- Email: [email protected]
Rate-dependent patterns of modulated ventricular parasystole
Rate-Dependent .katternsof Modulated VentricularParasystole J6ZSEF
TENCZER, MD, and LhZLI)
The effects of ventricular uacino on the arranhement of ventricular parasystolic‘ beats were studied-M 14 pat,ients. By analyzing the effects of various pacing rates and modalities, it was found that both rate and pattern of manifest parasystolic beats were intimately related to the rate and coupling interval of the paced rhythm. Our findings indicate that (i) fixed coupling of ectopic beats is not incompatible with parasystole; (2) modulated parasystole may manifest as fixed rate classic parasystole; (3) a
MD
parasystolic pacemaker can be entrained by a wide range of driving rates both above and below the intrinsic rate of the parasystole; and (4) with different driving rates, these rate-dependent patterns can be observed in the same patient. Our observations suggest that spontaneous or drug-induced changes in the heart rate can lead to major alterations in the frequency and patterns of ventricular parasystole. (Am J Cardiol 1988;57:578-581)
T ’
he.2 major electrophysiologic mechanisms believed to result in premature ventricular beats include the firing of a ventricular focus and reentry. The diagnosis of parasystole is established when ectopic beats occur with variable coupling times, form fusion complexes, and when interectopic intervals are simple multiples of a common denominator. Ectopic beats are usually considered to be reentrant if they are coupled ‘to the preceding beats at a fixed interval. However, recent experimental studies1-7 from Moe’s laboratory clearly show that these diagnostic characteristics do not reliably distinguish reentry from parasystole. Moe et al showed that coupled beats can result from both mechanisms, and the rate and manifestations of a parasystolic rhythm are sensitive functions of the driving frequency. Earlier, deviations from the classic pattern of parasystole were ascribed to variations in the degree of entrance or exit block around the parasystole, to capture ,and resetting of the pacemaker by extraneous impulses, to microreentry in the exit pathway of the parasystole, and to spontaneous fluctuations in the discharge rate.8-13Although recent reports indicate that From the Third Department of Medicine, Semmelweis sity Medical School, Budapest, Hungary. Manuscript July 8, 1985; revised manuscript received September accepted September 16,1985. Addresss for reprints: Jbzsef Tenczer, MD, Third ment of Medicine, Semmelweis University Medical Eiitviis utca 12, Budapest 1121, Hungary.
LIlTMANN,
electrotonic modulation may also be operative in human parasystole, the changes of parasystolic patterns induced by changes in the driving rate have not been systematically evaluated .14-lgOur study was therefore undertaken to analyze the effects of ventricular pacing on the patterns of modulated ventricular parasystole in humans.
Methods
Univerreceived 10, 1985,
We studied 14 patients with ventricular parasystole. Eight patients had third-degree atrioventricular (AV) block and 6 had high-grade AV block. In each patient a temporary pacemaker electrode had been inserted because of symptomatic AV block. After each patient gave informed consent, continuous and programmed right ventricular stimulation was performed by 2-ms square-wave impulses at twice diastolic threshold. The effects of different pacing rates on the patterns of parasystolic manifestation were studied. Two intervals were measured: intrinsic parasystolic cycle length [XX interval], which was the interval between 2 consecutive parasystolic beats not containing any interposed nonparasystolic beat, and modulated parasystolic cycle length, which was the measured or calculated interval between 2 consecutive parasystolic beats containing 1 or more nonparasystolic beats.
