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“Irregular” ventricular parasystole: The influence of sinus rhythm on a parasystolic focus
“Irregular” ventricular parasystole: The influence of sinus rhythm on a parasystolic focus Fifteen cases of ventricular parasystole were analyzed to determine whether the interectopic intervals were regular, as expressed by long intervals being exact multiples of the short ones, or not. The regularity of the interectopic intervals was assessed by means of the variation index: the ratio of the maximal difference between various measurements of the parasystolic cycle length and the mean parasystolic cycle length. Three out of 15 cases had a variation index less than 5, and were classified as “regular parasystole.” Twelve cases were associated with a variation index greater than 7.5, and were classified as “irregular parasystole.” The cases of irregular parasystole were then analyzed to determine whether the variability of the interectopic intervals was casual or dependent on action of the sinus beats. A parasystolic resetting by critically timed sinus impulses (a form of intermittent parasystole) was evident in three cases. The irregularity in the remaining nine cases was due to modulation (viz., due to electrotonic influence exerted by the sinus beats on the parasystolic focus). In every case of modulated parasystole a phase-response curve was constructed, which enabled an analysis of all the interectopic intervals on the basis of a time-dependent effect exerted by the sinus impulses on an otherwise rhythmic parasystolic focus. (ANI HEART J 1988;115:121.)
Giuseppe Oreto, M.D., * Gaetano Satullo, M.D.,* Francesco Luzza, M.D.,* Antonino Donato, M.D.,* Carmelo Maugeri Sacd, M.D.,* Francesco Arrigo, M.D.,* Faust0 Consolo, M.D., and Leo Schamroth, M.D., D-SC.** Messina, Italy,
and Johannesburg, South Africa
It is commonly thought that a parasystolic rhythm is the expression of a totally independent automatic focus. It has also been generally accepted that ectopic beats of parasystolic origin differ substantially from ventricular extrasystoles, lbecause in parasystole the ectopic impulses are delivered regularly by a totally protected and thus independent, rhythmic focus, whereas the ectopic impulses associated with an extrasystolic rhythm are forced or precipitated by the dominant rhythm. Schamroth and Marriott,’ in 1961, postulated that ventricular extrasystoles (namely, the ectopic beats dependent on, or linked to, the dominant rhythm) are due to a semiprotected ventricular ectopic pacemaker that can be electrotonically influenced by the sinus rhythm. This postulate was based on the ‘behavior of the ectopic rhythm during intermittent parasystole.
From the *Istituto Pluridisciplinare di Clinica Medica e Terapia Medica Gene&e e Speciale dell’ Universitd degli Studi di Messina, and **Department of Medicine, University of the Witwatersrand. Reprint requests: Professor L. Schamroth, Department of Medicine, Baragwanath Hospital, P.O. Bertsham 2013, Johannesburg, South Africa.
Steffen$ and Cohen et a1.3 also reported intermittent parasystole, as reflected by the resetting of a parasystolic focus by critically timed nonparasystolic impulses. The electrotonic influence of the sinus impulses on a parasystolic rhythm was first postulated by Schamroth and Marriott (1961)’ and confirmed experimentally by Jalife and Moe (1976),” who used an isolated canine false tendon in a three-bath preparation. Further laboratory confirmation was presented by Moe, u Jalife et al.,’ and Antzelevitch et al.*sg Consequent to such electrotonic influence, the parasystolic discharge may be delayed or accelerated with respect to its scheduled delivery. This phenomenon was defined as “modulation,” and is expressed by a biphasic phase-response curve, the shape of which indicates that relatively early sinus impulses delay the ensuing parasystolic discharge, whereas sinus beats that occur relatively late within the ectopic cycle accelerate the next parasystolic impulse.4 Thus, as a result of the modulation the parasystolic cycle may become variable to the extent that the classic signs of parasystole become less evident or indeed even disappear completely.
Oreto et al.
122
1.The variation index and final diagnosislisted for each case Table
Case
Variation
index
1
12.0
2 3 4 5 6
10.9 7.7 15.8 15.7 8.9
7
11.4 13.4
8 9 10 11 12 13 14 15
13.9 22.0 30.8 40.0 5.0 5.0 3.7
Diagnosis
Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedpsrasysto!e Intermittent parasystole Intermittent parasystole Intermittent parasystole Regularparasystole Regularparasystole Regularparasystole
Subsequent to the descriptions of experimental modulation, several clinical examples of modulated parasystole were published.10-20This article will show that deductive ECG analysis enables the recognition of the influence of sinus rhythm on ventricular parasystolic rhythm. METHODS
The material comprised 15 patients with ventricular parasystole.Each had a continuous ECG recording (paper speed= 25 mm/set), and 3.5 to 5-minute sectionsof these recordingswere analyzed. Eight of the patients were male, and seven were female. Their agesranged from 1 year to 79 years. Ten had no clinically evident organic heart disease,whereasfour had ischemicheart diseaseand one, a dilated cardiomyopathy. The tracings were selected by means of the following criteria: (1) ectopic ventricular beats with markedly variable coupling intervals, reflecting variations greater than 0.20 second; (2) the presence of fusion beats; and (3) interectopic intervals that were more or lessmathematically related (seebelow). Definition of terms. Terms were defined as follows: X = ectopic ventricular beat or fusion beat; X-X = interectopic interval; R = beat of sinus origin; R1, R,, RS, etc. = the first, second,third, etc., consecutive sinusbeats after an ectopic complex that is not interpolated; R, = the first sinusbeat after an interpolated ectopic complex. The sinus beats that follow R0 are defined as R1 (the second consecutive sinusbeat after the interpolated ectopic complex), Rz, and so on. All the intervals between consecutive ventricular complexes and the X-X intervals were measured. (All the measurementsare expressedin hundredths of a second.) The X-X intervals were further subdivided into groups accordingto the number of intervening sinusbeats (ISBs). The following calculations were made for each group: (1) the range of the X-X intervals; (2) the meanand SD of the X-X intervals; (3) the range of the X-R, intervals (the
intervals between an ectopic complex and the ensuing beat); (4) the number of parasystolic cycles contained within the X-X interval; and (5) the average duration of the apparent (manifest or calculated) parasystolic cycle. The parasystolic cycle length is obviously equal to the X-X interval when the X-X interval is madeup of a single parasystolic cycle. In order to calculate the apparent parasystolic cycle from long X-X intervals, it wasassumed that, in the presence of parasystole, any X-X interval results from an integer of ectopic cycles with identical duration. Thus the apparent ectopic cycle length may be obtained by dividing the X-X interval by the number of parasystolic cycles contained in the interval. Moreover, the‘global mean apparent cycle length was calculated for each caseby meansof the values obtained by all the X-X intervals observed in the whole recording. The X-X intervals starting from or ending with a fusion beat, however, were not included in the analysis whenever the fusion beat resembled a sinus complex rather than an ectopic beat; the reasonfor this is that when a fusion beat reflects initial vectors identical to those of the sinusbeat, the exact moment in which the parasystolic impulse is delivered cannot be assessed with certainty. The variation index. A variation index was then calculated for each patient to evaluate the regularity of the interectopic intervals; namely, t,he presenceof a mathematic relationship between the intervals. The following parametersare necessaryto obtain the variation index: (1) the maximal difference among different measurementsof the apparent parasystolic cycle (namely, the difference between the longest and the shortest manifest or calculated parasystolic cycle) and (2) the global mean ectopic cycle length. The variation index is the ratio of these two parameters. In other words, the index correspondsto the maximal variation amongdifferent values of the parasystolic cycle, expressed as percentage of the mean cycle length. For example, if the actual interectopic intervals, in hundredths of a second, are 104, 104, 210 (105 x 2), 100, 100,102,194 (97 X 2), and 102,the variation index results from the difference between 105 (the longest cycle) and 97 (the shortest cycle) expressed as a percentage of the averageapparent cycle length, or 101.6.Thus the index is equal to EV101.6X 100 = 7.9. In patients with a variation index greater than 7.5, the classification was “irregular parasystole” because of the marked variability of the edopic cycle. Every case of “irregular parasystole” was further evaluated to deduce the causeof the irregularity. The possible relationship between the influence of the sinusbeats on the ectopic focus and the variability of ,the manifest or calculated parasystolic cycle was carefully assessed in each case. The variation index was also calculated in 32 casesof complete atrioventricular block with idioventricular escaperhythm, characterized by QRS complexes wider than 0.11 second.A continuous strip of 3 to 5 minutes was analyzed in each case, and all the R-R intervals were measured.Casesin which were manifested capture beats, ventricular extrasystoles, or escape beats with variable morphologic characteristics were excluded.
Volume Number
115 1, Part 1
“%-regular”
240
372
134
132
243
246
ventricular
parasystole
123
242
375
132
246
246
Fig. 1. Case 1: A continuous recording of standard lead II. Numbers below the tracing reflect the interectopic intervals in hundredths of a second, whereas numbers above the tracing correspond to intervals between consecutiveventricular complexes.The diagram under the third strip showsthe effect of modulation. Vertical bars reflect the ectopic discharges.Line C reflects the scheduleddischarge.Line B reflects the intermediate discharge.Li.neA reflects the actual discharge.Numbers in line A reflect the time intervals between the delivery of the parasystolic impulse and the following sinus beat(s). The time intervals between an ectopic discharge and the secondconsecutive modulating sinus beat are shown in parentheses.The detailed analysis of each modulation is shown in line D. Stippled areasrepresent the refractory period of the ventricle.
Table
II. Data for each caseof modulated parasystole
Case
ectopic cycle length *
Deduced true parasystolic cycle length *
1 2 3 4 5 6 7 8 9
124.2 179.6 220.6 196.1 174.0 203.3 193.6 183.3 187.7
124 176 216 200 170 202 194 192 188
Mean
apparent
*Hundredths of a second. tPercentage of the true ectopic cycle. ~Maximal positive and negative variations
68 65 60 55 63 63 62.5 52 59
of the ectopic cycle effected by modulation,
RESULTS
In the cases of parasystole the variation
Reversal point of phase-response curvef
expressed
as a percentage
ranged from 3.7 to 40 (Table I). Based on this index, parasystole was classified as “regular” (an index < 5,
f 9 11 8 12 14 5 8 11 7.5
of the true
cases13 to 15) or “irregular” index
Percentage variations#
8 10 5.5 13.5 II 4 8 11.5 a
ectopiccycle.
(an index > ‘7.5, cases1
to 12). Further analysg revealed that the irregularity was due to modulation in nine cases and to parasystolic resetting by critically timed sinus
January 1988 124
Oreto
et al.
American
Journal
III. Case 1: Analysis of X-X intervals
Table
Duration
of X-X
intervals*
Group
No. of ISBs
Range
Mean
SD
No. of ECsj
A B c
1 2 4
128-135 240-247 368-385
131.2 242.6 374.5
1.8 3.0 3.6
1 2 3
*Hundredths of a second. TAssumed number of ectopic cycles contained #Mean manifest ectopic cycle length.
Table
Heart
IV.
within
A Bl B2 Cl c2
ECs#
131.2 121.3 124.8
Duration intervals
of X-R,
(range) 73-83 91-108 84-95
interval.
