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Effect of isoproterenol on the anterograde refractory period of the accessory pathway in patients with the Wolff-Parkinson-White syndrome
Effect of lsoproterenol on the Anterograde Refractory Period of the Accessory Pathway in Patients With the Wolff-Parkinson-White Syndrome HEIN
J. J. WELLENS,
MD,
FACC
PEDRO BRUGADA, MD DENIS ROY, MD JAMES WEISS, MD FRITS W. BAR, MD Maastricht,
The Netherlands
From the Department of Cardiology, Annadal Hospital, University of Limburg, Maastricht, The Netherlands. Manuscript received August 3 1, 1981; revised manuscript received January 5, 1982, accepted January 8, 1982. Address for reprints: Hein J. J. Wellens, MD, Department of Cardiology, University of Limburg, Annadal Hospital, Maastricht, The Netherlands.
180
July 1982
To evaluate the effect of beta adrenergic stimulation on the duration of the anterograde refractory period of the accessory pathway, isoproterenol was infused in seven patients with the Wolff-Parkinson-White syndrome. In two patients the effect of isoproterenol was studied durlng long-term oral amiodarone administration. To avoid rate-related changes induced by isoproterenol, the anterograde refractory period of the accessory pathway was determined using the single test stimulus method at identical basic cycle lengths. lsoproterenol shortened the anterograde refractory period of the accessory pathway in six of the seven patients studied. In two of the three patients with an initial anterograde refractory period of the accessory pathway of equal to or less than 290 ms, shortening measured 30 ms. In three patients having an anterograde refractory period of the accessory pathway of more than 290 ms, isoproterenol abbreviated these values by 30, 60 and 60 ms, respectively. The greatest amount of shortening was observed in patients having the longest initial values for the anterograde refractory period of their accessory pathway. In the two patients receiving oral amiodarone therapy, isoproterenol shortened the anterograde refractory period of the accessory pathway by 160 and 60 ms, respectively, indicating that the effect of isoproterenol can not be prevented by long-term oral amiodarone administration. Our observations may be of importance in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation. They suggest that beta adrenergic stimulation induced by hypotension or anxiety may result in shortening of the anterograde refractory period of the accessory pathway, leading to increased ventricular rates during atrial fibrillation.
Although the atrioventricular (A-V) nodal pathway is well known to change its conduction time and refractoriness under the influence of changes in autonomic tone, relatively little is known about the effect of these changes on the electrophysiologic properties of accessory A-V pathways. Such knowledge is important because in patients with the Wolff-Parkinson-White syndrome the anterograde electrophysiologic properties of the accessory A-V pathway play a role in determining the ventricular frequency during atria1 fibrillation.lms The effect of adrenergic stimulation on the anterograde conduction over the accessory pathway is of special interest because the onset of the arrhythmia is frequently accompanied by anxiety and a decrease in blood pressure leading to enhanced sympathomimetic activity. Recently Przybylski et a1.4reported reappearance of anterograde conduction over an accessory A-V pathway in patients no longer having anterograde conduction over that structure after vagal and beta adrenergic stimulation. This paper describes the effect of isoproterenol administration on seven patients with the Wolff-Parkinson-White syndrome. As will be shown, beta adrenergic stimulation may result in considerable shortening of the anterograde refractory period of the accessory A-V pathway in some of these patients.
The American Journal of CARDIOLOGY
Volume 50
IXOPROTERENOLIN WOLFF-PARKINSON-WHITESYNDROME-mWELLENSET AL.
