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Intermittent ventricular parasystolic bigeminy accompanied by reentrant ventricular extrasystoles
Intermittent VentricularParasystolic Bigeminy Accompanied by Reentrant VentricularExtrasystoles
Koichi Izumi, MD
Abstract: An
extremely rare case of intermittent ventricular parasystolic bigeminy is presented, in which coexisting reentrant ventricular extrasystoles of sinus origin, showing mainly trigeminy, and those of ventricular parasystolic origin, showing a close coupling to the ventricular parasystolic beat, are demonstrated. Such a unique case has never been reported. Timely parasystolic exit block occurring just prior to the anterograde ventricular activation of the sinus impulse was considered to be of critical importance in developing the reentrant extrasystolic trigeminy. Key words: exercise-induced ventricular parasystole, left bundle branch block pattern, ventricular parasystolic impulses, dilazep dihydrochloride.
nisms of intermittent octageminy were not determined with certainty, some ideas based on concealed reentry of the sinus impulse in the vicinity of the parasystolic focus were advanced.
Many cases of intermittent ventricular parasystolic bigeminy have already been reported. l-l* Reentrant ventricular extrasystole may sometimes bring on and terminate ventricular parasystolic bigeminy, and concealed intraventricular reentrant impulse of sinus beat may reset and precipitate ventricular parasystole.r3 On the other hand, occasionally, a late coupled reentrant ventricular extrasystole may be closely coupled with another reentrant ventricular extrasystole, and longitudinal dissociation in the reentrant pathway has been suggested as a mechanism of such a closely coupled ventricular extrasystole.‘4 In the report an extremely rare case of intermittent ventricular parasystolic bigeminy is accompanied by two different reentrant ventricular extrasystoles, viz. reentrant extrasystole caused by sinus impulse and that brought about by manifest reentry of the parasystolic impulse. This was observed in a patient with Parkinson’s disease after slight exercise (climbing and descending stairs). Although the exact mechaFrom Mouridai
Clinic. Atsugi, Kanagawa.
Case Report Electrocardiograms (ECGs) were recorded from a 75-year-old Japanese woman on April 2, 1987, after she climbed and descended stairs very slowly. The ECG tracings in panel 3 of Figure 1 and in Figures 2-4 are selected portions of the same record. There was no history of angina pectoris or myocardial infarction. Three years earlier (April 1984, age 73) she found it difficult to start walking and began to fall forward. She had taken neither reserpine nor phenothiazine drugs. She began to experience an occasional rise of blood pressure up to 184- 192/80-90 mmHg. Parkinson’s disease was indicated by the characteristic tremors affecting the hands that produces pill-rolling movement of the fingers and
Japan.
Reprint requests:KoichiIzumi,Mu, MouridaiClinic, 3-27-l 1 Mouridai, Atsugi, Kanagawa 243, Japan.
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Vol. 23 No. 2 April 1990
Fig. 1. Panel 1 (lead II, at rest). Ventricular quinquageminy and quadrigeminy caused by reentrant ventricular extrasystoles. Panel 2 (three standard leads, at rest). Disappearance of ventricular extrasystoles after the administration of dilazep. The ECG tracings to demonstrate intermittent ventricular parasystolic bigeminy in panel 3 and Figures 2 through 4 are selected portions in the same ECG taken after exercise procedure. Ventricular parasystolic exit block is tentatively marked by X, and ventricular fusion beat is marked by F. Interectopic intervals are shown in hundredths of a second under the baseline. Ladder diagrams are shown in panel 3-B of Figure 1 and records 1 through 2b of Figure 3. A = the atria; A-V = atrioventricular junction; V = ventricles; E = ectopic focus. The ventricular parasystolic rhythm is indicated by solid circles in E. The parasystollc focus is protected from sinus impulses but ectopic atria1 impulses can discharge and reset the ventricular parasystolic pacemaker late in its cycle (open circle) during the supernormal phase of the intervening sinus beat. The mechanism of parasystolic exit block with the subsequent concealed reentry of the sinus impulse to reset the parasystolic cycle (open circle) is illustrated.
thumb and the trunk. She responded favorably to combination tablets of levodopa (100 mg) and carbidopa ( 10 mg) given orally in combination with trihexyphenidyl and dihydroergotoxine mesilate. Reentrant ventricular extrasystoles with left bundle branch block (LBBB) pattern, showing mainly quadrigeminy, octageminy, and quinquageminy, were often recorded at rest (Fig. 1, panel 1). The arrhythmia tended to disappear after the administration of dilazep dihydrochloride 150 mg/day (Fig. 1, panel 2). After treatment, walking for less than 1 minute when blood pressure was 140/90 mmHg and there was no ventricular extrasystole (sinus rate, ap-
prox. 68/min) caused sporadic appearance of reentrant ventricular extrasystoles of 4 beats/mm (sinus rate, approx. 80/min). When this occurred, the extrasystoles disappeared after 1 minute (sinus rate, 78~’ min). On another occasion, walking for less than 1 minute when there was no ventricular extrasystole did not bring about extrasystoles. The occurrence of ventricular extrasystoles, in short, appeared to be partially related to exercise, an increase of heart rate, or an increase in blood pressure, and tended to disappear after the administration of dilazep dihydrochloride, although the arrhythmia was observed occasionally at rest during the treatment.
