Parasystole∗

Review Parasystole* DAVID

SCHERF,

M.D.,

F.A.c.c., KYUNG-HI-CHOI, RICHARD New

T

HE PRESENCE of a parasystolic a rare

finding

unrecognized ticular

interest

mias.

Thus

justified

in the a review

ventricular

disease.

problems

allows

of cardiac

DEFINITION

physicians

parasystole

by a similar rhythmical

with

mally irritable point in the ventricles” may be responsible. Under normal conditions the impulse of the basic (sinus) rhythm, as it spreads over the heart, depolarizes every cell and prevents specialized fibers from developing their own automaticity. Therefore, Fleming proposed that this irritable focus “lies in what may be called a backwater of primitive cardiac tissue and while stimuli can stream down this backwater physiological stimuli passing down the main channel are unable to disturb the point where ventricular stimuli arise,” and “ventricular extrasystoles are following a rhythm set by the two pacemakers, one at the sino-auricular node producing physiological beats and another at an irritable focus in the ventricles which is rhythmically discharging stimuli at the customary rate of ventricular stimulus production, thus giving rise to extrasystoles.“3 Kaufmann and Rothberger4 arrived accidentally and independently at a similar conclusion in the course of experiments on the cat’s heart in situ. When the atria were stimulated with rhythmic induction shocks, an extrasystolic arrhythmia with fixed coupling of the extrasystoles to the preceding beats was obtained. This result was observed regardless of the rates of the existing sinus rhythm and the extra rhythm, provided the latter was slower than the former. The first extrasystole could, of course, appear in any part of diastole. Since it was conducted back to the sinus node and depolarized it, both these rhythms were linked to each other; and the identical pattern of extrasystoles with fixed coupling was constantly registered. When rhythmical stimulation was applied to the ventricles and the resulting extrasystoles were not reversedly conducted to the atria, compensatory pauses were seen, and the coupling varied. However. the same groups of extrasystoles with the same variation of the coupling reappeared whenever the sinus and the extrasystolic cycles reached the lowest common multiple. If, for instance, the length of the sinus cycle was 7 time units and the

par-

arrhythseems

vast

majority

indicates

organic

the finer mechanism

is not fully interesting

known, insights

and

what

in some

physiology. AND HISTORICAL

DATA

Parasystole is defined as “a group of arrhythmias in which two (or rarely more) centers concurrently and independently produce impulses which yield contractions of the whole heart or parts of the heart, without any disturbance of conduction of the normal impulse being responsible for the arrhythmia.” l This definition eliminates complete A-V block in which two independent centers are simultaneously active. Another “pararrhythmia” which must be differentiated from parasystole is dissociation with interference in which an A-V rhythm is faster than the sinus rhythm. As the A-V beats are not reversedly conducted to the atria, the sinus impulses remain undisturbed. Since there is no A-V conduction disturbance? every sinus beat appearing outside of the refractory phase reaches the ventricles; the A-V rhythm is thereby disturbed. Thus both sinus and A-V rhythms are linked. not independent, to each other. The possibility that complex cardiac arrhythmias are caused by the coexistence of two independent rhythms originating in the same chamber occurred early to several authors, particularly Wenckebach.2 He recorded smoked-paper tracings and interpreted these as demonstrating simultaneous activity of two centers independent of each other. Later, Fleming3 attempted to explain premature ventricular contrac* From the Department OCTOBER

1963

York

“the

is not

disturbance

in the

New

M.D.

tions

of cardiac

of this since

York,

M.D., AHMAD BAHADORI, M.D. and

ORPHANOS,

frequently

rhythm

it remains

field

In addition,

of this arrhythmia we do know

by

even

particularly

of cases heart

although

P.

of Medicine,

New York Medical

527

mechanism. production

He postulated of stimuli

College, New York, N. Y.

that

at an abnor-

Scherf,

Kyung-Hi-Choi,

Bahadori

and Orphanos

FIG. 1. A, n ~y_bicalinstance of ventricular jmrasystole. Ectopic beats appear at different periods of diastole. Some ventricular complexes (at the end of the tracing) are mixed because the ventricles are in part activated by the sinus impulse and in part by the parasystolic impulse. Measurement with the aid of a caliper shows that an ectopic center in the ventricle forms rhythmic impulses; those impulses which appear outside of the refractory phase of a sinus beat B, a series of uentricula~ extrasystoles follorving sinus beats. elicit a response. On three occasions an ectopic beat is C, an intermittent parasystole. missing (exit block). On two occasions a series of automatic beats appears with fixed coupling to a sinus beat. After the first sinus beat five parasystolic beats appear. After the first, second and fifth automatic beat, sinus beats are conducted to the ventricles and cause premature contractions. These beats are aberrantly conducted and resemble the automatic beats. length of the extrasystolic cycle 9 time units, the pattern would be reproduced after 63 time units, provided the rate of both rhythms remained constant. When both rates had a simple relation to each other, i.e., they were equal or one twice as fast as the other, bigeminal groups would appear, or extrasystoles would be observed after every second or third sinus beat. If two centers fire impulses independently, the coupling is expected to vary. However, in most instances of clinical extrasystoles the coupling remains remarkably constant. Since Kaufmann and Rothberger attempted to explain extrasystoles by the presence of two independent rhythms, they were forced to postulate several auxiliary hypotheses. These were the basis of a great deal of the criticism which their theory soon encountered. It is an ironic fact (not uncommon in medicine) that most of the tracings by which these authors tried painstakingly to prove the presence of parasystole cannot be accepted today as representing this arrhythmia. The credit for publication of the first electrocardiographic demonstration of a parasystole belongs to Singer and Winterberg. In this case, the rate of the ectopic rhythm was slower than the sinus rhythm, whereas Kaufmann and Rothberger assumed the parasystolic center was more rapid because two extrasystoles follow each other directly usually at a rate superior to that of the existing sinus rhythm. VENTRICULAR The The

commonest characteristic

nodal parasystole sections.

form

PARASYSTOLE will

be

discussed

first.