TABLE
Methods
I
Clinical Data of the Seven Patients
Patients: Seven patients were studied. Data on age, sex, location of the accessory pathway and type of clinically documented tachycardia are given in Table I. In Patients 1 to 6 all medication was discontinued at least 5 half-lives before the study. Patient 6 was restudied 6 weeks later after receiving oral amiodarone (total dose 11,200 mg) during that time. Patient 7 was investigated while receiving oral amiodarone for 5 weeks (total dose 9,800 mg). Programmed stimulation protocol: After informed consent was obtained, a programmed stimulat,ion study was performed using a protocol previously described.s After baseline measurements were made using the single test stimulus technique during pacing of the high right atrium, the coronary sinus and the apex of the right ventricle, an intravenous infusion of isoproterenol was started. The initial dose of 0.25 g/min was gradually increased to a dose that resulted in a stable sinus rate that was 20 to 30 percent higher than that immediately before isoproterenol administration. The individual isoproterenol dosage required ranged from 1 to 5 g/min. Measurements during isoproterenol administration were made using the same basic cycle lengths and test stimulus intervals as before the drug. Atria1 fibrillation was not routinely initiated before and during isoproterenol administration. Therefore no data were obtained on the effect of isoproterenol on the ventricular rate during atria1 fibrillation. Definition of terms: The following terms are used in this study:
Case 1 : 4 ; 7
Age (yr) & Sex
Site of Accessory Pathway
Type of Arrhythmia
32M 19F 34M 44F 39M 37M 47M
Right septal Left lateral Left posterior Left septal Right septal Left lateral Left lateral
%T + AF CMT CMT CMT + AF CMT CMT
AF = atrial fibrillation; CMT = circus movement tachycardia.
Anterograde effective refractory period of the accessory pathway: the shortest possible premature beat interval during
single test stimulation of the atrium followed by A-V conduction over the accessory pathway. Effective refractory period atrium: the shortest possible premature beat interval during single test stimulation of the atrium resulting in atria1 activation. Effective refractory period of the ventricle: the shortest possible premature beat interval during single test beat stimulation of the ventricle resulting in ventricular activation. Retrograde effective refractory period of the accessor pathway: the shortest possible premature beat interval during
single test stimulation of the ventricle followed by ventriculoatrial (V-A) conduction over the accessory pathway. V-A conduction over an accessory pathway was determined by using methods previously described.”
Results Effect of isoproterenol on anterograde refractory period of accessory pathway: No patient experienced unpleasant effects during isoproterenol administration. In all patients anterograde conduction over the accessory pathway persisted. Isoproterenol shortened the anterograde refractory period of the accessory pathway in six of seven patients (Table II, Fig. 1 and 2). In all patients stimulation was performed from both the high right atrium and the coronary sinus. As the anterograde refractory period of the accessory pathway we selected the shortest value found during stimulation at one of these sites. The refractory period of the atrium given in Table II was determined at the same site of stimulation. In two of the three patients having an initial anterograde refractory period of the accessory pathway of 290 ms or less, the anterograde refractory period of the accessory pathway shortened
by 30 ms, reaching values of 220 and 230 ms, respectively. In the three patients with an anterograde refractory period of more than 290 ms who were not receiving drugs, the shortening in these values after isoproterenol ranged from 30 to 80 ms, resulting in an anterograde refractory period of the accessory pathway of 250,340 and 270 ms, respectively. In the two patients receiving oral amiodarone, isoproterenol administration resulted in shortening of the anterograde refractory period of the accessory pathway of, respectively, 180 and 60 ms, leading to new values of 320 and 280 ms. Our results suggest that the greatest amount of shortening is observed in patients having the longest initial value of the anterograde refractory period of accessory pathway. Effect of retrograde refractory period of atrium and ventricle: The changes in duration of the anterograde refractory period of the accessory pathway during isoproterenol administration differed from those of the refractory periods of the atrium and the ventricle. Only minimal shortening of these values was observed. The effect of isoproterenol on the retrograde refractory period of the accessory pathway could be measured in only three patients. In two of them shortening was observed measuring, respectively, 20 and 100 ms. In all patients the R-R interval shortened during circus movement tachycardia after isoproterenol administration (Fig. 1 and 2). This shortening was the result of abbreviation of the A-H interval. No appreciable shortening was observed in the H-V interval or in the retrograde conduction time over the accessory pathway (as measured by the V-A interval in the coronary sinus lead in patients with a left-sided accessory pathway). Discussion
Effect of beta adrenergic stimulation in WolffParkinson-White syndrome: Our results indicate that beta adrenergic stimulation may result in marked abbreviation of the anterograde refractory period of the accessory pathway in some patients with the WolffParkinson-White syndrome. In our patients the effect of isoproterenol on the anterograde effective refractory period of the accessory pathway differed from its effect on the refractory period of atria1 and ventricular tissue, suggesting that these accessory pathways are not composed of ordinary atria1 or ventricular muscle. This
July 1992
The American Journal of CARDIOLOGY
Volume 50
191
ISOPROTERENOL IN WOLFF-PARKINSON-WHITE
SYNDROME-WELLENS
ET AL.