Case 2: Analysis of X-X intervals (see footnotes to Table III) Duration
Group
any X-X
Mean
of X-X
intervals
No. of ISBs
Range
Mean
SD
No. of ECs
2 4 5 6 7
178-191 343-366 357-368 531-552 539-552
185.9 353.7 362.1 540.8 543.6
3.5 5.9 3.1 8.9 5.7
1 2 2 3 3
impulses in three cases (Table I). The true or unmodulated parasystolic cycle was not evident in any case of modulated parasystole, as two consecutive ectopic complexes, not separated by sinus beats, were not observed. The true ectopic cycle length, as well as the position of the reversal point in the phase-response curve, were deduced in each case by a method of trial and error (see below). Modulation was diagnosed by drawing a phase-response curve for each case, which explained the irregularities of the X-X intervals on the basis of a time-dependent modulating influence exerted by the sinus impulses on an otherwise regularly discharging parasystolic focus. The possibility of explaining all the X-X intervals with a single typical phase-response curve was considered as a fundamental diagnostic criterion for the recognition of parasystolic modulation. Table II shows that in the reported cases of modulated parasystole, the reversal point of the phaseresponse curve occurs between 52 % and 68 % of the ectopic cycle; the percentage variation of the ectopic cycle length induced by modulation ranges from +14 to -13.5%. Furthermore, it is evident that the deduced true ectopic cycle length is in every case coincident with, or very close to, the mean apparent (manifest or calculated) parasystolic cycle length. Intermittent parasystole caused by resetting of the ectopic focus was recognized in three cases on the basis of the following: (1) the relatively long X-X intervals were markedly irregular, whereas the short X-X intervals were nearly constant, and (2) when
Mean
ECs
185.9 176.8 181.5 180.3 181.2
Duration intervals
of X-R,
(range)
111-121 72-108 104-109 79-109 108-112
the long X-X intervals were not in multiples of the shorter ones, a resetting sinus impulse that occurred at a critical period of the ectopic cycle could be always identified. Furthermore, in most of such long X-X intervals the distance between the penultimate sinus beat and the ectopic complex ending the X-X interval was equal to a parasystolic cycle. In patients with atrioventricular block and idioventricular escape rhythm, the variation index was: <5 in 28 out of 32 patients, between 5 and 7.5 in three patients, and >7.5 in only one patient, in whom a variation index of 9 was manifested. DESCRIPTION
OF
CASES
Case 1. Fig. 1 reflects a typical example of ventricular paraystole. Analysis of the interectopic intervals, however, reveals some irregularities, expresse by a variation index of 12. For example, (1) the second X-X interval in the third strip (2.43 seconds) is less than twice the first X-X interval, which measures 1.34 seconds, and (2) the third X-X interval (3.75 seconds) is less than three times the first X-X interval. Table III shows that the long X-X intervals, belonging to groups B and C, are always slightly less than a multiple of the short (group A) X-X intervals, which contain a single ISB. Moreover, a definite difference, with minimal overlap, exists between the X-R, intervals associated with the different groups of X-X intervals. The group A X-X intervals reflect X-R, intervals shorter than those of the other groups.
Volume Number
115 1,Part
“Irregular”
1
ventricular
parasystole
125
. .” +6
A
. .
4
Y.
m... 4 it
.
+2 1
.
l
.. .
:"
.
..
0
;/ , I , , , , ‘;.y
-6-
:
-6 -
- .:
-10‘ 10
20
30
40
50
60
70 m
I 10
I 20
I 30
I 40
50
,: 70
60
, 60
I 90
%
.
“i- D
+l4
.
.*
. l . .
-2 -4 -6
-j , , , , , l*;.. ,
-10 -12 -14 -
10
20
30
40
50
60
7Cl
80
90
%
l
-..x’
.
, 10
20
30
40
50
60
70
60
90
%
Fig. 2. Phase-response curves. The curves labeled A, B, C, and D were derived from analyses of cases 1,2, 4, and 5, respectively.
This tracing may be interpreted as an expression of modulated parasystole on the basis of the following: (1) The group A X-X intervals reflect a single prolonged parasystolic cycle, because (n) the long X-X intervals are less than a multiple of the short (group A) X-X intervals and (b) the group A X-X intervals are associated with relatively short X-R, intervals. If modulation actually occurs, relatively early sinus beats are likely to effect a delay of the next parasystolic discharge, thereby prolonging the parasystolic cycle. (2) The reversal point of the phase-response curve must be later than about 0.83 second, namely, later than the longest X-R, interval associated with a group A X-X interval. This is because in prolonged parasystolic cycles,, containing but one single sinus beat, such an intervening beat occurs before the reversal point, namely, in the delay section of the phase-response curve. (3;) The true ectopic cycle length is less than 1.23 seconds, namely, less than the shortest group A X-X interval. Any group A X-X interval thus corresponds to a prolonged parasystolic cycle. On this basis, a phase-response curve was constructed by trial and error. The reversal point was fixed at 0.84 second, whereas the assumed true ectopic cycle length was progressively decreased by steps of 0.01 second, starting from the minimal
possible value of 1.27 seconds. The curve best fitting all the data was obtained with a cycle of 1.24 seconds. This curve is depicted in Fig. 2, A. The diagram under the third strip of Fig. 1 reflects the analysis of some X-X intervals based on the phaseresponse curve of Fig. 2, A. Case 2. The Fig. 3 reflects an example of ventricular parasystole, with variably coupled ectopic complexes and fusion beats. Many ectopic beats are interpolated. The X-X intervals are slightly irregular, as suggested by a variation index of 10.9. Analysis of the interectopic intervals (Table IV) shows that the long X-X intervals (groups B and 6) are slightly but consistently less than a multiple of the short X-X intervals belonging to group A. The X-X intervals for groups B and C were further divided into two subgroups on the basis of the number of ISBs. Thus the subgroups Bl and Cl contain four and six ISBs, respectively, whereas subgroups B2 and C2 are associated with five and seven ISBs, respectively. This is because the first ectopic beat is interpolated in the B2 and C2 X-X intervals, so that these intervals contain one ISB more than the Bl and Cl intervals, where no interpolation occurs. The group A X-X intervals, reflecting a single parasystolic cycle, contain two ISBs (R, and R,), because the first X beat is always interpolated. Analysis
126
Qreto et al.
Fig.
3. Case2: A continuous recording of standard lead II. Symbols asin Fig. 1. Fusion beats are labeled
F.
shows that the X-R, intervals associated with the group A X-X intervals are longer than those associated with the X-X intervals of groups B and C. On this basis it is possible to make the following assumptions: (1) The group A X-X intervals express a single prolonged parasystolic cycle. Thus they are longer than the calculated mean parasystolic cycle length resulting from division of the long X-X intervals by the number of parasystolic cycles contained within the X-X interval. (2) If every group A X-X interval corresponds to a prolonged parasystolic cycle, then the net modulating effect of beats R, and R, is delay of the ensuing ectopic impulse. Beat R,, however, is expected to effect but a minimal delay, as it occurs very early in the ectopic cycle. Thus beat R, also exerts a delaying effect on the ectopic impulse. This reveals that the reversal point of the phase-response curve is later than any R, beat associated with a group A X-X interval; and since the longest X-R, interval of group A is 1.21 seconds, the reversal point must occur later than 1.21 seconds from the beginning of the ectopic cycle. (3) The true or unmodulated parasystolic cycle must be shorter than the shortest group A X-X interval (1.78 sec-
onds), because any group A X-X interval expresses prolonged parasystolic cycle. On this basis a phase-response curve was obtained by trial and error. The curve is depicted in Fig. 2, B, and is based on a true parasystolic cycle of 1.76 second, with a reversal point at 1.23 seconds. A detailed interpretation of some interectopic intervals is reflected in the diagrams of Fig. 3. A group A X-X interval is diagrammed at the beginning of the second strip, where both R,, and R, beats delay the ensuing parasystolic discharge. The manifest ectopic cycle is consequently longer than the true parasystolic cycle. The group B and group C X-X interv are, on the contrary, made up of both shortened a prolonged parasystolic cycles. Case 4. Fig. 4 reflects sinus rhythm at a rate of about 80/min, complicated by several ectopic ventricular beats with variable coupling intervals. The X-X intervals are roughly related but somewhat irregular (variation index = 15.8). Analysis of the interectopic intervals, subdivided into three groups according to the number of ISBs (Table V), shows that: (1) the group A X-X intervals, containing a single ISB,
are associated with
X-R,
intervals
Volume Number
115 1, Part 1
‘irregular”
ventricular
parasystole
127
----__106=53%-+9%1+wl; 191=875%--2%1-4k
117SEi%--i&5%1-133;
97=48.5%-+9%1+181; 179=82%--3.5%[-71;
Fig. 4. Case 4: A continuous
Table
V. Case 4: Analysis
of X-X
intervals Duration
Group
No. of ISBs
A B c
1 4 6
63=315%*+3%[+6) 147=71.5%--8%1-?63;
recording
(see footnotes of X-X
50=25%-+?5Fi+31; 133=65.5%--1259&251;
of standard
to Table
41=ZQ5%-+2%[+41 126=62%--fts%[-$11
lead II. Symbols
as in Fig. 1.
III)
intervals
Mean
SD
No. of ECS
173-199
185.6
7.3
1
185.6
115-124
382-408 588-604
397.7 596.0
8.9
2 3
198.9
84-107 99-108
Range
remarkably longer than those associated with the other groups of X-X intervals, and (2) the X-X intervals belonging to groups B and C, are longer than a multiple of the short (group A) X-X intervals. Parasystolic modulation thus appears very likely. The phase-response curve may be constructed as follows: (1) Since the X-X intervals blelonging to groups B and C are longer than a multiple of the short X-X intervals, then the group A intervals express shortened parasystolic cycles, and/or the groups B and C X-X intervals contain prolonged ectopic cycles. (2) As the X-R, intervals associated with the group A X-X intervals are relatively long, beat RI is likely to provoke a shortening of the
6.6
Mean
198.7
ECs
Duration intervals
of X-R, (range)
parasystolic cycle length. When, on the other hand, the X-R, interval is relatively short (less than 1.15 seconds), beat R, delays the next parasystolic discharge, thereby prolonging the ectopic cycle. (3) The reversal point of the phase-response curve must be earlier than 1.15 seconds (the shortest X-R, interval of the group A X-X intervals) and later than 1.03 seconds (the longest X-R, interval associated with a group B or C X-X interval). (4) The true ectopic cycle length must be longer than 1.99 seconds; and this corresponds to the longest group A X-X interval. The reason for this is that any group A interval corresponds to a single shortened parasystolic cycle. On this basis the phase-response curve was con-.
128
Oreto et al.
Amerioeti
n
699
Fig.
5. Case 5: A continuous
/ . . *_
174
recording
A
of standard
January 1988 Heart Journel
516
lead II. Symbols
as in Fig. 1.
..! I
,
:
Fig. 6. Case 10: A continuous recording of standard lead II.‘Numbers above the tracing reflect the interectopic (X-X) intervals, whereas numbers below the tracing reflect X-R, intervals. Fusion beats are (V) and the parasystolic focus labeled F. The ladder diagram under the bottom strip reflects the ventricle (EF). Large dots represent the parasystolic discharges. The stippled areas express the protection or entrance block. The second complex of sinus origin occurs in the bottom strip outside the protected period and resets the focus. The asterisk indicates where the parasystolic impulse would have been delivered in the absence of resetting.