Results Pertinent clinical, electrocardiographic data and the various parasystolic patterns that occurred during ventricular pacing are summarized in Table I. Our
DepartSchool,
576
March 1, 1986
TABLE I incidence
Clinical and Electrocardiographic of Parasystolic Patterns
THE AMERICAN
JOURNAL
QF CARDIOLOGY
Volume 57
577
Data of
Pt
Clinical Diagnosis
EC’S Diagnosis
IPCL
irregular Form
Classic Form
ES Form
Entrainment Form
1 2 3 4 5 6 7 8 9 10 11 12 13 14
HCVD HCVD HCVD HCVD CAD CAD CAD CAD CAD CAD CAD CAD CAD CAD
TAVB HAVB HAVB TAVB TAVB HAVB TAVB TAVB HAVB TAVB HAVB HAVB HAVB HAVB
1480 1400 1200 1280 1320 1600 1200 1560 1400 1800 i280 7100 1440 1240
+ t + + t t t + t + f + -I+
+ 0 0 + t 0 + + 0 t t t t t
t 0 0 t t 0 t t + + + i+ t
+ t + t + t + + t t t t + t
CAD = coronary artery disease; ES = extrasystoie; HAVB = high-grade atrioventricular block; HCVD = hypertensive cardiovascular disease; IPCL = intrinsic parasvstolic cycle length; TAVB = third-degree atrioventricufar block; + . = present; 0 = absent.
cases were unique in that the parasystole was rarely or never disturbed by spontaneous nonparasystolic beats. Consequently, even minor pacing-induced deviations from the intrinsic parasystolic cycle length could be appreciated. By changing the rate of ventricular pacing and the coupling interval of the first paced beat to the parasystolic beat, significant fluctuations of the parasystolic cycle occurred in each patient. Ventricular pacing modulated the parasystolic firing to result in a fixed-rate, classic parasystole in 10 patients and in ventricular extrasystole with fixed coupling in 11 patients. The parasystolic rhythm was entrained at certain rates of the paced ventricular rhythm in each patient, i.e., the parasystolic pacemaker was forced to fire in simple harmonic relation to the driving rate both above and below its intrinsic rate. Several of our findings are illustrated by selected tracings from case 1. This patient had atria1 fibrillation, third-degree AV block and a ventricular escape rhythm. The escape rhythm behaved as a modulated parasystole, since extrastimuli induced during the first part of the parasystolic cycle delayed the next parasystolic beat, while extrastimuli elicited during the second part of the parasystolic cycle accelerated the next parasystolic discharge. This biphasic response of the parasystole to programmed extrastimuli is shown in Figure 1. The tracings in Figure 2 were selected from a long continuous recording. The intrinsic parasystolic cycle length during the study measured 1,520 ms. Ventricular pacing in lines 1 and 2 resulted in significant irregularity of the parasystole, with the shortest and longest manifest parasystolic cycles measuring 1,240 and 1,600 ms, respectively. The average cycle length of modulated parasystole calculated from the long interectopic intervals was 1,360 ms in line 1 and 1,335 ms in line 2. Entrainment of the parasystole both in the form of decreasing and increasing its intrinsic rate is demonstrated in lines 3 and 4. When ventricular pacing at a cycle length 40 ms longer than the intrinsic parasystolic cycle length was initiated with a coupling time of
360 ms, the parasystolic rate decreased to that of the driving rate [line 3). Ventricular pacing at a cycle length of 2,680 ms that was initiated with a coupling interval of 920 ms, in contrast, resulted in an increase of parasystolic rate (line 4). The interectopic intervals containing 2 parasystolic cycles now exactly equal the driving cycle length. Although parasystole appears to be regular, the interectopic intervals really contain an accelerated and a nonmodulated parasystolic cycle. Figure 3 shows concealed entrainment of parasystole. Concealment of the parasystole resulted from ventric-
-
.--~---------~
*
.
.e w= .
01
4
4
XS
4
‘: . .e
: 8
4
100
%
FIGURE 1. Case 1. Biphasic effects of ventricular extrastimuli on the intrinsic parasystolic cycle lengths. The modulated parasystotic cycle lengths (XSX) and the coupling intervals of the ventricular extrastimuli (XS) are expressed as a percent of the intrinsic parasystolic cycle length.
