Volume
124
Number
3
Mechanism
atrioventricular
Archana Patel, MD, Rick Pumill, Anthony N. Damato, MD Jersey
irregular parasystole
20. Kinoshita S. Concealed ventricular extrasystoles due to interference and due to exit block. Circulation 1975;52:230-7. 21. Kinoshita S, Takahashi K, Nakagawa K, Sagawa A. Tanabe Y, Kawasaki T. Mechanisms of concealed ventricular bigeminy: the concept of concealed conduction in the reentrant pathway. J Electrocardiol 1986;19:67-76. 22. Kinoshita S, Fujita K, Kanda K, Tanabe Y, Kawasaki T. A cause of paired ventricular extrasystoles. Circulation 1979;60: 1395-401. 23. Kinoshita S, Kato Y, Kawasaki T, Okimori K. Ventricular tachycardia initiated by late-coupled ventricular extrasystoles: the concept of longitudinal dissociation in the microreentry pathway. AM HEART J 1982;103:1090-5. 24. Kinoshita S, Nakagawa K, Kato Y, Yasukouchi T. Second degree entrance block with supernormal conduction in intermittent ventricular parasystole. J Electrocardiol1984;17:199-204. 25. Kinoshita S. Mechanisms of intermittent ventricular parasystole due to type II second degree entrance block. J Electrocardiol 1983;16:7-14. 26. Kinoshita S. Mechanisms of ventricular arrhythmias: a theoretical model derived from the concepts of “electrotonic interaction” and “longitudinal dissociation.” Am .I Cardiol 1983:52:1350-4.
13. Nau GJ, Aldariz AE, Acunzo RS, Halpern MS, Davidenko JM, Elizari MV, Rosenbaum MB. Modulation of parasystolic activity by nonparasystolic beats. Circulation 1982;66:462-9. 14. Castellanos A, Luceri RM, Moleiro F, Kayden DS, Trohman RG. Zaman L, Myerberg RJ. Annihilation, entrainment and modulation of ventricular parasystolic rhythms. Am d Cardiol 1984;54:317-22. 1.5. Kinoshita S. Mechanisms of ventricular parasystole. Circulation 197858715-22. 16. Kinoshita S. Konishi G. Mizutani M. Tanabe Y. Influence of sinus impulses on the parasystolic cycle length. J Electrocardiol 1989;22:285-91. 17. ,Jalife J, Moe GK. Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 1976;39:801-8. S, Konishi G, Kinoshita Y. Intermittent ventricu18. Kinoshita lar bigeminy as an expression of two-level Wenckebach periodicity in the reentrant pathway of extrasystoles. PACE Pacing Clin Electrophysiol 1990;13:119-22. 19. Kinoshita S, Konishi G, Kinoshita Y. Mechanism of ventricular extrasystoles with fixed coupling: a theoretical model derived from the concept of longitudinal dissociation in the reentram pathwayofextrasystoles. J Electrocardiol1990;23:24954.
lsorhythmic revisited
of
dissociation
MD, Daniel Goldman,
MD, and
City, N.J.
Control of the atria and ventricles by independent pacemakers defines atrioventricular (AV) dissociation. The term isorhythmic AV dissociation is used when the rates of the independent pacemakers approximate each other and there occurs rhythmic oscillations of the P-P interval within a limited range of PR and RP intervals. The pacemaker for the atria is usually the sinus node but may reside anywhere within the atria, while the pacemaker site for the ventricles may be within the AV junction or the ventricles. Either slowing of the sinus node discharge rate or the emergence of a slightly faster subsidiary pacemaker controlling the ventricles is the common
From the Division of Cardiology, Department of Medicine, Jersey City Medical Center, and Seton Hall University School of Graduate Medical Education. Received for publication Feb. 10, 1992; accepted March 20, 1992. Reprint requests: Anthony N. Damato, MD, Department of Medicine, Jersey City Medical Center. Jersey City, NJ 07304. 411139276
initiating event. As the P-to-QRS interval shortens, the P wave appears to be “marching” through the QRS complex and may come to be located to the right of it. A fixed RP interval may occur for a variable period of time, after which the P-P interval shortens and the P wave again appears to the left of the QRS complex. The term synchronization has been used to describe that period during which the RP interval remains fixed and constant. Fig. 1 is an example of isorhythmic AV dissociation in which all of the features defined above are present, i.e., AV conduction followed by AV dissociation, oscillation of the P waves within a narrow range of PR and RP intervals, a period of synchronization, acceleration of the P wave frequency, and reestablishment of sinus rhythm. Isorhythmic AV dissociation is an uncommonly encountered arrhythmia which, as will be discussed below, can vary somewhat in its electrocardiographic presentation. Little appears in many textbooks of cardiology and electrocardiography regarding the proposed mechanisms underlying this rhythm dis823
824
Patel et al.
