Abstract:
A multisite heart pacing with adjustable number of pacing sites is realized by using only one lead directly connected to the heart. The number and locations of pacing sites is regulated by increasing the amplitude of pacing pulses delivered by the electric field, and by changing orientation of the electric field. 
     Improved termination of high frequency cardiac arrhythmias and AF is achieved by
       regulating the number of pacing sites by choosing the pulse energy in the range 1/400-½ DE, where DE is energy of conventional cardioversion/defibrillation.   protection against inducing VF by choosing the direction and amplitude of the electric field, and by a proper synchronization with R wave of the ECG.   selection of the pacing frequency and amplitude based on the frequency spectrum of a high frequency cardiac arrhythmia.

Description:
REFERENCES CITED 
     US Patent References 
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         U.S. Pat. No. 7,127,292 October 2006 Warman et al. Addressing recurrent atrial fibrillation (AF pacing) 
         U.S. Pat. No. 7,120,490 October 2006 Chen et al. Atrial shock timing optimization 
         U.S. Pat. No. 7,020,517 March 2006 Welner et al. Fibrillation/tachycardia preventive system 
         U.S. Pat. No. 7,006,867 February 2006 Kroll Overdrive pacing from multiple atrial sites 
         U.S. Pat. No. 7,142,928 November 2006 Sharma et al. Stimulation near a blade cut in the myocardium 
         U.S. Pat. No. 5,489,293 February 1996 Pless et al. Method and apparatus for treating cardiac tachycardia 
         U.S. Pat. No. 5,275,621 January 1994 Mehra Method and apparatus for Terminating tachycardia 
         U.S. Pat. No. 5,275,621 January 1994 Mehra Method and apparatus for Terminating tachycardia 
       
     
       Foreign Patent References 
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                 0 393 265 
                 October, 1990 
                 EP 
               
               
                 1 062 971 
                 December, 2000 
                 EP 
               
               
                 2 025 236 
                 January, 1980 
                 GB 
               
               
                   
               
             
          
         
       
     
       Other Publications 
       [0000]    
       
         Sepulveda, N G, Roth, B J, Wikswo, J P. Current injection into a two-dimensional anisotropic bidomain. Biophys J, 55(5), 987-99, 1989. 
         Allessie M, et al. Regional control of atrial fibrillation by rapid pacing in conscious dogs. Circulation. 1991; 84:1689-1697. 
         Daoud E G et al. Response of Type I Atrial Fibrillation to Atrial Pacing in Humans. Circulation. 1996; 94:1036-1040. 
         Disertori M, et al. Antitachycardia pacing therapies to terminate atrial tachyarrhythmias: the AT500 Italian Registry. European Heart Journal Supplements. 2001; 3:16-24. 
         A. Pumir, V. Krinsky, Unpinning of a rotating wave in cardiac muscle by an electric field. J. Theor. Biol, 199, 311-319, 1999. 
         S. Takagi, et al. Unpinning and removal of a rotating wave in cardiac muscle Phys. Rev. Let. 2004, 93 (5), 058101. 
       
     
       DESCRIPTION 
       [0016]    The numbers in claims and descriptions below are given not in a restrictive sense, but to illustrate the preferred embodiment of the invention. E.g., the same approach can be realized not with only one lead connected to the heart as we claim here, but more leads can give the same results as well. 
       FIELD OF THE INVENTION 
       [0017]    The present invention relates generally to a method for termination high frequency cardiac arrhythmias and, in particular, to a method for termination paroxysmal atrial fibrillation (AF) by multi site pacing where the number of pacing sites is regulated by changing amplitude and orientation of the electric field. 
       BACKGROUND OF THE INVENTION 
       [0018]    The only successful method to terminate high frequency cardiac arrhythmias is cardioversion/defibrillation. It has several important drawbacks. A discharge of a defibrillator in a conscious patient is painful and extremely unpleasant. It has also potential damaging effects. 
         [0019]    On the other hand, exists a much more gentle method—antitachycardia pacing (ATP). It is not painful, its energy is several orders of magnitude less than that of cardioversion/defibrillation. ATP is successful against low frequency arrhythmias only (frequency not larger than 4 Hz). Its success rate decreases fast with increasing frequency of the arrhythmia, and high frequency cardiac arrhythmias (frequencies larger 4 Hz) and atrial fibrillation (AF) cannot be terminated by ATP. 
         [0020]    Allessie (1991) has tried to entrain AF. He found it is possible only locally, in a small vicinity (several cm) of the pacing electrode; outside of it AF is not entrained. 
         [0021]    An evident solution is to pace AF from so many sites that they cover atria dense enough. But many implanted pacing leads and their connecting wires would severely damage a contracting heart. 
         [0022]    A method for terminating high frequency arrhythmias and AF is needed that uses an energy level much lower than that of conventional cardioversion/defibrillation and can terminate arrhythmias that ATP cannot terminate. It is desirable the energy level be below the pain threshold. 
       SUMMARY OF THE INVENTION 
       [0023]    The present invention satisfies a need for a technique that permits to terminate high frequency arrhythmias and, in particular, AF with a pulse energy much smaller than that of cardioversion/defibrillation. 
         [0024]    We suggest to use heterogeneities naturally existing in the heart as pacing sites. Pacing from heterogeneities naturally existing in the heart has advantages over conventional pacing
       1. a multisite pacing can be achieved without connecting many electrodes to the heart.   2. the number and position of pacing sites can be regulated by changing the amplitude and the direction of the electric field.   3. energy of the electric field pulse needed for this is 2-400 times smaller than that used in cardioversion/defibrillation.       
 
