FR2533817A1 - Internal ECG detector using angled dual electrode - Google Patents

Abstract

The traces obtained from inside the chambers of the heart by this method have such clearly defined P, QRS, and T waves that it can be used to synchronise an artificial pacemaker. The normal ECG trace from the body surface has a well-defined P-wave, QRS complex and T-wave. However, the normal traces from conventional electrodes placed within the heart have insufficient differentiation between the P-wave and the QRS-complex if the electrode is in the auricle; and between the QRS complex and T-wave reactions, if in the ventricle. By using the angled dual electrode placed in the auricle, a trace can be obtained which has a single P-wave pulse. If placed in the ventricle, the trace has a clear QRS- complex and a negligible T-wave reaction.

Description

 The present invention relates to the fields of cardiology and methodologies for perceiving intracardiac electrical signals; and it relates more particularly to the methods and # devices for distinctly perceiving a localized endocardiac electrogram underlying the perception device and distinguishing it from all the unwanted wide field electrical events.

 The human heart is basically a pump through which blood is drawn into the orifices of the atria, or upper chambers, and then fills the ventricles, or lower chambers, through a connecting valve. Blood is then pumped out of the ventricles to the vital organs. Each cycle of this pump is triggered by a series of electrical events which occur in a specific order. It is the order and the ratio of these electrical events which partly determine the efficiency of the performance of the heart as a pump. The electrical cycle begins with spontaneous depolarization of the cells of the sinoatrial node, a small area of specialized tissue adjacent to the superior vena cava, at the upper right limit of the orifices of the atria. The depolarization forehead slowly extends into the node from the sinus and then through the perinodal tissues to activate the myocardium at the orifices of the atria. When the mass of myocardial tissue at the orifices of the atria is activated, an electrical event is produced which, when detected on the surface of the body, is called the "P wave."

When detected from within the heart chambers, this same event is referred to as the atrial orifice electrogram ". Characteristics of the atrial orifice electrogram as well as the recorded wave P, on the surface are a function of the mass of the myocardium at the orifices of the activated atria and of the specific activation sequence occurring in this human heart.

It is this sequence of electrical activation which results in the contraction of the myocardium at the orifices of the atria and the at least partial filling of the ventricles.

 The wave of electrical excitation of the atria orifices, however, would end at the fibrous boundary between the atria orifices and the ventricles stil nty had a conductive system for the specific ventricular multicomponent of the atria orifices (AV-) responsible for transmission electrical information through the fibrous boundary between the orifices of the atria and the ventricles.

The AV node is a small 1-2 cm structure located in the floor of the orifice of the right atrium halfway between the outlet of the coronary sinus and the central fibrous body of the heart. This structure, made up of three separate classes of cells, acts as an electrical filter providing a zone of slowed conduction between the orifices of the auricles and the ventricles sufficient to pe-zretre an appropriate ventricular filling. occurs partly through the ordinary myocardium at the orifices of the atria and partly through three specialized pathways inside the orifices of the atria responsible for the conduction of electrical information between the area immediately adjacent to the sinoatrial node and the upper regions , middle and lower of the atrioventricular node.The conduction inside the AV node is very sensitive to autonomous influences, effects of the use of cardiovascular drugs and coronary artery disease
As the electrical depolarization front advances through the AV node, it enters the AV or its bundle which is responsible for the transmission of electrical impulses between the anatomical orifice of the scallops and the ventricles This structure effectively crosses the fibrous skeleton # from the heart and extends a few centimeters below inside the membranous interventricular septum. At the top of the interventricular septum, the specialized AV conduction system is divided into two main branches, a right bundle and a left bundle; the left bundle then trifurcates into specialized fibers responsible for septal ventricular activation; activation of the upper part of the lateral ventricular myocardium and a posterior division responsible for the activation of the mass of the septum and the left ventricular myocardium. The right bundle is responsible for right ventricular activation.

 Although using special techniques, electrical activity can be detected from specialized areas of the cardiac conduction system, surface electrocardiography does not reveal any of the discrete electrical events that occur during activation of the nodes. AV, AV bundle, or any of the branches of the bundle. No electrical activity is discerned on the surface EKG following wave P until the mass of the ventricular myocardium begins to activate and an ORS complex is entered. This complex is generally of a significantly greater amplitude, when it is recorded on the surface of the body, than the P wave because of the much larger mass of the ventricular myocardium which generates it. When the recording comes from the inside the heart chambers, this event is called a "ventricular electrogram".

Events of repolarization of the ventricular myocardium, whether detected on the surface of the body or inside the ventricle, are designated by the name of wave T.

 Normal spontaneous diastolic depolarization of the sinus node followed by normal propagation of electrical excitation through the orifices of the atria and ventricles produces a normal heart rhythm with a frequency sensitive to influences from the nervous system that both alter the rate of discharge from a node of a sinus and speed of excitation of orifices of auricles and ventricular. A variety of disease states, however, can influence both the rhythm of the dominant natural cardiac drive mechanism as well as the pattern of electrical excitation of the human heart. Abnormal rhythms can be produced by intermittent failures of sinoauricular impulses to direct out of the sinus node, through myocardial abnormalities of the atrium orifice resulting in arrhythmias of the rapid atrium orifice such as palpitations or fibrillation, abnormal or absent nodal AV conduction which will result in the appearance of slow and inadequate intrinsic drive mechanisms from lower locations in the ventricle and abnormally slow heart rhythms; by diseases in one or all branches of the bundle resulting in partial or complete obstruction of the AV with still slow or inadequate cardiac regimes; as well as by abnormalities in the ventricular myocardium which may result in rapid tachycardias, ventricular fibrillation and death. The art of medicine has now reached the stage where many such faulty electrical depolarization sequences can be treated symptomatically by electronic stimulation of the heart through external or implanted electronic devices which are generally considered to be cardiac regulators.

 The simplest and most frequently used electronic device is a conventional WI regulator.

This device senses the ventricular electrogram and when the depolarization rate falls below a predetermined level, stimuli are sent to the ventricular myocardium resulting in a wave of electrical depolarization and a subsequent contraction of the ventricular myocardium. Such an electrical or return rescue system can be implanted at the ventricular level (vvi) or at the orifice of the atria (AAI) to correct anomalies either in the conduction of AV or in the function of the sinus node of the Newer regulation systems use electrodes at both the atrium and ventricular ports to sense and train at one or both locations to restore a more normal sequence of electrical excitation. the orifice of the atria and ventricular. Other implantable electrical devices have been used for the conversion of tachycardias of the orifices of the atria and / or ventricular as well as as part of the feeding power imparted to a device intended to end ventricular fibrillation.