578
MODULATED
PARASYSTOLE
ular pacing initiated with appropriate coupling intervals: in line 1, the pacing cycle length was 1,160 ms, in lines 2 and 3 it was 700 ms, and in lines 4 and 5 it was 620 ms. Cessation of ventricular pacing at each pacing rate resulted in instantaneous emergence of the parasystolic rhythm at its intrinsic rate. This proves that disappearance of the parasystole during ventricular pacing was a result of concealed entrainment rather than cessation of the parasystolic activity. Without the modulating effects of ventricular pacing, several parasystolic beats that fell outside the ventricular refractory period should have become manifest. In Figure 4, lines 1 and 2, ventricular pacing at a cycle length of 900 ms resulted in an apparently fixed rate parasystole with a cycle length of 1,220 to 1,280 ms. This cycle length was more than 2110ms shorter than the intrinsic parasystolic cycle length. Coupling time-dependent effects of ventricular stimulation at a cycle length of
520 ms are shown in Figure 4, lines 3 to 5. Ventricular pacing resulted in concealed entrainment of the parasystole in line 3. Cessation of pacing revealed once more that the intrinsic parasystolic cycle length was unchanged. With the same pacing rate, but with pacing initiated at a different coupling interval, the parasystole occasionally manifested in the form of ventricular extrasystoles with fixed coupling (Fig. 4, lines 4 and 51.
Discussion This study demonstrates the various responses of modulated ventricular parasystole to ventricular pacing. By changing the driving rate and the coupling interval of the paced ventricular rhythm, the following ectopic patterns were observed: (1) The parasystole manifested in the form of extrasystoles with fixed coupling, a pattern previously believed to suggest reentry. (2) The modulated parasystole manifested in the form
FIGURE 2. Case 1. Continuous ventricular pacing resulting in significant irregularity of the parasystole (lines 1 and 2) and significant entrainment of parasystole (lines 3 and 4). X = parasystolic beats; S = paced beats; F(XS) = fusion beats. Numbers above the tracings indicate the parasystolic cycle lengths and interectopic intervals; numbers below the tracings show cycle lengths of ventricular pacing. All intervals in this and subsequent illustrations are expressed in milliseconds.
March 1, 1986
of fixed (classic) parasystole with minimal fluctuations of the calculated cycle lengths. (3) By altering the ratio of the driving rate to the intrinsic rate of the parasystale, manifest and concealed entrainment of the parasystole was elicited. (4) Manipulations of the driving rate resulted in gross alterations of the paraystolic cycle lengths. Major spontaneous fluctuations of the parasystolic rate did not occur during undisturbed parasystole, and spontaneous exit block was never seen; therefore, these mechanisms do not explain the various patterns and rates of the ventricular parasystole induced by pacing. In contrast, each of the changes in rate and manifestation of the parasystole were easily explained by the mechanism of electrotonic modulation.1J~4~5J0
FIGURE 3. Case 1. Ventricular pacing at cycle lengths of 1,160,700 2 and 3 and lines 4 and 5 are continuous recordings. Abbreviations
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 57
579
In each of our cases paced impulses induced early in the parasystolic cycle delayed the subsequent discharge, whereas late extrastimuli accelerated the parasystole. Studies in biologic and mathematical models of modulated parasystole revealed that marked shifts in the rate and pattern of parasystole result from changes in the driving frequency.1-7 We are aware of only 1 clinical study in which the effects of pacing on ventricular parasystole were reported, and this study revealed disappearance of parasystole in 2 patients. In these cases, however, the intrinsic parasystolic cycle lengths were not known, clear-cut evidence supporting electrotonic modulation of the parasystole was absent, and there were significant fluctuations in the parasystolic cycle length. The reason of disappearance of
and 620 ms resulted in concealed as in Figure 2.
entrainment
of the parasystole.