         [0028]    We propose a method and apparatus for terminating high frequency arrhythmias—anti fibrillation pacing (AFP). An implanted device for AFP and an external device for AFP are disclosed. 
         [0029]    In heart preparations, AFP terminates high frequency cardiac arrhythmias and AF with pulses of much smaller energy than the cardioversion/defibrillating pulse, and with much higher success rate than conventional ATP. 
         [0030]    This summary of the invention and the advantages and features thereof have been presented here simply to point out some of the ways that the invention overcomes difficulties presented in the prior art and to distinguish the invention from the prior art and is not intended to operate in any manner as a limitation on the interpretation of claims that are presented initially in the patent application and that are ultimately granted. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0031]      FIG. 1 : The larger size R′ of an obstacle, the larger is depolarization e′ max  induced near it by an electric field Dimensionless coordinates: Obstacle size R′=R/λ, where R is obstacle size in mm, λ˜0.5 mm is the electronic constant of the tissue. Depolarization e′ max =e/e max , where e is depolarization in mV, e max  is depolarization near a very large obstacle. An analytical solution of the linearized model (Pumir, Krinsky, 1999). 
           [0032]      FIG. 2 : Increasing the number of pacing sites by increasing the electric field (a-c). Modifying positions of pacing sites by changing direction of the electric field (d,e). 
           [0033]    (a-c)—electric field is increased. a) E=0.45 V/cm—pacing from 1 electrode. Short arrows indicate direction of the wave propagation. The pacing wave looks like a moon since it is initiated near a circular obstacle. Far from it, the pacing wave has a circular shape, as usual. b) E=0.47 V/cm—pacing from 2 electrodes. c) E=0.58 V/cm—pacing from 4 electrodes. 
           [0034]    (d,e)—direction of the electric field (long arrow) is changed. Amplitude of the electric field is the same E=0.5 V/cm. Numerical simulation of the LR model. 
           [0035]      FIG. 3 : Pacing from heterogeneities (virtual electrodes) removes rotating waves. t=0.04 s: R 1  and R 2 —rotating waves. t=0.18 s: P—a pacing wave emitted from a heterogeneity (a white circle) by a pulse of Electric field E=1.25 V/cm. t=0.92 s: the tip R 2  approaches the front of pacing wave and collides with it. 
           [0036]    t=0.96 s: the tip R 2  disappeared but a new wave break is formed on the front of R 1 . Thus, a jump of the wave break position and its orientation (arrows) was induced (compare arrows at t=0.92 s and t=0.96 s). t=1.24 s: Rotating wave R 2  is terminated. R 1  is in the position to be terminated by the same mechanism. t=1.38 s: Rotating waves are removed. Pacing waves emitted from the heterogeneity (a white circle at the upper right corner) entrain the whole medium. Numerical simulation of the LR model. 
           [0037]      FIG. 4 : Pacing from an ATP fixed lead does not remove rotating waves. t=0.04 s: same as in  FIG. 3 . t=0.28 s: P—pacing wave  1  emitted from a fixed electrode (right lower corner). Dashed line is a boundary of the region paced by this wave. t=0.42 s: pacing wave  2 : the size of the paced region is increased. t=0.54 s: pacing wave  3  decays. A fuzzy front is seen instead of a sharp front observed at propagating waves. t=1.32 s: size of the paced region is decreased (compared to t=0.42 s). t=2.36 s: Rotating waves are not removed. A small paced region (at the lower right corner) enlarges and shrinks quasi periodically. Numerical simulation of the LR model. All parameters are same as in  FIG. 3   
           [0038]      FIG. 5 : A diagram illustrating an embodiment of controlling high frequency cardiac arrhythmias by AFP external device.  3 —defibrillating electrode,  4 —diagnostic catheter,  6 —catheter with stimulating electrodes,  8 —paddle electrodes,  11 —ECG electrodes,  17 —switch. 
           [0039]      FIG. 6 : A flow chart illustrating AFP external device.  3 —defibrillating electrode,  4 —diagnostic catheter, 13, 14, 15—controls to set manually the period of the stimulating pulses, the number of pulses and the energy of each pulse,  17 , 18 —switches. 
           [0040]      FIG. 7 : A flow chart illustrating AFP implanted device.  3 —defibrillating electrode,  18 —switch,  25 —stimulating electrode,  26 —defibrillating electrode,  27 —sensing electrode. 
       