A-V will be dealt with in separate features

of atria1

and

DIAGNOSIS

Parasystole is recognized three electrocardiographic

by the following signs (Fig. 1A) :

(1)

marked

variation

in

the

coupling

of the

ectopic beats; (2) regular appearance of the ectopic beats; and (3) appearance of combination, fusion or summation beats (mixed systoles). Variation in Coupling: The presence of parasystole should be suspected whenever ectopic premature beats are seen without a fixed coupling being present. In the usual type of extrasystole the coupling varies by only a few hundredths of a second. This is to be expected since all available data indicate that the extrasystole is initiated by the preceding beat. If two impulses are initiated independently, the coupling could not be fixed and will vary continuously as does the P-R interval in complete A-V block. There are, however, cases of parasystole in which the coupling gives the impression of being fixed. This will occur if the length of the ectopic interval is equal to or one half or one third of the sinus rhythm. This same phenomenon is observed in cases of complete A-V block. When one automatic cycle approximates two atria1 cycles, the P-R interval remains unchanged even in long strips of electrocardiographic tracings. When in parasystole both the ectopic and the sinus rhythm are approximately equal, it may happen that a series of ectopic beats will appear uninterrupted by sinus beats.6-g A corollary of this is that when the cycles of both rhythms vary greatly, the coupling also varies greatly. In some instances of parasystole the ectopic ventricular beats are reversedly conducted to the atria and the sinus node. As in atria1 parasystole, this leads to a linkage of both rhythms and a more constant coupling. THE AMERICANJOURNALOF

CARDIOLOGY

Parasystole

FIG. 2. Ckntricular parasystola.The four tracings were taken from a 68 year old man with coronary sclerosis and cirrhosis of the liver. All tracings in lead 11show atria1 fibrillation and ventricular parasystole. A, the third ventricular complex

represents a mixed systole.

The short intervals between the ectopic beats are 0.102 and 0.106 sec., a rate of about GO/ min. The longer interval between the mixed systole and the next rctopic beat is 0.212. Because in this tracing an ectopic beat appears after each conducted beat from the atria, a bigeminal rhythm is seen. However, the coupling is not constant. B was obtained on the same day as A. An ectopic beat at the beginning of the tracing is followed after 0.48 sec. by a premature contraction. The distance between the first and the third ectopic brat measures 0.210 sec.; that between the third and the fourth ectopic beat is 0.106 sec. C and D were obtained one week later; the patient had received daily 0.25 mg. of digoxin. C. in thr center of the tracing three ectopic beats succeed each other with intervals of 0.70 and 0.72 sec. A mixed beat follows. ‘The longer intervals between ectopic beats measure 0.152 and 0.222, that is, they are multiples of an ectopic period. D shows a similar grouping. Here, four ectopic beats follow each other, but between the third and fourth one an extrasystole is interpolated. The first two periods between these ectopic beats measure 0.72; the period with extrasystole measures 0.76 and the following is 0.70 sec. This shows a slight delay of the ectopic parasystolic beat following the extrasystole because of an exit block. Interesting is the fact that the ectopic beats appear occasionally as early as 0.28 sec. after the beginning of the preceding QRS complex, i.c, certainly shortly after the end of the absolute refractory phase.

When the sinus rhythm is rapid, there is no possibility for marked variations in the coupling for there is only a short interval between the end of the refractory period and the next systole available for the appearance of the ectopic beats. Regular A@earance of Ectopic Beats: The regular intervals between the ectopic beats indicate that a center is firing impulses regularly, independently from the basic rhythm (sinus rhythm, atria1 flutter or fibrillation). Each long interectopic interval in the course of which basic beats appear must be a multiple of one ectopic cycle. When two ectopic beats appear in succession, the ectopic cycle can, of course, be measured directly. If the ectopic beats appear rarely and the interectopic intervals are long, mistakes are easily possible since long intervals can be the multiple of many cycle lengths. The interectopic intervals vary by a few hundredths of a second. When the interectopic intervals are too long and the variation of the ectopic cycle is great, the mulOCTOBER

1963

tiplication of these factors associated with the error in measurement (up to 0.05 second) leads to results that may be incorrect. In such cases a common denominator can easily be found in the absence of parasystole; this too may lead to an erroneous interpretation. Formulas have been recommended which show up to what length an interectopic interval can still be used to prove the presence of rhythmic impulse formation.5~1fl~‘1 Because of the variations of the ectopic cycle, mathematical accuracy is rare. When two ectopic beats appear consecutively, measurement of this direct ectopic cycle is usually somewhat longer than those calculated from the interectopic intervals.’ s5,8,12,I3 The reason for this relative prolongation of the directly measured ectopic interval is not clear. Exceptions of this rule have been observed. It is interesting to note that in cases in which parasystole could be observed for long periods of time, changes in the rate of the sinus rhythm were accompanied by changes in the rate of

Scherf,

Kyung-Hi-Choi,

Bahadori

and Orphanos

FIG. 3. l$$ect of carotidsinusprrssurr. A, atria1 fibrillation and ventricular parasystole. B, carotid pressure prevents atria1 impulses from being conducted to the ventricles and leads to the appearance of an undisturbed ectopic rhythm. C and D were obtained from a patient with sinus rhythm, a prolonged P-R interval and parasystole. At the beginning of C and in D carotid sinus pressure inhibits the sinus rhythm and provokes an undisturbed ectopic rhythm. The rate of the latter suddenly doubles in II.

the ectopic rhythm.14s15 Thus in one case reported by Scherf and Boydg the ectopic rate rose from 35 to 41 as the sinus rate increased from 60 to 80. The same phenomenon is readily observed in experimental parasystole.16 Kaufmann and Rothberger first, and since then other investigators, have raised the question as to whether the directly measured ectopic cycles are not actually a multiple of the true ectopic period.‘?J7 This possibility will be discussed here in detail. When the parasystole is short, lasting only a few seconds, there may be a gradual lengthening of the ectopic cycles.l* The presence of several simultaneous parasystolic centers has been described.8Jga20 Fusion Beats: If two centers independent from each other send out impulses, from time to time both the ectopic and the regular impulses will spread over the heart simultaneously. Under these conditions each impulse will activate a part of the ventricles, leading to the appearance of a mixed ventricular complex which is known as a combination or summation It is obvious that the frequency or fusion beat. of appearance of these beats will depend on the relation between the sinus and the ectopic beats. PR~TECTI~N~FTHEECT~PIC~EN~R(PR~TE~TI~N ORENTRANCEBLOCK)