 The ability of any of these devices to function properly, however, is determined to an extent which is not small by the appropriateness of electrical signals perceived from either the interior of the orifice of the atrial, or ventricle, since an appropriate regulator output will be determined only by adequate consumed signal strength. In general, most prior devices use the same electrodes used for myocardial stimulation to detect depolarization of the myocardium in the absence of stimulation.

In general, most systems have consisted of an electrode pressed into the myocardium of the atrium or ventricular orifice and a second electrode either in the form of a ring located near the stimulation electrode along the body of the same catheter (bipolar perception), or the second electrode included in the envelope of the regulator itself (unipolar perception). Average signal amplitudes for P and ORS complexes detected using either unipolar or bipolar perception systems have been well described in the cardiac literature for more than ten years.

The need for implanted electrodes to provide a signal derived only from the myocardium with which they have been placed in contact has been recognized for a long time. Problems of electromechanical interference external to the patient, such as external magnetic or electric fields and those produced by devices such as electric shavers or microwave ovens, are now even recognized by the general public. In recent years, however, a growing awareness of the vulnerability of poor perception of cardiac electrical events due to the perception of other electrical events occurring inside the body has been increasingly recognized. for example, Symposium on Electromagnetic Interference, PACE,
Flight. 5, January-February 1982. Particularly in unipolar electrode systems, the perception of electrical signals from the skeletal muscle adjacent to the anode of the regulator itself (myopotential perception) has been recognized as a frequent cause of an incorrect prohibition of these regulators. Although conventional bipolar ring electrodes tend to reduce the incidence in which myopotential perception and electromagnetic interference is considered, these systems are also not immune to the electrical phenomenon produced by a distant field, the patient, or the environment. A perception system protected "against electromagnetic interference would be of great clinical value.

 When unipolar or bipolar contact electrode systems are placed inside the ventricle to sense activation of the ventricular myocardium (ventricular electrogram), in general, suitable ventricular electrogram signals of 10 to 12 mv occur and because of the relatively large mass of the ventricular myocardium compared to the atrial orifice myocardium, little or no electrical activity reflecting the depolarization of the atrial orifices is perceived by this catheter.

This is not the case, however, with electrograms derived from a variety of locations within the orifices of the atria. Here the electrical contact perception systems, whether unipolar or bipolar, have all suffered from the same # defect, and almost independently of their location inside the right appendix of the orifice of the atria, against the lateral wall of the right opening of the auricle, or inside the coronary sinus near the distal coronary sinus. The problem seems to be inherent in the cardiac anatomy. That is, the mass of the orifice of the atrium and, consequently, the amplitudes of the waves P are also generally quite small, at 1-2 mv even when they are perceived from the inside. Because the mass of the ventricular myocardium exceeds the mass of the myocardium of the atria orifices to such an extent, the ventricular depolarizations can be seen even from within the orifice of the atrium as events discrete electrics which, even if they occur at a certain distance, cannot be distinguished from the electrical events of the orifices of the atria in terms of both their signal amplitude and their morphology.

 This defect alone has had the virtual consequence of very slow development and growth in the use of systems with prevented atrium orifices (AAI) and synchronous P wave systems (VAT or VDD). It has become an almost insurmountable problem in the development of regulators with double recess requirement intended to perceive both at the levels of the orifice of the atria and ventricular (DDD systems).

The development of suitable rhythm converters at both the ventricular and atrial orifice levels has also been seriously hampered by the lack of signal distinction between the events of the atrial orifice and the ventricular orifice perceived by means of conventional regulation systems.

 Each of these prior art regulation techniques has attempted to develop a reliable trigger signal for the stimulation pulse by perceiving an electrogram by means of a catheter implanted through the veins inside the heart.

In general, the signals perceived in a heart cavity, or their absence, provided the information required to regularize this same heart cavity. Cardiologists have long sought a regulatory system in which the electrical activity in the upper part of the heart, i.e. the orifices of the atria, could be perceived and then the ventricle trained at a rate appropriate to the rate perceived at the orifices of the atria. The most common systems employ two catheters, one placed in contact with the appendix of the orifice of the right atrium, and a second in contact with the right ventricular apex. Thus, the signals perceived at the orifice of the atrium can be interpreted by the pulse generator and the stimuli can be delivered to the ventricle at an appropriate rate.

 There are some descriptions according to the prior art of simple catheters which could be used to perceive at the orifice of the atria and to act as regulators at the ventricular level.

In general, the element of perception in each case was constituted by electrodes similar to the stimulation electrodes; however, it is placed elsewhere along the length of the catheter shaft. For example, one or two ring electrodes placed at the orifice of the atrium to perceive the electrocardiogram of the orifice of the atrium was shown by Thaler, "P Wave Control,
R. Wave Inhibited Ventricular Stimulation Device ", US patent NO 4,091,817.

Other similar projects can be found in 0'Neill's patents, "Formable Cardiac Pace Lead and Method of
Assembly and Attachment to a Body Organ ", U.S. Patent No. 4,154,247; Berkovits," Single Catheter for trial and
Ventricular Stimulation "(single catheter for stimulating the atrium and ventricular orifice), US Patent NO 3,825,015; or Bures," Transvenous
Coaxial Catheter, "US Patent No. 3,865,118. In most cases, it was previously believed that it was essential to physically bring the internal surface of the orifice into contact. atrium with the electrodes since the heart wave is produced inside the myocardial tissue and the contact, as shown in figure 5 by O'Neill's electrode 715, or in figure 1 by electrodes 18 and 19 de Bures, was considered essential.

In some cases of the prior art, contact with the orifice of the atrium was not considered essential. A prior art device is described by Thaler, "P Wave Control, R Wave Inhibited
Ventricular Stimulation Device ", US patent NO 4,091,917, which shows a regulator that perceives the P wave from two circumferential ring electrodes E1 and E2, better shown in Figure 5, to produce a subsequent ventricular pattern .Thaler is characteristic of the complex circuit assembly that the prior art has attempted to imagine in order to distinguish P wave from ventricular depolarization and subsequent wave elements in the next heart wave complex. The problem is not trivial, since the P wave perceived from non-contacting ring electrodes is virtually identical to the following ORS complex. there is no reliable means by which to analyze spectrographically or otherwise distinguish by automatic means the P wave from the wave train
QRST which accompanies it. Another complex assembly forming circuit, used in connection with the regulation of the heart, is also shown and discussed in relation to Berkovits;
Lin, et al., "Variable PR Interval Pacemaker", US Patent No. 4,060,090; and Funke, "Arrythmia Prevention Apparatus", US Patent No. 3,937,226.