    
    
     PHYSICAL PRINCIPLES USED IN THE INVENTION 
       [0041]    The present invention satisfies the need for a technique that permits to use pacing for termination high frequency arrhythmias, in particular, AF. 
         [0042]    Numerous natural heterogeneities existing in the heart are used here as pacing sites. The size distribution of natural heterogeneities in the heart is wide: from microns to millimeters. This permits to control number of pacing sites from 1-2 to dozens. 
         [0043]    The physical mechanism is well known in cardiology: it is a change of membrane potential by an electric field near defects. This phenomenon was given name “Virtual electrodes” (Sepulveda at al, 1989). 
         [0044]    Virtual electrodes are believed to play an important role in defibrillation, exciting all tissue and thus terminating all propagating waves. Creating a large size virtual electrode by cutting the cardiac tissue with a blade was proposed in U.S. Pat. No. 7,142,928 in order to decrease almost twice the pacing threshold from a small fixed wire electrode. 
         [0045]    An electric field, applied to the heart creates depolarized and hyperpolarized regions near every heterogeneity, corresponding to redistributions of the intracellular and extracellular currents. If the induced depolarization is above the threshold, it can induce a propagating excitation wave. This mechanism was used in cardiology to explain how defibrillation works. We propose to use this effect for creating as many pacing sites as needed, from 1-2 to dozens. We verified in experiments with cardiac muscle preparations that 1-2 pacing sites were induced by a pulse of an electric field as low as 0.15-0.25 V/cm, 3-5 pacing sites—with 0.25-0.35 V/cm, dozens pacing sites—with 0.35-0.5 V/cm. To compare, electric field needed for defibrillation is huge, ˜6 V/cm. The electric field E needed to induce 3-5 pacing sites is ˜20 times less than that of defibrillation, needed to induce dozens pacing sites is more than 10 times less than that of defibrillation. Thus, in our proposed method, the pulse energy W(W˜E 2 ) may be hundreds times less than that of defibrillation. 
         [0046]    A more detailed description of the mechanism making our proposed method more powerful than ATP and requiring much less energy than defibrillation is below. 
         [0047]    The larger size of the obstacle, the larger is depolarization induced by an electric field near it ( FIG. 1 ). Pulses of electric field of small amplitude induce pacing only from the large size heterogeneities ( FIG. 2   a ). Increasing amplitude of the electric field induces pacing from smaller and smaller size heterogeneities ( FIG. 2   b, c ). For obstacles of generic shape (not circular), orientation of the electric field affects the position and the number of pacing sites ( FIG. 2   d,e ).  FIGS. 1 and 2  demonstrate that 
         [0048]    (i) increasing the intensity of the applied electric field with a fixed direction leads to wave emission from an increasingly large set of heterogeneities in the tissue. 
         [0049]    (ii) changing the direction of the applied electric field leads to wave emission from different sets of heterogeneities in the tissue. 
         [0050]    This permits to realize a multisite heart pacing with adjustable number of pacing sites. Increasing the number and changing location of pacing sites can be achieved by increasing the amplitude of pacing pulses delivered by the electric field, and by changing orientation of the electric field. 
         [0051]    A multisite heart pacing with adjustable number of pacing sites that we propose, results in an improved method for termination high frequency cardiac arrhythmias and AF. We call this method ‘anti fibrillation pacing’ (AFP). Let us compare our method with ATP. 
         [0052]    The conventional ATP is successful only against low frequency arrhythmias, and its success rate decreases fast with increasing frequency of the arrhythmia. The physical mechanism behind the ATP inability to terminate high frequency arrhythmias is:
       with low frequency pacing, all pacing waves propagate over the whole heart.   but with high frequency pacing, the propagation of the high frequency waves cannot be sustained.       
 