In complete A-V block, the two centers independently forming impulses are protected from each other by the conduction disturbance in the A-V system. When Wenckebach assumed that two independent centers may form impulses in the same heart chamber, he was forced to postulate a “dissociation” protecting

each center from the influence of the other. Fleming formulated his backwater theory and Kaufmann and Rothberger assumed a protective block, i.e., a conduction disturbance preventing the stimulus of the basic rhythm to enter the area where the ectopic center is located. This protection block has been compared to the localized bundle branch block.rO It is clear that in order to be effective this blocked area must surround the center in all directions. This theory has been accepted Vedoyazl tried to complement by most authors. it by assuming that there are two spherical zones of block surrounding the center, each one with a different refractory period. The zone closer to the center has a refractory period longer than the basic rhythm but shorter than the ectopic cycle. The outer zone has a refractory period shorter than the basic rhythm.21 There is no doubt that a center can form impulses without being disturbed by excitation waves spreading over the heart. Thus, experiments on dog hearts have shown that occasionally an A-V rhythm may not be disturbed by the impulses conducted from the atria down the A-V system.22J3 During A-V heart block in man interpolated ventricular extrasystoles have been seen ;24 this is possible only if the ectopic beat does not disturb the automatic In small strands of specialventricular center. ized fibers (erroneously called Purkinje fibers), both spontaneously and particularly after strophanthin administration, up to four independent centers have been found.25 This, however, requires very special conditions with poorly nourished tissue. Many authors refused to accept the theory of a barrier surrounding the center.gJ2 One of the most ardent opponents THE AMERICANJOURNALOFCARDIOLOGY

Parasystole

FIG. 4. Nodnl purasystole. These tracings taken in lead II show a nodal parasystole with ectopic beats appearing at difIn A on two occasions, in R once at the end of the tracings, mixed atria1 beats are obsrrved. ferent phases of diastole.

stated : “It is indeed difficult to picture to one’s muscle, mind a portion, say, of ventricular surrounded as it were, like Brunnhilde in the opera, by some barrier which on the one hand protects it from having to participate in the successive contractions of the ventricles, and on the other hand leaves it free to send out rhythmical impulses.“?6 It is well known that automatic impulse formation of the heart is associated with slow diastolic Such depolarization of the pacemaking fibers. a process in the parasystolic center should make it more irritable since diastolic depolarization of the center means a lower threshold of the In view of this, it is difficult to undercell. stand how the impulse from the basic rhythm does not depolarize the ectopic center. Also untenable for the same reason is the assumption that no block need be present and that the protection of the center depends on the relation of the strength of the conducted impulse’” and the irritability of the center. Rapid Impulse Formation in Parasystolic Center: Experiments on the dog heart in situ seem to provide an explanation for the mechanism of at least one type of protection. It could be shown in the dog that after intravenous adOCTOBER

1963

ministration of quinine to prevent fibrillation, mechanical or electric stimulation of the ventricles provoked chains of ectopic beats originating in the stimulated area.27 These ectopic beats exhibit the characteristics of parasystole, with full protection of the ectopic center. The rate of these beats was about 1 jO/min. but ocFurthermore, the casionally suddenly doubled. distance between two ectopic beats separated by a series of sinus beats was a multiple of the ectopic cycle, or was longer by half a cycle length. It was therefore concluded that the ectopic center forms impulses at a rate of about 300 and that usually only every second impulse spreads over the ventricles, the protection of the center being caused by the very speed of impulse formation. As long as this rate is maintained, the center cannot be influenced by other impulses spreading over the heart.27 Focal application on the dog heart of aconitine,27 acetylcholine and atropine,28 veratrine,16 hypertonic solutions of sodium chloride, sodium citrate or oxalatezg resulted in the formation of parasystole ; and in all these experiments the rate of impulse formation was rapid (Fig. 5). A similar phenomenon has been found in a

532

Scherf,

Kyung-Hi-Choi,

Bahadori

and Orphanos

FIG. 5. Experimntal parasyloles. These lead II tracings are from two diff‘ercnt experiments in which the exposed heart of the dog was treated focally with a 3.8 5:) solution of sodium oxalate in thr presence of artificial respiration. The sodium oxalate was applied in both experiments on the center of the wall of the- right ventricle and on the left ventricle just back of the left cardiac border. A, rhythmic rapid impulse formation began, at first with ectopic tachycardias originating in the right and then in the left ventricle; finally right ventricular ectopic beats arc interrupted by left ventricular ones. The interectopic intervals of the right ventricular beats in hundredths of a second measure: 48, 92, 48, 95, 92, 92, 92, 45, 95, 94, 48, 91, 94, 45; the interectopic intervals between the left ventricular complexes measure: 145, 94, 92, 92, 138, 98, 140 and 94. B, in the second tracing one sees at first the left ventricular and then a right \-entricular tachycardia with a period of 0.030 to 0.032 and then a kind of bigeminal rhythm, each distance between two ventricular ectopic beats of the same kind measuring 0.060 to 0.064. In both experiments, therefore, a double parasystole-parasystole originating from two centers-existed.