Ventricular
__._~
~-----~147~~g~~~l54~147~148~
~~-
145 -,,146-:
Parasystole With Reentrant Extrasystoles
_-. ---.. -200 --
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_. 152--
l
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179
148-
-.-_
Fig. 2. Ventricular parasystolic bigeminy is intermittently disrupted by reentrant extrasystolic trigeminy, which occurs due to parasystolic exit block (tentatively marked by X). Reentrant extrasystolic quinquageminy ensues from two successive parasystolic exit blocks. Note that reentrant ventricular extrasystoles have QRS complex with higher and seemingly narrower configuration.
Interpretation of the Electrocardiograms In ECG tracings taken after the exercise procedure when the patient was not treated with dilazep dihydrochloride (Fig. 1, panel 3), the sinus rate was around 86/min and the ventricular extrasystoles were of mainly two types. One is the dominant ventricular extrasystole with QRS of LBBB pattern (width, approx. 0.14) and slight slurring in the middle ascending portion of the R wave, showing ventricular bigeminy. The fluctuating coupling interval to the preceding sinus beat and the presence of fusion beats (marked by F) indicate ventricular parasystolic, showing mainly bigeminy with an intrinsic ectopic
cycle of around 1.43- 1.54 sec. The focus of the ventricular parasystole may be situated, for example, in or near the right bundle branch in the right ventricular outflow tract. The other, with a taller and seemingly slender QRS of the LBBB pattern (width, approx. 0.13 set) tends to give rise to trigeminy. These have a fixed coupling (0.49-0.53 set) to the preceding sinus beat (Figs. 1 and 2) and may represent reentrant ventricular extrasystoles. It appears that these reentrant beats with a short coupling interval ensued from exit block of the parasystolic impulse (tentatively marked by X). Consider that parasystolic exit block occurring timely just prior to the anterograde ventricular activation of the sinus impulse enabled the manifestation of reentrant beat of sinus
6a
6b
7a
8
10 Fig. 3. Some ideas based on the concealed reentry of the sinus impulse to reset the parasystolic pacemaker
are advanced with regard to the mechanisms involved in the development of octageminy. Curved arrows indicate: (1) manifest and concealed reentry of the sinus impulse, resetting the parasystolic cycle, and (2) manifest reentry of the parasystolic impulse. Coupling intervals of the ectopic beats are shown above the baseline in hundredths of a second.
Ventricular
origin. The partial depolarization of the tissue around the ectopic focus due to the blocked impulse may develop the area that recovers conductivity later and is capable of becoming a reentrant pathway for sinus impulse. This gives rise to the reentrant ventricular extrasystole of sinus origin, which has a short coupling interval and resets the ventricular parasystolic pacemaker. Moreover, the parasystolic beats are sporadically coupled by a reentrant beat induced by the parasystolic impulse itself, with a coupling interval of 0.46-0.50 sec. This represents manifest reentry, taking place around the exit pathway of the parasystolic focus. As observed in panel 3B of Figure 1 and record 5 of Figure 3, atria1 premature beats discharged and reset the ventricular parasystolic pacemaker late in its cycle during the supernormal phase of the intervening sinus beat with an escape interval of 1.58-1.59 sec. Two possible interpretations of the effect of parasystolic exit block and the occurrence of concealed reentry of the sinus impulse to reset the ectopic cycle in the development of octageminy are shown in Figure 3. In record 1 of Figure 3, since reentrant ventricular extrasystole has high QRS complex and short coupling interval, it is easy to discriminate between reentrant and parasystolic beats. The occurrence of two consecutive parasystolic exit blocks and the ensuing reentrant beat, with a prolonged reentrant time of 0.56 set, may be the cause of quinquageminy, with interval of 3.45 sec. The postextrasystolic pause following the reentrant beat is longer than that following parasystolic beat. Furthermore, the ascending portion of the inverted T wave of the reentrant beat appears to rise less steeply than that of the parasystolic beat. Thus, the ventricular beat terminating octageminy, with coupling interval of 0.56 set (record 2a, Fig. 3) may also represent a reentrant beat by virtue of the fact that the postextrasystolic pause following it (around 0.92 set) is almost the same as the pauses following the reentrant beats terminating trigeminy and quinquageminy in record 1 of Figure 3 (around 0.93-0.94 set). One possible explanation of octageminy may be as follows. In records 2a, 5, and 6a of Figure 3, the sinus cycle is around 0.70 sec. Suppose, as a simple illustration, that the parasystolic exit block occurs just prior to the ventricular activation of the second intervening sinus impulse, so that the ensuing concealed intraventricular reentry of the sinus impulse resets the parasystolic pacemaker. Then, the subsequent two successive parasystolic exit blocks and the resultant manifestation of reentrant beat by the seventh intervening sinus impulse may account for the development of octageminy terminated by the reen-
Parasystole With Reentrant Extrasystoles
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trant beat. On the other hand, in records 2b, 3, and 4 in Figure 3, two consecutive occurrences of parasystolic exit block with the subsequent intraventricular reentry of the sinus impulse resetting the parasystolic pacemaker and the parasystolic beat taking place afterward may explain the octageminy terminated by the parasystolic beat; this seems reasonable. In records 7a and 8 of Figure 3, the sinus cycle becomes slower (around 0.75-0.78 set). The role of the concealed reentry of the second intervening sinus impulse to reset the parasystolic cycle might be also assumed in developing the octageminy terminated by a reentrant beat with a longer coupling interval of 0.59 sec. However, as it is not necessary to assume such a mechanism in developing the hexageminy terminated by a reentrant beat with a coupling interval of 0.52-0.55 set in records 9 and 10 of Figure 3, three successive parasystolic exit blocks and the ensuing reentrant beat by the seventh intervening sinus impulse may be the most likely explanation with regard to the octageminy in records 7a and 8.