American
Fig. 1. A case of isorhythmic
September 1992 Heart Journal
AV dissociation. See text for explanation.
turbance. It is the purpose of this communication to review the limited number of experimental studies on this subject and the interacting mechanisms that have been reported for this cardiac rhythm disturbance. Earlier observers of this phenomenon questioned whether the discharge of two independent pacemakers at the same or nearly the same rates was a chance phenomenon or was the result of some sort of interaction, especially when the two pacemakers appeared synchronized over relatively long periods of time.lMg Segers’ demonstrated that hearts or fragments thereof with intrinsically different heart rates tended to synchronize when juxtaposed. Brief periods in which the independent pacemakers maintained the same rate were termed “accrochage” and longer periods were termed “synchronization.” From the results of these studies, the concept of an electronic interaction was considered to explain isorhythmic AV dissociation. Other concepts that have been proposed included mechanical or reflex interactions,2 a relationship of the sinus node artery pulse to sinus node rate, and the analogy of coupled relaxation oscillators.3-7 None of these proposed concepts adequately explained all of the electrocardiographic characteristics of isorhythmic AV dissociation as observed clinically. In 1965, EttingeriO reported a case of synchronization that occurred during ventricular pacing in a patient with Adams-Stokes attacks caused by intermittent AV conduction. In 1968, Waldo et al.ll reported on 11 patients undergoing cardiac surgery, all of whom had spontaneous isorhythmic AV dissociation. Using atria1 electrograms recorded from the surface of the heart at the time of surgery, they noted that during the period of synchronization (when the RP interval was constant and fixed), the atria were retrogradely activated by
an AV junctional pacemaker. They concluded that isorhythmic AV dissociation occurs when an atria1 rhythm alternates with an AV junctional rhythm caused either by slowing of the dominant atria1 pacemaker or acceleration of a latent pacemaker. They also observed that the retrogradely activated P waves were frequently biphasic (-,+), with the initial negative portion or the entire P wave buried within the QRS complex, thus making the morphology of the P wave on the surface electrocardiogram an inaccurate method of determining whether retrograde activation of the atria is present or not. This study highlighted the fact that when synchronization is the result of retrograde atria1 capture, AV dissociation is no longer present. Subsequently, a number of investigative groups 12-16studied isorhythmic AV dissociation in animals and man by pacing the bundle of His or the right ventricle at rates slightly in excess of the spontaneous atria1 rate. Fig. 2 is an example of one of the methods used in these studies. During studies of pacing-induced isorhythmic AV dissociation, the discharge rate of the artificial pacemaker needs to be finely tuned to the inherent atria1 rate to induce stable periods of this arrhythmia. Levy and Zieskei2 created complete AV block in dogs and studied isorhythmic AV dissociation by pacing the ventricles at rates approximating the sinus rate. They noted that the P wave rhythmically oscillated around the QRS complex. The blood pressure fell when the P wave followed the QRS complex, as opposed to when it preceded it. They attributed the fall in blood pressure to a loss of atria1 contribution to ventricular filling, since the timing of atria1 contraction relative to ventricular contraction is an important determinant of ventricular filling and stroke volume.17-20 At a less than optimum PR interval stroke volume and arterial blood pressure are de-
Volume Number
124 3
Isorhythmic
AV dissociation
825
2. Continuous rhythm strip showingisorhythmic AV dissociationduring right ventricular pacing at 69/min, in a patient with sinusrhythm and complete AV block. Starting with the fifth P wave (upper strip) the P-P interval increasesand the P wave beginsto appear closer to the QRS complex and thereafter to the right of the QRS complex (left portion of lower strip). Subsequently, the P-P interval decreasesand the P wave again appearsin front of the QRS complex.
Fig.
creased; with the reestablishment of an optimum PR interval, these hemodynamic parameters are normalized. Levy and Zieske12 noted that rhythmic oscillations of the P wave were always associated with pro-
nounced oscillations in the arterial blood pressure. However, when the amplitude of the blood pressure oscillations were attenuated, synchronization ceased, suggesting a cause-and-effect relationship. The authors postulated that the fall in blood pressure initiated baroreceptor reflexes operating through the sympathetic-parasympathetic pathways, causing the P wave frequency to increase and move back to the left of the QRS complex. To test this hypothesis, the investigators performed a series of denervation studies. In all five experiments in which vagotomy was first performed, synchronization could still be achieved. Subsequent stellate ganglionectomy prevented synchronization in four of the five experiments. Levy and Zieske concluded that blood pressure changes have an inverse effect on P wave frequency, acting through the baroreceptor reflex. They acknowledged that other mechanisms for changes in P wave frequency may also be operative. Levy and Zieske made no comment as to whether retrograde atria1 activation was present during periods of synchronization, although it seems unlikely given the destructive nature of the procedure to produce complete AV block in these animals (i.e., injection of 95 % ethanol into the region of the AV node). Thus it would appear that synchronization could occur in either the presence or the absence of retrograde atria1 activation. In a follow-up clinical study of seven cases (three with spontaneous isorhythmic AV disso-
ciation and four induced by ventricular pacing), Levy and Edelstein13 found that the inverse relationship between P wave frequency and arterial blood pressure was similar to that observed in experimental animal studies. Paulay et a1.14sl5 studied isorhythmic AV dissociation in dogs with intact AV conduction systems by pacing either the bundle of His or the right ventricle at rates approximating the sinus rate. Right atria1 and aortic pressures were recorded along with multiple bipolar atria1 electrograms, which allowed the sequence of atria1 activation to be determined. Synchronization with rhythmic oscillations of the P wave before and after the QRS complex occurred in animals with and without intact retrograde conduction. At times, fusion activation of the atria by the two independent pacemakers was also observed. These investigators found hemodynamic changes similar to those observed by Levy and Zieske. The loss of atria1 contribution to ventricular filling during synchronization caused a fall in aortic pressure, a rise in right atria1 pressure, and visible distention of the atria. Following upon these hemodynamic changes, accelerating forces caused the P-P interval to decrease with resumption of sinus rhythm and normalization of pressures. The mean percentage increase in sinus acceleration during ventricular pacing was ap11%. The effects of extrinsic cardiac proximately denervation on sinus acceleration were consistent. Acceleration of the sinus node rate could be significantly attenuated by bilateral stellate ganglionectomy and thoracic ganglionectomy, but not by bilateral vagotomy alone. It was also noted following bilateral
828
Pate1 et al.