series of clinical parasystoles: The rate of the ectopic center suddenly doubled, and the interectopic interval was equal to a multiple of the ectopic cycle or a multiple plus one half of one ectopic cycle (Fig. 2 and 3).30 The rate of the ectopic rhythm in these cases of clinical parasystole was also often 140-l 50 ; this was most probably the expression of a 2: 1 block of the ectopic center. It may be that most and even possibly all instances of parasystole originate from such rapid impulse formation. The reason why there is no paroxysmal tachycardia is that there is only a 2 : 1, 3 : 1 or 4: 1 response. This possibility has been mentioned in the past but has not been proved. It is supported by a case of clinical parasystole in which the ectopic focus located in the A-V node sent out impulses at a rate of 125/min.; suddenly the rate doubled, and the parasystolic rhythm changed into a paroxysmal tachycardia.3’ Kaufmann and Rothberger report a similar case in

which an atria1 parasystole is suddenly replaced by a paroxysmal tachycardia with a rate exactly as expected from the tracings showing the parasystole.4,3” Therefore, the “protection” block is not caused by a conor “entrance” duction disturbance but is due rather to a functional disturbance easily explained on the basis of known facts of cardiac physiology. The term protection is therefore more correct than the term protection “block.“g There is another important argument in favor of this explanation of the protection of the ectopic center. As long as it was believed that an area of block surrounded the parasystolic center forming slow impulses, the general opinion was that the ectopic rhythm was the expression of the normal automaticity (homogenetic impulse formation) of a ventricular center. The specialized fibers within the ventricles actually do form impulses at a slow rate, often similar to the rate of a parasystole. THE

AMERICAN

JOURNAL

OF CARDIOLOGY

Parasystole Hovvever, the centers responsible for atria1 parasystole also exhibit a s’ow rate, much slower than would be expected from an “automatic” atria1 or A-V nodal center.33 This fact would tend to show that parasystolic rhythms are abnormal and not caused by the automatic impulse originating in a protected center. Zntermittpnt Parasystole: The protection is not alvz-ays permanent, and this leads to the arrhythIn these mia called intermittent parasystole.g,2’ cases the parasystole appears to recur after a series of sinus beats. It is characteristic that parasystole” (Fig. 1C) the in “intermittent first beat of the arrhythmia is coupled to the preceding sinus beat by a fixed interval. It must be assumed that the sinus beat has provoked the first parasystolic beat and this type of parasystole may be likened to a tuning fork which continues to oscillate for a while after having been struck only once.34 Intermittent parasystole has also been described by others.’ ,34-36 Kaufmann and Rothberger discuss but do not prove temporary disappearance of protection.J In one patient the protection disappeared whenever the parasystolic beat followed closely the preceding P wave.g ExIT BLOCIC This aspect of parasystole is the one which As has been pointed has caused much criticism. out before, Kaufmann and Rothberger postulated that parasystole is the cause of clinical extrasystoles and that there is an exit block in all cases of parasystole preventing most of the impulses from the ectopic center from spreading When “parasystole over the rest of the heart. with simple interference” was discovered, the rate of the ectopic center was found to be slow, and it was not necessary to introduce the conBut, as was discussed in the cept of exit block. preceding section, it is most probable that an exit block exists in most cases of parasystole since most of these are caused by a rapid ectopic center. Obvious examples of exit block, meaning failure of the expected ectopic beat to appear even though it falls outside the refractory period, have been repeatedly published (Fig. lC).‘~6,12,31,36,37 Katz and associates38 described an atria1 parasystole with a rapid center and exit block. The term “exit block” is not quite accurate since a conduction disturbance need not always be responsible. If the impulses happen to be OCTOBER1963

just above threshold levels, it may happen that one occasional impulse may fail to elicit a response without the presence of a conduction disturbance. ATRIAL PARASYSTOLE As was shown earlier, atria1 parasystole has certain characteristics. If the sinus rhythm and the ectopic rhythm are regular and each ectopic beat invades the sinus node, there will be extrasystoles with fixed coupling. The disturbance is similar to what is found in dissociation with interference where the conducted beat links both rhythms by disturbing the impulse formation in the A-V node. This leads to the constant “coupling” of the conducted beat to the preceding A-V beat. Clinically, however, the sinus as well as the parasystolic rhythm vary in most patients continuously, and some of the parasystolic impulses arriving late in diastole do not reach the sinus node and are therefore followed by compensatory pauses (Fig. 4). All three main characteristics of parasystole mentioned above including the appearance of mixed P waves can be seen.“3s3g Instances of atria1 parasystole were repeatedly analyzed by Kaufmann and Rothberger but are now interpreted differently. The case of atria1 parasystole reported by Katz and associatesr6 with a rate of 375,lmin. and exit block was mentioned above. The first clear instance of this arrhythmia was described by Jervell.40 Other observations have been reported .41,42 In a complex arrhythmia the presence of an atria1 parasystole with two centers Antand an exit block has been assumed.43 tonen and associates described the appearance of an atria1 parasystole after the subsidence of an auricular flutter. The atria1 ectopic beat had a rate of 30/min. in one instance and 49 in another.44 In some tracings it is difficult to differentiate between atria1 parasystole and interatrial block. In the latter condition one atrium or part of one atrium is isolated from the other part and beats independently so that, as in parasystole, there is an independent atria1 rhythm in addition to the sinus rhythm. The diagnosis will be supported by the finding of an A-V block or a recent inferior wall infarction since these lesions often accompany the interatrial block. This disturbance is found in patients with serious heart disease. One should, therefore, hesitate to diagnose interatrial block in seem-

534

Scherf,

ingly healthy

people. It two completely different identical electrocardiograms.