 The problems of signal distinction at two levels, the orifice of the atrium and ventricular are combined when considering the effects of electrical stimulation through the regulator itself at the levels of either the orifice of the atrium is ventricular. When we try to perceive the depolarization ~ tion of the myocardium evoked by artificial electrical stimulation under 5 volts either unipolar or bipolar via the same electrodes used for this stimulation, there is an electrical phenomenon which occurs at the interface of the myocardium and electrode (known as "after-potential"), which is an event of a few volts of amplitude and lasting from 200 to 500 msec.

This after-potential completely "overwhelms" the response of the adjacent myocardium evoked in such a way that without an assembly forming an extremely complex circuit, the events of the stimulated myocardium cannot be perceived by the regulator itself. This resulted in the recognition and acceptance in the prior art of what has been called a "refractory to perception" period following all the stimulated or evoked polarizations. Although the "after-potential" occurs at the ventricular level as a result of ventricular stimulation alone, at the orifice of the atria, the stimulation is
of the atrium orifice or the ventricle results in a darkening of the electrogram of the atrium orifice for a significant period of time.

In any case, the efforts of the prior art have been largely unsuccessful and thwarted in terms of imagining an acceptable regulator of the type required.
VDD and DDD, synchronous in P, because of the inability of the prior art to successfully distinguish the P wave from the accompanying heart wave complex. This inability was exacerbated by the fact that the perception electrodes and the accompanying circuit assembly were overwhelmed by the strong stimulation pulse produced by the regulator itself, so that the regulator was blind to what concerns the success or failure of stimulating depolarization.

 A problem encountered with increasing frequency in complex two-cavity regulation systems is that of an activation of the orifice of the abnormal retrograde atria occurring as a result either of premature spontaneous ventricular depolarizations, or of ventricular regulations with reverse retrograde conduction through the AV node.

Retrograde conduction is a normal aptitude of the AV node and is found in 90% of patients with a dysfunction of the. sinus node; therefore, this problem is extremely significant for DDD control systems. Attempts to determine if retrograde conduction is responsible for any given P wave have relied # on the use of an extremely complex circuit assembly because of the inherent lack of ordinary electrical sensors to accurately analyze the direction in which the Myocardial activation occurs.

 This same difficulty is encountered in conventional ventricular perception systems if we try to use them to distinguish between the normally conducted impulses and those produced by abnormal foci inside the ventricles themselves, that is to say, to distinguish normal antegrade conduction from premature ventricular depolarizations.

This latter ability becomes extremely important when we consider the problem of regulators converting tachycardia. So far, due to the lack of an adequate sensor, only the regime with which ventricular events occur can be used to distinguish desired from unwanted tachycardias.

Tachycardias of the atrium orifice at normal sinus rhythm, with a conduction ratio of 1: 1, palpitation of the atrium orifice with variable conduction, as well as ventricular tachycardias can all occur at diets in excess compared to each pre-selected diet for the conversion of ventricular tachycardia. Thus #, when diet alone is used to determine the presence of ventricular tachycardia, significant diagnostic errors may and have resulted.

Therefore, what is clearly needed is a method and device by which
1. The local electrogram of the tissue adjacent to the regulating catheter can be discerned from all distant field electrical events produced by other areas of the same cavity, from electrical stimuli delivered, or from depolarization of the opposite cavity.

 2. The local electrogram is made insensitive to the effects of electromagnetic interference (EMI) and myopotential perception.

 3. The depolarization mentioned can be perceived without interference by the polarization effects at the interface of the myocardium and the electrode (post-potential perception).

4. The electrogram derived from the myocardium of the orifice of the atrium can be recorded at significantly higher amplitudes and with a clear-cut distinction of ventricular electrical events despite the greater magnitude by nature of the electrical forces producing the events. ventricular
5. local myocardial depolarizations recorded from multiple sites can be used to distinguish normal activation patterns from abnormal patterns.

 The development of such a discrete and specific electrical sensor when applied to the problems faced in the treatment of electrical disorders of heartbeats would result in the development of a generation of electrical devices which for the first time would be precise and reliable in treatment of cardiac arrhythmias.

 The present invention is an improvement in a method for perceiving the electrical activity of the heart comprising the steps of distinguishing a desired local cardiac electrical event from a complex series of waves, regulator stimuli and / or extracardiac electrical events by perceiving the electrogram. desired by means of one or more pairs of points situated in a plane approximately perpenicular to the depolariZation vector in the tissue of the heart close to the pair of points at which the local excitation wave is perceived. The signals perceived at this pair or at these pairs of points are then electrically "compared" to derive a specific differential signal to the desired local electrogram, and are substantially independent of all other elements of the complex heart wave or foreign electrical events by virtue of the fact that they are events far field "electrical fields. By this methodology, each cardiac electrical event loc al can be reliably and unambiguously perceived and chosen in any complex heart wave or all non-local electrical events, even if these non-local events produce signals of significantly greater magnitude.

 The distinction of the desired local electrogram is particularly characterized by the fact that the paired perception electrodes are not necessarily in contact with the myocardium (tissue of the heart).

In other words, the perception electrodes float freely inside the heart cavity. It is also particularly characterized by the fact that electrodes are dedicated to the perception of the electrogram, electrodes which are not used in the stimulation of the myocardium, thus allowing the perception of the electrical events evoked (stimulated) in an unobtrusive manner. by the effects of polarization at the myocardial-electrode interface (perception of potential).

 Specifically, the step of distinguishing the gram electrode inside the atrium cavity (wave P) from all other depolarization events, such as those which occur at the ventricular level, is particularly characterized by the fact that the perception electrodes are not in contact with the tissue of the heart. Whether placed in the top of the right side atrium or in the appendix of the right atrium orifice, the perception electrodes float freely inside the heart cavity.

 In a second embodiment of the present invention, the P wave distinguishing stamp also includes the perception of P wave signals at more than two points in the plane which is perpendicular to the depolarization vector in nearby cardiac tissue.

