In certain heart diseases, either congenital or acquired, natural pacing is replaced or assisted by artificial pacing induced by a pacemaker, which is generally implanted in the patient's chest. Pacemakers known in the art provide artificial excitatory pulses to the heart tissue to control the heart rhythm. Early pacemakers were asynchronous pulse generators that operated at a fixed invariant rate. Later, demand type pacemakers were developed, in which stimulation pulses are produced only when a naturally-occurring heartbeat is not detected within some maximum type period.
Cardiac pacemakers are required to deliver a stimulus pulse of sufficient magnitude and duration to cause an action potential to propagate from the point of excitation, leading to heart muscle contraction. Thus, the primary function of a pacemaker is to regulate heart rhythm rather than the contractility of the muscle. Furthermore, it is known in the art that the use of a pacemaker generally results in decreased contractility of the cardiac muscle and, consequently, a decreased cardiac output (CO) for a given heart rate.
The hemodynamic effect of different types of pacemakers has long been researched. For example, Wessale et al., in an article entitled “Stroke Volume and Three Phase Cardiac Output Rate Relationship with Ventricular Pacing,” Pacing Clin Electophysiol 13 (May, 1990), pp. 673-680, describe a three-phase relationship between pacing rate and cardiac output. At a low pacing rate CO increases with increasing rate. There is an intermediate range of rates in which CO stays steady, and above which a further rate increase will cause a decrease in CO. This, of course, causes a major problem for the patient, since a demand for a higher pacing rate typically stems from a demand for an increase in tissue oxygen supply. Research and clinical experience show that with various types of pacemakers, some cardiac output augmentation may take place initially, but is not maintained on a long-term basis and may even deteriorate compared to the situation before beginning pacing. (See, for example, Wirtzfeld et al., “Physiological Pacing: Present Status and Future Developments,” Pacing Clin Electrophysiol 10 (January, 1987), pp. 41-47.
Talit et al., in “The Effect of External Cardiac Pacing on Stroke Volume,” Pacing Clin Electophysiol 13 (May, 1990), pp. 598-602, evaluated the hemodynamic effects of external cardiac pacing on ten subjects and found a decrease of 23% in stroke volume and 14% decrease in cardiac output when compared to the values of these parameters that were obtained prior to pacing.
It is a principle of pacing that the optimal pacing mode is that which gives optimal hemodynamics, thus making the patient the most comfortable. This principle has guided researchers to attempt to regulate the mechanical performance of the heart by synchronization of the contraction of the heart chambers using sequential A/V or multisite pacing. Attempts have also been made to provide pacemakers with improved physiological sensing capabilities, for use in giving feedback to the pacemaker.
FIG. 1A is a schematic diagram illustrating elements of a pacemaker pulse generator 20 for pacing a heart 22, as is known in the art. Such pacemakers are described, for example, in Design of Cardiac Pacemakers, John G. Webster, ed. (IEEE Press, Piscataway, N.J., 1995), which is incorporated herein by reference. Pacemaker 20 comprises a battery 24 or other power source, which charges a tank capacitor 28 via a charge pump 26 (or voltage multiplier). To apply a pacing pulse to heart 22, a switch 30 is closed, transferring stored charge from capacitor 28 via a DC-blocking capacitor 34 to electrodes 36. Switch 30 is then opened, and a discharge switch 32 is preferably closed in order to remove charge buildup on capacitor 28.
FIG. 1B is a timing diagram illustrating a typical pacing signal 38 generated by pacemaker 20 across electrodes 36. Switch 30 is closed for a very short period, typically between 0.1 and 1.5 ms in order to produce a sharp, narrow, cathodic (negative voltage) pacing pulse 40 with a total discharge of 0.1-50 μC. The amplitude and duration of the pulse are programmable in order to adjust the stimulus that is applied to the heart. Typically, for safety and reliability of pacing, the amplitude of the pulse is set empirically to roughly twice the rheobase, which is the minimum electrical current that will cause the myocardial cell membranes to depolarize. The pacing pulse duration is set to up to twice the chronaxie time, which is the pulse duration that will cause depolarization at twice the rheobase current. A longer duration or higher amplitude has been considered undesirable, because it would tend to discharge battery 24 prematurely without any improvement in the pacemaker performance or in the physiological performance of the heart or the safety of the pacing. In fact, substantial research and product development efforts in the pacing field have been dedicated to finding pacing methods and waveforms that reduce the amount of energy that must be applied to the heart, in order to prolong battery and circuit lifetime.