Kyung-Hi-Choi,

is interesting that mechanisms cause

A-V NODAL PARASYSTOLE This condition can be diagnosed if (a) the ectopic beats have the same ventricular complexes as the sinus beats but no P wave is visiblegr3r or (b) a P wave does precede the ventricular complex by a normal or shortened P-R interval but it is inverted in leads II, III and aVF, and positive in lead aVR. Several instances of this form of parasystole were originally published as atria1 parasystole.21,45’46 In the observation of Attinger46 the parasystole is readily diagnosed as the ectopic beats do not influence the impulse formation in the sinus node. Other instances of A-V nodal parasystole were described.47-4g Scherf, Bornemann and YildizSO published four observations of this disturbance of rhythm and a case described by Frey may also fall in this group.51 In an observation by Holzmann (Ref. 19, Fig. 128) the sinus node was also unaffected by the ectopic rhythm. The sinus rate was 65 and the ectopic rate lOO/min. with a 3:l and 4:l exit block. After exercise the sinus rate rose to 78 and the parasystolic rate to 112. In an interesting case observed by Castellanos and associatesr8 a ventricular extrasystole is conducted back to the atria and provokes an A-V nodal parasystole. COUPLING When extrasystoles are discussed, the term coupling is used to represent the distance between the extrasystole and the preceding beat which provoked it. Therefore, when both rhythms are independent as in parasystole, this It was used originally term is not quite correct. by Kaufmann and Rothberger when they attempted to explain all extrasystoles by a parasystolic mechanism. The fixed coupling seen in over 90 per cent of clinical extrasystoles was explained by these authors on the assumption that the autonomic nerves regulate both rhythms and made them vary in a parallel manner. However, as was conceded later by Rothberger, this attempt was not successful. In many of the classical texts on cardiac arrhythmias, parasystoles are discussed under the heading of extrasystoles. The relation of these two distinct entities will be discussed later. In the typical parasystole the coupling varies.

Bahadori

and Orphanos

The shortest possible coupling will be found when the ectopic beat happens to arrive just after the refractory period of the ventricular complex of the basic rhythm; the longest possible coupling will have the same duration as a cycle of the basic rhythm, and a mixed ventricular complex will appear. Of great interest are the observations in which a parasystole was registered and then suddenly, without a change in the form of the ventricular complexes, the coupling becomes fixed, and true extrasystoles appear.12 ,14,37,52 The finer mechanism in the ectopic center that causes this change in the impulse formation is not known. Presumably the protection disappears, and after-potentials in the ectopic center provoke extrasystoles with fixed coupling. Cases have been described in which extrasystolic beats are seen only following parasystolic beats.53 This phenomenon is also unexplained. CAROTID SINUS PRESSURE AND CHOLINERCIC DRUGS The slowing of atria1 and A-V parasystolic rhythms by carotid sinus pressure is an interesting phenomenon.33p50 This is in contradistinction to paroxysmal atria1 tachycardia which is never slowed by this method. The response in tachycardia is an all or none reaction. The tachycardia remains uninfluenced or is suddenly and completely stopped. The effect of carotid pressure on ventricular parasystole is even more remarkable, since vagal effects on the mammalian ventricle are minimal or absent. Ventricular contraction is not influenced at all, and the effect on impulse formation is rare and only minor in degree. There are four clear effects of carotid pressure on ventricular parasystole (Fig. 3). 1. When carotid pressure is applied and the sinus rhythm is inhibited, the parasystolic center can continue undisturbed. This finding was first described by Vedoyaz’,45 in a patient with A-V rhythm. In this case the ventricular complexes of the parasystolic rhythm had the same form as the supraventricular beats. Later we observed this phenomenon frequently.34t64e65 The identical effect is seen in experimental parasystole during faradic stimulation of the vagus nerve.r6 fzg This action of carotid pressure is easily understood, and it is surprising that it has not been described earlier. 2. Carotid pressure exerted in the course of a parasystolic rhythm may slow it down. Thus, THE

AMERICAN

JOURNAL

OF

CARDIOLOGY

Parasystole in one instance described, it went from 134 to 112/min. and from 128 to 110,5J in another case39 from 177 to 157 and in a third instance30 from 85 to 72. Since the rates in complete A-V heart block are rarely influenced by carotid sinus pressure, these observations are of particular interest. One explanation is that the same lesion causing A-V block may also destroy the vagus nerves in the conduction system so that carotid sinus pressure becomes ineffective. 3. Parasystole can be provoked by carotid In one case after parasystole sinus pressure. had stopped, it could be brought out again temporarily several times by carotid sinus In another observation, an inpressure.36 terpolated ventricular extrasystole appeared during A-V block while carotid sinus pressure was applied. This is only possible if the automatic center in the ventricle is protected and therefore undisturbed.2d 4. On the other hand, the disappearance of the protection of a parasystolic center has been described during carotid sinus pressure.g In another observation an exit block was seen during the pressure since an ectopic beat failed to appear (Ref. 56, Fig. 188~). carbamylcholine injected intraSimilarly, venously provoked parasystole6 or slowed its rate (Ref. 56, Fig. 189). This drug was used by Vedoya and associates4j in order to enhance the effect of carotid sinus pressure. EFFECTS OF DIGITALIS, STROPHANTHINE,AMYL NITRITE, EXERCISE Digitalis: The appearance of parasystole during digitalis or strophanthine administration has been observed by othersgJ2z15 and by us. In one instance the arrhythmia disappeared when digitalis was discontinued.8 In another patient the parasystole changed to a bigeminal rhythm with the administration of digitalisI In many cases under our observation we witnessed the end of a parasystole under digitalis therapy. In 1 patient the disappearance of parasystole was observed following digitalis ; it reappeared after administration of atropine.‘j Digitalis had been administered to 2 patients who developed atria1 parasystole, and in another similar observation the arrhythmia subsided with the administration of potassium.44 One cannot rule out the possibility that the appearance and disappearance of parasystole in the above instances was fortuitous and the relation to digitalis therapy wholly accidental. OCTOBER1963