In one embodiment, the heart signal is perceived at three or four points on this plane, which are also spaced around a circle extending in the plane from which two or more differential perception signals are derived.

 In addition, the sequence of activation of the normal atrium or ventricular orifice, i.e. activation occurring from the normal extension of electrical activity in the heart, can be distinguished abnormal activation sequences, such as those produced by tachyarrhythmias, single premature depolarizations or retrograde conduction, using two or more sensors in various parts of the atrium or ventricle. The characteristics of the sensor in each zone would be identical to those previously described, with the addition that the logic would be applied to the perceived signals indicative of the activation sequence of each activated electrogram so that the normal and abnormal activation models could be reliably distinguished.

The invention will be better understood, and other objects, characteristics, details and advantages thereof will appear more clearly during the explanatory description which follows, made with reference to the appended schematic drawings given only. as an example illustrating several embodiments of the invention and in which
Figure 1 is a graph showing the time relationship between a conventional surface electrocardiogram and atrial orifice and ventricular electrograms derived from the appendix of the right atrium orifice and the right ventricular apex, comparison with electrograms recorded from perception probes of the present invention; ;
- Figure 2 is a graph showing the time relationship between a conventional surface electrocardiogram of a normal heartbeat, a conventional atrium orifice appendage electrogram, and the electrogram of the upper right and lower right part of the orifice of the atrium derived from the perception probe of the present invention.

This contrasts with the temporal relationship between a retrograde heartbeat, illustrated by a conventional surface electrocardiogram, compared # to an electrocardiogram of the orifice of the conventional atrium and the electrograms of the upper right and lower right perceived by a probe of the present invention;
- Figure 3 is a schematic fragmentary view of a catheter comprising the sensor of the present invention adjacent to the myocardial tissue.

- Figure 4 is a sectional sectional view taken through lines 4-4 of Figure 3;
- Figure 5 is a side elevational view taken through lines 5-5 of Figure 3;
- Figure 6 is a schematic view of the orifice of the right atrium and the ventricle of a human heart having a catheter according to the present invention implanted therein;
- Figure 6a is a schematic enlargement of the encircled part of Figure 6, designated by the reference numerals 6a;
- Figure 6b is a schematic enlargement of the encircled portion of Figure 6 generally designated by the number 6b;
- Figure 7 is a fragmentary schematic view of a ventricular perception and ventricular stimulation probe in the top of the ventricle;
- Figure 8 is a schematic fragmentary view of a probe for perceiving the orifice of the atrium and for stimulating the orifice of the atrium in the shape of a "J" placed in the orifice of the right atrium;
FIG. 9 is a diagrammatic section view showing a single filament catheter having a number of perception electrodes placed inside the orifice of the atrium;
- Figure 10 is a schematic fragmentary view of part of the catheter, shown on an enlarged scale, in which two electrodes are provided for perception;
- la.figure It is a schematic view of a catheter on an enlarged scale showing an embodiment in which four electrodes are used;
- Figure 12 is a fragmentary schematic view of a catheter portion showing an embodiment in which three electrodes are used; and FIG. 13 is an operating diagram indicating the methodology of the present invention.

 The present invention comprises a method by which localized cardiac electrical activity is perceived in such a way that a local cardiac signal is perceived distinctly from all other unwanted electrical signals, whether produced in other regions of the same heart cavity, in other heart chambers, or occur as electrical events outside the heart, such as signals produced in a skeletal muscle or an extrinsic electrical "noise".

 The electromagnetic field mechanism on which the methodology of the present invention is based is not well understood a However, by perceiving the heart wave at two or three points located substantially in a plane perpendicular to the direction of the local depolarization vector in near or adjacent myocardial tissue; and then differentially amplifying these signals to two or more, it has been discovered that a high amplitude local electrogram is produced with an extremely high signal-to-noise ratio. For example, it has been found that the existence of the much higher amplitude QRS complex, the next T wave, or the massive stimulation pulse produced by an associated regulator, have no effect on the effectiveness of the present methodology for reliably perceiving the much smaller P wave in the heart and reliably distinguish by this means the P wave from any other natural or artificially introduced electrical activity.

 Figure -1 illustrates on line 10 a surface or conventional skin electrocardiogram (EKG) of a normal heartbeat showing the P 12 wave which is the surface representation of the myocardial depolarization of the orifice of the atrium, followed by the ORS 14 complex, which similarly reflects the depolarization of the ventricular myocardium; and then the wave T 16, which reflects the ventricular repolarization.

Line 18 is an EKG EKG electrocardiogram of the orifice of the conventional atrium as typically measured by prior art ring electrode probes, either "floating" in the orifice of the atrium or in contact with the appendix of the orifice of the right atrium. The EKG EKG electrocardiograms of the orifices of conventional atria typically have a bipolar P wave response, generally designated by the reference number 20, followed by a bipolar ORS response of somewhat smaller amplitude, generally designated by the reference number 22. The shape ORS 22 response waveform is generally the same as P20 wave response but tends to be smoother and lower in amplitude. However, even in a normal individual, a heart wave complex can differ significantly from that measured in another individual or that measured in the same individual at another time. Slight variations in the intervals between the responses of different components compared to those shown in line 18 in the EKG
EKG of the atrium orifice, including variations in the relative amplitudes of each component response, should be expected in an abnormal heart.

The variations in the shape of the wave and the amplitude of the response of wave P 20 and in the response ORS 22 are such that it becomes very difficult, even for a human observer, to distinguish perfectly between the two in all circumstances. It is even more difficult for an assembly forming an electronic circuit and for logic to distinguish reliably between the response of wave P 20 and the response ORS 22 than it is for a human observer, and this hindrance has generally led to a limitation of the development of current cardiac regulators.

 Line 24 is a conventional ventricular electrogram derived from a conventional contact electrode system showing the relatively large response generally designated by the reference number 26 to ventricular activation corresponding to the ORS and T waves identified in the surface electrocardiogram of line 10. The EKG ventricular surface electrocardiogram has no discernible response corresponding to wave P 12.

 Line 28 is an electrogram taken from the appendix of the orifice of the right atrium from an orthogonal probe used and imagined according to the present invention. The perceived signal is a response generally designated by the reference number 30 indicative of a wave P and in the form of an acute tip, discrete, of 2 10 mu and of duration 15-40 msec with virtually no another response to some other cardiac electrical event. Line 32 is a perceived ventricular electrogram according to the present invention showing a large, discrete ORS response, generally designated by the reference number 34, with a very small T wave response generally designated by the reference number 36 with no other discernible responses to some other cardiac event, including the T wave from the orifice of the atrium.

