD10is described herein as having separate processors, microprocessor60may perform both the functions ascribed to it herein and digital signal analysis functions ascribed to DSP100herein. Moreover, although described herein in the context of microprocessor based PCD embodiment IMD10, the invention may be embodied in various implantable medical devices that include one or more processors, which may be microprocessors, DSPs, FPGAs, or other digital logic circuits. Further, in some embodiments, IMD10may not include or utilize DSP100to measure QRS complex widths and Q-T intervals. For example, IMD10may include analog slope or threshold detecting amplifier circuits to identify the beginning and end points of QRS complexes or Q-waves and T-waves, as is known in the art. In such embodiments of IMD10, pacer timing/control circuit78may receive the output of these amplifier circuits, and provide an indication of the occurrence of these events to microprocessor60so that microprocessor may measure QRS complex widths and/or Q-T intervals.

IMD10may detect ventricular and/or atrial tachycardias or fibrillations of heart16using tachycardia and fibrillation detection techniques and algorithms known in the art. For example, the presence of a ventricular or atrial tachycardia or fibrillation may be confirmed by detecting a sustained series of short R-R or P-P intervals of an average rate indicative of tachycardia, or an unbroken series of short R-R or P-P intervals. IMD10is also capable of delivering one or more anti-tachycardia pacing (ATP) therapies to heart16, and cardioversion and/or defibrillation pulses to heart16via one or more of electrodes48,52,54and56.

Electrodes48,52,54and56, are coupled to a cardioversion/defibrillation circuit90, which delivers cardioversion and defibrillation pulses under the control of microprocessor60. Circuit90may include energy storage circuits such as capacitors, switches for coupling the storage circuits to electrodes48,52,54and56, and logic for controlling the coupling of the storage circuits to the electrodes to create pulses with desired polarities and shapes. Microprocessor60may employ an escape interval counter to control timing of such cardioversion and defibrillation pulses, as well as associated refractory periods.

FIG. 4is a timing diagram illustrating example electrogram (EGM) signals that represent electrical activity within heart16. Signal110is a right atrial EGM. IMD10may digitally process atrial EGM110to measure a width116of QRS complex118. Signal110may be detected using electrodes38and40of RA lead14C in a bipolar configuration, or one of electrodes38and40and housing electrode48in a unipolar configuration.

In general, it is preferred that IMD10digitally process signals that include far-field QRS complexes118, such as right atrial EGM110, to measure widths116. Processing these signals is preferred because such signals include QRS complexes that are more “global” in that they reflect depolarization of both ventricles18,22, and thus the widths116of far-field QRS complexes118more accurately reflect ventricular synchrony. In addition to atrial EGM signal110, IMD10may detect signals that include far-field QRS complexes using two or more housing electrodes48. Detecting cardiac signals via housing electrodes48may enable embodiments of IMD10that do not include an atrial lead.

In order to measure QRS complex width116, DSP100first identifies far-field QRS complex118within signal110. DSP100may identify QRS complex118within signal110by any methods known in the art. For example, DSP100may receive indications of the occurrence of an R-wave120or122from pacer timing/control circuit78, and identify QRS complex118based on these indications. As another example, DSP100may identify QRS complex118by detecting a number of threshold-crossings of the digital signal provided by A/D converter98, or zero-crossings of the first derivative of the digital signal occurring within a time window. As yet another example, DSP100may detect QRS complexes within signals110-114using techniques described in commonly assigned U.S. Pat. No. 6,029,087, to Wohlgemuth, and titled “Cardiac Pacing System With Improved Physiological Event Classification Based on DSP” (“Wohlgemuth '087 Patent”).

DSP100may measure width116as a period of time from a beginning point124to an ending point126. DSP100may identify beginning point124and ending point126as threshold-crossings of the digital signal or zero-crossings of the first derivative of the digital signal.

Signals112and114are right and left ventricular EGMs, respectively, and may be detected via RV lead14C and LV coronary sinus lead14B, respectively. Signals112and114may be detected using bipolar electrode pairs30,32and34,36, or one electrode from each pair and housing electrode48in a unipolar configuration.

IMD10may digitally process signal114to measure a Q-T interval128. For example, DSP100may receive an indication of delivery of a pacing pulse130from pacer timing/control circuitry78, and measure Q-T interval128as the period of time from pacing pulse130to detection of T-wave132within the digital signal provided by A/D converter98. T-wave132may, for example, be detected using techniques described in the above-referenced Wohlgemuth '087 Patent.