Volume Number
Table
115 1, Part 1
VI.
‘irregular”
ventricular
parasystole
129
Case 5: Analysis of X-X intervals (see footnotes to Table III) Duration
of X-X
intervals
Group
No. of ISBs
Range
Mean
SD
No. of ECs
Mean ECs
A B C
1 4 6
159-195 503-520 685-703
177.5 513.8 695.2
9.4 4.8 5.6
1 3 4
117.5 171.3 173.8
strutted by trial and error. A family of phaseresponse curves was drawn; the reversal point was fixed at 1.10 seconds, whereas the tested ectopic cycle length was initially the shortest plossible (2.0 seconds) and was subsequently increased by steps of 0.02 second. The best curve (Fig. 2, C) was obtained by use of a true ectopic cycle length of f!.O seconds. The diagrams in Fig. 4 explain some X-X intervals according to the phase-response curve o:f Fig. 2, C. Case 5. Fig. 5 shows a typical pattern of ventricular parasystole. The interectopic interval.s, however, are somewhat irregular and only roughly related, as expressed by a variation index of 15.7. Analysis of the X-X intervals (Table VI) shows that: (1) the group A X-X intervals, containing a single ISB, are remarkably variable, more than the intervals belonging to groups B and C, and (2) t.he group A X-X intervals are associated with X-R, intervals shorter than those of the other groups. The gross variations of the short X-X intervals may be explained by modulation. Despite the fact that the true parasystolic cycle is not immediately evident from the tracing, the phase-response curve may be deductively drawn as follows: (1) As the group A X-X intervals are markedly irregular (from 1.59 to 1.95 seconds), some of them (the very short ones) correspond to shortened parasystolic cycles, whereas the very long ones reflect prolonged parasystolic cycles. (2) The relatively short group A X-X intervals are associated with long X-R, intervals, whereas the relatively long group A X-X intervals are associated with short X-R, intervals. This is evident from the top strip of Fig. 6 where the first X-X interval measures 1.62 seconds and .!hasan X-R, interval of 1.18 seconds. The third X-,X interval, however, measures 1.86 seconds, and its X-R, interval is 1.05 seconds. This suggests that beat R1, occurring at 1.18 seconds from the ectopic complex, accelerates the ensuing parasystolic discharge, whereas beat R1, occuring 1.05 seconds after the ectopic beat, delays the next parasystolic impulse. (3) The true ectopic cycle thus is longer than 1.59 seconds (the shortest group A X-X interval) and shorter than 1.95 seconds (the longest group A X-X
Duration intervals
of X-R, (range)
96-118 116-139 116-133
interval). Furthermore, the reversal point of the phase-response curve must be later than 0.96 second (the shortest X-R, interval associated with a group A X-X interval) and earlier than 1.18 seconds (the longest X-R, interval associated with a group A X-X interval). The phase-response curve was constructed by trial and error. Initially, an assumed true cycle length of 1.60 seconds (the shortest possible) was used, and then the postulated ectopic cycle length was increased by steps of 0.02 second until a satisfactory curve was obtained. The best curve fitting all the data was obtained by use of a true cycle length of 1.70 seconds, with reversal point at about 63 % of the cycle. This curve is shown in Fig. 2, D. The modulating effect of the sinus beats is also reflected in the diagram of Fig. 5. DISCUSSION
The data suggest the following: (1) In most cases of ventricular parasystole the interectopic intervals are more or less irregular. (2) Apart from the examples of intermittent parasystole, where the ectopic focus is discharged and thus reset by the sinus impulses, the irregularity is often and most likely due to modulation. The presence of a mathematic relationship between the interectopic intervals is a fundamental diagnostic criterion for the diagnosis of parasystole. Indeed, in uncomplicated parasystole the long X-X intervals would have to be in simple multiples of the short X-X intervals or in multiples of the calculated ectopic cycle. Furthermore, the shortest X-X intervals are expected to be constant, particularly when they express a single parasystolic cycle. In several published examples of ventricular parasystole, however, the mathematic relationship between the interectopic intervals is somewhat approximate. Neither are the long X-X intervals exact multiples of the short X-X intervals, nor are the short intervals truly constant. The only clinical condition where an exactly regular ventricular parasystole occurs is that of artificial ventricular pacing with an asynchronous pacemaker discharging at a rate lower
430
Qreto et al.
than the sinus rate. Spontaneous parasystole, by contrast, is always associated with some irregularities of the interectopic intervals. This is not surprising, since a biologic pacemaker is not exactly regular. Accordingly, some variability of the parasystolic cycle can be accepted as “normal.” The results in the cases of idioventricular escape rhythm, however, suggest that the cycle of an idioventricular focus is but minimally variable, as revealed by a low variation index. These data cannot be simply applied to parasystole, since the behavior of a protected pacemaker could be different from that of a nonprotected automatic focus. Nevertheless, it is evident that a ventricular escape pacemaker that cannot be disturbed by extraneous impulses will discharge regularly. Thus the marked variations often manifested by the parasystolic cycle probably result from the influence of the sinus impulses. Causes of irregular interectopic intervals. Irregularity of the X-X intervals in the presence of parasystole may be due to several mechanisms, including the following: (1) The parasystolic cycle undergoes spontaneous variations, totally independent of external events. (2) The ectopic cycle variations depend on changes in autonomic nervous tone or hormonal factors. For example, isoproterenol increases the rate of a parasystolic focus.21 (3) The manifest ectopic cycle appears irregular, despite the constancy of the true ectopic cycle. This occurs when the conduction time from the focus to the surrounding myocardium is variable, as in a Wenckebach form of ectopic-ventricular block. (4) The sinus or dominant rhythm affects the parasystolic focus in one of the following ways: (a) resetting of the ectopic center, if the protection does not extend throughout the ectopic cycle2s3; ‘(b) modulationnamely, delayed or accelerated discharge from an electrotonic influence*; or (c) annihilation-that is, termination of the ectopic rhythm by a critically timed sinus impulse.22,23 (5) The sinus rhythm induces ectopic beats owing to postulated reentry or reflection mechanism. If postulated reentry occurs within, or very close to, the parasystolic focus, the resulting premature extrasystolic complex will be identical to the parasystolic beat.24-26The interectopic intervals would thus theoretically become irregular, since some ectopic complexes are automatic (parasystolic) and some others are postulated as reciprocating. fhe variation index. Although some irregularity of the interectopic intervals does not exclude parasystole, the maximal variation of the manifest ectopic cycle still compatible with the diagnosis of uncomplicated parasystole has not been established. It has
been reported that the shortest interectopic intervals can vary up to 0.27 second, although these variations do not usually exceed 0.12 second.27z2s The index proposed here-the variation indexexpresses the maximal difference among the short X-X intervals observed in the same tracing, independently of their length. Furthermore, since the maximal observed variation is expressed as a percentage of the mean parasystolic cycle, it is also possible to compare the irregularity of X-X intervals observed among patients with different parasystolic cycle lengths. It must, however, be stressed that measurements of the interectopic intervals and related calculations must be limited to a relatively brief (no longer than 5 minutes) continuous strip of resting ECG, because changes in autonomic tone or spontaneous fluctuations of the ectopic cycle length are more likely to occur in long than in brief recordings. With relatively long recordings we have at times observed slight variations of the ectopic cycle length that were apparently independent of the sinus rhythm but clearly related to the sinus rate. This was evident in case 11, where at the beginning of the recording the sinus rate was ll5i min, and the ectopic cycle measured 1.21 set; whereas 15 minutes later the sinus rate decreased to lOO/min, and the parasystolic cycle was prolonged to 1.28 seconds. Apart from those cases of intermittent parasystole, the cases reported here are associated with variation indices ranging from 3.7 to 15.8. It is worth noting that when the irregularity of X-X intervals was irrelevant, as expressed by a very low variation index (cases 13 to 15), it was not possible to recognize any influence of sinus rhythm on the ectopic focus. These cases may thus be defined as “regular” or “true” parasystole. Regular parasystole, however, does not rule out a modulating influence of the sinus rhythm on the parasystolic focus. Thus a minimal degree of modulation leading to negligible changes of the ectopic cycle cannot be recognized by analysis of the clinical ECG. When, in contrast, the variation index was greater than 7.5, canalysis of the recording revealed a definite mechanism responsible for the irregular X-X intervals. Thus, if ventricular parasystole is associated with irregular X-X intervals, it is necessary to determine whether this irregularity is random or depends on the effect of sinus beats The results of the present research suggest that when the variation index is very high (>22), parasystolic resetting (intermittent parasystole) is probably involved. The higher variation index in intermittent parasystole than in modulated parasystole is not surprising, since the ectopic cycle variations effected
Volume Number
115 1, Part 1
by modulation are ;;maller than those caused by the resetting of the focus. Thus the maximal modulated change of the ectopic cycle was 14%, whereas variations as great as 50% were observed in intermittent parasystole. It should be noted that a significant difference in the variation index between modulated and intermittent parasystole can be expecfted only in the presence of typical parasystole. Modulation, indeed, can even be associated with ectopic cycle variations remarkably higher than those reported here.14,16When this occurs, however, the classical signs of parasystole disappear as a consequence of the excessive ectopic cycle variability, and parasystole becomes atypical to the extent that it cannot be recognized at first glance. The diagnosis of intermittent parasystole. Intermittent parasystole is usually easily recognized on the basis of the following: (1) The short interectopic intervals are constant, whereas the long intervals appear variable and often appear not to be mathematically related to the short X-X intervals. (2) The X-R, intervals associated with the X-R,-X intervals are variable despite the constancy of the X-R,X intervals. This rules out the possibility that beat R, exerts a modulating effect. (3) Analysis of the relationship between the manifest or inapparent parasystolic impulses and the sinus beats reveals that when a sinus complex occurs in a short critical period of the ectopic cycle, the ectopic focus is discharged and reset. Fig. 6 reflects a case of intermittent lparasystole characterized by constancy of the short X-X intervals. The diagram shows that the irregularity of X-X intervals is due to resetting of the parasyatolic focus by the sinus beats that occur during the final part of the ectopic cycle. This case thus reflects an early, or phase 3, protection block. The diagnosis of modulated parasystole. Recognition of modulation is more difficult than that of intermittency. Thus the relationship between the variability of X-X intervals and the timing of the sinus beats can be easily established only if the “pure” or unmodulated ectopic cycle is revealed by two consecutive ectopic beats not separa.ted by any sinus complex. When, on the other hand, the true ectopic cycle is not available, the recognition of modulation can be very difficult, particularly when the irregularity of the X-X intervals is so slight as to appear irrelevant. In the cases reported here, modulation was diagnosed by deductive analysis of the X-X intervals, grouped according to the number of ISBs. When (a) the relatively long X-X intervals are always longer than a multiple of the short X-X intervals (case 4) or
Yrregulai-”
ventricular
parasystole
131
VII. Correlation between X-RI-X and R1-X intervals and between X-R,-X and X-R, intervals
Table
r Values
Case 1 2 3 4 5 6 7 8 9 The r values obtained See text. *p < 0.01.