 Lines 10, 18 and 24, in comparison with lines 28 and 32, dramatically illustrate the localized and discrete responses obtained in intracardiac electrograms derived according to the present invention compared to those which can be perceived by the device and methods of the Prior art. Not only is the signal-to-noise ratio significantly better in the electrograms shown in lines 28 and 32 of the present invention, but the duration of the response is indicative of a localized or near-field cardiac event. only. -A probe placed, for example, in the appendix of the orifice of the right atrium produces a response as illustrated in line 28, and is absolutely not affected by any cardiac activity in the ventricle whatsoever, in brutal contrast with an electrogram of the orifice of the conventional atrium as illustrated by line 18.

 The figure ? further illustrates that the present invention only perceives near field events in the heart and provides a peak of acute depolarization in response to them with an extremely high signal-to-noise ratio. The EKG surface electrocardiogram 10 was reproduced as the first line 16 in Figure 2 and an electrogram of the orifice of the conventional atrium as the line 18 in Figure 2.

This is compared to electrograms perceived by a catheter having multiple orthogonal perception electrodes, i.e. an electrogram from a perception electrode in the upper part of the orifice. right atrium illustrated at line 38 and the electrogram from a perception electrode located in the lower part of the opening of the right atrium at line 40. During normal anterograde conduction, a P wave response 42, perceived in the upper part of the opening of the right atrium, arises, as it is clearly indicated on line 38, at a time during the initial phases of wave P.

However, the P wave as it is perceived by the electrodes in the lower part of the orifice of the right atrium at line 40 shows a P 44 wave response appearing at a later time in comparison with the 42 response. This interval is indicative of the normal propagation delay within the heart from the upper parts to the lower parts of the orifice of the atrium. In each case, the electrograms taken in the upper or lower regions of the right atrium orifice have virtually no response to the massive ventricular signal that is produced in the underlying ventricular heart cavity.

 Referring again to Figure 2, a conventional surface electrogram of a retrograde propagating heart wave is illustrated in line 46, in which the response of the P wave 12 'is inverted, and follows the ORS complex. The same perception electrodes as those used in Figure 1, the performance of which is shown on lines 38 and 40, produce an electrogram as shown in line 48 from the top of the orifice of the right atrium and in the lower part of the orifice of the right atrium as shown in line 50.The response of the upper part of the orifice of the right atrium and, as before, a sharp P-wave response 52, and in the case of the lower part of the opening of the right auricle, a sharp P wave response 54. The waveforms of the EKG surface electrocardiograms 48 and 50 are essentially identical to those shown in the surface electrocardiograms 38 and 40 , except that their time sequence with respect to each other is reversed. The response of the wave P of the upper part of the orifice of the right auricle 52 is clearly later in time than the response of the lower part of the orifice of the right auricle 54, (this depolarization of the the orifice of the retrograde auricle results in an inversion of the wave P 12 ').

However, an electrogram of the orifice of the conventional atrium, like the one shown in line 53, corresponding to a retrograde heart wave, can virtually be distinguished from the electrogram of the orifice of the conventional atrium corresponding to a wave normal heart as shown in line 18.

Thus, by using multiple perception sites according to the present invention, for the first time the sequence of propagation of events inside a specific heart cavity can be precisely detected, and then used to distinguish normal heartbeats. abnormal.

 FIG. 3 illustrates the implementation of the method of the present invention in a human heart.

A fragmentary sectional view of a heart generally designated by the reference number 56 is schematically illustrated in FIG. 3, showing a single filamentous catheter 58, which is inserted through one of the major veins, in accordance with conventional medical practice, in the heart 56. Figure 3 shows a generalized location in the heart and should be at least read as including any location within the orifice of the atrium or ventricle. The catheter 58 is provided with at least two electrodes 60 arranged so as to lie in a plane which is approximately perpendicular to the depolarization vector 62 in the tissue of the adjacent myocardium 64. The depolarization vector 62 mathematically symbolizes the direction of the wave advancing in myocardial tissue 64, and is perpendicular to the wave front at each point. The perceived signals received at the electrodes 60 are then transmitted by conventional flexible conductors included inside the catheter 58 to a regulator circuit (not shown).

 A conventional regulator circuit could be used, although it is expected that the invention will give rise to many regulators which have hitherto been unworkable.

 Figure 4 is a schematic section taken through lines 4-4 of Figure 3, illustrating the proximity of the electrodes 60 within the catheter 58 adjacent to the myocardial tissue 64. It has been determined according to the present invention that the electrodes 60, whatever their angular orientation inside the plane illustrated in FIG. 4, will only perceive electrical activity in the immediate vicinity of the electrodes 60.

The electrodes 60 will not produce a response to cardiac activity occurring in other chambers of the heart, in muscle tissue which may be outside but adjacent to the heart, or to outside electromagnetic interference. It should also be noted that in FIG. 4 the cathSter 58 and the electrode 60-in particular do not touch and need not touch the inner wall of the heart 56 in order to produce useful signals as is wrongly believed in prior art.

 Figure 5 is a section in side elevation taken through lines 5-5 of Figure 3, and illustrates the arrangement of the electrodes 60 of catheter 58 in a plane symbolized by the dotted line 68 which is generally and approximately perpendicular to the vector of local depolarization 62 in the adjacent myocardial tissue 64.

 FIG. 6 illustrates in a schematic sectional view of the heart 56 the insertion of the catheter 58 inside the cavities filled with fluid of the heart, namely the orifice of the right atrium 70 and the right ventricle 72. The electrodes of perception-60 in the embodiment of perception of the orifice of the atrium and ventricular stimulation, shown in FIG. 6, are located in the upper part of the orifice of the right atrium in region 6a shown in Figure 6a on an enlarged scale. The catheter 58 extends through the orifice of the atrium 70, through the tricuspid valve 74, and extends down to the tip 76 of the heart 56. A stimulation end 78 is provided at the end of catheter 58 for implantation inside the ventricular apex 76, as shown on an enlarged scale in FIG. 6b, illustrating the region of the heart 56 generally designated by 6b in FIG. 6. A stimulation end 78 is provided at the end of catheter 58 for direct contact with the myocardial tissue of the ventricular apex 76.

