Changes in Ventricular Effective Refractory Periods After Two Extrastimuli and Ventricular Electrical Instability J. BYTESNIK, K. LEFFLEROVA, V. BICIK, and R. C I H A K From the Institute for Glinical and Experimental Medicine, Prague, Czechoslovakia BYTESNIK, J., ETAL.: Changes in Ventricular Effective Refractory Periods After Two Extrastimuli and
Ventricular Electrical Instability. Using programmed stimulation with one and three extrastimuli delivered in the right ventricular apex, we compared the effective refractory period (ERP) during sinus rhythm (ERP-SR) and during the third extrastimulus (ERP-S3) in patients without ventricuJar tachycardias (controJ group, n = 87) and in patients with documented ventricular tachycardia (VT group, n = 76). The protocol was not completed to determine EfiP-S3 in one patient in the control group and in 15 patients in the VT group. We observed a significantly greater change (i.e., shortening) in ERP after two extrastimuli in the VT group compared with patients without VT (AERP = 45 ± 20 msec in the control group and 70 ± 16 msec in the VT group, P< 0.001). This electrophysioiogical phenomenon, along with conduction delay, may play an important role in VT induction. (PACE, Vol. 15, November, Part II 1992) ventricular tachycardia, reentry mechanism, programmed ventricular stimulation, effective refractoryperiod
Introduction Programmed ventricular stimulation [PVS) is widely used in the evaluation of patients with ventricular tachycardias (VT). Many studies have examined the sensitivity and specificity of stimulation protocols with respect to the location and number of extrastimuli delivered during spontaneous or paced rhythms. The controllable and uncontrollable variables of electrical stimulation studies have been discussed in detail.^ When PVS is used as a diagnostic tool in patients without documented yet suspected ventricular tachyarrhythmias, the results of PVS are taken as a guide to therapy. The focus of attention has been on the inducibility or noninducibility of VT during PVS. Less interest has been dedicated to other electrophysiological phenomena observed during PVS. The purpose of this study was to analyze the changes in ventricular effective refractory
Address for reprints: J. ByteSnfk, Institute for Clinical and Experimental Medicine, Prague Vldeftsk^ 800, Prague 4, Czechoslovakia.
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periods [ERP) after extrastimuli and to try to correlate them with the manifestations of ventricular electrical instability. Patients and Methods Two groups of patients were tested. Group I (control) included 87 individuals (59 men, 28 women) with a mean age of 45.6 ± 15.4 years, who had no symptoms of hemodynamically serious tachyarrhythmia before PVS and in the 3 months thereafter. All patients had 48-hour electrocardiographic monitoring and exercise ECG without documented VT. In group II [VT group), there were 76 patients (56 men, 20 women) witb a mean ago of 48.1 ± 11.1 years, who had electrocardiographically documented VT or ventricular fibrillation at least 1 month after an acute myocardial infarction. The clinical characteristics of both groups are summarized in Tables I and II. PVS was performed under the following conditions: All patients in both groups were clinically stable and in sinus rhythm;
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Table 1. Group 1 (Control, n - 87) Main Diagnosis Ischemic heart disease Sick sinus syndrome Mitral vaive proiapse Ventricular preexcitation Hypertrophic cardiomyopattiy Other cardiac disorders No apparent cardiac disease Indication for PVS Ventricular extrasystoles (isolated or paired) Paroxysmal supraventricuiar tachycardia [with normal QRS) Bradyarrhythmias
20 15 10 8 5 14 15
two bi- or tripolar electrode catheters [6 French [USCI, Div. CR Bard, Billerica, MA, USA]) were inserted percutaneously through a femoral vein and positioned in the high right atrium and at the right ventricular apex. Our stimulation protocol and recording techniques have been defined previously.^ Ventricular stimuli 1 msec in duration at twice diastolic threshold were delivered at the right ventricular apex with a Biotronik Inc. (Lake Oswego, OR, USA) UHS 20 programmable stimu-
51 (59%) 29 (33%) 7 (8%)
They had no manifestations of ongoing myocardial ischemia, no cardiac failure, and no metabolic disorder; and Antiarrhythmic agents had been discontinued for at least 5 elimination half-lives except for ten patients in group II, who had received amiodarone in the last month before PVS.