Lines
580
MODULATED
PARASYSTOLE
FIGURE 4. Case 1. Ventricular pacing at a cycle length of 900 ms results in “classic” (fixed) parasystole (lines 1 and 2). Depending on the coupling time at which ventricular pacing was initiated, ventricular pacing resulted in concealed entrainment of the parasystole or in extrasystoles with fixed coupling (lines 3,4 and 5). Lines 1 and 2 and lines 3, 4 and 5 are continuous recordings. Abbrevlations as in previous figures.
the parasystolic beats in these cases therefore remains uncertain.14 Castellanos et alI8 reported 2 cases with concealed 1:l entrainment of the parasystole by the sinus rhythm, and 2 other cases in which pacemaker annihilation was suggested. By analyzing several previously published cases of parasystole, Moe2 and Jalifel’ and their co-workers found that many unusual patterns of parasystolic manifestation were easily explained by electrotonic modulation. Our prospective study using ventricular stimulation demonstrated for the first time that various rate-dependent patterns of modulated parasystole can be reproducibly elicited, and changes in the driving rate may result in several manifestations of parasystole in the same patient. Our study in humans confirmed the characteristics of ratedependent patterns of modulated parasystole described in the biologic and mathematical mode1.l.zThe most striking difference between experimental parasystolic models and our clinical parasystoles was that the periodic@ of ectopic patterns in our study did not occur regularly at all pacing frequencies, presumably because some of the paced beats fell around the unstable crossover period of the phase-response curves, causing inconstant or even opposite modulating ef-
fects. Moreover, the operative parasystolic cycle length and driving cycle length ratios could not be measured directly within wide frequency ranges because parasystolic firing was constantly concealed. Our findings allow us to draw certain conclusions with regard to clinical diagnosis of ventricular ectopy and assessment of drug effects. First, widely used criteria used to differentiate reentrant from parasystolic beats must be supplemented. Spontaneous or pacinginduced variations of basic heart rate may contribute to the differential diagnosis. Second, concealed entrainment may be a mechanism of disappearance of parasystolic beats. Third, a change of heart rate by itself may cause major changes in the incidence and pattern of ventricular ectopic beats. Fourth, favorable and unfavorable effects of antiarrhythmic drug therapy on ventricular ectopy may be the result of druginduced changes in the heart rate instead of a direct antiarrhythmic effect.
References 1. Jalife J, Moe GK. Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 1976;39:801-808. 2. Moe GK, Jalife J, Mueller WJ, Moe B. A mathematical model of parasystole and its application to clinical arrhythmias. Circulation 1977;56:968-979.
March 1. 1986
3. Moe GK, Jalife J. An appraisal of “efficacy” in the treatment of ventricular premature beats. Life Sci 1978;22:1189-1196. 4. Jalife J, Moe GK. A biologic model of parasystole. Am J Cardiol 1979; 43:761-772. 5. Antzelevitch C, Jalife J, Moe GK. Electrotonic modulation of pacemaker activity. Further biological and mathematical observations on the behavior of modulated parasystole. Circulation 1982;66:1225-1232. 6. Rosenthal JE, Ferrier GR. Contribution of variable entrance and exit block in protected foci to arrhythmogenesis in isolated ventricular tissues. Circulation 1983$7:1-E. 7. Antzelevitch C, Bernstein MJ, Feldman HN, Moe GK. Parasystole, reentry and tachycardia: a canine preparation of cardiac arrhythmias occurring across inexcitable segments of tissue. Circulation 1983:68:1101-1115. 6. Katz LN. Pick A. Clinical Electrocardiography. Part I. The Arrhythmias. Philadelphia: Lea 6 Febiger, 1956:147-157. 9. Scherf D, Schott A, Reid EC. Chamsai DG. Intermittent parasystole. Cardiologio 1957;30:217-228. 10. Steffens TG. Intermittent ventricular parasystole due to entrance block failure. Circulation 1971;44:442-445. 11. Cohen H, Langendorf R, Pick A. Intermittent parasystole-mechanism of protection. Circulation 1973;48:761-774. 12. Pick A. The electrophysiologic basis of parasystole and its variants. In: Wellens HJJ, Lie KI, Janse MJ, eds. The Conduction System of the Heart.