Correlation X-R,-X/R,-X -0.15 0.92* 0.99* 0.99* 0.35 0.43 0.98* for every case of modulated
Correlation X-R,-XIX-R, 0.75* -0.18 -0.89* -0.88* -0.06 -0.06 -0.90* parasystole
are shown.
(b) the relatively long X-X intervals are always less than a multiple of the short X-X intervals (cases 1 and 2), the irregularity cannot be coincidental but depends on a definite mechanism. Thus, had the variability of X-X intervals occurred by chance, the long X-X intervals would have been both longer and shorter than a multiple of the short X-X intervals. A further observation that can suggest modulation is the excessive variability of the short X-X intervals in the presence of nearly constant or less variable long X-X intervals (case 5). It is worth noting that in all the analyzed casesof modulated parasystole, the true ectopic cycle deduced from analysis of the tracings coincides with the mean apparent (manifest or calculated) parasystolic cycle obtained by evaluation of all the X-X intervals (Table II). The difference between true ectopic cycle and mean apparent ectopic cycle is minimal, ranging from 0.002 to 0.087 second. This may be of practical importance, because the deductive calculation of the true ectopic cycle is complex, and an assumed value of the parasystolic cycle length may be accepted only if this value enables the construction of the best phase-response curve; namely, a curve that explains all the actual X-X intervals. Calculation of the mean apparent parasystolic cycle instead is much more simple. This parameter therefore could be used to approximate the true ectopic cycle length. The phase-response curve thus could be directly constructed starting from the mean apparent cycle. This would prevent the need for repetitive sequential attempts to discover the true ectopic cycle. The lack of difference between the deduced true ectopic cycle and the apparent mean parasystolic cycle is not casual, since it occurs in all
132
Oreto et al.
the cases. It is due to the fact that in every case both prolonged and shortened parasystolic cycles occur. And since all the phase-response curves are quite symmetric, resulting in positive and negative variations of the ectopic cycle that are nearly identical, a compensation between prolonged and shortened cycles occurs. Thus the mean manifest parasystolic cycle obtained from a sufficiently large number of X-X intervals is substantially identical to the true ectopic cycle. A simple procedure for the recognition of parasystolic modulation was proposed by Nau et al.l” Their method is based on the correlation between X-R,-X interval (interectopic interval containing a single ISB) and R,-X interval. When a positive correlation between these occurs, modulation may be recognized. In two of the nine cases of modulated parasystole reported here, this method could not be applied, since no X-X intervals containing a single ISB were present. However, a positive correlation was found in four cases out of the remaining seven (Table VII). Table VII shows also that a significant correlation between X-R,-X and X-R, occurred in four cases, three of which also reflect a correlation between X-R,-X and R,-X. Hence the procedure proposed by Nau et al.l” appears useful, although it cannot be applied to all the cases and may sometimes lead to underdiagnosis. Conclusions. This study suggests that parasystolic modulation is a very common phenomenon, although the analyzed sample is too small to provide reliable data on the incidence of modulation. Although parasystole was first recognized in the early years of this century, several aspects of this arrhythmia are still controversial, despite recent experimental and clinical progress. Evidence that the sinus rhythm can deeply affect a parasystolic focus has even put into question the very definition of parasystole. It is now clear that a precise distinction between parasystolic (or independent) rhythm and extrasystolic (or dependent) rhythm is no longer possible, since both rhythms are more or less linked to the sinus or dominant rhythm. Hence ectopic ventricular complexes with features suggesting an extrasystolic rather than parasystolic origin could be, at times, the expression of a parasystolic rhythm where the ectopic cycle undergoes large modulated variations, to the extent that parasystole becomes unrecognizable. Data supporting this point of view have been recently reported.2gp30 This work was supported by the Sicilian Research Council (Progetto Finalizzato: Rapporti fra elettrogenesi e prognosi delle extrasistoli ventricolari) and the South African Medical Research Council.
American
January W88 Heart Journal
REFERENCES
1. Schamroth L, Marriott HJL. Intermittent ventricular parasystole with observations on its relationship to extrasystolic bigeminy. Am J Cardiol 1961;7:799-809. 2. Steffens TG. Intermittent ventricular parasystole due to entrance block failure. Circulation 1971;44:442-5. 3. Cohen H, Langendorf R, Pick A. Intermittent parasystolemechanism of protection. Circulation 1973;48:761-74. 4. Jalife J, Moe GK. Effects of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 1976;39:801-8. 5. Moe GK, Jalife J, Mueller WJ. Reciprocation between pacemaker sites: re-entrant parasystole? In: Kulbertus HE, ed. Reentrant arrhythmias. Mechanism and treatment. Lancaster, Pa: MTP Press, 1977:271. 6. Moe GK, Jalife J, Mueller WJ, Moe B. A mathematical model of parasystole and its application to clinical arrhythmias. Circulation 1977;56:968-79. I. Jalife J, Antzelevitch C, Moe GK. The case for modulated parasystole. PACE 1982;5:911-26. 8. Antzelevitch C, Jalife J, Moe GK. Electrotonic modulation of pacemaker activity: further biological and mathematical observations on the behaviour of modulated parasystole. Circulation 1982;66:1225-32, 9. 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;68:1101-15. 10. Nau GJ, Aldariz AE, Acunzo RS, et al. Modulation of parasystolic activity by non-parasystolic beats. Circulation 1982;66:462-9. 11. Castellanos A, Melgarejo E, Dubois R, Luceri RM. Modulation of ventricular parasystole by extraneous depolarizations. J Electrocardiol 1984;17:195-8. 12. Castellanos A, Luceri RM, Moleiro F, et al. Annihilation, entrainment and modulation of ventricular parasystolic rhythms. Am J Cardiol 1984;54:317-22. 13. Oreto G, Satullo G, Luzza F, Arrigo F. Parasistolia modulata. Un’aritmia “in attesa” di criteri diagnostici. Analisi deduttiva di un case. G ltal Cardiol 1984;14:1081-6. 14. Oreto G, Luzza F, Satullo G, Coglitore S, Schamroth L. Intermittent ventricular bigeminy as an expression of modulated parasystole. Am J Cardiol 1985;55:1634-7. 15. Oreto G, Luzza F, Satullo G, Arrigo F, Schamroth L. Modulation of A-V junctional parasystole. Electrocardiographic calculation of the phase-response curve. Am J Cardiol 1986; 57:694-8. 16. Oreto G, Satullo G, Luzza F, Consolo F, Schamroth L. “Supernormal” modulation of ventricular parasystole: the triphasic phase-response curve. Am J Cardiol 1986;58:28390. Oreto G, Luzza F, Satullo G, Coglitore S, Schamroth L. Sinus modulation of atria1 parasystole. Am J Cardiol 1986;58: 1097-g. 18. Oreto G, Donato A, Satullo G, Luzza F, Schamroth L. Modulated ventricular parasystole manifesting as apparent Wenckebach exit block. Am J Cardiol 1986;58:1101-4. 19. Saoudi N, Kimura S, Stafford W, Castellanos A, Myerburg RJ. Modulation et annihilation des pace-makers ventricuiaires parasystoliques. Arch Ma1 Coeur 1985;78:1495-501. 20. Tenczer J, Littmann L. Rate-dependent patterns of modulated ventricular parasystole. Am J Cardiol 1986;57:576-81. 21. Castellanos A, Mendoza IJ, Luceri RM, et al. Concealment of manifest and exposure of concealed ventricular parasystole produced by isoproterenol. Am J Cardiol 1985;55:1344-9. 22. Jalife J, Antzelevitch C. Phase resetting and annihilation of pacemaker activity in cardiac tissue. Science 19’79;206: II.
695-7.
23. Jalife J, Antzelevitc C. Pacemaker annihilation: diagnostic and therapeutic implication. AM HEART J 1980;100:128-30, 24. Kuo CS, Surawicz B. Coexistence of ventricular parasystole
Volume Number
115 1, Part 1
and ventricular couplets: mechanism and clinical significance. Am J Cardiol 1979;44:435-41. 25. Singer DH, Parameswaran R, Drake FT, Meyers SN, DeBoer AA. Ventricular parasystole and re-entry: clinical-electrophysiological correlations. AM HEART J 1974;88:79-87. 26. Kinoshita S. Intermittent parasystole originating in the reentrant path of ventricular extrasystoles. Chest 1977; 72:201-6. 27. Chung EK. Principles of cardiac arrhythmias. Chapt. 10. Baltimore: Williams and Wilkins, 1976.
“Irregular”
ventricular
parasystole
28. Schamroth L. Disorders of cardiac rhythm. 2nd ed. Oxford: Blackwell Scientific Publications, 1980. 29. Oreto G, Luzza F, Satullo G, Schamroth L. Modulated ventricular parasystole as a mechanism for concealed bigeminy. Am J Cardiol 1986;58:954-8. 30. Oreto G, Satullo G, Luzza F. Concealed ventricular quadrigeminy linked to atria1 quadrigeminy: a manifestation of modulated parasystole. J Electrocardiol 1987;20:176-84.
Evaluation of Bjijrk-Shiley prosthetic real-time two-dimensional Doppler echocardiographic flow mapping
valves
by
We studied the value of two-dimensional Doppler echocardiographic color flow mapping for identifying normal transvalve flow profiles and valve malfunction in 20 patients with Bjlirk-Shiley prosthetic valves. Seven patients had BjBrk-Shiley prosthetic valves in the aortic position alone, seven in the mitral position, and six had prosthetic valves in both the aortic and mitral positions. In 10 patients with normally functioning mitral valves, the ratios of the maximal major and minor Doppler-imaged orifice flow diameters to the valve ring diameters were 25 f 3% (mean + SD) and 24 + 3%, respectively, similar to values reported in in vitro studies. No mitral regurgitation was found in these patients by two-dimensional Doppler echocardiographic flow mapping or by spectral Doppler. Of the 10 clinically normal aortic Bjiirk-Shiley valves, no valvular regurgitation was found by color flow mapping, whereas mild aortic regurgitation was found in two patients with the use of spectral Doppler. Malfunction of six valves was documented in five patients and was confirmed by cardiac catheterization and/or surgery. These included one case of focal fibrous ingrowth involving primarily the minor orifice of a mitral prosthetic valve, one case of mitral valve prosthetic thrombosis with decreased major and minor orifice flow diameters and valvular regurgitation, and four cases of paravalvular regurgitation involving prosthetic valves in the aortic position (three patients) and the mitral position (one patient). Two-dimensional Doppler echocardiographic flow mapping provides new observations that may aid in identifying Bjiirk-Shiley prosthetic valve malfunction. By localizing precisely the site of prosthetic stenosis or regurgitation, it may also assist in defining the cause of valve malfunction. (AM HEART J 1988;115:133.)
Howard Dittrich, M.D.,* Pascal Nicod, M.D.,* Brian Hoit, M.D.,** Nancy Dalton, R.D.M.S.,* and David Sa.hn, M.D.*** Sun Diego, Calif.