535

A definite relation between the drug and the arrhythmia will be established only when repeated trials in the same patient will affect the parasystole in a constant manner. Amy/ Yitrate: Holzmann observed the disof parasystole during inhalation appearance of amyl nitrite.8 It reappeared soon after without being influenced by the duration of the diastole. has Exercise: After exercise the arrhythmia been observed to disappear? but also, although more rarely, to appear.6 In the A-V nodal parasystole described by Holzmann’g the rate increased after exercise while Winterbergt7 reported no change in the rate of the ventricular ectopic center after exercise. PARASYSTOLE AND EXTRASYSTOLES Originally the impulse formation that leads to extrasystoles or paroxysmal tachycardia was differentiated from the one leading to sinus or A-V rhythm. The latter was called homogenetic and the former heterogenetic.68 When the attempt was made to explain extrasystoles by rhythmic, independent impulse formation (parasystole), Lewis58b5g declared that he was “unable to rewrite with sufficient confidence those distinctions between homogenetic and heterogenetic impulses” which he employed in the previous edition of his book. Later it was demonstrated experimentally that extrasystoles are caused by the preceding beat and are not the expression of an active rhythm. Extrasystoles are forced beats originating passively.“O This was shown on the dog heart in situ in two ways. When constant bigeminy existed, every extra beat provoked by mechanical or electric stimulation was followed by an extrasystole identical to the one following the sinus beat.27 When constant bigeminy existed and the sinus beats were inhibited by vagus stimulation, the extrasystoles also disappeared in contrast to the parasystolic beats which are independent.61,62 It is assumed that in cases of extrasystole the impulse from the dominant rhythm spreads over the ectopic center and it becomes depolarized more than once because of after potentials.60,63 If parasystole is actually not the consequence of a slow homogenetic impulse formation but caused by rapid impulses with exit block, the question arises whether rapid impulse formation in parasystole and paroxysmal tachycardia are identical. While it is true that a parasystole without exit block presents the picture of a

536

Scherf,

Kyung-Hi-Choi,

paroxysmal tachycardia, some observations appear to speak against the assumption that the two mechanisms are identical. Thus carotid sinus pressure does not slow the paroxysmal tachycardia rhythm as it does the parasystolic rhythm. There are two ways in which rhythmic impulses as formed in a parasystolic center can lead to what would fall into the definition of extrasystole.63 One is the formation of subthreshold impulses which can elicit a response only during the supernormal phase of excitability following a normal, “provoking” beat. The duration of this period is very short, and therefore a beat originating in a parasystolic center will appear to have a fixed coupling. A second possibility would be based on the phenomenon in nerves described by Wedensky.6” He found that subthreshold faradic stimulation of the nerve of a nerve-muscle preparation does not lead to any visible effect; if one suprathreshold effecti1.e stimulus is applied to the nerve, the excitability changes and the same stimuli which were subthreshold before become temporarily capable of eliciting a response. The same phenomenon was observed when the stimuli were caused by local application of crystals of sodium chloride to the nerve instead of the faradic current.“5 Stimulation of the Purkinje fibers of the dog heart with subthreshold condenser discharges also showed no response unless spontaneously or followin,g one electric induction shock, one excitation wave spread over the preparation; then a series of condenser discharges became effective.@ This hyperexcitability following the spread of an impulse lasts longer and appears later than the supernormal phase and therefore seems to be based on a different mechanism.“’ In a disturbance of rhythm caused by such a phenomenon, the coupling is not expected to be absolutely fixed. However, it has been found that, in parasystole with a very rapid center, the variations in the coupling will be small.“Y This is necessarily so since the impulses cannot elicit a response if they fall during the refractory phase and the impulses appearing late in this phase may be conducted with some delay. The ectopic impulses fall, therefore, in a narrow range, and the coupling can show only minor variations. CLINICAL DATA Review of the literature up to 1951 and personal observations revealed only 53 cases of

Bahadori

and

Orphanos

parasystole.’ Since that time many more have been published. It has been estimated that parasystole is observed in 0.04 per cent of routine electrocardiograms.Y The sex of the patient was given in 47 of the cases; 31 were male. In 50 per cent of the cases the age was between 40 and 60.’ Forty-nine of the patients had ventricular parasystole, and of these only 10 had no evidence of organic heart disease. The most frequently encountered conditions were coronary sclerosis and rheumatic fever. Parasystole has been observed in children.“7~68~fig Clinical Sign$cance: It has been said that the presence of parasystole indicates heart disease.12 This, however, is certainly not the case in atria1 parasystole which doubtlessly can appear in normal hearts,33 but it seems that it would apply to the ventricular form. Some of the patients with ventricular parasystole and a supposedly normal heart”’ actually had a history of hypertension (155!/95), toxemia of pregnancy, influenza, nephritis or other conditions which may well have involved the heart. It should not be forgotten, however, that even ventricular tachycardia or attacks of ventricular fibrillation have been observed in “healthy” hearts. We once observed a classic ventricular parasystole in one of our young co-workers who The showed no evidence of heart disease. arrhythmia disappeared when he stopped smoking. We do not agree with the opinion that the presence of ventricular parasystole has the same practical importance as extrasystoleszl The symptoms of parasystole are similar to those caused by extrasystoles, and this is the diagnosis usually made on auscultation. The arrhythmia is often temporary but has been observed once in the atria1 form for one year68 or 15 months,5T and one case has been reported in which the atria1 parasystole persisted for six years.4” SUMMARY Parasystole is defined, and the history of the discovery of this arrhythmia is reviewed. An attempt is made to explain the protection of the ectopic parasystolic center and exit block on the The special basis of known physiologic facts. aspects of atrial, A-V nodal and intermittent parasystole are discussed. The relations of extrasystoles with fixed coupling and parasystolic mechanisms are pointed out. Finally, the action of carotid sinus pressure, digitalis, amyl nitrite and exercise on parasystole are considered. ‘I’IIE AMERICAN

JOURNAL

OF

CARDIOLOGY

Parasystole few remarks are made about portance of parasystole.

A

the clinical

im-

22.

I,EWIS. ‘1’. and \\:\:H~Ix, P. 11. ‘I‘hr- rffrcts of prrmature contractions in \ agotomized dogs. \vith especial

rcfcrcncc

to

atriowntricular

rhythm.

Heart, 5: 335.