TABLE II Values for the Electrophyslologic Variables Before and During lsoproterenol Administration* Anterograde
Retrograde
ERPAP
Case
Medication
EBPRv
ERPAP
ERPA~,
BCL
Is-
Is+
Is-
Is+
Is-
ISS
Is-
Is+
1
-
430
330
250
210
200
200
190
200
190
3 4 5
-
430 500 500
420 260 250 290
340 230 220 290
200 210 200 230
210 200 190 230
250 190 240 240
230 190 240 NM
190 190 240
190 180 190 NM
6 7
Am Am
550 600
340 300 500
280 270 320
250 270 280
270 250 270
420 330 270
3N2Mo 270
240 270
2N3Mo 270
* All values are in milliseconds. Am = amiodarone; AP = accessory pathway; Atr = atrium; BCL = basic cycle length; ERP = effective NM = not measured; - = absent; + = present.
finding seems to be in conflict with the pathohistologic studies discussed by Sherf and Neufeld.7 In these studies the accessory bundles are described as composed of atria1 or ventricular working myocardial cells. However, in the absence of knowledge about the correlation between structure and function, our suggestion remains speculative.
Effects
on ventricular
refractory
period; Is = isoproterenol;
rate in atria1 fibrillation:
It has previously been reported that in the Wolff-Parkinson-White syndrome the ventricular rate during atria1 fibrillation relates to the duration of the anterograde refractory period of the accessory pathway.‘-” Although we did not compare the ventricular rates during atria1 fibrillation in relation to changes in the
CONTROL
FIGURE 1. Patient 7. A, before isoproterenol administration coronary sinus pacing with a basic cycle length of 600 msec shows that the anterograde refractory period of the accessory pathway measures 500 ms. B, premature beats given with shorter coupling intervals initiate a circus movement tachycardia with anterograde conduction over the atrioventricular node and ventriculoatrial conduction over a left lateral accessory pathway. Leads 1, II, Ill, VI, Vs, a high right atrial lead (HRA), a distal coronary sinus lead (CSd) and a His bundle electrogram were recorded simultaneously.
182
July 1982
The American
Journal of CARDIOLOGY
Volume 50
ISOPROTERENOL
duration of the anterograde refractory period of the accessory pathway before and during isoproterenol administration, we believe that our observations explain why, in some patients, the shortest R-R interval during atria1 fibrillation is less than the measured anterograde refractory period of the accessory pathway using the single test stimulation technique at rest. Sympathetic discharge after the onset of atria1 fibrillation may shorten the anterograde refractory period of the accessory pathway, leading to high ventricular rates resulting in serious hemodynamic consequences. The abbreviation of the anterograde refractory period of the accessory pathway during sympathetic stimulation may theoretically result in such rapid ventricular rates during atria1 fibrillation that deterioration in ventricular fibrillation occurs. Denes et a1.8reported that beta adrenergic blockade by propranolol had little effect on the duration of the anterograde refractory period of the accessory pathway as assessed with the single test stimulus technique. In their patients measurements were made at rest suggesting a normal level of sympathetic activity. It would be of interest to study the effect of beta adren-
IN WOLFF-PARKINSON-WHITE
SYNDROME--WELLENS
ET AL.