BjGrk-Shiley prosthetic valve malfunction has been occasionally reported as a dramatic clinical event that requires prompt recognition and surgical correction.’ Other types of valve malfunction are more From the *Department of the Medicine, Division of Cardiology, University of California-San Diego; the **Veterans Administration Medical Center; and the ***Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, University of California-San Diego. Received for publication Feb. 18, 1987; accepted July 20, 1987. Reprint requests: Howard Dittrich, M.D., Cardiology D-vision H-811A, UCSD Medical Center, 225 Dickinson St., San Diego, CA 92103.
indolent and slowly progressive. Many noninvasive techniques have been used with mixed results for detecting prosthetic valve malfunction, including phonocardiography,2,3 cineradiography,4 and echocardiography.5-7 Limitations described with each of these techniques depend in part on the type of prosthetic valve being evaluated. In the case of Bjiirk-Shiley prosthetic valves and other mechanical valves, echocardiography is limited by problems of transducer alignment, reverberations from nonbiologic materials, and side lobe artifacts. Spectral 133
Giuseppe Oreto, M.D., * Gaetano Satullo, M.D.,* Francesco Luzza, M.D.,* Antonino Donato, M.D.,* Carmelo Maugeri Sacd, M.D.,* Francesco Arrigo, M.D.,* Faust0 Consolo, M.D., and Leo Schamroth, M.D., D-SC.** Messina, Italy,
and Johannesburg, South Africa
It is commonly thought that a parasystolic rhythm is the expression of a totally independent automatic focus. It has also been generally accepted that ectopic beats of parasystolic origin differ substantially from ventricular extrasystoles, lbecause in parasystole the ectopic impulses are delivered regularly by a totally protected and thus independent, rhythmic focus, whereas the ectopic impulses associated with an extrasystolic rhythm are forced or precipitated by the dominant rhythm. Schamroth and Marriott,’ in 1961, postulated that ventricular extrasystoles (namely, the ectopic beats dependent on, or linked to, the dominant rhythm) are due to a semiprotected ventricular ectopic pacemaker that can be electrotonically influenced by the sinus rhythm. This postulate was based on the ‘behavior of the ectopic rhythm during intermittent parasystole.
From the *Istituto Pluridisciplinare di Clinica Medica e Terapia Medica Gene&e e Speciale dell’ Universitd degli Studi di Messina, and **Department of Medicine, University of the Witwatersrand. Reprint requests: Professor L. Schamroth, Department of Medicine, Baragwanath Hospital, P.O. Bertsham 2013, Johannesburg, South Africa.
Steffen$ and Cohen et a1.3 also reported intermittent parasystole, as reflected by the resetting of a parasystolic focus by critically timed nonparasystolic impulses. The electrotonic influence of the sinus impulses on a parasystolic rhythm was first postulated by Schamroth and Marriott (1961)’ and confirmed experimentally by Jalife and Moe (1976),” who used an isolated canine false tendon in a three-bath preparation. Further laboratory confirmation was presented by Moe, u Jalife et al.,’ and Antzelevitch et al.*sg Consequent to such electrotonic influence, the parasystolic discharge may be delayed or accelerated with respect to its scheduled delivery. This phenomenon was defined as “modulation,” and is expressed by a biphasic phase-response curve, the shape of which indicates that relatively early sinus impulses delay the ensuing parasystolic discharge, whereas sinus beats that occur relatively late within the ectopic cycle accelerate the next parasystolic impulse.4 Thus, as a result of the modulation the parasystolic cycle may become variable to the extent that the classic signs of parasystole become less evident or indeed even disappear completely.
Oreto et al.
122
1.The variation index and final diagnosislisted for each case Table
Case
Variation
index
1
12.0
2 3 4 5 6
10.9 7.7 15.8 15.7 8.9
7
11.4 13.4
8 9 10 11 12 13 14 15
13.9 22.0 30.8 40.0 5.0 5.0 3.7
Diagnosis
Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedparasystole Modulatedpsrasysto!e Intermittent parasystole Intermittent parasystole Intermittent parasystole Regularparasystole Regularparasystole Regularparasystole
Subsequent to the descriptions of experimental modulation, several clinical examples of modulated parasystole were published.10-20This article will show that deductive ECG analysis enables the recognition of the influence of sinus rhythm on ventricular parasystolic rhythm. METHODS
The material comprised 15 patients with ventricular parasystole.Each had a continuous ECG recording (paper speed= 25 mm/set), and 3.5 to 5-minute sectionsof these recordingswere analyzed. Eight of the patients were male, and seven were female. Their agesranged from 1 year to 79 years. Ten had no clinically evident organic heart disease,whereasfour had ischemicheart diseaseand one, a dilated cardiomyopathy. The tracings were selected by means of the following criteria: (1) ectopic ventricular beats with markedly variable coupling intervals, reflecting variations greater than 0.20 second; (2) the presence of fusion beats; and (3) interectopic intervals that were more or lessmathematically related (seebelow). Definition of terms. Terms were defined as follows: X = ectopic ventricular beat or fusion beat; X-X = interectopic interval; R = beat of sinus origin; R1, R,, RS, etc. = the first, second,third, etc., consecutive sinusbeats after an ectopic complex that is not interpolated; R, = the first sinusbeat after an interpolated ectopic complex. The sinus beats that follow R0 are defined as R1 (the second consecutive sinusbeat after the interpolated ectopic complex), Rz, and so on. All the intervals between consecutive ventricular complexes and the X-X intervals were measured. (All the measurementsare expressedin hundredths of a second.) The X-X intervals were further subdivided into groups accordingto the number of intervening sinusbeats (ISBs). The following calculations were made for each group: (1) the range of the X-X intervals; (2) the meanand SD of the X-X intervals; (3) the range of the X-R, intervals (the
intervals between an ectopic complex and the ensuing beat); (4) the number of parasystolic cycles contained within the X-X interval; and (5) the average duration of the apparent (manifest or calculated) parasystolic cycle. The parasystolic cycle length is obviously equal to the X-X interval when the X-X interval is madeup of a single parasystolic cycle. In order to calculate the apparent parasystolic cycle from long X-X intervals, it wasassumed that, in the presence of parasystole, any X-X interval results from an integer of ectopic cycles with identical duration. Thus the apparent ectopic cycle length may be obtained by dividing the X-X interval by the number of parasystolic cycles contained in the interval. Moreover, the‘global mean apparent cycle length was calculated for each caseby meansof the values obtained by all the X-X intervals observed in the whole recording. The X-X intervals starting from or ending with a fusion beat, however, were not included in the analysis whenever the fusion beat resembled a sinus complex rather than an ectopic beat; the reasonfor this is that when a fusion beat reflects initial vectors identical to those of the sinusbeat, the exact moment in which the parasystolic impulse is delivered cannot be assessed with certainty. The variation index. A variation index was then calculated for each patient to evaluate the regularity of the interectopic intervals; namely, t,he presenceof a mathematic relationship between the intervals. The following parametersare necessaryto obtain the variation index: (1) the maximal difference among different measurementsof the apparent parasystolic cycle (namely, the difference between the longest and the shortest manifest or calculated parasystolic cycle) and (2) the global mean ectopic cycle length. The variation index is the ratio of these two parameters. In other words, the index correspondsto the maximal variation amongdifferent values of the parasystolic cycle, expressed as percentage of the mean cycle length. For example, if the actual interectopic intervals, in hundredths of a second, are 104, 104, 210 (105 x 2), 100, 100,102,194 (97 X 2), and 102,the variation index results from the difference between 105 (the longest cycle) and 97 (the shortest cycle) expressed as a percentage of the averageapparent cycle length, or 101.6.Thus the index is equal to EV101.6X 100 = 7.9. In patients with a variation index greater than 7.5, the classification was “irregular parasystole” because of the marked variability of the edopic cycle. Every case of “irregular parasystole” was further evaluated to deduce the causeof the irregularity. The possible relationship between the influence of the sinusbeats on the ectopic focus and the variability of ,the manifest or calculated parasystolic cycle was carefully assessed in each case. The variation index was also calculated in 32 casesof complete atrioventricular block with idioventricular escaperhythm, characterized by QRS complexes wider than 0.11 second.A continuous strip of 3 to 5 minutes was analyzed in each case, and all the R-R intervals were measured.Casesin which were manifested capture beats, ventricular extrasystoles, or escape beats with variable morphologic characteristics were excluded.
Volume Number
115 1, Part 1
“%-regular”
240
372
134
132
243
246
ventricular
parasystole
123
242
375
132
246
246
Fig. 1. Case 1: A continuous recording of standard lead II. Numbers below the tracing reflect the interectopic intervals in hundredths of a second, whereas numbers above the tracing correspond to intervals between consecutiveventricular complexes.The diagram under the third strip showsthe effect of modulation. Vertical bars reflect the ectopic discharges.Line C reflects the scheduleddischarge.Line B reflects the intermediate discharge.Li.neA reflects the actual discharge.Numbers in line A reflect the time intervals between the delivery of the parasystolic impulse and the following sinus beat(s). The time intervals between an ectopic discharge and the secondconsecutive modulating sinus beat are shown in parentheses.The detailed analysis of each modulation is shown in line D. Stippled areasrepresent the refractory period of the ventricle.
Table
II. Data for each caseof modulated parasystole
Case
ectopic cycle length *
Deduced true parasystolic cycle length *
1 2 3 4 5 6 7 8 9
124.2 179.6 220.6 196.1 174.0 203.3 193.6 183.3 187.7
124 176 216 200 170 202 194 192 188
Mean
apparent
*Hundredths of a second. tPercentage of the true ectopic cycle. ~Maximal positive and negative variations
68 65 60 55 63 63 62.5 52 59
of the ectopic cycle effected by modulation,
RESULTS
In the cases of parasystole the variation
Reversal point of phase-response curvef
expressed
as a percentage
ranged from 3.7 to 40 (Table I). Based on this index, parasystole was classified as “regular” (an index < 5,
f 9 11 8 12 14 5 8 11 7.5
of the true
cases13 to 15) or “irregular” index
Percentage variations#
8 10 5.5 13.5 II 4 8 11.5 a
ectopiccycle.
(an index > ‘7.5, cases1
to 12). Further analysg revealed that the irregularity was due to modulation in nine cases and to parasystolic resetting by critically timed sinus
January 1988 124
Oreto
et al.
American
Journal
III. Case 1: Analysis of X-X intervals
Table
Duration
of X-X
intervals*
Group
No. of ISBs
Range
Mean
SD
No. of ECsj
A B c
1 2 4
128-135 240-247 368-385
131.2 242.6 374.5
1.8 3.0 3.6
1 2 3
*Hundredths of a second. TAssumed number of ectopic cycles contained #Mean manifest ectopic cycle length.
Table
Heart
IV.
within
A Bl B2 Cl c2
ECs#
131.2 121.3 124.8
Duration intervals
of X-R,
(range) 73-83 91-108 84-95
interval.