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JOURNAL
OF CARDIOLOGY
Volume 57
5
Structure, Function and Clinical Implications. Leiden: Stenfert Kroese, 1976:143-162. 13. Tenczer J, Littmann L. Double irregular ventricular parasystole: ratedependent entrance block and “supernormal” exit conduction. Circulation 1978;58:723-731. 14. Furuse A, Shindo G, Makuuchi H, Saigusa M, Matsuo H, Takayanagi K, moue H. Apparent suppression of ventricular parasystole by cardiac pacing. Jpn Heart J 1979:20:843-851. 15. Furuse A, Matsuo H, Saigusa M. Effects of intervening beats on ectopic cycle length in a patient with ventricular porasystole. Jpn Heart J 1981; 22:201-209. 16. Nau GJ, Aldariz AE, Acunzo RS, Halpern MS, Davidenko JM;EIizari MV, Rosenbaum MB. Modulation of pamsystolic activity by nonparasystolic beats. Circulation 1982;66:462-469. 17. Jalife J, Antzelevitch C, Moe GK. The case for modulated parasystole. PACE 1982;5:911-926. 16. Castellanos A, Luceri R, Moleiro F, Kayden D, Thorman R, Zaman L, Myerburg R. Annihilation, entrainment and modulation of ventricular parasystolic rhythm. Am J Cardiol 1984:54:317-322. 19. Castellanos A, Melgarejo E, Dubois R, Luceri R. Modulation of ventricular parasystole by extraneous depolarizations, J Electrocardiol 1984;17:195-198. 20. Weidmann S. Effect of current flow on the membrane potential of cardiac muscle. J Physiol (Lond) 1951;115:227-236.
TENCZER, MD, and LhZLI)
The effects of ventricular uacino on the arranhement of ventricular parasystolic‘ beats were studied-M 14 pat,ients. By analyzing the effects of various pacing rates and modalities, it was found that both rate and pattern of manifest parasystolic beats were intimately related to the rate and coupling interval of the paced rhythm. Our findings indicate that (i) fixed coupling of ectopic beats is not incompatible with parasystole; (2) modulated parasystole may manifest as fixed rate classic parasystole; (3) a
MD
parasystolic pacemaker can be entrained by a wide range of driving rates both above and below the intrinsic rate of the parasystole; and (4) with different driving rates, these rate-dependent patterns can be observed in the same patient. Our observations suggest that spontaneous or drug-induced changes in the heart rate can lead to major alterations in the frequency and patterns of ventricular parasystole. (Am J Cardiol 1988;57:578-581)
T ’
he.2 major electrophysiologic mechanisms believed to result in premature ventricular beats include the firing of a ventricular focus and reentry. The diagnosis of parasystole is established when ectopic beats occur with variable coupling times, form fusion complexes, and when interectopic intervals are simple multiples of a common denominator. Ectopic beats are usually considered to be reentrant if they are coupled ‘to the preceding beats at a fixed interval. However, recent experimental studies1-7 from Moe’s laboratory clearly show that these diagnostic characteristics do not reliably distinguish reentry from parasystole. Moe et al showed that coupled beats can result from both mechanisms, and the rate and manifestations of a parasystolic rhythm are sensitive functions of the driving frequency. Earlier, deviations from the classic pattern of parasystole were ascribed to variations in the degree of entrance or exit block around the parasystole, to capture ,and resetting of the pacemaker by extraneous impulses, to microreentry in the exit pathway of the parasystole, and to spontaneous fluctuations in the discharge rate.8-13Although recent reports indicate that From the Third Department of Medicine, Semmelweis sity Medical School, Budapest, Hungary. Manuscript July 8, 1985; revised manuscript received September accepted September 16,1985. Addresss for reprints: Jbzsef Tenczer, MD, Third ment of Medicine, Semmelweis University Medical Eiitviis utca 12, Budapest 1121, Hungary.