ergic blockade during atria1 fibrillation in patients with the Wolff-Parkinson-White syndrome, especially during exercise. Effect of amiodarone: Amiodarone is the drug that most consistently lengthens the duration of the anterograde refractory period of the accessory pathway.gJO However, our observations suggest that the drug does not protect against the abbreviation of the anterograde refractory period of the accessory pathway after beta adrenergic stimulation. This can be of clinical importance. Although our experience indicates that in patients with the Wolff-Parkinson-White syndrome and documented atria1 fibrillation the incidence of atria1 fibrillation diminishes after amiodarone administration, episodes of atria1 fibrillation may still occur. When accompanied by sympathetic stimulation as during exercise or anxiety the ventricular rate during the arrhythmia may still be life-threatening. Therapeutic implications: We believe that the results of our study with isoproterenol should influence the approach to patients with the Wolff-ParkinsonWhite syndrome. They suggest that in patients with this syndrome suffering from arrhythmias the effect of beta
ISOPROTERENOL
FIGURE 2. Same patient. A, during isoproterenol administration the anterograde refractory period of the accessory pathway shortens to 320 ms. B, again at shorter premature beat intervals a circus movement tachycardia is initiated. Note that the R-R interval of the tachycardia has decreased from 430 (Fig. 1) to 360 ms. This shortening is the result of abbreviation of the A-H interval during isoproterenol administration. Comparison between Figures 1 and 2 suggests a shortening in intraatrial conduction time after isoproterenol. We are reluctant to accept this as proved, however, because of (1) a possible change in catheter positions, and (2) a possible decrease in atrial dimensions because of beta adrenergic stimulation by isoproterenol.
July 1982
The American Journal of CARDIOLOGY
Volume 50
183
ISOPROTERENOL IN WOLFF-PARKINSON-WHITE
SYNDROMEPWELLENS
ET AL
adrenergic stimulation on the anterograde refractory period of the accessory pathway should be evaluated. If marked abbreviation of the refractory period results, the changes in R-R interval during pacing-induced atria1 fibrillation should be studied while the patient is receiving isoproterenol. When isoproterenol administration results in R-R intervals during atria1 fibrillation of 220 ms or less the value of adding a beta adrenergic blocking agent to the antiarrhythmic drug regimen should be evaluated. Przybylski et a1.4showed that, in some patients with prior electrocardiographic documentation of anterograde conduction over an accessory A-V pathway but not showing A-V conduction over this structure during sinus rhythm in current electrocardiograms, anterograde A-V conduction over the accessory pathway could be reinstituted during vagal stimulation or intravenous
isoproterenol administration. Although these patients are different from ours, because our patients always had anterograde conduction over the accessory pathway during sinus rhythm, their observations and ours indicate that the electrophysiologic properties of accessory pathways in the Wolff-Parkinson-White syndrome are not constant. In patients with intermediate values for the duration of the anterograde refractory period of the accessory pathway, sympathetic stimulation may possibly have life-threatening consequences if atria1 fibrillation supervenes. These considerations and the impressive results from the group at Duke University” suggest that surgical interruption of the accessory pathway should play an increasingly important role in the management of patients with the Wolff-Parkinson-White syndrome.