The high voltage stimulation pulse is delivered by a conventional regulator at the 78 end to initiate the required ventricular contraction according to established medical principles. The stimulation end 78 may be any conventional end which may include any fixation device (not shown) which facilitates implantation and anchoring of the end 78 inside the myocardial tissue adjacent to the ventricular apex 76.

 FIG. 7 illustrates another embodiment of the present invention in which the catheter 58 is shown to include the perception electrodes 80 included within the ventricle 72 as illustrated in a schematic and fragmentary view on an enlarged scale of the ventricle 72 The electrodes 80 are placed near the tissue of the ventricular myocardium 82 in the ventricular wall of the heart 56. As before, the signals perceived by the electrodes 80 are connected through conventional flexible conductors to a conventional regulator circuit for implementation. and the subsequent production of a stimulation pulse delivered to the end 78.

 When the perception is practiced according to the methods of the prior art, the application of a large stimulation pulse to the terminal electrode 78 completely submerges the perception circuits attached to the stimulation means placed inside the ventricle.

Consequently, the cardiac activity which could be triggered by the stimulation pulse delivered at the end 78 cannot be reliably perceived by any method known in the prior art.
However, when electrical cardiac activity is perceived at the location of the electrodes 80, which are located in a plane which is approximately perpendicular to the near depolarization vector in the adjacent myocardial tissue 82, and the perceived signals are separated in a differential amplifier, a discrete localized electrogram response 34 as shown # in line 32 of Figure 1 is reliably produced, and is unaffected by the stimulation pulse applied to the end electrode 78, even in the The application shown in Figure 7, where the perception electrodes 80 are within 1 to 3 cm of the location where the stimulation pulse is applied.

 Consequently, the method of the present invention gives rise to the first true requirement regulator. In other words, the pacing pulse can be produced only in response to whether an anterior ventricular pacing pulse has produced a heart contraction or not.

FIG. 8 illustrates a third embodiment according to the present invention in which cardiac stimulation is provided in the appendix of the orifice of the right atrium generally designated by the reference number 86, illustrated in a fragmentary schematic view on an enlarged scale . The catheter 88 is given the shape of an iFJII to allow the perception of the orifice of the atrium in the upper part of the wall of the orifice of the lateral atrium or in Appendix of the orifice of the atrium right 86 by means of electrodes 90. Also, the electrodes 90 are generally arranged in a plane approximately perpendicular to the near depolarization vector in the tissue of the adjacent myocardium (not indicated). The end of the catheter 88 is provided with an end of pacing 92, similar to the conventional pacing end 78 shown and described with respect to Figure 7 The appendix to the orifice of atrium 86 as shown in Figure 8 is close to the outlet of the right ventricle generally designated by the reference number 94
Despite an electrical activity which could be associated with the ventricle or the outlet channel 94, the electrodes 90 inside the appendix of the atrium orifice 86 perceive only close-field cardiac activity and close to produce a high signal-to-noise signal as shown in line 28 in Figure 1.

 The present invention allows the implementation of a fourth embodiment as shown in Figure 9, where the perception of depolarization of the local myocardium from multiple locations can be achieved.

The electrograms are recorded from the lower region of the orifice of the right atrium 98 by means of electrodes 100 and near the floor of the orifice of the atrium 102 by means of electrodes 104.

As before, the signals from the upper part of the orifice of the right atrium are perceived by electrodes 60. Each of the electrodes 60, 100 and 104 lies in a plane which is generally perpendicular to the near depolarization vector in the tissue. of the adjacent myocardium Each of the electrodes 60, 100 and 104 will produce a discrete, tip-shaped response indicative of local cardiac activity close to the type shown in lines 38, 40, 48 and 50 of Figure 2.

 Each of the electrodes 60, 100 and 104 is coupled through corresponding flexible conducers inside the catheter 106 to a regulating circuit (not shown) for the subsequent implementation and the appropriate production of a stimulation pulse. The use of multiple perception electrodes as illustrated in FIG. 9 gives rise to a cardiac implementation which will be based on the continuous progression of cardiac activity inside the heart, and not simply on its absence or presence.

 Thus, it is evident that the methodology and the probe of the present invention can be used in each location within or near the heart structure in a wide variety of probe shapes. For example, although the perception has been shown both in the appendix of the atrium orifice, in various locations inside the atrium orifice, and in the ventricle, # il it is also possible that a probe may be placed in the coronary sinus. Also, only local or near field events in the coronary sinus would be received by the lead, and this event could be reliably monitored without interference from nearby large signal amplitude sources.

 Figures 10-12 illustrate different embodiments of the probe in an enlarged scale of a fragmentary schematic view. For example, the probe illustrated on an enlarged scale in FIG. 10 has been symbolically used in each of the previous figures and consists of two opposite electrode plates 108 and 110. Each electrode plate has a corresponding flexible wire conductor 112 and 114, respectively. The electrodes 108 and 110 are arranged circumferentially around the catheter 116 on the surface of an imaginary cylinder 118. The surface of the cylinder 118 can actually be located just well below the physical surface 120 of the catheter 116. The skin of the catheter 116, which can be a protective and insulating external plating, is cut to expose the electrodes 108 and 110 and allow them to have direct contact with the surrounding blood.

 The electrodes 108 and 110 are thus coupled through the conductors 112 and 114 respectively to a differential amplifier 122, shown diagrammatically in FIG. 10, the efficiency of which is the tripping pulse shown and described in FIGS. 1 and 2.

Although the conductors 112 and 114 have been shown schematically as straight wires, in practice the conductors are made up of multi-strand roll wires with an extremely high fatigue tolerance, which is used to lend themselves to bending expected from within a human heart. In the case illustrated in FIG. 10 where only two points, the electrodes 108 and 110, are used to perceive the near depolarization vector 150, two signals are used to supply the conventional differential amplifier 122. What comes out of the differential amplifier 122, the peak-shaped response, is coupled to the assembly forming a circuit for producing pulsations and for implementation 124, which may be of conventional design, included inside a regulator placed in a subcutaneously, schematically and generally designated by the reference number 126.

The implementation and logic circuit 124 sensitively produces a stimulation pulse according to principles well known in the art based on the trigger pulse supplied by the differential amplifier 122. The stimulation pulse is then coupled through a flexible conductor conventional 128, which is returned through catheter 116 (not shown) at the end of the stimulation electrode.