American
September 1992 Heart Journal
RAP
0.w
1000
MSEC
Fig. 3. Phasic oscillations in P-P frequency, brachial artery pressure (BAP), and right atria1 pressure
(RAP) in a patient with right ventricular pacing-induced isorhythmic AV dissociation.S, pacemakerstimulus interval; IAE, intraatrial electrogram intervals. (From Paulay KL, Damato AN. AM HEART J 1972;83:5-11.)
Fig. 4. A caseof isorhythmic AV dissociationshowinga limited range of PR intervals. Seetext for expla-
nation. stellate ganglionectomy and thoracic ganglionectomy that the rise in right atria1 pressure upon repeat pacing was minimal. Partial restoration of right atria1 pressure by infusion of de&ran resulted in a 4% to 5 % increase in sinus acceleration in these denervated animals. From these results, the authors conclude that right atria1 stretch may be an additional factor causing sinus acceleration. The positive chronotropic effects of increasing right atria1 pressure and of stretch applied to the region of the sinoatrial node have been demonstrated previously.21, 22 Similar findings were observed by Paulay et a1.15in a follow-up clinical report of nine patients studied by
right ventricular pacing. Fig. 3 is reproduced from that report and shows the characteristic phasic changes in P-P interval, brachial artery, and right atria1 pressures. The inverse changes in brachial artery and right atria1 pressure occur simultaneously and are followed by sinus acceleration, reestablishment of an optimal PR interval, and reversal of the hemodynamic alterations. Eight of nine patients demonstrated sinus node acceleration ranging from 4 % to 41.7 5%.One patient not demonstrating sinus acceleration was suspected of having the sick sinus syndrome. Using ventricular pacing, Diedrich and Djonlagic”
Volume
124
Number
3
Isorhythmic
AV dissociation
827
Fig. 5. Isorhythmic AV dissociationwith a relatively long period of synchronization terminated by an antegrade atria1 capture beat. See text for explanation.
studied isorhythmic AV dissociation in cats with intact AV conduction systems. They observed P wave oscillations and concomitant hemodynamic changes similar to those reported by Levy and Zieske and by Paulay et a1.i4,r5 However, unlike Levy and Zieske, Diedrich and Djonlagic found no inhibition of accelerating forces acting on the P-P interval when aortic pressure oscillations were attenuated. They also noted that synchronization persisted when right atria1 pressure was held constant. In their studies, neither vagotomy nor pharmacologic blockage of the parasympathetic and adrenergic nervous systems abolished synchronization. The authors conceded that variations in aortic and right atria1 pressure play an important role in the biologic control system. This leads to synchronization by baroreceptors operating through the parasympathetic and adrenergic nervous system or by a direct influence upon pressure in the sinus node artery. They felt, however, that the dominant mechanism responsible for synchronization was stretching of the sinus node fibers during contraction of the atria against a closed tricuspid valve. From the limited number of experimental studies
on this subject, it would appear that the development of isorhythmic AV dissociation and the particular electrocardiographic patterns resulting therefrom are dependent upon several interacting factors, which include: (1) the relative discharge rates of the dominant atria1 and subsidiary pacemakers; (2) the presence or absence of retrograde conduction; (3) the hemodynamic consequences of the timing of atria1 contraction; (4) the chronotropic response to atria1 stretch; (5) the magnitude of accelerating forces acting to increase P wave frequency (baroreceptor-mediated autonomic nervous system output and atria1 stretch); and (6) responsiveness of the sinus node itself to these accelerating forces. The presence or absence of accelerating forces, their magnitude, and time of onset can cause variations in the oscillations of P waves both to the left and right of the QRS complex. Fig. 4 illustrates a short period of isorhythmic AV dissociation in which the P wave always remains visible to the left of the QRS complex. This is probably the result of the early onset of accelerating forces that limits the range of P wave oscillations. The reports by Levy and Zieskei2
828
Pate1 et al.