References 1. Castellanos A Jr, Myerburg RJ, Craparo K, Befeler B, Agha AS. Factors affecting ventricular rates during atrial flutter and fibrillation in pre-excitation (Wolff-Parkinson-White) syndrome. Br Heart J 1973;35:81 l-6. 2. Wellens HJJ, Durrer D. Wolff-Parkinson-White syndrome and atrial fibrillation: relation between refractory period of the accessory pathway and ventricular rate during atrial fibrillation. Am J Cardiol 1974;34:777-82. 3. Campbell RWF, Smith RA, Gallagher JJ, Pritchett ELC, Wallace AG. Atrial fibrillation in the pre-excitation syndrome. Am J Cardiol 1977;40:514-20. 4. Przybylskl J, Chlale P, Halpern S, Nau G, Elizarl MV, Rosenbaum MB. Unmasking of ventricular pre-excitation by vagal stimulation or isoproterenol administration. Circulation 1980;61:1030-6. 5. Ross DL, Farre J, Bar FWHM, et al. Comprehensive clinical electrophysiologic studies in the investigation of documented or suspected tachycardias. Circulation 1980;61: 1010-6. 6. Wellens HJJ, Farre J, Ross D, Vanagt EJ, Bar FW. Preoperative localization of bypass tract(s) in the Wolff-Parkinson-White syn-
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July 1982
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Volume 50
7. 8.
9.
10.
11.
drome. In: Bircks W, Loogen F, Schulte HD, Seipel L, eds. Medical and Surgical Management of Tachyarrhythmias. Berlin: Springer Verlag, 1980:94-105. Sherf L, Neufeld H. The Pre-excitation Syndrome: Facts and Theories. New York: Yorke, 1978:92-l 10. Denes P, Cummings JM, Slmpson R, et al. Effects of propranolol on anomalous pathway refractoriness and circus movement tachycardias in patients with pre-excitation. Am J Cardiol 1978; 41:1061-7. Wellens HJJ, Lie K, B&r FW, et al. Effects of amiodarone in the Wolff-Parkinson-White syndrome. Am J Cardiol 1976;38:18994. Wellens HJJ, Bar FW, Dassen WRM, Brugada P, Vanagt EJ, Farre J. Effects of drugs in the Wolff-Parkinson-White syndrome. Am J Cardiol 1980;46:665-9. Gallagher JJ, Sealy WC, Kasell JH. Intra-operative localization and division of accessory pathways associated with the WolffParkinson-White syndrome. In Ref 6, 114-37.
J. J. WELLENS,
MD,
FACC
PEDRO BRUGADA, MD DENIS ROY, MD JAMES WEISS, MD FRITS W. BAR, MD Maastricht,
The Netherlands
From the Department of Cardiology, Annadal Hospital, University of Limburg, Maastricht, The Netherlands. Manuscript received August 3 1, 1981; revised manuscript received January 5, 1982, accepted January 8, 1982. Address for reprints: Hein J. J. Wellens, MD, Department of Cardiology, University of Limburg, Annadal Hospital, Maastricht, The Netherlands.
180
July 1982
To evaluate the effect of beta adrenergic stimulation on the duration of the anterograde refractory period of the accessory pathway, isoproterenol was infused in seven patients with the Wolff-Parkinson-White syndrome. In two patients the effect of isoproterenol was studied durlng long-term oral amiodarone administration. To avoid rate-related changes induced by isoproterenol, the anterograde refractory period of the accessory pathway was determined using the single test stimulus method at identical basic cycle lengths. lsoproterenol shortened the anterograde refractory period of the accessory pathway in six of the seven patients studied. In two of the three patients with an initial anterograde refractory period of the accessory pathway of equal to or less than 290 ms, shortening measured 30 ms. In three patients having an anterograde refractory period of the accessory pathway of more than 290 ms, isoproterenol abbreviated these values by 30, 60 and 60 ms, respectively. The greatest amount of shortening was observed in patients having the longest initial values for the anterograde refractory period of their accessory pathway. In the two patients receiving oral amiodarone therapy, isoproterenol shortened the anterograde refractory period of the accessory pathway by 160 and 60 ms, respectively, indicating that the effect of isoproterenol can not be prevented by long-term oral amiodarone administration. Our observations may be of importance in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation. They suggest that beta adrenergic stimulation induced by hypotension or anxiety may result in shortening of the anterograde refractory period of the accessory pathway, leading to increased ventricular rates during atrial fibrillation.