Discussion Since a case of ventricular parasystolic bigeminy in which the long interectopic interval is around 1.72- 1.76 set and the short (intrinsic) ectopic cycle is around 0.84-0.86 set has already been reported,2 it is possible that ventricular parasystolic bigeminy represents a 2 : 1 exit block, but this seems unlikely. Clinical ECG studies of intermittent ventricular parasystole associated with reentrant ventricular extrasystoles have already been reported.‘~‘3~‘5-18 On the other hand, clinical ECG studies demonstrating intermittent ventricular extrasystoles occurring in pairs are few.14,15*19In this regard, the case presented in this report is unique, as the mechanism of developing reentrant ventricular extrasystolic trigeminy disrupting the ventricular parasystolic bigeminy due to the parasystolic exit block occurring just prior to the ventricular activation of sinus impulse is different from any of the previously reported cases. The ECG tracings in Figure 3 seem to indicate a role for concealed reentry of the sinus impulse to reset the parasystolic cycle in the genesis of the long pauses of octageminy. This may well be the possible explanation for some of them, but certainly not in all of them, particularly not for octageminy, when the sinus rate becomes slower. This is the first clinical report to demonstrate an intricate mechanism of parasystolic exit block with the subsequent manifest reentry of the sinus impulse in developing reentrant
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Journal of Electrocardiology Vol. 23 No. 2 April 1990
extrasystolic trigeminy disrupting parasystolic bigeminy. Moreover, ventricular parasystolic bigeminy complicated by reentrant ventricular extrasystoles of sinus origin, showing trigeminy, and coexisting reentrant ventricular extrasystoles of ventricular parasystolic origin, showing a close coupling to the ventricular parasystolic beat, has never been described. A second plausible explanation for ventricular trigeminy might be ventricular parasystole with intermittent triggered activity; the parasystolic activity itself could be concealed and its triggered activity then conducted. Triggered activity might also explain the sporadic occurrence of paired ventricular extrasystoles with a closer coupling interval of 0.46-0.50 sec. Furthermore, both the parasystolic activity and its triggered beat could be concealed, and this could cause octageminy. Therefore, it would be necessary to consider these possibilities, but it does not follow that these possibilities exist, inasmuch as examples of ventricular parasystole accompanied by triggered beat appear never to have been reported. A third plausible explanation for the observed phenomenon would be as follows. The parasystolic activity is concealed, but the electrical activity generated causes reentry and brings about the reentrant beat, which is not of sinus origin. However, this view seems not to be supported by Figure 3, in which the ventricular extrasystoles terminate the long pauses with a prolonged coupling interval of 0.55-0.59 set as the sinus rate becomes slower. The occurrence of activity of ventricular automatic pacemaker, which is sensitive to the sympathetic influence and catecholamines20-22 in relation to an acute increase in blood pressure23 and stretching of the bundle branch system and myocardium, may cause ventricular parasystolic bigeminy, while anxiety at rest, hypoxia, and an increase in sinus rate cause dispersion of the refractoriness in the bundle branches-ventricular myocardium and timely recovery from refractoriness of the reentrant pathway in the bundle branch may lead to the induction of the reentrant ventricular extrasystoles. In this regard, since atrioventricular (A-V) junctional parasystole, reported previously,24 tended to disappear after the administration of dipyridamole, a coronary vasodilator, 75 mgday, according to the patient, hypoxia also seems to be a factor in causing A-V junctional or ventricular parasystole. Dilazep dihydrochloride (tetrahydro- lH- 1,4-diazepine-1,4(5H)-dipropanol bis(3,4,5_trimethoxy benzoate) dihydrochloride monohydrate) is a tertiary diamine derivative of trimethoxybenzoic acid. The following mechanisms have been suggested to account for antiarrhythmic effects of dilazep. (1) It causes marked and persisting increase in myocardial
blood floods. In accordance with the adenosine hypothesis,26 it has been suggested that coronary vasodilating effect of dilazep is primarily due to local potentiation on the vasculature of adenosine endogenously released from cardiac tissue,27 while adenosine potentiation by dilazep has been suggested to be essentially related to its ability to prevent the uptake or degradation of adenosine as the latter passes through the lungs via the pulmonary circulation.28 (2) Dilazep has a local anesthetic effect like that of class 1 agents and a depressant effect on the myocardial membrane. It decreases the magnitude of sodium slow inward current and potassium outward current as well as sodium fast inward current.29-30 By lengthening the effective refractory period of the ventricular myocardium, it may convert unidirectional block to bidirectional block, which seems to explain the efficacy in the treatment of ventricular arrhythmias.29 (3) On the other hand, dilazep has been found to suppress epinephrine or adrenalineinduced ventricular extrasystoles,3’.32 but antiarrhythmic properties resembling beta-adrenergic blocking agents, or calcium antagonist appear not to have been studied extensively.