American
September 1992 Heart Journal
ture. and by Paulay et al. l5 both illustrate some periods during isorhythmic AV dissociation in which phasic variations in acceleration of P wave frequency sometimes resulted in limited migration of the P wave to the left of the QRS complex and failure to reestablish AV conduction. Fig, 5 of this report illustrates an example of isorhythmic AV dissociation with synchronization and without retrograde atria1 capture in which acceleration of the sinus rate does not occur and AV conduction is reestablished following an antegrade atria1 capture beat. In such cases, failure of sinus acceleration could be the result of an absence of significant hemodynamic changes despite a suboptimal PR interval, absence of significant atria1 stretch, inadequate sensing or output from the baroreceptor reflex arc, or sinus node unresponsiveness. In a strict sense, the term isorhythmic AV dissociation should only be applied to those cases in which retrograde conduction to the atria is not present and the atria and ventricles remain dissociated throughout the entire spectrum of PR and RP intervals, except when AV conduction is reestablished. The presence of retrograde conduction with retrograde activation of the atria interposes a period in which the atria and ventricles are not dissociated. The major problem with a strict application of the term lies in the difficulty in determining from electrocardiographic tracings whether the P wave morphology represents antegrade or retrograde activation of the atria. This is made more difficult by the fact that at times only a portion of the P wave can be seen. A change from a totally positive P wave (leads 2, 3, and AVF) to a totally negative P wave suggests retrograde activation (Fig. 6). A change from a pos-
itive P wave to a biphasic (-,+) P wave suggests partial or total retrograde activation, while a totally unchanged upright P wave suggests the absence of retrograde activation. Conclusions. Isorhythmic AV dissociation, an uncommonly encountered arrhythmia, involves various physiologic mechanisms that determine the different electrocardiographic patterns observed during this rhythm disturbance. From a small number of experimental and human studies done since 1965, it appears that these factors include (1) the relative discharge rates of the dominant and subsidiary pacemakers; (2) the presence or absence of retrograde conduction; (3) the hemodynamic consequences of the timing of atria1 contraction; (4) the magnitude of accelerating forces occurring through baroreceptor reflex mechanisms acting to increase P wave frequency; (5) the chronotropic response to sinoatrial stretch; and (6) responsiveness of the sinus node to accelerating forces. The absence, presence, or magnitude of the above-mentioned interacting factors are responsible for the varied electrocardiographic manifestations of this rhythm disturbance. REFERENCES
1. Segers M. Les phenomenes de synchronization au niveau du co&r. Arch Intern Physiol 1946;54:87-106. 2. Rosenbaum MB. Leneschkin E. Effect of ventricular svstole _ on auricular rhythm In auriculoventricular block. Circulation 1955;11:240-61. 3. James TN. Pulse and impulse in the sinus node. Henry Ford Hosp Med J 1957;15:275-99. 4. Grant RP. The mechanism of AV arrhythmias. Am J Med 1956;20:334-44. 5. Nadeau RA, James TN. Behavior of atrioventricular nodal rhythm following direct perfusion of the sinus node. Can J Physiol Pharmacol 1966;44:317-24.
Volume Number
124 3
6. Roberge 7. 8. 9. 10.
FA, Nadeau RA. Simulation of sinus node activity by an electronic relaxation oscillator. Can J Physiol Pharmacol 1966;44:301-15. Roberge FA, Nadeau RA, James TN. Nature of the PR interval. Cardiovasc Res 1968;2:19-30. Marriott HJL. Atrioventricular synchronization and accrochage. Circulation 1957;14:38-43. Schubart AF, Marriott HJL, Gorten RJ. Isorhythmic dissociation. Atrioventricular dissociation with synchronization. Am J Med 1958;24:209-14. Ettinger P. Synchronization during electrical pacing. AM
Isorhythmic
12. 13.
AL, Vitkainen KJ, Harris PD, Malm JR, Hoffman BF. The mechanism of synchronization in isorhythmic AV dissociation. Some observations on the morphology and polarity of the P wave during retrograde capture of the atria. Circulation 1968;38:880-98. Levy MN, Zieske H. Mechanism of synchronization in isorhythmic dissociation. I. Experiments on dogs. Circ Res 1970;27:429-43. Levy MN, Edelstein J. Mechanisms of synchronization in isorhythmic AV dissociation. II. Clinical studies. Circulation 1970;72:689-99.
829
AN. Atrioventricular interaction in iso14. Paulay KL, Damato rhythmic dissociation. AM HEART J 19'71;82:647-53. interaction in man 15. Paulay KL, Damato AN. Atrioventricular during pacing-induced isorhythmic AV dissociation. AM
HEART J 1972;83:5-11. 16. Diedrich KW, Djonlagic 17.
H. Mechanism of synchronization in isorhythmic dissociation. Cardiology 1973;58:129-38. Brockman SK. Dynamic function of atria1 contraction in regulation of cardiac performance. Am J Physiol 1963;204:597-
603. 18. Brunwald
HEART J 1965;70:110-4. 11. Waldo
AV dissociation
19.