Case 2: Analysis of X-X intervals (see footnotes to Table III) Duration
Group
any X-X
Mean
of X-X
intervals
No. of ISBs
Range
Mean
SD
No. of ECs
2 4 5 6 7
178-191 343-366 357-368 531-552 539-552
185.9 353.7 362.1 540.8 543.6
3.5 5.9 3.1 8.9 5.7
1 2 2 3 3
impulses in three cases (Table I). The true or unmodulated parasystolic cycle was not evident in any case of modulated parasystole, as two consecutive ectopic complexes, not separated by sinus beats, were not observed. The true ectopic cycle length, as well as the position of the reversal point in the phase-response curve, were deduced in each case by a method of trial and error (see below). Modulation was diagnosed by drawing a phase-response curve for each case, which explained the irregularities of the X-X intervals on the basis of a time-dependent modulating influence exerted by the sinus impulses on an otherwise regularly discharging parasystolic focus. The possibility of explaining all the X-X intervals with a single typical phase-response curve was considered as a fundamental diagnostic criterion for the recognition of parasystolic modulation. Table II shows that in the reported cases of modulated parasystole, the reversal point of the phaseresponse curve occurs between 52 % and 68 % of the ectopic cycle; the percentage variation of the ectopic cycle length induced by modulation ranges from +14 to -13.5%. Furthermore, it is evident that the deduced true ectopic cycle length is in every case coincident with, or very close to, the mean apparent (manifest or calculated) parasystolic cycle length. Intermittent parasystole caused by resetting of the ectopic focus was recognized in three cases on the basis of the following: (1) the relatively long X-X intervals were markedly irregular, whereas the short X-X intervals were nearly constant, and (2) when
Mean
ECs
185.9 176.8 181.5 180.3 181.2
Duration intervals
of X-R,
(range)
111-121 72-108 104-109 79-109 108-112
the long X-X intervals were not in multiples of the shorter ones, a resetting sinus impulse that occurred at a critical period of the ectopic cycle could be always identified. Furthermore, in most of such long X-X intervals the distance between the penultimate sinus beat and the ectopic complex ending the X-X interval was equal to a parasystolic cycle. In patients with atrioventricular block and idioventricular escape rhythm, the variation index was: <5 in 28 out of 32 patients, between 5 and 7.5 in three patients, and >7.5 in only one patient, in whom a variation index of 9 was manifested. DESCRIPTION
OF
CASES
Case 1. Fig. 1 reflects a typical example of ventricular paraystole. Analysis of the interectopic intervals, however, reveals some irregularities, expresse by a variation index of 12. For example, (1) the second X-X interval in the third strip (2.43 seconds) is less than twice the first X-X interval, which measures 1.34 seconds, and (2) the third X-X interval (3.75 seconds) is less than three times the first X-X interval. Table III shows that the long X-X intervals, belonging to groups B and C, are always slightly less than a multiple of the short (group A) X-X intervals, which contain a single ISB. Moreover, a definite difference, with minimal overlap, exists between the X-R, intervals associated with the different groups of X-X intervals. The group A X-X intervals reflect X-R, intervals shorter than those of the other groups.
Volume Number
115 1,Part
“Irregular”
1
ventricular
parasystole
125
. .” +6
A
. .
4
Y.
m... 4 it
.
+2 1
.
l
.. .
:"
.
..
0
;/ , I , , , , ‘;.y
-6-
:
-6 -
- .:
-10‘ 10
20
30
40
50
60
70 m
I 10
I 20
I 30
I 40
50
,: 70
60
, 60
I 90
%
.
“i- D
+l4
.
.*
. l . .
-2 -4 -6
-j , , , , , l*;.. ,
-10 -12 -14 -
10
20
30
40
50
60
7Cl
80
90
%
l
-..x’
.
, 10
20
30
40
50
60
70
60
90
%
Fig. 2. Phase-response curves. The curves labeled A, B, C, and D were derived from analyses of cases 1,2, 4, and 5, respectively.
This tracing may be interpreted as an expression of modulated parasystole on the basis of the following: (1) The group A X-X intervals reflect a single prolonged parasystolic cycle, because (n) the long X-X intervals are less than a multiple of the short (group A) X-X intervals and (b) the group A X-X intervals are associated with relatively short X-R, intervals. If modulation actually occurs, relatively early sinus beats are likely to effect a delay of the next parasystolic discharge, thereby prolonging the parasystolic cycle. (2) The reversal point of the phase-response curve must be later than about 0.83 second, namely, later than the longest X-R, interval associated with a group A X-X interval. This is because in prolonged parasystolic cycles,, containing but one single sinus beat, such an intervening beat occurs before the reversal point, namely, in the delay section of the phase-response curve. (3;) The true ectopic cycle length is less than 1.23 seconds, namely, less than the shortest group A X-X interval. Any group A X-X interval thus corresponds to a prolonged parasystolic cycle. On this basis, a phase-response curve was constructed by trial and error. The reversal point was fixed at 0.84 second, whereas the assumed true ectopic cycle length was progressively decreased by steps of 0.01 second, starting from the minimal
possible value of 1.27 seconds. The curve best fitting all the data was obtained with a cycle of 1.24 seconds. This curve is depicted in Fig. 2, A. The diagram under the third strip of Fig. 1 reflects the analysis of some X-X intervals based on the phaseresponse curve of Fig. 2, A. Case 2. The Fig. 3 reflects an example of ventricular parasystole, with variably coupled ectopic complexes and fusion beats. Many ectopic beats are interpolated. The X-X intervals are slightly irregular, as suggested by a variation index of 10.9. Analysis of the interectopic intervals (Table IV) shows that the long X-X intervals (groups B and 6) are slightly but consistently less than a multiple of the short X-X intervals belonging to group A. The X-X intervals for groups B and C were further divided into two subgroups on the basis of the number of ISBs. Thus the subgroups Bl and Cl contain four and six ISBs, respectively, whereas subgroups B2 and C2 are associated with five and seven ISBs, respectively. This is because the first ectopic beat is interpolated in the B2 and C2 X-X intervals, so that these intervals contain one ISB more than the Bl and Cl intervals, where no interpolation occurs. The group A X-X intervals, reflecting a single parasystolic cycle, contain two ISBs (R, and R,), because the first X beat is always interpolated. Analysis
126
Qreto et al.
Fig.
3. Case2: A continuous recording of standard lead II. Symbols asin Fig. 1. Fusion beats are labeled
F.
shows that the X-R, intervals associated with the group A X-X intervals are longer than those associated with the X-X intervals of groups B and C. On this basis it is possible to make the following assumptions: (1) The group A X-X intervals express a single prolonged parasystolic cycle. Thus they are longer than the calculated mean parasystolic cycle length resulting from division of the long X-X intervals by the number of parasystolic cycles contained within the X-X interval. (2) If every group A X-X interval corresponds to a prolonged parasystolic cycle, then the net modulating effect of beats R, and R, is delay of the ensuing ectopic impulse. Beat R,, however, is expected to effect but a minimal delay, as it occurs very early in the ectopic cycle. Thus beat R, also exerts a delaying effect on the ectopic impulse. This reveals that the reversal point of the phase-response curve is later than any R, beat associated with a group A X-X interval; and since the longest X-R, interval of group A is 1.21 seconds, the reversal point must occur later than 1.21 seconds from the beginning of the ectopic cycle. (3) The true or unmodulated parasystolic cycle must be shorter than the shortest group A X-X interval (1.78 sec-
onds), because any group A X-X interval expresses prolonged parasystolic cycle. On this basis a phase-response curve was obtained by trial and error. The curve is depicted in Fig. 2, B, and is based on a true parasystolic cycle of 1.76 second, with a reversal point at 1.23 seconds. A detailed interpretation of some interectopic intervals is reflected in the diagrams of Fig. 3. A group A X-X interval is diagrammed at the beginning of the second strip, where both R,, and R, beats delay the ensuing parasystolic discharge. The manifest ectopic cycle is consequently longer than the true parasystolic cycle. The group B and group C X-X interv are, on the contrary, made up of both shortened a prolonged parasystolic cycles. Case 4. Fig. 4 reflects sinus rhythm at a rate of about 80/min, complicated by several ectopic ventricular beats with variable coupling intervals. The X-X intervals are roughly related but somewhat irregular (variation index = 15.8). Analysis of the interectopic intervals, subdivided into three groups according to the number of ISBs (Table V), shows that: (1) the group A X-X intervals, containing a single ISB,
are associated with
X-R,
intervals
Volume Number
115 1, Part 1
‘irregular”
ventricular
parasystole
127
----__106=53%-+9%1+wl; 191=875%--2%1-4k
117SEi%--i&5%1-133;
97=48.5%-+9%1+181; 179=82%--3.5%[-71;
Fig. 4. Case 4: A continuous
Table
V. Case 4: Analysis
of X-X
intervals Duration
Group
No. of ISBs
A B c
1 4 6
63=315%*+3%[+6) 147=71.5%--8%1-?63;
recording
(see footnotes of X-X
50=25%-+?5Fi+31; 133=65.5%--1259&251;
of standard
to Table
41=ZQ5%-+2%[+41 126=62%--fts%[-$11
lead II. Symbols
as in Fig. 1.
III)
intervals
Mean
SD
No. of ECS
173-199
185.6
7.3
1
185.6
115-124
382-408 588-604
397.7 596.0
8.9
2 3
198.9
84-107 99-108
Range
remarkably longer than those associated with the other groups of X-X intervals, and (2) the X-X intervals belonging to groups B and C, are longer than a multiple of the short (group A) X-X intervals. Parasystolic modulation thus appears very likely. The phase-response curve may be constructed as follows: (1) Since the X-X intervals blelonging to groups B and C are longer than a multiple of the short X-X intervals, then the group A intervals express shortened parasystolic cycles, and/or the groups B and C X-X intervals contain prolonged ectopic cycles. (2) As the X-R, intervals associated with the group A X-X intervals are relatively long, beat RI is likely to provoke a shortening of the
6.6
Mean
198.7
ECs
Duration intervals
of X-R, (range)
parasystolic cycle length. When, on the other hand, the X-R, interval is relatively short (less than 1.15 seconds), beat R, delays the next parasystolic discharge, thereby prolonging the ectopic cycle. (3) The reversal point of the phase-response curve must be earlier than 1.15 seconds (the shortest X-R, interval of the group A X-X intervals) and later than 1.03 seconds (the longest X-R, interval associated with a group B or C X-X interval). (4) The true ectopic cycle length must be longer than 1.99 seconds; and this corresponds to the longest group A X-X interval. The reason for this is that any group A interval corresponds to a single shortened parasystolic cycle. On this basis the phase-response curve was con-.
128
Oreto et al.
Amerioeti
n
699
Fig.
5. Case 5: A continuous
/ . . *_
174
recording
A
of standard
January 1988 Heart Journel
516
lead II. Symbols
as in Fig. 1.
..! I
,
:
Fig. 6. Case 10: A continuous recording of standard lead II.‘Numbers above the tracing reflect the interectopic (X-X) intervals, whereas numbers below the tracing reflect X-R, intervals. Fusion beats are (V) and the parasystolic focus labeled F. The ladder diagram under the bottom strip reflects the ventricle (EF). Large dots represent the parasystolic discharges. The stippled areas express the protection or entrance block. The second complex of sinus origin occurs in the bottom strip outside the protected period and resets the focus. The asterisk indicates where the parasystolic impulse would have been delivered in the absence of resetting.
Volume Number
Table
115 1, Part 1
VI.