23. 1. SCHERF, D. and Scrro rr. 12. Extrasystolrs and :\llird Grune Arrhythmias, p. 1 i 1. New York. 1953. and Stratton. 2. WENCKERACH. K. F. I)ic Arhythmic als :\usdruck bestimmter Funktions-stocrungcn drs Hcrzens. Leipzig, 1903. Engelmann. 3. FLEMING. G. B. Triplr rhythm of thr heart due to ventricular rwtras)xloles. Qwf. J. .\I&, 5: 318, 1911. 4. KAUFMANN. R. and R(~I HBKKGER, Cl. .J. Beitrag zur Kenntnis dcr Entstrhungsweise cxtrasystolischcr Allorhythmien. %tsc hr. ,qes.ruprr. .\fd.. 5 : 349, 1917; 7: 199, 1919: 3: 103, 1919: 11: 40, 1920; 13: 1. 1922. 5. SINGER, Ii. and \Z’IR.I.I,.KR~R(:. H. l:xtrasystolrn als Interferenzerschrinung. Jl’ll”?l. .Inlz. inn. MPd., 1: 391. 1920. 6. ECKEY, P. Untrrsuchungrn zur I:ragc dcr Hxtrasystolcn Entstehrlng durch Interfrrcnz zweier Rhythmen. ZImtrhE~ Arch. klin. Allcd.. 181 : 229, 1937. 7. GALLAVARDIPS, L. awl P~onww. R. 11 propos d’un cas dlx parasystolir dc rythmc lent. iixh. n1nz. coeur, 43: 743, 1950. 8. HOLZMANN. M. Beitrag zur Krnntnis drr Parasystolie. Heloet. .blcd. ilcln. 1 : 723, 1935. 9. SCRERF. D. and Boyn. 1,. .J. Thrrc unusual cases of parasystolr. Am. Heart \J.. 39: 650. 1950. 10. MOBIT~, 1Y. Ucbrr \ rrschirdenr Iintstehungsweise extrasystolischer :\rhythmirn beim Menschen, tin Beitrag zur Fragr der Interferrnz mchrerer Rhythmen. Ztschr. ges. u.uprr. Med.. 34 : 490, 1923. 11. FEHER, S. Ein Fall van Parasystolie nach Flatterarrhythmie. w’ wn. .Arch. inn. .Qfvd.. 15: 29, 192X. 12. FALTITSCHEK, F. and Scae~~, D. Klinischer Beitrag zur Parasystolieflag?. J4’1cn. .Irc/~. iw. Med., 23: 269, 1932. 13. SCHOTT. A. B&ragzur Fragc dcr Parasystole. %tschl-. ges. expw. .bfed., 55: 762. 1027. 14. SCHERF, D. and SCHOTT, A. Parasystolr durch einfache Interferenz mit Uebergang in Bigeminie. Klir,. Wc/1ns&., 9: 2191, 1930. 15. SCHAMROTH, L. and MARRIOTT: H. .J. L. Intcrmittent ventricular parasystole with observations on its relationship to catrasystolic bigeminy. Am. J. Card&., 7: 79’). 1961. 16. SCHER~, D. and CLIILK, F. H. Exprrimcntal parasystole. ilm. Heart .J.. 42: 212, 1951. 17. WINTERBERG, H. Extrasystolrn als Interfewnzerscheinung, Wien. Arch. inn. Med.. 6: 251, 1923. 18. CASTELLANOS, A., .JR.. MAYER. 3. W. and LEMBERG, L. Intermittent parasystole with disturbance in impulse formation and impulse conduction. Acta

cardiol., 17: 49, 1762. 19. HOLZMANN, M. Die Rhythmusstorrunqen

20.

21.

1963

25. 26. 2

i

28.

29.

30.

31.

32.

33. 34.

35.

36. 37.

38.

39.

40.

med. scaudinm. 79: 239, 1932. 41. 42.

drs HerBerlin,

zens. In: Handbuch f. innrre Medizin. 1960. Springer. ZANDER, E. Zur Fragr van der Extrasystolie als Interferenzerscheinung mehrerer Herzrhythmen. Acta med. scandinuu., 67: 1, 1927. VEDOYA, R. Parasistolia. Buenos Aires, 1944. .4. Lopez.

OCTOBER

24.

1914. S(:~IERF, I>. An rxpcrimrntal study of rrriprocdting .lrt/,. In,. Med., 6:: 372. 1941. rhvthm. ~;c:&RP. 1).and Bo\ D. J,. .J. Clinical rlcctrocardiography. cd. 4. p. 415. I,ondon. 1053. JIrinrmann. \\ ACFISTI:IN.hf. L~ntrrsuchllnqvn am Purkinje%/,illl. $‘\. r\prr. .lr. %ur Entstrhnngswrisr drr I,:xtrasystolrn untl dcr rxtrasystolischcn .\llorhythmicn. %/SC/~?.yes. r.xpw Med.. 51 : 810. 1926; 58: 333, 1927; 70: 375. 1930. S(:IiI:RI’. D., (:IIiCIc. F. 13.. Sl:Ll.\Rp. M. M. and ‘l’ERRANOVA, K. Furthrr csprrimcnts on rspwimrntal parasystolc and rxtrasvstolrs in groups. Aoc. sot. Rqw. Rwl. 2 ‘\dN/.>7:: 28. 1951. SCHI:RP. 0.. BLIIMENFEL.D, S. and YII.DIZ. hl. Lxtras);stolrs and parasystolc. :ln,. Jimi .J.. 64: 357, 1962. Scmxv, I). and RoRNEMANN: C. Parasystolr with a rapid vrntricular center. ;l,,i. II,rr,/ .J.. 02: 320, 1061. Ros~:Na~.rwx~~, 15. and \I~IKTERBI-RC;. H. l_I~bcr den dircktcn Nachwris der .4ustrittshlnrkierung hei pinrm Fall? van Parasystolc. J1’1w. :2rth. inn. .ZIrn.. 10: 333. 1929. KAIJFIIANN, R. and RO.rIIRI~R(:ER. (:. .J. L-rber Extrasystolrn und das HIrrvortrrtFn dw ;\utomatic untrqrordnrtrr Zentrrn. K/r,!. JE;hnsc/~., 1: 2150. 1921. S(:HF.RF, D.. Ylr.olz, M. and DE .\RLv.S. I). Atria1 parasystolc. A4m. Heart J., 57: 507. 1959. SCHERI:. D., S~xwr~, A,, R~rn. F:. C. and CIIAMSAI, I). Cc. Intct.mittent parasystolr. Grrtiioloqin, 30: 217, 1957. LANGENDOR~~. K. and PICK. .\. Mrchanisms of intermittent ventricular hisrminy. II. (:ll-~7ll0/ifJll> 11: 431, 1955. MUI.L.ER. P. and BARON, B. CXinical stud& on parasystolc. :li,j. Hmrt J.. 45: 441. 195.1. VEDOYA. R. and BATTINI, A. R. Un cas dr pararritmia mostrando el mccanismo qui ronducr al bigrrninismo cxtrasistolico. Rri,. mqmt. cnrdml., 6: 313. 1939. K~rz: L,. N., J~~XIIELBACHER. J. I.. and S,IR.&USS, S. An unusual cast of auricular parasystolc showing exit block. .4m. Heart .I.. 14: 571. 1937. BIX. H. H. The electrocardiographic pattern of initial stimulation in the lrft auriclr. sinni I&@. .J. (Haltimorr), 2: 37, 1953. .fERVELI.. r\. Ein Fall van Vorhofpal-asystoli(-. .lcln