E, Frahm CJ. Studies on Starling’s law of the heart. Circulation 1961;24:633-42. Skinner SN Jr, Mitchell JH, Wallace AG, Sarnoff SJ. Hemodynamic timing of atria1 systole. Am J Physiol 1963;205:499-
503. 20. Mitchell 21. 22.
JH, Gupta DN, Payne RM. Influence on effective ventricular stroke volume. Circ Brooks C McC, Lu HH, Lange G, Mangi R, Effects of localized stretch on the sinoatrial heart. Am J Physiol 1966;211:1197-202. Lange G, Lu HH, Chang A, Brooks C McC. on the isolated cat sinoatrial node. Am 211:1192-6.
of atria1 systole Res 1965;17:11-8. Shaw R, Geoly K. region of the dog Effect of Stretch J Physiol 1966;
124
Number
3
Mechanism
atrioventricular
Archana Patel, MD, Rick Pumill, Anthony N. Damato, MD Jersey
irregular parasystole
20. Kinoshita S. Concealed ventricular extrasystoles due to interference and due to exit block. Circulation 1975;52:230-7. 21. Kinoshita S, Takahashi K, Nakagawa K, Sagawa A. Tanabe Y, Kawasaki T. Mechanisms of concealed ventricular bigeminy: the concept of concealed conduction in the reentrant pathway. J Electrocardiol 1986;19:67-76. 22. Kinoshita S, Fujita K, Kanda K, Tanabe Y, Kawasaki T. A cause of paired ventricular extrasystoles. Circulation 1979;60: 1395-401. 23. Kinoshita S, Kato Y, Kawasaki T, Okimori K. Ventricular tachycardia initiated by late-coupled ventricular extrasystoles: the concept of longitudinal dissociation in the microreentry pathway. AM HEART J 1982;103:1090-5. 24. Kinoshita S, Nakagawa K, Kato Y, Yasukouchi T. Second degree entrance block with supernormal conduction in intermittent ventricular parasystole. J Electrocardiol1984;17:199-204. 25. Kinoshita S. Mechanisms of intermittent ventricular parasystole due to type II second degree entrance block. J Electrocardiol 1983;16:7-14. 26. Kinoshita S. Mechanisms of ventricular arrhythmias: a theoretical model derived from the concepts of “electrotonic interaction” and “longitudinal dissociation.” Am .I Cardiol 1983:52:1350-4.
13. Nau GJ, Aldariz AE, Acunzo RS, Halpern MS, Davidenko JM, Elizari MV, Rosenbaum MB. Modulation of parasystolic activity by nonparasystolic beats. Circulation 1982;66:462-9. 14. Castellanos A, Luceri RM, Moleiro F, Kayden DS, Trohman RG. Zaman L, Myerberg RJ. Annihilation, entrainment and modulation of ventricular parasystolic rhythms. Am d Cardiol 1984;54:317-22. 1.5. Kinoshita S. Mechanisms of ventricular parasystole. Circulation 197858715-22. 16. Kinoshita S. Konishi G. Mizutani M. Tanabe Y. Influence of sinus impulses on the parasystolic cycle length. J Electrocardiol 1989;22:285-91. 17. ,Jalife J, Moe GK. Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 1976;39:801-8. S, Konishi G, Kinoshita Y. Intermittent ventricu18. Kinoshita lar bigeminy as an expression of two-level Wenckebach periodicity in the reentrant pathway of extrasystoles. PACE Pacing Clin Electrophysiol 1990;13:119-22. 19. Kinoshita S, Konishi G, Kinoshita Y. Mechanism of ventricular extrasystoles with fixed coupling: a theoretical model derived from the concept of longitudinal dissociation in the reentram pathwayofextrasystoles. J Electrocardiol1990;23:24954.
lsorhythmic revisited
of
dissociation
MD, Daniel Goldman,
MD, and
City, N.J.
Control of the atria and ventricles by independent pacemakers defines atrioventricular (AV) dissociation. The term isorhythmic AV dissociation is used when the rates of the independent pacemakers approximate each other and there occurs rhythmic oscillations of the P-P interval within a limited range of PR and RP intervals. The pacemaker for the atria is usually the sinus node but may reside anywhere within the atria, while the pacemaker site for the ventricles may be within the AV junction or the ventricles. Either slowing of the sinus node discharge rate or the emergence of a slightly faster subsidiary pacemaker controlling the ventricles is the common
From the Division of Cardiology, Department of Medicine, Jersey City Medical Center, and Seton Hall University School of Graduate Medical Education. Received for publication Feb. 10, 1992; accepted March 20, 1992. Reprint requests: Anthony N. Damato, MD, Department of Medicine, Jersey City Medical Center. Jersey City, NJ 07304. 411139276
initiating event. As the P-to-QRS interval shortens, the P wave appears to be “marching” through the QRS complex and may come to be located to the right of it. A fixed RP interval may occur for a variable period of time, after which the P-P interval shortens and the P wave again appears to the left of the QRS complex. The term synchronization has been used to describe that period during which the RP interval remains fixed and constant. Fig. 1 is an example of isorhythmic AV dissociation in which all of the features defined above are present, i.e., AV conduction followed by AV dissociation, oscillation of the P waves within a narrow range of PR and RP intervals, a period of synchronization, acceleration of the P wave frequency, and reestablishment of sinus rhythm. Isorhythmic AV dissociation is an uncommonly encountered arrhythmia which, as will be discussed below, can vary somewhat in its electrocardiographic presentation. Little appears in many textbooks of cardiology and electrocardiography regarding the proposed mechanisms underlying this rhythm dis823
824
Patel et al.