‘irregular”
ventricular
parasystole
129
Case 5: Analysis of X-X intervals (see footnotes to Table III) Duration
of X-X
intervals
Group
No. of ISBs
Range
Mean
SD
No. of ECs
Mean ECs
A B C
1 4 6
159-195 503-520 685-703
177.5 513.8 695.2
9.4 4.8 5.6
1 3 4
117.5 171.3 173.8
strutted by trial and error. A family of phaseresponse curves was drawn; the reversal point was fixed at 1.10 seconds, whereas the tested ectopic cycle length was initially the shortest plossible (2.0 seconds) and was subsequently increased by steps of 0.02 second. The best curve (Fig. 2, C) was obtained by use of a true ectopic cycle length of f!.O seconds. The diagrams in Fig. 4 explain some X-X intervals according to the phase-response curve o:f Fig. 2, C. Case 5. Fig. 5 shows a typical pattern of ventricular parasystole. The interectopic interval.s, however, are somewhat irregular and only roughly related, as expressed by a variation index of 15.7. Analysis of the X-X intervals (Table VI) shows that: (1) the group A X-X intervals, containing a single ISB, are remarkably variable, more than the intervals belonging to groups B and C, and (2) t.he group A X-X intervals are associated with X-R, intervals shorter than those of the other groups. The gross variations of the short X-X intervals may be explained by modulation. Despite the fact that the true parasystolic cycle is not immediately evident from the tracing, the phase-response curve may be deductively drawn as follows: (1) As the group A X-X intervals are markedly irregular (from 1.59 to 1.95 seconds), some of them (the very short ones) correspond to shortened parasystolic cycles, whereas the very long ones reflect prolonged parasystolic cycles. (2) The relatively short group A X-X intervals are associated with long X-R, intervals, whereas the relatively long group A X-X intervals are associated with short X-R, intervals. This is evident from the top strip of Fig. 6 where the first X-X interval measures 1.62 seconds and .!hasan X-R, interval of 1.18 seconds. The third X-,X interval, however, measures 1.86 seconds, and its X-R, interval is 1.05 seconds. This suggests that beat R1, occurring at 1.18 seconds from the ectopic complex, accelerates the ensuing parasystolic discharge, whereas beat R1, occuring 1.05 seconds after the ectopic beat, delays the next parasystolic impulse. (3) The true ectopic cycle thus is longer than 1.59 seconds (the shortest group A X-X interval) and shorter than 1.95 seconds (the longest group A X-X
Duration intervals
of X-R, (range)
96-118 116-139 116-133
interval). Furthermore, the reversal point of the phase-response curve must be later than 0.96 second (the shortest X-R, interval associated with a group A X-X interval) and earlier than 1.18 seconds (the longest X-R, interval associated with a group A X-X interval). The phase-response curve was constructed by trial and error. Initially, an assumed true cycle length of 1.60 seconds (the shortest possible) was used, and then the postulated ectopic cycle length was increased by steps of 0.02 second until a satisfactory curve was obtained. The best curve fitting all the data was obtained by use of a true cycle length of 1.70 seconds, with reversal point at about 63 % of the cycle. This curve is shown in Fig. 2, D. The modulating effect of the sinus beats is also reflected in the diagram of Fig. 5. DISCUSSION
The data suggest the following: (1) In most cases of ventricular parasystole the interectopic intervals are more or less irregular. (2) Apart from the examples of intermittent parasystole, where the ectopic focus is discharged and thus reset by the sinus impulses, the irregularity is often and most likely due to modulation. The presence of a mathematic relationship between the interectopic intervals is a fundamental diagnostic criterion for the diagnosis of parasystole. Indeed, in uncomplicated parasystole the long X-X intervals would have to be in simple multiples of the short X-X intervals or in multiples of the calculated ectopic cycle. Furthermore, the shortest X-X intervals are expected to be constant, particularly when they express a single parasystolic cycle. In several published examples of ventricular parasystole, however, the mathematic relationship between the interectopic intervals is somewhat approximate. Neither are the long X-X intervals exact multiples of the short X-X intervals, nor are the short intervals truly constant. The only clinical condition where an exactly regular ventricular parasystole occurs is that of artificial ventricular pacing with an asynchronous pacemaker discharging at a rate lower
430
Qreto et al.
than the sinus rate. Spontaneous parasystole, by contrast, is always associated with some irregularities of the interectopic intervals. This is not surprising, since a biologic pacemaker is not exactly regular. Accordingly, some variability of the parasystolic cycle can be accepted as “normal.” The results in the cases of idioventricular escape rhythm, however, suggest that the cycle of an idioventricular focus is but minimally variable, as revealed by a low variation index. These data cannot be simply applied to parasystole, since the behavior of a protected pacemaker could be different from that of a nonprotected automatic focus. Nevertheless, it is evident that a ventricular escape pacemaker that cannot be disturbed by extraneous impulses will discharge regularly. Thus the marked variations often manifested by the parasystolic cycle probably result from the influence of the sinus impulses. Causes of irregular interectopic intervals. Irregularity of the X-X intervals in the presence of parasystole may be due to several mechanisms, including the following: (1) The parasystolic cycle undergoes spontaneous variations, totally independent of external events. (2) The ectopic cycle variations depend on changes in autonomic nervous tone or hormonal factors. For example, isoproterenol increases the rate of a parasystolic focus.21 (3) The manifest ectopic cycle appears irregular, despite the constancy of the true ectopic cycle. This occurs when the conduction time from the focus to the surrounding myocardium is variable, as in a Wenckebach form of ectopic-ventricular block. (4) The sinus or dominant rhythm affects the parasystolic focus in one of the following ways: (a) resetting of the ectopic center, if the protection does not extend throughout the ectopic cycle2s3; ‘(b) modulationnamely, delayed or accelerated discharge from an electrotonic influence*; or (c) annihilation-that is, termination of the ectopic rhythm by a critically timed sinus impulse.22,23 (5) The sinus rhythm induces ectopic beats owing to postulated reentry or reflection mechanism. If postulated reentry occurs within, or very close to, the parasystolic focus, the resulting premature extrasystolic complex will be identical to the parasystolic beat.24-26The interectopic intervals would thus theoretically become irregular, since some ectopic complexes are automatic (parasystolic) and some others are postulated as reciprocating. fhe variation index. Although some irregularity of the interectopic intervals does not exclude parasystole, the maximal variation of the manifest ectopic cycle still compatible with the diagnosis of uncomplicated parasystole has not been established. It has
been reported that the shortest interectopic intervals can vary up to 0.27 second, although these variations do not usually exceed 0.12 second.27z2s The index proposed here-the variation indexexpresses the maximal difference among the short X-X intervals observed in the same tracing, independently of their length. Furthermore, since the maximal observed variation is expressed as a percentage of the mean parasystolic cycle, it is also possible to compare the irregularity of X-X intervals observed among patients with different parasystolic cycle lengths. It must, however, be stressed that measurements of the interectopic intervals and related calculations must be limited to a relatively brief (no longer than 5 minutes) continuous strip of resting ECG, because changes in autonomic tone or spontaneous fluctuations of the ectopic cycle length are more likely to occur in long than in brief recordings. With relatively long recordings we have at times observed slight variations of the ectopic cycle length that were apparently independent of the sinus rhythm but clearly related to the sinus rate. This was evident in case 11, where at the beginning of the recording the sinus rate was ll5i min, and the ectopic cycle measured 1.21 set; whereas 15 minutes later the sinus rate decreased to lOO/min, and the parasystolic cycle was prolonged to 1.28 seconds. Apart from those cases of intermittent parasystole, the cases reported here are associated with variation indices ranging from 3.7 to 15.8. It is worth noting that when the irregularity of X-X intervals was irrelevant, as expressed by a very low variation index (cases 13 to 15), it was not possible to recognize any influence of sinus rhythm on the ectopic focus. These cases may thus be defined as “regular” or “true” parasystole. Regular parasystole, however, does not rule out a modulating influence of the sinus rhythm on the parasystolic focus. Thus a minimal degree of modulation leading to negligible changes of the ectopic cycle cannot be recognized by analysis of the clinical ECG. When, in contrast, the variation index was greater than 7.5, canalysis of the recording revealed a definite mechanism responsible for the irregular X-X intervals. Thus, if ventricular parasystole is associated with irregular X-X intervals, it is necessary to determine whether this irregularity is random or depends on the effect of sinus beats The results of the present research suggest that when the variation index is very high (>22), parasystolic resetting (intermittent parasystole) is probably involved. The higher variation index in intermittent parasystole than in modulated parasystole is not surprising, since the ectopic cycle variations effected
Volume Number
115 1, Part 1
by modulation are ;;maller than those caused by the resetting of the focus. Thus the maximal modulated change of the ectopic cycle was 14%, whereas variations as great as 50% were observed in intermittent parasystole. It should be noted that a significant difference in the variation index between modulated and intermittent parasystole can be expecfted only in the presence of typical parasystole. Modulation, indeed, can even be associated with ectopic cycle variations remarkably higher than those reported here.14,16When this occurs, however, the classical signs of parasystole disappear as a consequence of the excessive ectopic cycle variability, and parasystole becomes atypical to the extent that it cannot be recognized at first glance. The diagnosis of intermittent parasystole. Intermittent parasystole is usually easily recognized on the basis of the following: (1) The short interectopic intervals are constant, whereas the long intervals appear variable and often appear not to be mathematically related to the short X-X intervals. (2) The X-R, intervals associated with the X-R,-X intervals are variable despite the constancy of the X-R,X intervals. This rules out the possibility that beat R, exerts a modulating effect. (3) Analysis of the relationship between the manifest or inapparent parasystolic impulses and the sinus beats reveals that when a sinus complex occurs in a short critical period of the ectopic cycle, the ectopic focus is discharged and reset. Fig. 6 reflects a case of intermittent lparasystole characterized by constancy of the short X-X intervals. The diagram shows that the irregularity of X-X intervals is due to resetting of the parasyatolic focus by the sinus beats that occur during the final part of the ectopic cycle. This case thus reflects an early, or phase 3, protection block. The diagnosis of modulated parasystole. Recognition of modulation is more difficult than that of intermittency. Thus the relationship between the variability of X-X intervals and the timing of the sinus beats can be easily established only if the “pure” or unmodulated ectopic cycle is revealed by two consecutive ectopic beats not separa.ted by any sinus complex. When, on the other hand, the true ectopic cycle is not available, the recognition of modulation can be very difficult, particularly when the irregularity of the X-X intervals is so slight as to appear irrelevant. In the cases reported here, modulation was diagnosed by deductive analysis of the X-X intervals, grouped according to the number of ISBs. When (a) the relatively long X-X intervals are always longer than a multiple of the short X-X intervals (case 4) or
Yrregulai-”
ventricular
parasystole
131
VII. Correlation between X-RI-X and R1-X intervals and between X-R,-X and X-R, intervals
Table
r Values
Case 1 2 3 4 5 6 7 8 9 The r values obtained See text. *p < 0.01.
Correlation X-R,-X/R,-X -0.15 0.92* 0.99* 0.99* 0.35 0.43 0.98* for every case of modulated
Correlation X-R,-XIX-R, 0.75* -0.18 -0.89* -0.88* -0.06 -0.06 -0.90* parasystole
are shown.