References 1. Langendorf R, Pick A: Mechanisms of intermittent ventricular bigemlny. II. parasystole, and parasystole or reentry with conduction disturbance. Circulation 11:431, 1955 2. Scherf D, Bomemann C: Parasystole with a rapid ventricular center. Am Heart J 62:320, 1961 3. Moulopoulos DS, Sideris DA: Effect of parasystole on ventricular response to atria1 fibrillation: report of a case. Cardiologia 54:257, 1969 4. Jacobson LB: Spontaneous ventricular parasystole initiating ventricular tachycardia. J Electrocardiol 6:63, 1973 5. Cohen H, Langendorf R, Pick A: Intermittent parasystole: mechanism of protection. Circulation 48: 76 1, 1973 6. Kinosbita S: Wenckebach phenomenon of entrance block in intermittent ventricular parasystole. Chest 66:530, 1974 Kinosbita S, Tanabe Y: Second degree entrance block in intermittent ventricular parasystole. Chest 67:236, 1975 Lightfoot PR: Intermittent parasystole with concealed extrasystollc bigemlny during myocardial infarction. Am Heart J 93:229, 1977 Lightfoot PR: Parasystole simulating ventricular bigeminy with Wenckebach-type coupling prolongation. J Electrocardlol 11:385, 1978
Ventricular 10. Oreto G, Luzza F, Satullo G et al: Intermittent ventricular bigeminy as an expression of modulated parasystole. Am J Cardiol 55:1634, 1985 Il. Oreto G, Donato A, Satullo G et al: Modulated ventricular parasystole manifesting as apparent Wenckebach exit block. Am J Cardiol 58: 1101, 1986 12. Kinoshita S: Mechanisms of intermittent ventricular parasystole due to type II second degree entrance block. J Electrocardiol 16:7, 1983 13. Kinoshita S: Mechanisms of ventricular parasystole. Circulation 58:715, 1978 14. Kinoshita S, Fujita K, Kanda K et al: A cause of paired ventricular extrasystoles. Circulation 60: 1395, 1979 15. Singer DH, Parameswaran R, Drake FT, et al: Ventricular parasystole and reentry: clinical-electrophysiological correlations. Am Heart J 88:79, 1974 16. Kinoshita S: Intermittent parasystole originating in the reentrant path of ventricular extrasystoles. Chest 72:201, 1977 17. Kuo CS, Surawicz B: Coexistence of ventricular parasystole and ventricular couplets: mechanism and clinical significance. Am J Cardiol44:435, 1979 18. Surawicz B, Kuo CS, Reddy P: Reentry near the site of the ventricular parasystolic focus: an ECG study of patients with artificial ventricular pacemakers. J Electrocardiol 13: 103, 1980 19. Schamroth L: Electrocardiographic effects of eyeball compression. Am J Cardiol 2:321, 1958 20. Coumel P, Leclercq JF, Attuel et al: Automatic influences: sympathetic drive and the genesis of ventricular arrhythmias. p. 457. In Novula OS (ed): Cardiac arrhythmias: electrophysiology, diagnosis and management. Williams 8 Wilkins, Baltimore, 1979 2 1. Zipes DP, Foster PR, Troup PJ, Pedersen DH: Atria1 induction of ventricular tachycardia: reentry versus triggered automaticity. Am J Cardiol 44: 1, 1979 22. Wu D, Kou HC, Hung JS: Exercise-triggered paroxysmal ventricular tachycardia: a repetitive rhythmic activity possibly related to afterdepolarization. Ann Intern Med 95:410, 1981
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23. Sideris DA, Chrysos DN, Maliaras GK et al: Effect of acute hypertension on the cardiac rhythm. experimental observations. J Electrocardiol 2 1: 183, 1988 24. Izumi K: Atrio-ventricular junctional parasystole: modulation by sinus impulses. J Electrocardiol20:45, 1987 25. Lenke D, Brock N, Zechel HJ: Zur Pharmacologic von 1, 4-Bis-[3-(3,4,5-trimethoxybenzoyl-oxy)-propylJperhydro- 1,4diazepin (Dilazep I.N.N.): einer neuen koronaraktiven Substanz. Arzneim-Forsch 22:639, 1972 26. Rubio R, Beme RM: Release of adenosine by the normal myocardium in dogs and its relationship to the regulation of coronary resistance. Circ Res 25:407, 1969 26. Buyniski JP, Losada M, Bierwagen ME, Cardier RW: Cerebral and coronary vascular effects of a symmetrical N,N’-disubstituted hexahydrodiazepine. J Pharm Exp Ther 181:522, 1972 28. Sano N: Enhancement of coronary vasodilating action of adenosine by dilazep and dipyridamole in the dog. JJ Pharmacol 24:471, 1974 (in Japanese) 29. Ohno M, Isomura S, Kawabe T et al: Antiarrhythmic effect of dilazep: effect on the electrophysiological properties of ventricular muscle in the in situ studies of dog’s heart. Rinsho-to-kenkyu 56:609, 1979 (in Japanese) 30. Kotake H, Hasegawa J, Yamazaki J et al: The effect of dilazep on membrane potential and membrane currents in the rabbit sino-atria1 node cell. Rinsho-tokenkyu 61:2017, 1984 (in Japanese) 3 1. Sano N, Kawada M, Fukutomi Y: Antiarrhythmic effect of dilazep: effect of dilazep on ouabain and epinephrine-induced ventricular tachycardias, and on aconitine-induced atria1 arrhythmia. Kiso-to-rinsho 8:2013, 1974 (in Japanese) 32. Komori S, Ishii M, Hashimoto K: Antiarrhythmic effects of coronary vasodilators on canine ventricular arrhythmia models. Coronary 1:397, 1984 (in Japanese)
Koichi Izumi, MD
Abstract: An
extremely rare case of intermittent ventricular parasystolic bigeminy is presented, in which coexisting reentrant ventricular extrasystoles of sinus origin, showing mainly trigeminy, and those of ventricular parasystolic origin, showing a close coupling to the ventricular parasystolic beat, are demonstrated. Such a unique case has never been reported. Timely parasystolic exit block occurring just prior to the anterograde ventricular activation of the sinus impulse was considered to be of critical importance in developing the reentrant extrasystolic trigeminy. Key words: exercise-induced ventricular parasystole, left bundle branch block pattern, ventricular parasystolic impulses, dilazep dihydrochloride.