American
Fig. 1. A case of isorhythmic
September 1992 Heart Journal
AV dissociation. See text for explanation.
turbance. It is the purpose of this communication to review the limited number of experimental studies on this subject and the interacting mechanisms that have been reported for this cardiac rhythm disturbance. Earlier observers of this phenomenon questioned whether the discharge of two independent pacemakers at the same or nearly the same rates was a chance phenomenon or was the result of some sort of interaction, especially when the two pacemakers appeared synchronized over relatively long periods of time.lMg Segers’ demonstrated that hearts or fragments thereof with intrinsically different heart rates tended to synchronize when juxtaposed. Brief periods in which the independent pacemakers maintained the same rate were termed “accrochage” and longer periods were termed “synchronization.” From the results of these studies, the concept of an electronic interaction was considered to explain isorhythmic AV dissociation. Other concepts that have been proposed included mechanical or reflex interactions,2 a relationship of the sinus node artery pulse to sinus node rate, and the analogy of coupled relaxation oscillators.3-7 None of these proposed concepts adequately explained all of the electrocardiographic characteristics of isorhythmic AV dissociation as observed clinically. In 1965, EttingeriO reported a case of synchronization that occurred during ventricular pacing in a patient with Adams-Stokes attacks caused by intermittent AV conduction. In 1968, Waldo et al.ll reported on 11 patients undergoing cardiac surgery, all of whom had spontaneous isorhythmic AV dissociation. Using atria1 electrograms recorded from the surface of the heart at the time of surgery, they noted that during the period of synchronization (when the RP interval was constant and fixed), the atria were retrogradely activated by
an AV junctional pacemaker. They concluded that isorhythmic AV dissociation occurs when an atria1 rhythm alternates with an AV junctional rhythm caused either by slowing of the dominant atria1 pacemaker or acceleration of a latent pacemaker. They also observed that the retrogradely activated P waves were frequently biphasic (-,+), with the initial negative portion or the entire P wave buried within the QRS complex, thus making the morphology of the P wave on the surface electrocardiogram an inaccurate method of determining whether retrograde activation of the atria is present or not. This study highlighted the fact that when synchronization is the result of retrograde atria1 capture, AV dissociation is no longer present. Subsequently, a number of investigative groups 12-16studied isorhythmic AV dissociation in animals and man by pacing the bundle of His or the right ventricle at rates slightly in excess of the spontaneous atria1 rate. Fig. 2 is an example of one of the methods used in these studies. During studies of pacing-induced isorhythmic AV dissociation, the discharge rate of the artificial pacemaker needs to be finely tuned to the inherent atria1 rate to induce stable periods of this arrhythmia. Levy and Zieskei2 created complete AV block in dogs and studied isorhythmic AV dissociation by pacing the ventricles at rates approximating the sinus rate. They noted that the P wave rhythmically oscillated around the QRS complex. The blood pressure fell when the P wave followed the QRS complex, as opposed to when it preceded it. They attributed the fall in blood pressure to a loss of atria1 contribution to ventricular filling, since the timing of atria1 contraction relative to ventricular contraction is an important determinant of ventricular filling and stroke volume.17-20 At a less than optimum PR interval stroke volume and arterial blood pressure are de-
Volume Number
124 3
Isorhythmic
AV dissociation
825
2. Continuous rhythm strip showingisorhythmic AV dissociationduring right ventricular pacing at 69/min, in a patient with sinusrhythm and complete AV block. Starting with the fifth P wave (upper strip) the P-P interval increasesand the P wave beginsto appear closer to the QRS complex and thereafter to the right of the QRS complex (left portion of lower strip). Subsequently, the P-P interval decreasesand the P wave again appearsin front of the QRS complex.