(b) the relatively long X-X intervals are always less than a multiple of the short X-X intervals (cases 1 and 2), the irregularity cannot be coincidental but depends on a definite mechanism. Thus, had the variability of X-X intervals occurred by chance, the long X-X intervals would have been both longer and shorter than a multiple of the short X-X intervals. A further observation that can suggest modulation is the excessive variability of the short X-X intervals in the presence of nearly constant or less variable long X-X intervals (case 5). It is worth noting that in all the analyzed casesof modulated parasystole, the true ectopic cycle deduced from analysis of the tracings coincides with the mean apparent (manifest or calculated) parasystolic cycle obtained by evaluation of all the X-X intervals (Table II). The difference between true ectopic cycle and mean apparent ectopic cycle is minimal, ranging from 0.002 to 0.087 second. This may be of practical importance, because the deductive calculation of the true ectopic cycle is complex, and an assumed value of the parasystolic cycle length may be accepted only if this value enables the construction of the best phase-response curve; namely, a curve that explains all the actual X-X intervals. Calculation of the mean apparent parasystolic cycle instead is much more simple. This parameter therefore could be used to approximate the true ectopic cycle length. The phase-response curve thus could be directly constructed starting from the mean apparent cycle. This would prevent the need for repetitive sequential attempts to discover the true ectopic cycle. The lack of difference between the deduced true ectopic cycle and the apparent mean parasystolic cycle is not casual, since it occurs in all
132
Oreto et al.
the cases. It is due to the fact that in every case both prolonged and shortened parasystolic cycles occur. And since all the phase-response curves are quite symmetric, resulting in positive and negative variations of the ectopic cycle that are nearly identical, a compensation between prolonged and shortened cycles occurs. Thus the mean manifest parasystolic cycle obtained from a sufficiently large number of X-X intervals is substantially identical to the true ectopic cycle. A simple procedure for the recognition of parasystolic modulation was proposed by Nau et al.l” Their method is based on the correlation between X-R,-X interval (interectopic interval containing a single ISB) and R,-X interval. When a positive correlation between these occurs, modulation may be recognized. In two of the nine cases of modulated parasystole reported here, this method could not be applied, since no X-X intervals containing a single ISB were present. However, a positive correlation was found in four cases out of the remaining seven (Table VII). Table VII shows also that a significant correlation between X-R,-X and X-R, occurred in four cases, three of which also reflect a correlation between X-R,-X and R,-X. Hence the procedure proposed by Nau et al.l” appears useful, although it cannot be applied to all the cases and may sometimes lead to underdiagnosis. Conclusions. This study suggests that parasystolic modulation is a very common phenomenon, although the analyzed sample is too small to provide reliable data on the incidence of modulation. Although parasystole was first recognized in the early years of this century, several aspects of this arrhythmia are still controversial, despite recent experimental and clinical progress. Evidence that the sinus rhythm can deeply affect a parasystolic focus has even put into question the very definition of parasystole. It is now clear that a precise distinction between parasystolic (or independent) rhythm and extrasystolic (or dependent) rhythm is no longer possible, since both rhythms are more or less linked to the sinus or dominant rhythm. Hence ectopic ventricular complexes with features suggesting an extrasystolic rather than parasystolic origin could be, at times, the expression of a parasystolic rhythm where the ectopic cycle undergoes large modulated variations, to the extent that parasystole becomes unrecognizable. Data supporting this point of view have been recently reported.2gp30 This work was supported by the Sicilian Research Council (Progetto Finalizzato: Rapporti fra elettrogenesi e prognosi delle extrasistoli ventricolari) and the South African Medical Research Council.
American
January W88 Heart Journal
REFERENCES
1. Schamroth L, Marriott HJL. Intermittent ventricular parasystole with observations on its relationship to extrasystolic bigeminy. Am J Cardiol 1961;7:799-809. 2. Steffens TG. Intermittent ventricular parasystole due to entrance block failure. Circulation 1971;44:442-5. 3. Cohen H, Langendorf R, Pick A. Intermittent parasystolemechanism of protection. Circulation 1973;48:761-74. 4. Jalife J, Moe GK. Effects of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 1976;39:801-8. 5. Moe GK, Jalife J, Mueller WJ. Reciprocation between pacemaker sites: re-entrant parasystole? In: Kulbertus HE, ed. Reentrant arrhythmias. Mechanism and treatment. Lancaster, Pa: MTP Press, 1977:271. 6. Moe GK, Jalife J, Mueller WJ, Moe B. A mathematical model of parasystole and its application to clinical arrhythmias. Circulation 1977;56:968-79. I. Jalife J, Antzelevitch C, Moe GK. The case for modulated parasystole. PACE 1982;5:911-26. 8. Antzelevitch C, Jalife J, Moe GK. Electrotonic modulation of pacemaker activity: further biological and mathematical observations on the behaviour of modulated parasystole. Circulation 1982;66:1225-32, 9. 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;68:1101-15. 10. Nau GJ, Aldariz AE, Acunzo RS, et al. Modulation of parasystolic activity by non-parasystolic beats. Circulation 1982;66:462-9. 11. Castellanos A, Melgarejo E, Dubois R, Luceri RM. Modulation of ventricular parasystole by extraneous depolarizations. J Electrocardiol 1984;17:195-8. 12. Castellanos A, Luceri RM, Moleiro F, et al. Annihilation, entrainment and modulation of ventricular parasystolic rhythms. Am J Cardiol 1984;54:317-22. 13. Oreto G, Satullo G, Luzza F, Arrigo F. Parasistolia modulata. Un’aritmia “in attesa” di criteri diagnostici. Analisi deduttiva di un case. G ltal Cardiol 1984;14:1081-6. 14. Oreto G, Luzza F, Satullo G, Coglitore S, Schamroth L. Intermittent ventricular bigeminy as an expression of modulated parasystole. Am J Cardiol 1985;55:1634-7. 15. Oreto G, Luzza F, Satullo G, Arrigo F, Schamroth L. Modulation of A-V junctional parasystole. Electrocardiographic calculation of the phase-response curve. Am J Cardiol 1986; 57:694-8. 16. Oreto G, Satullo G, Luzza F, Consolo F, Schamroth L. “Supernormal” modulation of ventricular parasystole: the triphasic phase-response curve. Am J Cardiol 1986;58:28390. Oreto G, Luzza F, Satullo G, Coglitore S, Schamroth L. Sinus modulation of atria1 parasystole. Am J Cardiol 1986;58: 1097-g. 18. Oreto G, Donato A, Satullo G, Luzza F, Schamroth L. Modulated ventricular parasystole manifesting as apparent Wenckebach exit block. Am J Cardiol 1986;58:1101-4. 19. Saoudi N, Kimura S, Stafford W, Castellanos A, Myerburg RJ. Modulation et annihilation des pace-makers ventricuiaires parasystoliques. Arch Ma1 Coeur 1985;78:1495-501. 20. Tenczer J, Littmann L. Rate-dependent patterns of modulated ventricular parasystole. Am J Cardiol 1986;57:576-81. 21. Castellanos A, Mendoza IJ, Luceri RM, et al. Concealment of manifest and exposure of concealed ventricular parasystole produced by isoproterenol. Am J Cardiol 1985;55:1344-9. 22. Jalife J, Antzelevitch C. Phase resetting and annihilation of pacemaker activity in cardiac tissue. Science 19’79;206: II.
695-7.
23. Jalife J, Antzelevitc C. Pacemaker annihilation: diagnostic and therapeutic implication. AM HEART J 1980;100:128-30, 24. Kuo CS, Surawicz B. Coexistence of ventricular parasystole
Volume Number
115 1, Part 1
and ventricular couplets: mechanism and clinical significance. Am J Cardiol 1979;44:435-41. 25. Singer DH, Parameswaran R, Drake FT, Meyers SN, DeBoer AA. Ventricular parasystole and re-entry: clinical-electrophysiological correlations. AM HEART J 1974;88:79-87. 26. Kinoshita S. Intermittent parasystole originating in the reentrant path of ventricular extrasystoles. Chest 1977; 72:201-6. 27. Chung EK. Principles of cardiac arrhythmias. Chapt. 10. Baltimore: Williams and Wilkins, 1976.
“Irregular”
ventricular
parasystole
28. Schamroth L. Disorders of cardiac rhythm. 2nd ed. Oxford: Blackwell Scientific Publications, 1980. 29. Oreto G, Luzza F, Satullo G, Schamroth L. Modulated ventricular parasystole as a mechanism for concealed bigeminy. Am J Cardiol 1986;58:954-8. 30. Oreto G, Satullo G, Luzza F. Concealed ventricular quadrigeminy linked to atria1 quadrigeminy: a manifestation of modulated parasystole. J Electrocardiol 1987;20:176-84.
Evaluation of Bjijrk-Shiley prosthetic real-time two-dimensional Doppler echocardiographic flow mapping
valves
by
We studied the value of two-dimensional Doppler echocardiographic color flow mapping for identifying normal transvalve flow profiles and valve malfunction in 20 patients with Bjlirk-Shiley prosthetic valves. Seven patients had BjBrk-Shiley prosthetic valves in the aortic position alone, seven in the mitral position, and six had prosthetic valves in both the aortic and mitral positions. In 10 patients with normally functioning mitral valves, the ratios of the maximal major and minor Doppler-imaged orifice flow diameters to the valve ring diameters were 25 f 3% (mean + SD) and 24 + 3%, respectively, similar to values reported in in vitro studies. No mitral regurgitation was found in these patients by two-dimensional Doppler echocardiographic flow mapping or by spectral Doppler. Of the 10 clinically normal aortic Bjiirk-Shiley valves, no valvular regurgitation was found by color flow mapping, whereas mild aortic regurgitation was found in two patients with the use of spectral Doppler. Malfunction of six valves was documented in five patients and was confirmed by cardiac catheterization and/or surgery. These included one case of focal fibrous ingrowth involving primarily the minor orifice of a mitral prosthetic valve, one case of mitral valve prosthetic thrombosis with decreased major and minor orifice flow diameters and valvular regurgitation, and four cases of paravalvular regurgitation involving prosthetic valves in the aortic position (three patients) and the mitral position (one patient). Two-dimensional Doppler echocardiographic flow mapping provides new observations that may aid in identifying Bjiirk-Shiley prosthetic valve malfunction. By localizing precisely the site of prosthetic stenosis or regurgitation, it may also assist in defining the cause of valve malfunction. (AM HEART J 1988;115:133.)
Howard Dittrich, M.D.,* Pascal Nicod, M.D.,* Brian Hoit, M.D.,** Nancy Dalton, R.D.M.S.,* and David Sa.hn, M.D.*** Sun Diego, Calif.
BjGrk-Shiley prosthetic valve malfunction has been occasionally reported as a dramatic clinical event that requires prompt recognition and surgical correction.’ Other types of valve malfunction are more From the *Department of the Medicine, Division of Cardiology, University of California-San Diego; the **Veterans Administration Medical Center; and the ***Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, University of California-San Diego. Received for publication Feb. 18, 1987; accepted July 20, 1987. Reprint requests: Howard Dittrich, M.D., Cardiology D-vision H-811A, UCSD Medical Center, 225 Dickinson St., San Diego, CA 92103.
indolent and slowly progressive. Many noninvasive techniques have been used with mixed results for detecting prosthetic valve malfunction, including phonocardiography,2,3 cineradiography,4 and echocardiography.5-7 Limitations described with each of these techniques depend in part on the type of prosthetic valve being evaluated. In the case of Bjiirk-Shiley prosthetic valves and other mechanical valves, echocardiography is limited by problems of transducer alignment, reverberations from nonbiologic materials, and side lobe artifacts. Spectral 133