LIlTMANN,
electrotonic modulation may also be operative in human parasystole, the changes of parasystolic patterns induced by changes in the driving rate have not been systematically evaluated .14-lgOur study was therefore undertaken to analyze the effects of ventricular pacing on the patterns of modulated ventricular parasystole in humans.
Methods
Univerreceived 10, 1985,
We studied 14 patients with ventricular parasystole. Eight patients had third-degree atrioventricular (AV) block and 6 had high-grade AV block. In each patient a temporary pacemaker electrode had been inserted because of symptomatic AV block. After each patient gave informed consent, continuous and programmed right ventricular stimulation was performed by 2-ms square-wave impulses at twice diastolic threshold. The effects of different pacing rates on the patterns of parasystolic manifestation were studied. Two intervals were measured: intrinsic parasystolic cycle length [XX interval], which was the interval between 2 consecutive parasystolic beats not containing any interposed nonparasystolic beat, and modulated parasystolic cycle length, which was the measured or calculated interval between 2 consecutive parasystolic beats containing 1 or more nonparasystolic beats.
Results Pertinent clinical, electrocardiographic data and the various parasystolic patterns that occurred during ventricular pacing are summarized in Table I. Our
DepartSchool,
576
March 1, 1986
TABLE I incidence
Clinical and Electrocardiographic of Parasystolic Patterns
THE AMERICAN
JOURNAL
QF CARDIOLOGY
Volume 57
577
Data of
Pt
Clinical Diagnosis
EC’S Diagnosis
IPCL
irregular Form
Classic Form
ES Form
Entrainment Form
1 2 3 4 5 6 7 8 9 10 11 12 13 14
HCVD HCVD HCVD HCVD CAD CAD CAD CAD CAD CAD CAD CAD CAD CAD
TAVB HAVB HAVB TAVB TAVB HAVB TAVB TAVB HAVB TAVB HAVB HAVB HAVB HAVB
1480 1400 1200 1280 1320 1600 1200 1560 1400 1800 i280 7100 1440 1240
+ t + + t t t + t + f + -I+
+ 0 0 + t 0 + + 0 t t t t t
t 0 0 t t 0 t t + + + i+ t
+ t + t + t + + t t t t + t
CAD = coronary artery disease; ES = extrasystoie; HAVB = high-grade atrioventricular block; HCVD = hypertensive cardiovascular disease; IPCL = intrinsic parasvstolic cycle length; TAVB = third-degree atrioventricufar block; + . = present; 0 = absent.
cases were unique in that the parasystole was rarely or never disturbed by spontaneous nonparasystolic beats. Consequently, even minor pacing-induced deviations from the intrinsic parasystolic cycle length could be appreciated. By changing the rate of ventricular pacing and the coupling interval of the first paced beat to the parasystolic beat, significant fluctuations of the parasystolic cycle occurred in each patient. Ventricular pacing modulated the parasystolic firing to result in a fixed-rate, classic parasystole in 10 patients and in ventricular extrasystole with fixed coupling in 11 patients. The parasystolic rhythm was entrained at certain rates of the paced ventricular rhythm in each patient, i.e., the parasystolic pacemaker was forced to fire in simple harmonic relation to the driving rate both above and below its intrinsic rate. Several of our findings are illustrated by selected tracings from case 1. This patient had atria1 fibrillation, third-degree AV block and a ventricular escape rhythm. The escape rhythm behaved as a modulated parasystole, since extrastimuli induced during the first part of the parasystolic cycle delayed the next parasystolic beat, while extrastimuli elicited during the second part of the parasystolic cycle accelerated the next parasystolic discharge. This biphasic response of the parasystole to programmed extrastimuli is shown in Figure 1. The tracings in Figure 2 were selected from a long continuous recording. The intrinsic parasystolic cycle length during the study measured 1,520 ms. Ventricular pacing in lines 1 and 2 resulted in significant irregularity of the parasystole, with the shortest and longest manifest parasystolic cycles measuring 1,240 and 1,600 ms, respectively. The average cycle length of modulated parasystole calculated from the long interectopic intervals was 1,360 ms in line 1 and 1,335 ms in line 2. Entrainment of the parasystole both in the form of decreasing and increasing its intrinsic rate is demonstrated in lines 3 and 4. When ventricular pacing at a cycle length 40 ms longer than the intrinsic parasystolic cycle length was initiated with a coupling time of
360 ms, the parasystolic rate decreased to that of the driving rate [line 3). Ventricular pacing at a cycle length of 2,680 ms that was initiated with a coupling interval of 920 ms, in contrast, resulted in an increase of parasystolic rate (line 4). The interectopic intervals containing 2 parasystolic cycles now exactly equal the driving cycle length. Although parasystole appears to be regular, the interectopic intervals really contain an accelerated and a nonmodulated parasystolic cycle. Figure 3 shows concealed entrainment of parasystole. Concealment of the parasystole resulted from ventric-
-
.--~---------~
*
.