Fig.
creased; with the reestablishment of an optimum PR interval, these hemodynamic parameters are normalized. Levy and Zieske12 noted that rhythmic oscillations of the P wave were always associated with pro-
nounced oscillations in the arterial blood pressure. However, when the amplitude of the blood pressure oscillations were attenuated, synchronization ceased, suggesting a cause-and-effect relationship. The authors postulated that the fall in blood pressure initiated baroreceptor reflexes operating through the sympathetic-parasympathetic pathways, causing the P wave frequency to increase and move back to the left of the QRS complex. To test this hypothesis, the investigators performed a series of denervation studies. In all five experiments in which vagotomy was first performed, synchronization could still be achieved. Subsequent stellate ganglionectomy prevented synchronization in four of the five experiments. Levy and Zieske concluded that blood pressure changes have an inverse effect on P wave frequency, acting through the baroreceptor reflex. They acknowledged that other mechanisms for changes in P wave frequency may also be operative. Levy and Zieske made no comment as to whether retrograde atria1 activation was present during periods of synchronization, although it seems unlikely given the destructive nature of the procedure to produce complete AV block in these animals (i.e., injection of 95 % ethanol into the region of the AV node). Thus it would appear that synchronization could occur in either the presence or the absence of retrograde atria1 activation. In a follow-up clinical study of seven cases (three with spontaneous isorhythmic AV disso-
ciation and four induced by ventricular pacing), Levy and Edelstein13 found that the inverse relationship between P wave frequency and arterial blood pressure was similar to that observed in experimental animal studies. Paulay et a1.14sl5 studied isorhythmic AV dissociation in dogs with intact AV conduction systems by pacing either the bundle of His or the right ventricle at rates approximating the sinus rate. Right atria1 and aortic pressures were recorded along with multiple bipolar atria1 electrograms, which allowed the sequence of atria1 activation to be determined. Synchronization with rhythmic oscillations of the P wave before and after the QRS complex occurred in animals with and without intact retrograde conduction. At times, fusion activation of the atria by the two independent pacemakers was also observed. These investigators found hemodynamic changes similar to those observed by Levy and Zieske. The loss of atria1 contribution to ventricular filling during synchronization caused a fall in aortic pressure, a rise in right atria1 pressure, and visible distention of the atria. Following upon these hemodynamic changes, accelerating forces caused the P-P interval to decrease with resumption of sinus rhythm and normalization of pressures. The mean percentage increase in sinus acceleration during ventricular pacing was ap11%. The effects of extrinsic cardiac proximately denervation on sinus acceleration were consistent. Acceleration of the sinus node rate could be significantly attenuated by bilateral stellate ganglionectomy and thoracic ganglionectomy, but not by bilateral vagotomy alone. It was also noted following bilateral
828
Pate1 et al.
American
September 1992 Heart Journal
RAP
0.w
1000
MSEC
Fig. 3. Phasic oscillations in P-P frequency, brachial artery pressure (BAP), and right atria1 pressure
(RAP) in a patient with right ventricular pacing-induced isorhythmic AV dissociation.S, pacemakerstimulus interval; IAE, intraatrial electrogram intervals. (From Paulay KL, Damato AN. AM HEART J 1972;83:5-11.)
Fig. 4. A caseof isorhythmic AV dissociationshowinga limited range of PR intervals. Seetext for expla-
nation. stellate ganglionectomy and thoracic ganglionectomy that the rise in right atria1 pressure upon repeat pacing was minimal. Partial restoration of right atria1 pressure by infusion of de&ran resulted in a 4% to 5 % increase in sinus acceleration in these denervated animals. From these results, the authors conclude that right atria1 stretch may be an additional factor causing sinus acceleration. The positive chronotropic effects of increasing right atria1 pressure and of stretch applied to the region of the sinoatrial node have been demonstrated previously.21, 22 Similar findings were observed by Paulay et a1.15in a follow-up clinical report of nine patients studied by
right ventricular pacing. Fig. 3 is reproduced from that report and shows the characteristic phasic changes in P-P interval, brachial artery, and right atria1 pressures. The inverse changes in brachial artery and right atria1 pressure occur simultaneously and are followed by sinus acceleration, reestablishment of an optimal PR interval, and reversal of the hemodynamic alterations. Eight of nine patients demonstrated sinus node acceleration ranging from 4 % to 41.7 5%.One patient not demonstrating sinus acceleration was suspected of having the sick sinus syndrome. Using ventricular pacing, Diedrich and Djonlagic”
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Fig. 5. Isorhythmic AV dissociationwith a relatively long period of synchronization terminated by an antegrade atria1 capture beat. See text for explanation.