ERPISil
Electrophysiological Study Patients in both groups underwent an electrophysiological study in the postabsorptive state, without sedation. Under fluoroscopic guidance,
Table II. Group II (VT. n = 76) ERP(%1
Main Diagnosis Ischemic heart disease Dilated cardiomyopathy Other cardiac disorders No apparent cardiac disease Indications for PVS Sustained VT 60 (VT evolved into ventricular fibrillation in 13) Nonsustained VT (^ 6 consecutive ventricular extrasystoles)
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44 (post Ml 38) 5 16 11
c . i . Sj
C.I.
Sj
= ERP
20
= ERP
20
= seaming by steps of 10 R5
16
Figure 1. Determination of the effective refractory period (ERP) during sinus rhythm and ERP after two extrastimuli (ERP-S3). The coupling intervals (c.i.J of three consecutive extrastimuli Si, S2, and S3 are shown schematically.
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lator. The ventricular ERP was measured during stable sinus rhythm [ERP-SR). The technique involves the introduction of progressively earlier ventricular extrastimuli after every eighth sinus beat starting in late diastole until ventricular refractoriness is reached. The measurement was performed with a 10-msec accuracy. ERP of the ventricle was the longest V-Si interval that failed to evoke a ventricular response. Three consecutive extrastimuli [Si, S2, S3) were delivered at the same site. The coupling interval (CI) of Si was 20 msec longer than ERP, as was the CI of S2. Next, scanning with S3 in steps of 10 msec was performed (Fig. 1), starting the scanning with the CI of S3 being the same as that of S2 and gradually shortening by 10-msec steps until ERP was reached [ERPS3). ERP-S3 was tbe longest S2-S3 interval that failed to evoke a ventricular response (Figs. 2 and 3). When VT was induced, attempts were made to terminate it by electrical stimulation. If sinus rhythm was restored and stabilized, scanning was continued within 1-2 minutes to measure ERP-S3 precisely.
Statistical Analysis All data were tested for statistical significance using two sample and paired t-tests. Statistical significance was defined as a P value < 0.05. N u m e r i c values are expressed as a mean ± standard, deviation. Results The PVS protocol was completed in 86 o f the 87 patients of group I and in 61 of the 76 patitmts of group II. In one patient of group I the m e a s u r e ment of ERP-S3 was not made accurately b e c a u s e of frequent ventricular extrasystoles. In 45 o f the 76 VT group patients, VT was induced. Data concerning VT induction and termination during PVS are summarized in Table III. The PVS protocol was not completed in 15 patients [because of DC c a r d i oversion or antiarrhythmic drug administration). We did not observe any significant differe n ces in sinus rhythm cycle length during scanning by Si and S3 in groups I and II, and between both groups (Table IV). The values of ERP-SR and ERP-
. 435
BU1-2
Figure 2. The determination of the ventricular effective refractory period during sinus rhythm. c.i. = coupling intervaJ; HRA = bipolar eiectrogram of the high right atrium.
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Nr.i35
c i 270- 270-
190ms
Figure 3. Determination of ERP-S3 in the same patient as in Figure 2. c.i. = coupling interval.
S3 found in both groups are summarized in Table V. The shortening of ERP. expressed as AERP [i.e., ERP-SR - ERP-S3), in the VT group was significantly more marked than in the control group [Tahle VI). When comparing the values of ERP-SR, ERPS3, and ERP in subgroups of the VT group, no significant differences were found in AERP between
the patients with induced VT during PVS and those in whom VT was not induced [Table VII). Discussion It is well known that the pacing protocols used during electrophysiological testing cannot induce VT in all patients with histories of VT.^-^ There are more factors influencing the situation. In an anatomically defined circuit, duration of the refractory period and conduction velocity deter-
Table Ml. VT Induction During PVS (Three Extrastimuli in SR) Group 1 (n = 87): oroup II (n — foj.
0
Cycle Length (msec)
AC
45
Nonsustained VT:
14
Sustained VT: Termination: —Spontaneously —Electrical stimulation —DC cardioversion —Antiarrhythmic drug injection
31
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Table IV.