FIG. 11 schematically illustrates a fragment of the catheter 130, which is provided with four perception electrodes 132 - 138. As in the case of the electrodes 108 and 110 of FIG. 10, the electrodes 132-138 are each located on the surface of an original cylinder 140, defined inside the catheter 130. In practice, the cylindrical support surface, described here as an imaginary cylinder 140, can actually be located below the coating of the catheter 130, or be a non-cylindrical ring. conductor serving as the support for the electrodes 132-138. In the case where four electrodes are used as shown in figure 11, true signals perceived orthogonally can be derived. For example, the electrodes 132-138 are also spaced around the circumference of the catheter 130, thus being separated by 90 degrees the each other. The electrode 134 is paired with the electrode 138 and the electrode 136 paired with the electrode 132. Each of the pairs is conducted through its flexible conductors corresponding to an associated differential amplifier. For example, electrodes 134 and 138 supply the absorbed signals to the differential amplifier 142, while electrodes 136 and 132 supply the absorbed signals to the differential amplifier 144. The outputs of the differential amplifiers 142 and 144 are then supplied as input signals for implementation and the pulse generating circuit assembly 146, similar to
The circuit assembly 124, included inside the subcutaneous regulator 148. The output signals of the two differential amplifiers then comprise a signal "X" and a signal "Y", which can then be subsequently implemented to obtain a signal of absolute magnitude whatever the angular orientation of the catheter 130 inside the plane which is perpendicular to the local depolarization vector, symbolized by the arrow 150 in FIGS. 10-12.

In the embodiment of Figure 12, the electrodes 152-156 are also spaced apart on the surface of an imaginary cylinder 158 defined inside the catheter 160. In this embodiment where three electrodes are used, each of the electrodes can be 120 degrees apart, although it has been determined that perception is also possible if two of the electrodes, for example electrodes 152 and 156, are diametrically opposed on opposite ends of a diameter, while the electrode 154 is placed halfway between them, separated by 90 degrees from each of the electrodes 152 and 156. In each case, the electrodes 152 156 can be associated in each logical manner to form pairs of electrodes from which a signal is derived. pseudo-orthogonal. For example,
The electrode 156 can be arbitrarily chosen as the common electrode and a first signal can be developed between the electrodes 152 and 156 in the differential amplifier 162. A second signal can be developed in a similar way through the electrodes 156 and 154 and be supplied as an input signal to the differential amplifier 164. The outputs of the differential amplifiers 162 and 164 thus include a pseudo-X and "Y" signal which can be subsequently implemented by the circuit 146 in the manner described in connection with figure 11.

 FIGS. 10-12 illustrate that the electrodes are clearly two-dimensional, even if we have spoken of them as if they were points in connection with the perception environments in the applications described in connection with FIGS. 1-9. Clearly, point perception is a mathematical concept that is never realized in practice. However, the electrodes are small enough that the point perception is approached. The diameter of the cathGter can be in the range of 1 to 4 millimeters, and it has been experimentally determined that the optimum area for each electrode is approximately 1 to 4 square millimeters. It has been discovered that the amplitude of the signal is degraded if the area of each electrode is increased to, for example, 10 square millimeters.

 By examining FIGS. 10-12 generally, the arrow 150 symbolically represents the direction of the depolarization vector in the adjacent myocardial tissue close to the perception electrodes of each of the catheters The angular orientation of the electrodes with respect to the depolarization vector is also immaterial as long as the electrodes are close to each other i.e. in a range of 1 cm or less from each other, and as long as the geometric center of each electrode is generally in a plane substantially perpendicular to the depolarization vector 150. It appears that the maximum perception occurs when the plane of the surface of each electrode is approximately parallel to an imaginary plane in which the depolarization vector would be. Small variations around this ideal do not significantly degrade the possibility or the effectiveness of the present invention.

 In addition, in each of the embodiments described in connection with Figures 1-9, the perception electrodes were arranged inside the heart so as not to be in contact with the tissue of the adjacent myocardium. This is exactly contrary to the opinion of the prior art that it is necessary to bring the electrodes into contact with the tissue in order to obtain a reliable and useful signal. This was generally true in the case where a stimulation pulse is supplied to the heart, but turns out to be erroneous with respect to the signals of perception. In fact, the efficiency of the perception of a local electrical cardiac event from the tissue of the near myocardium is increased - if no contact is made.

Chronic contact leads to fibrous degeneration, which results in total or partial covering of the contacting part of the catheter with body tissue.

It has been discovered that fibrous degeneration generally attenuates the signal which can be perceived from the electrodes thus covered. Although this is not fully understood, it appears that local electrical cardiac # fading can be more effectively perceived if the electrodes are not in direct physical contact with the tissue of the adjacent myocardium. is included in the methodology of the present invention contrary to the teachings of the prior art, so that the electrodes touch or are attached to the adjacent tissue In fact, the electrodes described in relation to each of the embodiments shown in Figures 10-12 are slightly inserted into the respective catheter, so that even if the catheter were to come into physical contact with the adjacent tissue, the electrodes themselves would not come into physical contact.

 Figure 13 is an operating diagram generally summarizing the practice of the process discussed in connection with the embodiments described in Figures 2-9 with the probes as illustrated in Figures 10-12. The operating diagram in Figure 13 illustrates a single heart cycle.

 A heart wave is perceived in step 166 to give rise to a local electrogram as described above. In the case of the catheter of FIG. 10, a single signal is produced at the output of the differential amplifier 122, while the embodiments of FIGS. 11 and 12 each produce a multipolar signal coming from the corresponding multiplicity # of the differential amplifiers .

 In any case, a certain number of pairs of signals are perceived in step 166, each associated pair being differentiated in step 168 to produce one or more trigger or response pulses. In the illustrated embodiment, the differentiation has been described as performed by an analog differential amplifier. However, any equivalent means could also be used, such as making the perceived signals digital and taking their arithmetic mean in step 166.

 The trigger signals derived in step 166 are then implemented in step 168 in any of the different means in an arbitrarily large number according to well understood study principles and according to principles which one may hope to develop. once a reliable perceived signal can be obtained as in the present invention.