studied isorhythmic AV dissociation in cats with intact AV conduction systems. They observed P wave oscillations and concomitant hemodynamic changes similar to those reported by Levy and Zieske and by Paulay et a1.i4,r5 However, unlike Levy and Zieske, Diedrich and Djonlagic found no inhibition of accelerating forces acting on the P-P interval when aortic pressure oscillations were attenuated. They also noted that synchronization persisted when right atria1 pressure was held constant. In their studies, neither vagotomy nor pharmacologic blockage of the parasympathetic and adrenergic nervous systems abolished synchronization. The authors conceded that variations in aortic and right atria1 pressure play an important role in the biologic control system. This leads to synchronization by baroreceptors operating through the parasympathetic and adrenergic nervous system or by a direct influence upon pressure in the sinus node artery. They felt, however, that the dominant mechanism responsible for synchronization was stretching of the sinus node fibers during contraction of the atria against a closed tricuspid valve. From the limited number of experimental studies
on this subject, it would appear that the development of isorhythmic AV dissociation and the particular electrocardiographic patterns resulting therefrom are dependent upon several interacting factors, which include: (1) the relative discharge rates of the dominant atria1 and subsidiary pacemakers; (2) the presence or absence of retrograde conduction; (3) the hemodynamic consequences of the timing of atria1 contraction; (4) the chronotropic response to atria1 stretch; (5) the magnitude of accelerating forces acting to increase P wave frequency (baroreceptor-mediated autonomic nervous system output and atria1 stretch); and (6) responsiveness of the sinus node itself to these accelerating forces. The presence or absence of accelerating forces, their magnitude, and time of onset can cause variations in the oscillations of P waves both to the left and right of the QRS complex. Fig. 4 illustrates a short period of isorhythmic AV dissociation in which the P wave always remains visible to the left of the QRS complex. This is probably the result of the early onset of accelerating forces that limits the range of P wave oscillations. The reports by Levy and Zieskei2
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ture. and by Paulay et al. l5 both illustrate some periods during isorhythmic AV dissociation in which phasic variations in acceleration of P wave frequency sometimes resulted in limited migration of the P wave to the left of the QRS complex and failure to reestablish AV conduction. Fig, 5 of this report illustrates an example of isorhythmic AV dissociation with synchronization and without retrograde atria1 capture in which acceleration of the sinus rate does not occur and AV conduction is reestablished following an antegrade atria1 capture beat. In such cases, failure of sinus acceleration could be the result of an absence of significant hemodynamic changes despite a suboptimal PR interval, absence of significant atria1 stretch, inadequate sensing or output from the baroreceptor reflex arc, or sinus node unresponsiveness. In a strict sense, the term isorhythmic AV dissociation should only be applied to those cases in which retrograde conduction to the atria is not present and the atria and ventricles remain dissociated throughout the entire spectrum of PR and RP intervals, except when AV conduction is reestablished. The presence of retrograde conduction with retrograde activation of the atria interposes a period in which the atria and ventricles are not dissociated. The major problem with a strict application of the term lies in the difficulty in determining from electrocardiographic tracings whether the P wave morphology represents antegrade or retrograde activation of the atria. This is made more difficult by the fact that at times only a portion of the P wave can be seen. A change from a totally positive P wave (leads 2, 3, and AVF) to a totally negative P wave suggests retrograde activation (Fig. 6). A change from a pos-
itive P wave to a biphasic (-,+) P wave suggests partial or total retrograde activation, while a totally unchanged upright P wave suggests the absence of retrograde activation. Conclusions. Isorhythmic AV dissociation, an uncommonly encountered arrhythmia, involves various physiologic mechanisms that determine the different electrocardiographic patterns observed during this rhythm disturbance. From a small number of experimental and human studies done since 1965, it appears that these factors include (1) the relative discharge rates of the dominant and subsidiary pacemakers; (2) the presence or absence of retrograde conduction; (3) the hemodynamic consequences of the timing of atria1 contraction; (4) the magnitude of accelerating forces occurring through baroreceptor reflex mechanisms acting to increase P wave frequency; (5) the chronotropic response to sinoatrial stretch; and (6) responsiveness of the sinus node to accelerating forces. The absence, presence, or magnitude of the above-mentioned interacting factors are responsible for the varied electrocardiographic manifestations of this rhythm disturbance. REFERENCES
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FA, Nadeau RA. Simulation of sinus node activity by an electronic relaxation oscillator. Can J Physiol Pharmacol 1966;44:301-15. Roberge FA, Nadeau RA, James TN. Nature of the PR interval. Cardiovasc Res 1968;2:19-30. Marriott HJL. Atrioventricular synchronization and accrochage. Circulation 1957;14:38-43. Schubart AF, Marriott HJL, Gorten RJ. Isorhythmic dissociation. Atrioventricular dissociation with synchronization. Am J Med 1958;24:209-14. Ettinger P. Synchronization during electrical pacing. AM
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AL, Vitkainen KJ, Harris PD, Malm JR, Hoffman BF. The mechanism of synchronization in isorhythmic AV dissociation. Some observations on the morphology and polarity of the P wave during retrograde capture of the atria. Circulation 1968;38:880-98. Levy MN, Zieske H. Mechanism of synchronization in isorhythmic dissociation. I. Experiments on dogs. Circ Res 1970;27:429-43. Levy MN, Edelstein J. Mechanisms of synchronization in isorhythmic AV dissociation. II. Clinical studies. Circulation 1970;72:689-99.
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JH, Gupta DN, Payne RM. Influence on effective ventricular stroke volume. Circ Brooks C McC, Lu HH, Lange G, Mangi R, Effects of localized stretch on the sinoatrial heart. Am J Physiol 1966;211:1197-202. Lange G, Lu HH, Chang A, Brooks C McC. on the isolated cat sinoatrial node. Am 211:1192-6.
of atria1 systole Res 1965;17:11-8. Shaw R, Geoly K. region of the dog Effect of Stretch J Physiol 1966;