         [0055]    The high frequency waves decay with distance. Due to the Wenckebach rhythm transformation, generically every second wave decays (more rare, every third wave decays). Thus, only near the pacing electrode, the frequency of the propagating waves is the frequency of pacing; at a distance, the frequency of propagating waves becomes lower. The low frequency waves can capture only the low frequency arrhythmias, but not the high frequency arrhythmias. 
         [0056]    To terminate a high frequency pathological source of waves, the pacing electrode should be situated close to it. With conventional fixed pacing leads, this can be achieved by chance only. Pacing from cardiac heterogeneities permits to regulate the number and the position of pacing sites, and thus to avoid this problem. 
         [0057]    We illustrate numerically in  FIGS. 3 ,  4  how, for geometrical reasons, a conventional fixed pacing lead may fail to pace away a set of rotating waves, whereas virtual electrodes in the tissue permits to pace away a set of rotating waves. On  FIG. 3 , only one heterogeneity used for pacing is shown. 
       The AFP Device 
       [0058]    An embodiment for AFP external device is shown in  FIG. 5 . The device for controlling high frequency cardiac arrhythmias consists of the following main parts: Pulse generating block  12 . Arrhythmia Frequency spectrum analyzer  16 , Pulse Energy selector  21 , Pacing Frequency selector  22 . 
         [0059]    Pulse generating block  12  is tuned by controls  13 ,  14 ,  15  to set manually the period of the pulses, the number of pulses and the energy of a pulse. Pulse generating block  12  is connected to defibrillating electrodes  3 , to switch  18  and to memory  20 . The Pulse generating block  12  is different from the cardioverter/defibrillator and the ATP pacemaker: it is able to deliver pulses with time interval much shorter than usually needed to charge the defibrillators capacitor, and to pace from defibrillating electrodes, it should supply 1-2 orders of magnitude less pulse energy than a defibrillator. 
         [0060]    Defibrillating electrode: In a preferred embodiment of the invention, it is an intracardiac defibrillating electrode, a catheter. In second preferred embodiment, it may be an implanted intracardiac electrode. External defibrillating patches can be used as well, but not for the case where pulses below the pain threshold are needed. 
         [0061]    Pulse Energy selector  21  obtains data from ECG/EMG amplifier  10  and is connected to the memory  20 . Pacing Frequency selector  22  obtains data from ECG/EMG amplifier  10  and is connected to the memory  20 . All of them obtain data from Memory as well and send data to Monitor with recommendations to clinician the values to be set for the period of the pulses, the number of pulses and the energy of a pulse. 
         [0062]    More details are shown in  FIG. 6 . Arrhythmia Frequency spectrum analyzer  16  obtains data from ECG/EMG amplifier  10  and is connected to the memory  20 . Frequency Spectrum analyzer  16  is intended to 
         [0063]    a) help to choose the pacing frequency for pacing from virtual electrodes 
         [0064]    b) protect from delivering an electric field pulse near the T wave on the ECG. 
         [0065]    Function a) is needed since during AF, the EMG/ECG records are not periodic, and choice of the pacing interval even by a well trained medical personnel may be erroneous. In a stationary device, the analyzer supplies on line frequencies and amplitudes of 3 largest peaks in the Fourier spectrum of the arrhythmia, and the whole Fourier spectrum. 
         [0066]    Function b) is intended for an additional protection against induction of VF when AFP is applied in atria. Usually, synchronization of the cardioverter/defibrillator with the R wave is used. But since AFP delivers several electric field pulses, all of them cannot be synchronized with the R wave. Instead, the EMG/ECG automatic analyzer for AFP protects from delivering an electric field pulse near the T wave on the ECG. 
         [0067]    Flow chart of an implanted device is shown in  FIG. 7 . Pulse generating block  23  delivers pulses either from an implanted ATP electrode  25  or from defibrillation electrodes  3 . For pacing from an implanted electrode, it chooses standard pacing amplitude applied for ATP. 
         [0068]    For pacing from defibrillation electrodes, it permits to choose the energy of pulses from interval: 0.01 J-1 J for intracardiac defibrillating electrodes, the time interval between pulses 100 ms-250 ms, and the number of pulses 4-8 pulses. 