 A means by which the signals can be implemented in step 168 allows for variable amplitude regulation. The voltage of a train of pacing pulses can be varied depending on the success of the single previous pulse, or the percentage of success of a group of previous pulses in stimulating a heart contraction in response. Thus, if the stimulation pulse does not succeed in causing depolarization of the heart muscle because of its insufficient strength, this failure will be perceived and the lack of response or trigger pulse at the output of the differential amplifier coupled to the electrodes of perception will be noted to the assembly forming the implementation circuit in step 168. The following subsequent pulsation can then be produced with a predetermined increase in the force of the stimulus. Iteration may continue until a favorable pulse rate has been reached, in which case the regulation pulse rate may be kept stable until the heart conditions change again. This can be expected, for example, in conditions in which the sensitivity of the myocardial tissue is impaired by pharmaceuticals or ischemia.

 Thus, the magnitude of the current of the stimulation pulse can be increased depending on the success of the anterior pulse or any group of anterior pulses in creating a heart contraction or any predetermined pattern of cardiac activity.

 The criterion on which the spacing in time of the stimulation pulses or the magnitude of the pulsations can be conditioned can be determined in a wide variety of ways according to well understood medical principles. The manner in which the information is implemented by the perception method described here is not limited or restricted in any way by the perception method.

 Step 170 may include decision logic which may result in a decision to prevent the production of a heartbeat pulse, thereby returning the regulator to its initial condition in step 172. On the other hand, a decision may be made, based on objective criteria, to produce or initiate pacing, thereby entering step 174, in which the appropriate stimulus is produced and delivered. After that, the regulator can return to its original position and return to its original state in step 176.

 As a result of the implementation in step 170, a decision is made according to implementation rules whether or not to produce a stimulation pulse, and if so, what type of stimulation pulse.

Not only can the pulse setting and amplitude vary, as described above, but the location of the pulse application can also be chosen. For example, two stimulation electrodes may be provided on the same catheter or different catheters to provide a selection of points at which a stimulus can be delivered to the adjacent heart tissue.

In addition, bifurcated or multiple-ended catheters can provide the delivery of an appropriate stimulus to each of a large number of cardiac locations, for example, the ventricular apex on the one hand, and the appendix of the orifice. the headset on the other hand.

Similarly, selective stimulation in the orifice of the atrium and the ventricle could easily be practiced according to the cardiac activity which has been observed in accordance with the present process at any point or at all points inside the heart. .

 Thus, Figure 13 illustrates the flexibility and power of the perception methodology of the present invention. Because one is able to reliably and distinctly pick up the local electrical heart wave out of the confusion of electronic signals, both natural and artificial, which are present in the human heart, the heart can be tuned for the first time. a virtually unlimited and arbitrary way.

The ability of the method to perceive a local heart wave event at each location within the heart significantly increases the ability to detect hitherto uncontrolled conditions and types within the heart and to selectively respond to them .

Claims (10)

 R E V E N D I C A T I O N S  thus said local cardiac signal can be reliably and unambiguously perceived or detected and chosen from said other intracardiac signals.  compare the signals perceived or detected at said pair of points in said plane to derive a difference signal indicative of said local cardiac signal and substantially independent of said other intracardiac signals,  distinguish a local cardiac signal from other intracardiac signals by perceiving or detecting the local cardiac wave at a pair of points situated in a plane approximately perpendicular to the vector of depolarization in the near cardiac tissue, and  1 Improvement to a process for perceiving or detecting cardiac activity, characterized in that it comprises the steps of  2. Improvement according to claim 1, characterized in that the aforementioned step of distinguishing the aforementioned local cardiac signal by the perception or detection of the cardiac activity at the aforementioned pair of points in the aforementioned plane comprises the perception or detection of said cardiac activity at a location inside said plane close to the aforementioned cardiac tissue in which none of the points of said pair is in contact with said cardiac tissue.  3.- Method for distinguishing the local cardiac signal from the intracardiac signals in a heart, characterized in that it comprises the steps of  perceive or detect cardiac activity in said heart at at least two locations located close to each other, each of said locations being located on or near a plane approximately perpendicular to the depolarization vector in the myocardial tissue close to said locations, and  differentiate between signals perceived in at least two locations in order to derive a triggering pulse which testifies to said local cardiac signal,  thus said local heart signal can be reliably; and without ambiguity, perceived or detected and chosen from the heart wave without being taken into account -the choice of said locations in said heart.  4. A method according to claim 3, characterized in that the aforementioned perc # eption or detection step of the aforementioned local heart signal comprises the perception or detection of said local heart signal at three locations located in the above-mentioned plane or close to it, the three aforementioned locations being associated so as to comprise two pairs of locations, one of the aforementioned three locations serving as a common location with said association for purpose.  5.- Method according to one of claims 3 or 4, characterized in that the aforementioned step of perception or detect the aforementioned cardiac signal comprises the perception or detection of the local cardiac signal in three equally spaced locations.  6.- Method according to claim 3, characterized in that the aforementioned step of perception or detection of the aforementioned local cardiac signal at the aforementioned locations comprises the perception or detection of said local cardiac signal in each of said locations by means of an electrode generally located in a plane approximately parallel to the aforementioned depolarization vector in the aforementioned near myocardial tissue.  7.- Method according to one of claims 3 or 6, characterized in that the aforementioned step of perception or detection of said local heart signal comprises perception or detection at each location by means of an electrode having a convoluted surface.  8.- Method according to claim 7, characterized in that the aforementioned perception or detection step at the signal  aforementioned local heart using the aforementioned electrode  includes the perception or detection of said local signal by a  electrode having a geometric extent circumscribed by a planar geometric surface in the interval from 1 to 4 square millimeters, and in that each of the aforementioned locations is separated from each of the other aforementioned locations by a distance of not more than 10 millimeters.  9.- A method for distinctly perceiving or detecting a local cardiac signal of a heart wave complex and an extra-cardiac electromagnetic noise, characterized in that it comprises the steps of  perceive or detect local electrical activity in a heart at a number of close points located on or near a plane approximately perpendicular to the depolarization vector defined in the tissue of the near myocardium;  differentiate said local electrical activity perceived or detected at said number of points to obtain at least one triggering pulse indicating said local cardiac signal;  implementing said trigger pulse (s) to determine whether a stimulation pulse should be produced; and  producing said stimulation pulse to couple said stimulation pulse to a heart to stimulate the contraction thereof.  thus the regulation of true requirement of said heart can be carried out.  10.- Method according to claim 9, characterized in that the aforementioned perception or detection step of the aforementioned electrical activity comprises the perception or detection at a number of aforementioned points with a corresponding number of electrodes located in said number of points, in which none of said electrodes is in physical contact with the aforementioned near myocardial tissue.