nisms of intermittent octageminy were not determined with certainty, some ideas based on concealed reentry of the sinus impulse in the vicinity of the parasystolic focus were advanced.
Many cases of intermittent ventricular parasystolic bigeminy have already been reported. l-l* Reentrant ventricular extrasystole may sometimes bring on and terminate ventricular parasystolic bigeminy, and concealed intraventricular reentrant impulse of sinus beat may reset and precipitate ventricular parasystole.r3 On the other hand, occasionally, a late coupled reentrant ventricular extrasystole may be closely coupled with another reentrant ventricular extrasystole, and longitudinal dissociation in the reentrant pathway has been suggested as a mechanism of such a closely coupled ventricular extrasystole.‘4 In the report an extremely rare case of intermittent ventricular parasystolic bigeminy is accompanied by two different reentrant ventricular extrasystoles, viz. reentrant extrasystole caused by sinus impulse and that brought about by manifest reentry of the parasystolic impulse. This was observed in a patient with Parkinson’s disease after slight exercise (climbing and descending stairs). Although the exact mechaFrom Mouridai
Clinic. Atsugi, Kanagawa.
Case Report Electrocardiograms (ECGs) were recorded from a 75-year-old Japanese woman on April 2, 1987, after she climbed and descended stairs very slowly. The ECG tracings in panel 3 of Figure 1 and in Figures 2-4 are selected portions of the same record. There was no history of angina pectoris or myocardial infarction. Three years earlier (April 1984, age 73) she found it difficult to start walking and began to fall forward. She had taken neither reserpine nor phenothiazine drugs. She began to experience an occasional rise of blood pressure up to 184- 192/80-90 mmHg. Parkinson’s disease was indicated by the characteristic tremors affecting the hands that produces pill-rolling movement of the fingers and
Japan.
Reprint requests:KoichiIzumi,Mu, MouridaiClinic, 3-27-l 1 Mouridai, Atsugi, Kanagawa 243, Japan.
177
178
Journal of Electrocardiology
Vol. 23 No. 2 April 1990
Fig. 1. Panel 1 (lead II, at rest). Ventricular quinquageminy and quadrigeminy caused by reentrant ventricular extrasystoles. Panel 2 (three standard leads, at rest). Disappearance of ventricular extrasystoles after the administration of dilazep. The ECG tracings to demonstrate intermittent ventricular parasystolic bigeminy in panel 3 and Figures 2 through 4 are selected portions in the same ECG taken after exercise procedure. Ventricular parasystolic exit block is tentatively marked by X, and ventricular fusion beat is marked by F. Interectopic intervals are shown in hundredths of a second under the baseline. Ladder diagrams are shown in panel 3-B of Figure 1 and records 1 through 2b of Figure 3. A = the atria; A-V = atrioventricular junction; V = ventricles; E = ectopic focus. The ventricular parasystolic rhythm is indicated by solid circles in E. The parasystollc focus is protected from sinus impulses but ectopic atria1 impulses can discharge and reset the ventricular parasystolic pacemaker late in its cycle (open circle) during the supernormal phase of the intervening sinus beat. The mechanism of parasystolic exit block with the subsequent concealed reentry of the sinus impulse to reset the parasystolic cycle (open circle) is illustrated.
thumb and the trunk. She responded favorably to combination tablets of levodopa (100 mg) and carbidopa ( 10 mg) given orally in combination with trihexyphenidyl and dihydroergotoxine mesilate. Reentrant ventricular extrasystoles with left bundle branch block (LBBB) pattern, showing mainly quadrigeminy, octageminy, and quinquageminy, were often recorded at rest (Fig. 1, panel 1). The arrhythmia tended to disappear after the administration of dilazep dihydrochloride 150 mg/day (Fig. 1, panel 2). After treatment, walking for less than 1 minute when blood pressure was 140/90 mmHg and there was no ventricular extrasystole (sinus rate, ap-
prox. 68/min) caused sporadic appearance of reentrant ventricular extrasystoles of 4 beats/mm (sinus rate, approx. 80/min). When this occurred, the extrasystoles disappeared after 1 minute (sinus rate, 78~’ min). On another occasion, walking for less than 1 minute when there was no ventricular extrasystole did not bring about extrasystoles. The occurrence of ventricular extrasystoles, in short, appeared to be partially related to exercise, an increase of heart rate, or an increase in blood pressure, and tended to disappear after the administration of dilazep dihydrochloride, although the arrhythmia was observed occasionally at rest during the treatment.