.e w= .
01
4
4
XS
4
‘: . .e
: 8
4
100
%
FIGURE 1. Case 1. Biphasic effects of ventricular extrastimuli on the intrinsic parasystolic cycle lengths. The modulated parasystotic cycle lengths (XSX) and the coupling intervals of the ventricular extrastimuli (XS) are expressed as a percent of the intrinsic parasystolic cycle length.
578
MODULATED
PARASYSTOLE
ular pacing initiated with appropriate coupling intervals: in line 1, the pacing cycle length was 1,160 ms, in lines 2 and 3 it was 700 ms, and in lines 4 and 5 it was 620 ms. Cessation of ventricular pacing at each pacing rate resulted in instantaneous emergence of the parasystolic rhythm at its intrinsic rate. This proves that disappearance of the parasystole during ventricular pacing was a result of concealed entrainment rather than cessation of the parasystolic activity. Without the modulating effects of ventricular pacing, several parasystolic beats that fell outside the ventricular refractory period should have become manifest. In Figure 4, lines 1 and 2, ventricular pacing at a cycle length of 900 ms resulted in an apparently fixed rate parasystole with a cycle length of 1,220 to 1,280 ms. This cycle length was more than 2110ms shorter than the intrinsic parasystolic cycle length. Coupling time-dependent effects of ventricular stimulation at a cycle length of
520 ms are shown in Figure 4, lines 3 to 5. Ventricular pacing resulted in concealed entrainment of the parasystole in line 3. Cessation of pacing revealed once more that the intrinsic parasystolic cycle length was unchanged. With the same pacing rate, but with pacing initiated at a different coupling interval, the parasystole occasionally manifested in the form of ventricular extrasystoles with fixed coupling (Fig. 4, lines 4 and 51.
Discussion This study demonstrates the various responses of modulated ventricular parasystole to ventricular pacing. By changing the driving rate and the coupling interval of the paced ventricular rhythm, the following ectopic patterns were observed: (1) The parasystole manifested in the form of extrasystoles with fixed coupling, a pattern previously believed to suggest reentry. (2) The modulated parasystole manifested in the form
FIGURE 2. Case 1. Continuous ventricular pacing resulting in significant irregularity of the parasystole (lines 1 and 2) and significant entrainment of parasystole (lines 3 and 4). X = parasystolic beats; S = paced beats; F(XS) = fusion beats. Numbers above the tracings indicate the parasystolic cycle lengths and interectopic intervals; numbers below the tracings show cycle lengths of ventricular pacing. All intervals in this and subsequent illustrations are expressed in milliseconds.