         [0069]    Pulse generating block  23  receives data from microprocessor  21  and operates a switch  18 . In an implanted device, Frequency Spectrum analyzer  16  contains several band pass filters to avoid overloading of a microprocessor with calculations of Furrier spectrum. Frequency Spectrum analyzer  16  obtains data from sensing electrode  27  and sends data to memory  20  and to the microprocessor  21 . Microprocessor  21  selects Pulse Energy and Pacing Frequency and sends these data to the Pulse generating block  23 . Microprocessor  21  operates also defibrillator  24 . 
       DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT OF THE INVENTION 
       [0070]    The preferred embodiment of the invention is: an external AFP device, used for clinical investigations. An arrhythmia with frequency higher than that permitting to use ATP is detected. The arrhythmia frequency is above the threshold for ATP not more than by 50%. 
         [0071]      FIG. 5  is a diagram illustrating an embodiment of controlling high frequency cardiac arrhythmias by anti-fibrillation pacing (AFP) external device. AFP External Device  1  is coupled to a patient&#39;s heart  2  with diagnostic catheter  4  and defibrillating electrode  3 , that may be either an implanted defibrillating electrode or a catheter. ATP external device  5  is connected to a patient&#39;s heart  2  via catheter  6  with monopolar or bipolar stimulating electrodes. Defibrillator  7  is connected to the patient chest  9  via paddle electrodes  8 . ECG amplifier  10  is connected via switch  17  to ECG electrodes  11 . Switch  17  disconnects ECG amplifier  10  from ECG electrodes  11  when AFP external device  1  delivers AFP pulses to the heart. 
         [0072]      FIG. 6  is a flow chart illustrating AFP external device. Pulse generating block  12  is connected to defibrillating electrode  3 . Controls  13 ,  14 ,  15  are connected to Pulse generating block  12 . They permit to set manually the period of the stimulating pulses (control  13 ), the number of pulses (control  14 ) and the energy of each pulse (control  15 ). Frequency spectrum analyzer  16  is connected to ECG amplifier  10  and diagnostic catheter via switch  18 . Switch  18  disconnects ECG/EMG amplifier  10  from diagnostic catheter  4  when Pulse generating block  12  delivers AFP pulses to the heart. 
         [0073]    Frequency spectrum analyzer  16  is connected to monitor  19  where it displays the Fourier spectrum of AF or other high frequency arrhythmia to help medical personnel to chose pacing frequency for ATP or AFP.Pulse generating block  12  and Frequency spectrum analyzer  16  are connected to memory  20 . 
         [0074]    AFP External Device  1  may be realized as a box containing all these elements, or it can use an external PC as ECG/EMG analyzer  16 , memory  20  and monitor  19 . 
         [0075]      FIG. 7  is a flow chart illustrating AFP implanted device. Pulse generating block  23  is connected to the heart via defibrillating electrode  3  when it delivers AFP pacing and via stimulating electrode  25  when it delivers ATP pacing. Defibrillator  24  is connected to heart via defibrillating electrode  26  which may be same as defibrillating electrode  3 . Frequency spectrum analyzer  16  is connected to heart via sensing electrode  27 . All is controlled by Microprocessor  21 . 
         [0076]    This summary of the invention and the advantages and features thereof have been presented here simply to point out some of the ways that the invention overcomes difficulties presented in the prior art and to distinguish the invention from the prior art and is not intended to operate in any manner as a limitation on the interpretation of claims that are presented initially in the patent application and that are ultimately granted. 
       CONCLUSION 
       [0077]    While particular embodiments of the invention have been disclosed herein in detail, this has been done for the purposes of illustration only, and is not intended to limit the scope of the invention as defined in the claims that follow. It is to be understood that various substitutions, alterations, or modifications can be made to the disclosed embodiment without departing from the spirit and scope of the claims. The above described implementations are simply those presently preferred or contemplated by the inventors, and are not to be taken as limiting the present invention to the disclosed embodiments. It is therefore to be understood, that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described without actually departing from the spirit and scope of the present invention.