Ventricular
__._~
~-----~147~~g~~~l54~147~148~
~~-
145 -,,146-:
Parasystole With Reentrant Extrasystoles
_-. ---.. -200 --
--1’19,-~_~~59-_~~44~~~4g~-.-~148~-~-_147:-:_
_. 152--
l
lzumi
179
148-
-.-_
Fig. 2. Ventricular parasystolic bigeminy is intermittently disrupted by reentrant extrasystolic trigeminy, which occurs due to parasystolic exit block (tentatively marked by X). Reentrant extrasystolic quinquageminy ensues from two successive parasystolic exit blocks. Note that reentrant ventricular extrasystoles have QRS complex with higher and seemingly narrower configuration.
Interpretation of the Electrocardiograms In ECG tracings taken after the exercise procedure when the patient was not treated with dilazep dihydrochloride (Fig. 1, panel 3), the sinus rate was around 86/min and the ventricular extrasystoles were of mainly two types. One is the dominant ventricular extrasystole with QRS of LBBB pattern (width, approx. 0.14) and slight slurring in the middle ascending portion of the R wave, showing ventricular bigeminy. The fluctuating coupling interval to the preceding sinus beat and the presence of fusion beats (marked by F) indicate ventricular parasystolic, showing mainly bigeminy with an intrinsic ectopic
cycle of around 1.43- 1.54 sec. The focus of the ventricular parasystole may be situated, for example, in or near the right bundle branch in the right ventricular outflow tract. The other, with a taller and seemingly slender QRS of the LBBB pattern (width, approx. 0.13 set) tends to give rise to trigeminy. These have a fixed coupling (0.49-0.53 set) to the preceding sinus beat (Figs. 1 and 2) and may represent reentrant ventricular extrasystoles. It appears that these reentrant beats with a short coupling interval ensued from exit block of the parasystolic impulse (tentatively marked by X). Consider that parasystolic exit block occurring timely just prior to the anterograde ventricular activation of the sinus impulse enabled the manifestation of reentrant beat of sinus
6a
6b
7a
8
10 Fig. 3. Some ideas based on the concealed reentry of the sinus impulse to reset the parasystolic pacemaker
are advanced with regard to the mechanisms involved in the development of octageminy. Curved arrows indicate: (1) manifest and concealed reentry of the sinus impulse, resetting the parasystolic cycle, and (2) manifest reentry of the parasystolic impulse. Coupling intervals of the ectopic beats are shown above the baseline in hundredths of a second.
Ventricular
origin. The partial depolarization of the tissue around the ectopic focus due to the blocked impulse may develop the area that recovers conductivity later and is capable of becoming a reentrant pathway for sinus impulse. This gives rise to the reentrant ventricular extrasystole of sinus origin, which has a short coupling interval and resets the ventricular parasystolic pacemaker. Moreover, the parasystolic beats are sporadically coupled by a reentrant beat induced by the parasystolic impulse itself, with a coupling interval of 0.46-0.50 sec. This represents manifest reentry, taking place around the exit pathway of the parasystolic focus. As observed in panel 3B of Figure 1 and record 5 of Figure 3, atria1 premature beats discharged and reset the ventricular parasystolic pacemaker late in its cycle during the supernormal phase of the intervening sinus beat with an escape interval of 1.58-1.59 sec. Two possible interpretations of the effect of parasystolic exit block and the occurrence of concealed reentry of the sinus impulse to reset the ectopic cycle in the development of octageminy are shown in Figure 3. In record 1 of Figure 3, since reentrant ventricular extrasystole has high QRS complex and short coupling interval, it is easy to discriminate between reentrant and parasystolic beats. The occurrence of two consecutive parasystolic exit blocks and the ensuing reentrant beat, with a prolonged reentrant time of 0.56 set, may be the cause of quinquageminy, with interval of 3.45 sec. The postextrasystolic pause following the reentrant beat is longer than that following parasystolic beat. Furthermore, the ascending portion of the inverted T wave of the reentrant beat appears to rise less steeply than that of the parasystolic beat. Thus, the ventricular beat terminating octageminy, with coupling interval of 0.56 set (record 2a, Fig. 3) may also represent a reentrant beat by virtue of the fact that the postextrasystolic pause following it (around 0.92 set) is almost the same as the pauses following the reentrant beats terminating trigeminy and quinquageminy in record 1 of Figure 3 (around 0.93-0.94 set). One possible explanation of octageminy may be as follows. In records 2a, 5, and 6a of Figure 3, the sinus cycle is around 0.70 sec. Suppose, as a simple illustration, that the parasystolic exit block occurs just prior to the ventricular activation of the second intervening sinus impulse, so that the ensuing concealed intraventricular reentry of the sinus impulse resets the parasystolic pacemaker. Then, the subsequent two successive parasystolic exit blocks and the resultant manifestation of reentrant beat by the seventh intervening sinus impulse may account for the development of octageminy terminated by the reen-
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l
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trant beat. On the other hand, in records 2b, 3, and 4 in Figure 3, two consecutive occurrences of parasystolic exit block with the subsequent intraventricular reentry of the sinus impulse resetting the parasystolic pacemaker and the parasystolic beat taking place afterward may explain the octageminy terminated by the parasystolic beat; this seems reasonable. In records 7a and 8 of Figure 3, the sinus cycle becomes slower (around 0.75-0.78 set). The role of the concealed reentry of the second intervening sinus impulse to reset the parasystolic cycle might be also assumed in developing the octageminy terminated by a reentrant beat with a longer coupling interval of 0.59 sec. However, as it is not necessary to assume such a mechanism in developing the hexageminy terminated by a reentrant beat with a coupling interval of 0.52-0.55 set in records 9 and 10 of Figure 3, three successive parasystolic exit blocks and the ensuing reentrant beat by the seventh intervening sinus impulse may be the most likely explanation with regard to the octageminy in records 7a and 8.