Although the atrioventricular (A-V) nodal pathway is well known to change its conduction time and refractoriness under the influence of changes in autonomic tone, relatively little is known about the effect of these changes on the electrophysiologic properties of accessory A-V pathways. Such knowledge is important because in patients with the Wolff-Parkinson-White syndrome the anterograde electrophysiologic properties of the accessory A-V pathway play a role in determining the ventricular frequency during atria1 fibrillation.lms The effect of adrenergic stimulation on the anterograde conduction over the accessory pathway is of special interest because the onset of the arrhythmia is frequently accompanied by anxiety and a decrease in blood pressure leading to enhanced sympathomimetic activity. Recently Przybylski et a1.4reported reappearance of anterograde conduction over an accessory A-V pathway in patients no longer having anterograde conduction over that structure after vagal and beta adrenergic stimulation. This paper describes the effect of isoproterenol administration on seven patients with the Wolff-Parkinson-White syndrome. As will be shown, beta adrenergic stimulation may result in considerable shortening of the anterograde refractory period of the accessory A-V pathway in some of these patients.
The American Journal of CARDIOLOGY
Volume 50
IXOPROTERENOLIN WOLFF-PARKINSON-WHITESYNDROME-mWELLENSET AL.
TABLE
Methods
I
Clinical Data of the Seven Patients
Patients: Seven patients were studied. Data on age, sex, location of the accessory pathway and type of clinically documented tachycardia are given in Table I. In Patients 1 to 6 all medication was discontinued at least 5 half-lives before the study. Patient 6 was restudied 6 weeks later after receiving oral amiodarone (total dose 11,200 mg) during that time. Patient 7 was investigated while receiving oral amiodarone for 5 weeks (total dose 9,800 mg). Programmed stimulation protocol: After informed consent was obtained, a programmed stimulat,ion study was performed using a protocol previously described.s After baseline measurements were made using the single test stimulus technique during pacing of the high right atrium, the coronary sinus and the apex of the right ventricle, an intravenous infusion of isoproterenol was started. The initial dose of 0.25 g/min was gradually increased to a dose that resulted in a stable sinus rate that was 20 to 30 percent higher than that immediately before isoproterenol administration. The individual isoproterenol dosage required ranged from 1 to 5 g/min. Measurements during isoproterenol administration were made using the same basic cycle lengths and test stimulus intervals as before the drug. Atria1 fibrillation was not routinely initiated before and during isoproterenol administration. Therefore no data were obtained on the effect of isoproterenol on the ventricular rate during atria1 fibrillation. Definition of terms: The following terms are used in this study:
Case 1 : 4 ; 7
Age (yr) & Sex
Site of Accessory Pathway
Type of Arrhythmia
32M 19F 34M 44F 39M 37M 47M
Right septal Left lateral Left posterior Left septal Right septal Left lateral Left lateral
%T + AF CMT CMT CMT + AF CMT CMT
AF = atrial fibrillation; CMT = circus movement tachycardia.
Anterograde effective refractory period of the accessory pathway: the shortest possible premature beat interval during
single test stimulation of the atrium followed by A-V conduction over the accessory pathway. Effective refractory period atrium: the shortest possible premature beat interval during single test stimulation of the atrium resulting in atria1 activation. Effective refractory period of the ventricle: the shortest possible premature beat interval during single test beat stimulation of the ventricle resulting in ventricular activation. Retrograde effective refractory period of the accessor pathway: the shortest possible premature beat interval during
single test stimulation of the ventricle followed by ventriculoatrial (V-A) conduction over the accessory pathway. V-A conduction over an accessory pathway was determined by using methods previously described.”