After pacing switch 30 is opened, discharge switch 32 is closed, typically for about 20 ms, causing an anodic (positive voltage) discharge phase 42 to appear across electrodes 36. The specific duration and amplitude of this phase of the pacing waveform are not significant from the point of view of pacing, since it is intended only to remove residual charge and does not provide any stimulation to the heart.
A number of authors have suggested varying the shape and/or duration of the pacing pulse in order to obtain improved pacing effects or to reduce the pulse amplitude or charge flux needed to provide a desired level of stimulation. Among other techniques, biphasic pulses (including both cathodic and anodic portions) or bursts of pulses have been used for defibrillation and antitachycardic pacing.
For example, U.S. Pat. No. 5,531,764 to Adams et al. describes an implantable defibrillator having programmable shock waveforms of different shapes and magnitudes in different combinations and sequences.
Fain et al., in their work “Improved Internal Defibrillation Efficacy with a Biphasic Waveform,” in the American Heart Journal 117 (February, 1989), pp. 358-64, show that a biphasic truncated exponential shock waveform significantly reduces the initial voltage and energy requirements for effective defibrillation.
Fromer et al., in an article entitled “Ultrarapid Subthreshold Stimulation for Termination of Atrioventricular Node Reentrant Tachycardia,” in Journal of the American College of Cardiology 20 (October, 1992), pp. 879-83, describe the application of a train of stimuli to intracardiac electrodes in order to terminate tachycardic episodes without the need for cardioversion. The train ranged from 4 to 16 pulses, each 2 ms long. The pulse train was thus meant, under certain circumstances, to take the place of or precede more drastic defibrillative measures, and not to pace the heart.
Similarly, Hedberg, et al., in U.S. Pat. No. 5,622,687, describe an implantable defibrillator which applies a train of low-energy defibrillation pulses in order to defibrillate the heart with a lower total energy flux than would ordinarily be required using conventional defibrillation pulses. The train includes between 2 and 10 pulses, preferably about 10 ms apart. The width of the pulses is not specified. The pulses may be either monophasic or biphasic. In any case, the clinical and technical considerations in generating signals of the type employed by a defibrillator are entirely different from those involved in pacing the heart.
Kinsley, et al., in an article entitled “Prolongation and Shortening of Action Potentials by Electrical Shocks in Frog Ventricular Muscle,” in the American Journal of Physiology 6 (Heart Circ. Physiol. 35, 1994), pp. H2348-H2358, describe measurements of contraction length and intracellular action potential following application of shocks to heart tissue. By varying the strength of the shocks, the contraction strength of the tissue could be increased, and the action potentials lengthened or shortened. The authors propose that such techniques could be used in defibrillation, but make no suggestion with regard to pacing the heart.
U.S. Pat. No. 4,312,354, to Walters, describes a pacemaker with a circuit for pulse width modulation of the stimulus pulses applied to the heart. The purpose of the modulation is not to directly affect the pacing itself, but rather to afford a means for indicating to an external telemetry unit a control state of the pacemaker.
Thakor, et al., in an article entitled “Effect of Varying Pacing Waveform Shapes on Propagation and Hemodynamics in the Rabbit Heart,” in The American Journal of Cardiology 79 (Mar. 20, 1997), pp. 36-43, describe experiments using biphasic pacing pulses to increase the speed of electrical conduction in heart muscle fibers. Both monophasic and biphasic pulses of 2 to 8 ms total duration were applied to isolated muscle fibers using unipolar electrodes. The biphasic pulses consisted of a single cathodic pulse immediately followed by a single anodic pulse, or vice versa. The article reports that propagation of the resulting electrical potentials along the fibers was significantly faster for the biphasic stimulation. It was observed that pacing with an anodic/cathodic biphasic pulse resulted in faster electrical conduction, and led to an earlier development of pressure in the muscle fiber and a shorter duration of the pressure waveform than did monophasic pulses. The authors suggest that the biphasic pulse could be associated with the ability to augment muscular contraction.
PCT patent application PCT/IL97/00012, published as WO 97/25098, to Ben-Haim et al., which is incorporated herein by reference, describes methods for modifying the force of contraction of at least a portion of a heart chamber by applying a non-excitatory electric field to the heart at a delay after electrical activation of the portion. The non-excitatory field is such as does not induce activation potentials in cardiac muscle cells, but rather modifies the cells' response to the activation. The non-excitatory field may be applied in combination with a pacemaker or defibrillator, which applies an excitatory signal (i.e., pacing or defibrillation pulses) to the heart muscle.