For ease of illustration, only a portion of each of EGM signals110-114representing a single cardiac cycle of heart16is shown inFIG. 4. However, it is understood that DSP100measures multiple QRS complex widths and/or Q-T intervals over multiple cardiac cycles. As will be described in greater detail below, DSP100measures these values in response to delivery of pacing pulses130to left ventricle22. The values for QRS complex widths116and/or Q-T intervals128measured by DSP100may be stored in RAM62for later analysis by microprocessor60. Microprocessor60analyzes the measured values to, for example, identify the smallest QRS complex width116or the largest Q-T interval128.

In various embodiments of IMD10, microprocessor60may measure intervals134between intrinsic and/or paced atrial depolarizations, e.g., P-waves136, and intrinsic right ventricular depolarizations, e.g., R-waves120. In other embodiments of IMD10, microprocessor60may measure intervals138between P-waves136and intrinsic left ventricular depolarizations, e.g., R-waves122. In either case, microprocessor60controls pacer timing/control circuitry78to test delivery of pacing pulses130at a variety of pacing intervals140timed from P-wave136. Microprocessor60may control circuit to test pacing intervals140within a range around either interval134or interval138, depending on the embodiment of IMD10.

DSP100measures one or both of a QRS complex width116and Q-T interval128for each pacing interval140tested. Microprocessor60selects the tested pacing interval140that microprocessor60determines provides the best synchronization between contractions of right and left ventricles18and22, e.g., the pacing interval140that resulted in the shortest QRS complex width116, the longest Q-T interval128, or the average of the pacing intervals140that resulted in the shortest QRS complex width116and the longest Q-T interval128, respectively. Microprocessor60then controls delivery of pacing pulses to left ventricle22based on the selected pacing interval140, as will be described in greater detail below.

FIG. 5is a flow diagram illustrating an example method that IMD10may employ to deliver cardiac resynchronization therapy according to the invention. In general, IMD10, and more particularly microprocessor60of IMD10, determines a timing of left ventricular pacing that synchronizes the paced contractions of left ventricle22with contractions of right ventricle18resulting from intrinsic depolarizations of right ventricle18(150). Processor60determines the timing of left ventricular pacing based on measured characteristics of electrogram signals, e.g., QRS complex widths16and/or Q-T intervals28. Processor60controls pacing of left ventricle22based on the determined timing (52). Processor60periodically retests the timing of left ventricular pacing, e.g., hourly, daily, or monthly, to account for longer-term changes in the condition of patient12.

FIGS. 6-9further illustrate the method ofFIG. 5according to various embodiments of the invention. In particular,FIGS. 6 and 8illustrate methods that may be employed by IMD10to determine the timing of left ventricular pacing for synchronization with intrinsic right ventricular depolarizations.FIG. 6illustrates a method that may be employed by IMD10to determine the timing based on a measured interval between an atrial depolarization and an intrinsic right ventricular depolarization, e.g., interval134(FIG. 4).FIG. 8illustrates a method that may be employed by IMD10to determine the timing based on a measured interval between an atrial depolarization and an intrinsic left ventricular depolarization, e.g., interval138(FIG. 4).

The method illustrated inFIG. 6may be applied in situations where IMD10is coupled to a right ventricular lead14A that includes electrodes for sensing electrical activity in right ventricle18, such as bipolar electrodes30and32. The method illustrated inFIG. 8may be applied whether or not IMD10is coupled to right ventricular lead14A, requiring only that IMD10be coupled to left ventricular lead14B for pacing and sensing left ventricle22, e.g., via electrodes34and36.FIGS. 7 and 9illustrate methods for pacing left ventricle22based on the timing as determined according to the methods illustrated inFIGS. 6 and 8, respectively.

As shown inFIG. 6, IMD10measures an interval134between an intrinsic or pace atrial depolarization, e.g., P-wave136, and an intrinsic right ventricular contraction, e.g. R-wave120, as described above (160). In some embodiments, IMD10may measure a plurality of such A-RV intervals134and determine an average of the measured A-RV intervals. IMD10then delivers pacing pulses to left ventricle22at a variety of pacing intervals140measured from an intrinsic or paced P-wave136(162). IMD10may test pacing intervals140within a range around the determined A-RV interval134.

IMD10then identifies the pacing interval140that provides synchronization of left ventricular pacing with intrinsic right ventricular contractions, as described above (164). As described above, IMD10may measure QRS complex widths116and/or Q-T intervals128corresponding to each pacing interval140. IMD10selects one of the tested pacing intervals140based on the measured values. For example, IMD10may select the tested pacing interval140which results in the smallest QRS complex width116or longest Q-T interval128. Where IMD10measures both, IMD10may select a pacing interval140by averaging the pacing intervals that resulted in the smallest QRS complex width116or longest Q-T interval128, respectively.