March 1, 1986
of fixed (classic) parasystole with minimal fluctuations of the calculated cycle lengths. (3) By altering the ratio of the driving rate to the intrinsic rate of the parasystale, manifest and concealed entrainment of the parasystole was elicited. (4) Manipulations of the driving rate resulted in gross alterations of the paraystolic cycle lengths. Major spontaneous fluctuations of the parasystolic rate did not occur during undisturbed parasystole, and spontaneous exit block was never seen; therefore, these mechanisms do not explain the various patterns and rates of the ventricular parasystole induced by pacing. In contrast, each of the changes in rate and manifestation of the parasystole were easily explained by the mechanism of electrotonic modulation.1J~4~5J0
FIGURE 3. Case 1. Ventricular pacing at cycle lengths of 1,160,700 2 and 3 and lines 4 and 5 are continuous recordings. Abbreviations
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 57
579
In each of our cases paced impulses induced early in the parasystolic cycle delayed the subsequent discharge, whereas late extrastimuli accelerated the parasystole. Studies in biologic and mathematical models of modulated parasystole revealed that marked shifts in the rate and pattern of parasystole result from changes in the driving frequency.1-7 We are aware of only 1 clinical study in which the effects of pacing on ventricular parasystole were reported, and this study revealed disappearance of parasystole in 2 patients. In these cases, however, the intrinsic parasystolic cycle lengths were not known, clear-cut evidence supporting electrotonic modulation of the parasystole was absent, and there were significant fluctuations in the parasystolic cycle length. The reason of disappearance of
and 620 ms resulted in concealed as in Figure 2.
entrainment
of the parasystole.
Lines
580
MODULATED
PARASYSTOLE
FIGURE 4. Case 1. Ventricular pacing at a cycle length of 900 ms results in “classic” (fixed) parasystole (lines 1 and 2). Depending on the coupling time at which ventricular pacing was initiated, ventricular pacing resulted in concealed entrainment of the parasystole or in extrasystoles with fixed coupling (lines 3,4 and 5). Lines 1 and 2 and lines 3, 4 and 5 are continuous recordings. Abbrevlations as in previous figures.
the parasystolic beats in these cases therefore remains uncertain.14 Castellanos et alI8 reported 2 cases with concealed 1:l entrainment of the parasystole by the sinus rhythm, and 2 other cases in which pacemaker annihilation was suggested. By analyzing several previously published cases of parasystole, Moe2 and Jalifel’ and their co-workers found that many unusual patterns of parasystolic manifestation were easily explained by electrotonic modulation. Our prospective study using ventricular stimulation demonstrated for the first time that various rate-dependent patterns of modulated parasystole can be reproducibly elicited, and changes in the driving rate may result in several manifestations of parasystole in the same patient. Our study in humans confirmed the characteristics of ratedependent patterns of modulated parasystole described in the biologic and mathematical mode1.l.zThe most striking difference between experimental parasystolic models and our clinical parasystoles was that the periodic@ of ectopic patterns in our study did not occur regularly at all pacing frequencies, presumably because some of the paced beats fell around the unstable crossover period of the phase-response curves, causing inconstant or even opposite modulating ef-
fects. Moreover, the operative parasystolic cycle length and driving cycle length ratios could not be measured directly within wide frequency ranges because parasystolic firing was constantly concealed. Our findings allow us to draw certain conclusions with regard to clinical diagnosis of ventricular ectopy and assessment of drug effects. First, widely used criteria used to differentiate reentrant from parasystolic beats must be supplemented. Spontaneous or pacinginduced variations of basic heart rate may contribute to the differential diagnosis. Second, concealed entrainment may be a mechanism of disappearance of parasystolic beats. Third, a change of heart rate by itself may cause major changes in the incidence and pattern of ventricular ectopic beats. Fourth, favorable and unfavorable effects of antiarrhythmic drug therapy on ventricular ectopy may be the result of druginduced changes in the heart rate instead of a direct antiarrhythmic effect.
References 1. Jalife J, Moe GK. Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 1976;39:801-808. 2. Moe GK, Jalife J, Mueller WJ, Moe B. A mathematical model of parasystole and its application to clinical arrhythmias. Circulation 1977;56:968-979.
March 1. 1986
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