2 14 14 1
SR Before
SR Before S1S2S3
Group (n Group (n =
i 86) II 61)
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899 ± 163
898 ± 159
NS
893 ± 130 NS
895 ± 121 NS
NS
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Table V.
Group 1 (n = 86) Group II (n = 61)
ERP-SR (msec)
ERP-S3 (msec)
263 ± 31
217 ± 30
278 ± 30 P < 0.01
208 ± 33 (NS)
Table VI. AERP' (ERP-SR - ERP-S3) Group 1 (n - 86) Group II (n = 61)
45 ±: 20 msec 70 ±: 16 msec P < 0.001
Table VII. EPS VT Induced Protocol Completed (n = 30)
ERP-SR (msec) AERP (SR - S3 ) (msec)
285 ± 32 70 ± 16
VT not Induced (n = 31) NS 271 ± 2 5 (P < 0.7) NS 68 ± 14
mine if reentry can occur. Short refractory periods and slow conduction favor reentry.^ Normally, atrial, His-Purkinje, and ventricular refractory periods are directly related to the basic drive cycle
length. That is, refractory periods tend to decrease with decreasing basic cycle length.^ During ventricular extrasystoles, a new balance of refractoriness and conduction velocity could develop in the different zones along the reentrant pathway. In the present study, we compared the right ventricular ERP during sinus rhythm and after two extrastimuli, as a model of paired extrasystoles. The measurement of ventricular ERP was performed with a 10-msec accuracy. It is concordant with the conclusions of other studies that have examined the variability of ventricular refractoriness measurements.^ We found a significantly more marked shortening of ERP after two extrastimuli (ERP-S3) in the VT group compared with patients without VT, This phenomenon of more pronounced shorten:ing of ventricular ERP after extrasystoles may play an important role in the genesis of VT. A larger number of extrastimuli and a shorter Cl of extrastimuli would lead to shortening of refractoriness in the reentrant circuit. When the conduction delay in some part of the potential reentrant circuit is sufficient, the wave front of the last extrastimulus can penetrate the previously blocked site and is able to start and sustain reentry.^ According to this hypothesis the shortening of ventricular refractoriness plays an important role in VT induction. Previous observations have shown that the shortening of refractoriness by a shorter cycle length was more marked in the normal compared to the ischemic myocardium.^ Some zones of the ischeniic myocardium show no changes in refractoriness during cycle length shortening. Consequently, a dispersion of refractoriness in different areas of the ventricular myocardium occurs. Provided that these results are confirmed in a greater number of patients and that this model reflects the changes occurring during spontaneous salvos of extrasystoles, the determination of postextrastimulus ERP changes could be helpful in evaluating the effects of antiarrhythmic drugs.
References 1. Brugada P, Wellens HJJ. Standard diagnostic programmed electrical stimulation protocols in patients with paroxysmal recurrent tachycardias. PACE 1984; 7:1121-1128. 2. ByteSnfk J, Fabian J. Elektrofyziologick^ diagnostika. [in Czechoslovakian) Kardiologiia 1987; 13(Suppl.):147-164.
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Prystowsky EN. Electrophysiologic-electropharmacologic testing in patients with ventricular arrhythmias. PACE 1988; 11:225-251. Rosen MR, Janse MJ, Myerburg RJ. Arrhythmias induced by coronary artery occlusion: What are the electrophysiological mechanisms? In DJ Hearse, AS Manning, MJ Janse (eds.): Life-Threatening Arrhyth-
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mias During Ischemia and Infarction. New York, Raven Press, 1987, pp. 11-47. 5. Denes P, Wu D, Dhingra R, et a l The effects of cycle length on cardiac refractory periods in man. Circulation 1974; 49:32-41. 6. Kadish AH. Schmaltz S, Morady F. Variability in the measurement of human ventricular refractoriness. PACE 1991; 14:1393-1401. 7. Moroe K, Coelho A, Chun Y-H, et al. Observations
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on the initiation of sustained ventricular tachycardia by programmed stimulation. PACE 1991; 14: 452-459. Gough WB, Mehra R, Restivo M, et al. Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog. 13. Correlation of activa^^^^ and refractory maps. Circ Res 1985; 57432-442
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