Discussion Since a case of ventricular parasystolic bigeminy in which the long interectopic interval is around 1.72- 1.76 set and the short (intrinsic) ectopic cycle is around 0.84-0.86 set has already been reported,2 it is possible that ventricular parasystolic bigeminy represents a 2 : 1 exit block, but this seems unlikely. Clinical ECG studies of intermittent ventricular parasystole associated with reentrant ventricular extrasystoles have already been reported.‘~‘3~‘5-18 On the other hand, clinical ECG studies demonstrating intermittent ventricular extrasystoles occurring in pairs are few.14,15*19In this regard, the case presented in this report is unique, as the mechanism of developing reentrant ventricular extrasystolic trigeminy disrupting the ventricular parasystolic bigeminy due to the parasystolic exit block occurring just prior to the ventricular activation of sinus impulse is different from any of the previously reported cases. The ECG tracings in Figure 3 seem to indicate a role for concealed reentry of the sinus impulse to reset the parasystolic cycle in the genesis of the long pauses of octageminy. This may well be the possible explanation for some of them, but certainly not in all of them, particularly not for octageminy, when the sinus rate becomes slower. This is the first clinical report to demonstrate an intricate mechanism of parasystolic exit block with the subsequent manifest reentry of the sinus impulse in developing reentrant
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extrasystolic trigeminy disrupting parasystolic bigeminy. Moreover, ventricular parasystolic bigeminy complicated by reentrant ventricular extrasystoles of sinus origin, showing trigeminy, and coexisting reentrant ventricular extrasystoles of ventricular parasystolic origin, showing a close coupling to the ventricular parasystolic beat, has never been described. A second plausible explanation for ventricular trigeminy might be ventricular parasystole with intermittent triggered activity; the parasystolic activity itself could be concealed and its triggered activity then conducted. Triggered activity might also explain the sporadic occurrence of paired ventricular extrasystoles with a closer coupling interval of 0.46-0.50 sec. Furthermore, both the parasystolic activity and its triggered beat could be concealed, and this could cause octageminy. Therefore, it would be necessary to consider these possibilities, but it does not follow that these possibilities exist, inasmuch as examples of ventricular parasystole accompanied by triggered beat appear never to have been reported. A third plausible explanation for the observed phenomenon would be as follows. The parasystolic activity is concealed, but the electrical activity generated causes reentry and brings about the reentrant beat, which is not of sinus origin. However, this view seems not to be supported by Figure 3, in which the ventricular extrasystoles terminate the long pauses with a prolonged coupling interval of 0.55-0.59 set as the sinus rate becomes slower. The occurrence of activity of ventricular automatic pacemaker, which is sensitive to the sympathetic influence and catecholamines20-22 in relation to an acute increase in blood pressure23 and stretching of the bundle branch system and myocardium, may cause ventricular parasystolic bigeminy, while anxiety at rest, hypoxia, and an increase in sinus rate cause dispersion of the refractoriness in the bundle branches-ventricular myocardium and timely recovery from refractoriness of the reentrant pathway in the bundle branch may lead to the induction of the reentrant ventricular extrasystoles. In this regard, since atrioventricular (A-V) junctional parasystole, reported previously,24 tended to disappear after the administration of dipyridamole, a coronary vasodilator, 75 mgday, according to the patient, hypoxia also seems to be a factor in causing A-V junctional or ventricular parasystole. Dilazep dihydrochloride (tetrahydro- lH- 1,4-diazepine-1,4(5H)-dipropanol bis(3,4,5_trimethoxy benzoate) dihydrochloride monohydrate) is a tertiary diamine derivative of trimethoxybenzoic acid. The following mechanisms have been suggested to account for antiarrhythmic effects of dilazep. (1) It causes marked and persisting increase in myocardial
blood floods. In accordance with the adenosine hypothesis,26 it has been suggested that coronary vasodilating effect of dilazep is primarily due to local potentiation on the vasculature of adenosine endogenously released from cardiac tissue,27 while adenosine potentiation by dilazep has been suggested to be essentially related to its ability to prevent the uptake or degradation of adenosine as the latter passes through the lungs via the pulmonary circulation.28 (2) Dilazep has a local anesthetic effect like that of class 1 agents and a depressant effect on the myocardial membrane. It decreases the magnitude of sodium slow inward current and potassium outward current as well as sodium fast inward current.29-30 By lengthening the effective refractory period of the ventricular myocardium, it may convert unidirectional block to bidirectional block, which seems to explain the efficacy in the treatment of ventricular arrhythmias.29 (3) On the other hand, dilazep has been found to suppress epinephrine or adrenalineinduced ventricular extrasystoles,3’.32 but antiarrhythmic properties resembling beta-adrenergic blocking agents, or calcium antagonist appear not to have been studied extensively.