43.

HOL.ZMANN, M. Beitrag zur KPnntnis der Vorhofparasystole. Cardiologia, 36: 223. 1960. M.\SSIF. E. and \YALSH, T. .I. Clinical Vrctorcardiqraphy and Electrocardioqaphy. Chicago, 1360. Year Book Publishers. RF.NSCHLER. H. E. and HAMM, .I. Ungewoehnlichr supra\rentrikulaere Rhythmusstoerung. Drutsches

.4rch. klin. Afed., 205: 543, 1959. 44.

ANTTONEN, V. M., LESKLNNEN, E. and Observations on atria1 parasystolc. in/~rn. E~mninc. 50: 247, 1961.

RAIJI\IIO, H. d?lrl. mrd.

538

Scherf,

Kyung-Hi-Choi,

45. VEDOYA, R., DUMAS, J. J. and URDAPILLETA, V. Comentarios sobre dos cases de parasistolia. Rec. argent. cardiol., 15: 364, 1948. 46. ATTINGER, E. Zur Pathologic des Vorhofrhythmus und der P-Zacke. Schweiz. med. Wchnschr., 70: 782, 1940. Parasistolia. Presentation de dos 47. GENTILE, C. cases, consideraciones sobre 10s latidos auriculares de fusion. Rev. argent. cardial., 17: 92, 1950. 48. PICK, A. Parasystole. Circulation, 8: 243, 1953. 49. PICK, A., LANGENDORF,R. and KATZ, L. N. Depression of cardiac pacemaker by premature impulses. Am. Heart J., 41: 49, 1951. 50. SCHERF, D., BORNEMANN,C. and YILDIZ, M. A-V nodal parasystole. Am. Heart J., 60: 179, 1960. 51. FREY, W. Der innere Mechanismus der verschiedenen Formen van extrasystolischen Arhythmien. Zenhalbl. Herz. Gef. Krankh., 10: 145, 1918. 52. ROTHBERGER, C. J. Normale und pathologische Physiologie des Herzens. Ergebn. Physiol., 32: 472, 1931. 53. SCHERF, D. and SCHOTT, A. Coupled extrasystoles and automatic ventricular rhythms. Am. Heart J., 41: 291, 1951. 54. GOLBEY, M., LADOPOULOS,C. P., ROTH, F. H. and SCHERF, D. Changes of ventricular impulse formation during carotid pressure in man. Circulation, IO: 735, 1954. 55. MULLER, P. Klinischer Beitrag zur Parasystolie. Cardiologia, 35: 288, 1959. 56, SPANG, K. Die Rhythmusstoerungen des Herzens. Stuttgart, 1957. Thieme. 57. HILL, I. G. W. and CAMERON, J. D. S. A case of parasystole showing simple interference dissociation. Am. Heart J., 1 I : 140, 1936. 58. LEWIS, T. The Mechanism and Graphic Registra-

Bahadori

59.

60. 61.

62.

63. 64.

65.

66.

67.

68.

69.

and Orphanos

tion of the Heart Beat, ed. 3. London, 1925 Shaw and Sons. ILIESCU, C. C. and SEBASTIANI,A. The causation of extrasystolic irregularities of the heart beat, with special reference to the hypothesis of parasystole. Heart, IO: 101, 1923. SCHERP, D. Extrasystolie und Automatie. Wien. klin. Wchnschr., 43: 1527, 1930. GOLDENRERG,M. and ROTIIBERGER,C. J. Experimentelle Beitraege zur Kenntnis der StrophantinExtrasystolen. Ztxhr.ges. exper. MPd., 79: 705, 1931. SCHERF, D. Experimental digitalis and strophanthin extrasystoles. Exper. MPd. & Surgery, 2: 70, 1944. SCHERP, D. The mechanism and treatment of extrasystoles. Prog. Card&was. Dir., 2: 370, 1960. WEDENSKY, N. E. Ueber die Beziehung zwischen Reizung und Erregung im Tetanus. Ber. Akad. Wiss. St. Petersburg, 54: 96, 1936. MOGENDOWITSCH,M. R. Zur Frage ueber die Erregungssummation in einer alterierten Nervenstrecke. Arch. ges Physiol., 226: 104, 1930. GOLDENBERG,M. and ROTHBERGER,C. J. Untersuchungen an der spezifischen Muskulatur de Hundeherzens. Ztschr. ges. exper. Med., 90: 508, 1933. Die Aktivierung der fuer den SAMOJLOFF, A. Muskel unterschwelligen indirekten Reize durch einen maximalen Nerveneinzelreiz. Arch. ges. Physiol., 225: 482, 1930. HEINZ, R. E. and ELDRIDGE, F. L. Ventricular parasystole in a five-year-old child. Am. Heart J., 53: 624, 1957. SCHWARTZ, N. 1~.and MARRIOTT, H. J. L. Unusual dysrhythmia in a normal child. Am. J. Cardiol., IO: 302. 1962.

THE AMERICANJOURNAL OF CARDIOLOGY