IMD10calculates and stores the difference between the selected pacing interval140and the measured A-RV interval134(166) for use in pacing left ventricle22, as will be described in greater detail with reference toFIG. 7. In some embodiments, A-RV intervals134may be measured and pacing intervals140may be tested individually for paced and intrinsic P-waves136. In such embodiments, IMD10may calculate and store differences determined using each of paced and intrinsic P-waves134, and apply the respective differences to pace left ventricle22depending on whether a paced or intrinsic P-wave134has been detected.

FIG. 7illustrates a method that may be employed by IMD10to pace left ventricle22based on a calculated difference between the selected pacing interval140and the measured A-RV interval134. If the difference is equal to zero (170), IMD10delivers pacing pulses to left ventricle22upon detection of intrinsic ventricular depolarizations, e.g., R-waves120(172,174). If the difference is greater than zero (170), i.e., if the selected pacing interval140is greater than the measured A-RV interval134, IMD10delivers pacing pulses to left ventricle22upon expiration of a counter initiated upon detection of intrinsic ventricular depolarizations, e.g., R-waves120(178,180). The counter is set to measure an amount of time equal to the determined difference between the selected pacing interval140and the measured A-RV interval134. Calculating the difference between the selected pacing interval140and the measured A-RV interval134, and pacing left ventricle22based on the difference, as opposed to the selected pacing interval140, allows IMD10to maintain ventricular synchrony despite beat-to-beat variation in the A-RV interval.

If the difference is less than zero (170), i.e., if pacing pulses must be delivered to left ventricle22prior to intrinsic ventricular depolarizations to provide ventricular synchrony, IMD10periodically determines a current A-RV interval134(184,192), and determines a current pacing interval140as the sum of the current A-RV interval and the difference (186,192). IMD10may determine current A-RV intervals and current pacing intervals every10,20,32or100cardiac cycles, for example.

IMD10delivers pacing pulses to left ventricle22the current pacing interval140after detection of a paced or intrinsic P-wave136(188,190). Periodically determining current A-RV intervals and current pacing intervals allows IMD10to maintain ventricular synchrony despite beat-to-beat variation in the A-RV interval and despite the necessity of delivering pacing pulses to left ventricle22prior to intrinsic right ventricular depolarizations. As mentioned above, IMD10may periodically, e.g. hourly, weekly, or monthly, perform the method illustrated inFIG. 6to recalculate the difference. Periodically recalculating the difference may allow IMD10to address longer-term changes in the condition of patient12.

FIG. 8illustrates a method that may be employed by IMD10to determine the timing based on a measured interval138between a paced or intrinsic atrial depolarization, e.g. a P-wave136, and an intrinsic left ventricular depolarization, e.g., an intrinsic R-wave122(FIG. 4) (200). A single such A-LVSENSE interval138may be measured, or an average of several such A-LVSENSE intervals138may be determined.

IMD10then delivers pacing pulses to left ventricle22at a variety of pacing intervals140measured from an intrinsic or paced P-wave136(202). IMD10may test pacing intervals140within a range around the determined A-LVSENSE interval138. IMD10identifies the pacing interval140that provides synchronization of left ventricular pacing with intrinsic right ventricular contractions, e.g., based on measured QRS complex widths116and/or Q-T intervals128, as described above (204). IMD10calculates and stores a difference between the selected pacing interval140and the determined A-LVSENSE interval138(206). Separate intervals and differences may be determined for intrinsic and paced atrial depolarizations, as described above.

FIG. 9illustrates a method that may be employed by IMD10to pace left ventricle22based on a calculated difference between a selected pacing interval140and the determined A-LVSENSE interval138. IMD10periodically determines a current A-LVSENSE interval138(210,218), and determines a current pacing interval140as the sum of the current A-LVSENSE interval and the difference (212,218). IMD10may determine current A-RV intervals and current pacing intervals every 10, 20, 32 or 100 cardiac cycles, for example. IMD10delivers pacing pulses to left ventricle22upon expiration of a counter initiated upon detection of a paced or intrinsic P-wave136(214,216). The counter is set to measure an amount of time equal to the determined current pacing interval140.

A number of embodiments of the invention have been described. However, one skilled in the art will appreciate that the invention can be practiced with embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation, and the invention is limited only by the claims that follow.