References 1. Langendorf R, Pick A: Mechanisms of intermittent ventricular bigemlny. II. parasystole, and parasystole or reentry with conduction disturbance. Circulation 11:431, 1955 2. Scherf D, Bomemann C: Parasystole with a rapid ventricular center. Am Heart J 62:320, 1961 3. Moulopoulos DS, Sideris DA: Effect of parasystole on ventricular response to atria1 fibrillation: report of a case. Cardiologia 54:257, 1969 4. Jacobson LB: Spontaneous ventricular parasystole initiating ventricular tachycardia. J Electrocardiol 6:63, 1973 5. Cohen H, Langendorf R, Pick A: Intermittent parasystole: mechanism of protection. Circulation 48: 76 1, 1973 6. Kinosbita S: Wenckebach phenomenon of entrance block in intermittent ventricular parasystole. Chest 66:530, 1974 Kinosbita S, Tanabe Y: Second degree entrance block in intermittent ventricular parasystole. Chest 67:236, 1975 Lightfoot PR: Intermittent parasystole with concealed extrasystollc bigemlny during myocardial infarction. Am Heart J 93:229, 1977 Lightfoot PR: Parasystole simulating ventricular bigeminy with Wenckebach-type coupling prolongation. J Electrocardlol 11:385, 1978
Ventricular 10. Oreto G, Luzza F, Satullo G et al: Intermittent ventricular bigeminy as an expression of modulated parasystole. Am J Cardiol 55:1634, 1985 Il. Oreto G, Donato A, Satullo G et al: Modulated ventricular parasystole manifesting as apparent Wenckebach exit block. Am J Cardiol 58: 1101, 1986 12. Kinoshita S: Mechanisms of intermittent ventricular parasystole due to type II second degree entrance block. J Electrocardiol 16:7, 1983 13. Kinoshita S: Mechanisms of ventricular parasystole. Circulation 58:715, 1978 14. Kinoshita S, Fujita K, Kanda K et al: A cause of paired ventricular extrasystoles. Circulation 60: 1395, 1979 15. Singer DH, Parameswaran R, Drake FT, et al: Ventricular parasystole and reentry: clinical-electrophysiological correlations. Am Heart J 88:79, 1974 16. Kinoshita S: Intermittent parasystole originating in the reentrant path of ventricular extrasystoles. Chest 72:201, 1977 17. Kuo CS, Surawicz B: Coexistence of ventricular parasystole and ventricular couplets: mechanism and clinical significance. Am J Cardiol44:435, 1979 18. Surawicz B, Kuo CS, Reddy P: Reentry near the site of the ventricular parasystolic focus: an ECG study of patients with artificial ventricular pacemakers. J Electrocardiol 13: 103, 1980 19. Schamroth L: Electrocardiographic effects of eyeball compression. Am J Cardiol 2:321, 1958 20. Coumel P, Leclercq JF, Attuel et al: Automatic influences: sympathetic drive and the genesis of ventricular arrhythmias. p. 457. In Novula OS (ed): Cardiac arrhythmias: electrophysiology, diagnosis and management. Williams 8 Wilkins, Baltimore, 1979 2 1. Zipes DP, Foster PR, Troup PJ, Pedersen DH: Atria1 induction of ventricular tachycardia: reentry versus triggered automaticity. Am J Cardiol 44: 1, 1979 22. Wu D, Kou HC, Hung JS: Exercise-triggered paroxysmal ventricular tachycardia: a repetitive rhythmic activity possibly related to afterdepolarization. Ann Intern Med 95:410, 1981
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23. Sideris DA, Chrysos DN, Maliaras GK et al: Effect of acute hypertension on the cardiac rhythm. experimental observations. J Electrocardiol 2 1: 183, 1988 24. Izumi K: Atrio-ventricular junctional parasystole: modulation by sinus impulses. J Electrocardiol20:45, 1987 25. Lenke D, Brock N, Zechel HJ: Zur Pharmacologic von 1, 4-Bis-[3-(3,4,5-trimethoxybenzoyl-oxy)-propylJperhydro- 1,4diazepin (Dilazep I.N.N.): einer neuen koronaraktiven Substanz. Arzneim-Forsch 22:639, 1972 26. Rubio R, Beme RM: Release of adenosine by the normal myocardium in dogs and its relationship to the regulation of coronary resistance. Circ Res 25:407, 1969 26. Buyniski JP, Losada M, Bierwagen ME, Cardier RW: Cerebral and coronary vascular effects of a symmetrical N,N’-disubstituted hexahydrodiazepine. J Pharm Exp Ther 181:522, 1972 28. Sano N: Enhancement of coronary vasodilating action of adenosine by dilazep and dipyridamole in the dog. JJ Pharmacol 24:471, 1974 (in Japanese) 29. Ohno M, Isomura S, Kawabe T et al: Antiarrhythmic effect of dilazep: effect on the electrophysiological properties of ventricular muscle in the in situ studies of dog’s heart. Rinsho-to-kenkyu 56:609, 1979 (in Japanese) 30. Kotake H, Hasegawa J, Yamazaki J et al: The effect of dilazep on membrane potential and membrane currents in the rabbit sino-atria1 node cell. Rinsho-tokenkyu 61:2017, 1984 (in Japanese) 3 1. Sano N, Kawada M, Fukutomi Y: Antiarrhythmic effect of dilazep: effect of dilazep on ouabain and epinephrine-induced ventricular tachycardias, and on aconitine-induced atria1 arrhythmia. Kiso-to-rinsho 8:2013, 1974 (in Japanese) 32. Komori S, Ishii M, Hashimoto K: Antiarrhythmic effects of coronary vasodilators on canine ventricular arrhythmia models. Coronary 1:397, 1984 (in Japanese)