Results Effect of isoproterenol on anterograde refractory period of accessory pathway: No patient experienced unpleasant effects during isoproterenol administration. In all patients anterograde conduction over the accessory pathway persisted. Isoproterenol shortened the anterograde refractory period of the accessory pathway in six of seven patients (Table II, Fig. 1 and 2). In all patients stimulation was performed from both the high right atrium and the coronary sinus. As the anterograde refractory period of the accessory pathway we selected the shortest value found during stimulation at one of these sites. The refractory period of the atrium given in Table II was determined at the same site of stimulation. In two of the three patients having an initial anterograde refractory period of the accessory pathway of 290 ms or less, the anterograde refractory period of the accessory pathway shortened
by 30 ms, reaching values of 220 and 230 ms, respectively. In the three patients with an anterograde refractory period of more than 290 ms who were not receiving drugs, the shortening in these values after isoproterenol ranged from 30 to 80 ms, resulting in an anterograde refractory period of the accessory pathway of 250,340 and 270 ms, respectively. In the two patients receiving oral amiodarone, isoproterenol administration resulted in shortening of the anterograde refractory period of the accessory pathway of, respectively, 180 and 60 ms, leading to new values of 320 and 280 ms. Our results suggest that the greatest amount of shortening is observed in patients having the longest initial value of the anterograde refractory period of accessory pathway. Effect of retrograde refractory period of atrium and ventricle: The changes in duration of the anterograde refractory period of the accessory pathway during isoproterenol administration differed from those of the refractory periods of the atrium and the ventricle. Only minimal shortening of these values was observed. The effect of isoproterenol on the retrograde refractory period of the accessory pathway could be measured in only three patients. In two of them shortening was observed measuring, respectively, 20 and 100 ms. In all patients the R-R interval shortened during circus movement tachycardia after isoproterenol administration (Fig. 1 and 2). This shortening was the result of abbreviation of the A-H interval. No appreciable shortening was observed in the H-V interval or in the retrograde conduction time over the accessory pathway (as measured by the V-A interval in the coronary sinus lead in patients with a left-sided accessory pathway). Discussion
Effect of beta adrenergic stimulation in WolffParkinson-White syndrome: Our results indicate that beta adrenergic stimulation may result in marked abbreviation of the anterograde refractory period of the accessory pathway in some patients with the WolffParkinson-White syndrome. In our patients the effect of isoproterenol on the anterograde effective refractory period of the accessory pathway differed from its effect on the refractory period of atria1 and ventricular tissue, suggesting that these accessory pathways are not composed of ordinary atria1 or ventricular muscle. This
July 1992
The American Journal of CARDIOLOGY
Volume 50
191
ISOPROTERENOL IN WOLFF-PARKINSON-WHITE
SYNDROME-WELLENS
ET AL.
TABLE II Values for the Electrophyslologic Variables Before and During lsoproterenol Administration* Anterograde
Retrograde
ERPAP
Case
Medication
EBPRv
ERPAP
ERPA~,
BCL
Is-
Is+
Is-
Is+
Is-
ISS
Is-
Is+
1
-
430
330
250
210
200
200
190
200
190
3 4 5
-
430 500 500
420 260 250 290
340 230 220 290
200 210 200 230
210 200 190 230
250 190 240 240
230 190 240 NM
190 190 240
190 180 190 NM
6 7
Am Am
550 600
340 300 500
280 270 320
250 270 280
270 250 270
420 330 270
3N2Mo 270
240 270
2N3Mo 270
* All values are in milliseconds. Am = amiodarone; AP = accessory pathway; Atr = atrium; BCL = basic cycle length; ERP = effective NM = not measured; - = absent; + = present.
finding seems to be in conflict with the pathohistologic studies discussed by Sherf and Neufeld.7 In these studies the accessory bundles are described as composed of atria1 or ventricular working myocardial cells. However, in the absence of knowledge about the correlation between structure and function, our suggestion remains speculative.
Effects
on ventricular
refractory
period; Is = isoproterenol;
rate in atria1 fibrillation:
It has previously been reported that in the Wolff-Parkinson-White syndrome the ventricular rate during atria1 fibrillation relates to the duration of the anterograde refractory period of the accessory pathway.‘-” Although we did not compare the ventricular rates during atria1 fibrillation in relation to changes in the
CONTROL
FIGURE 1. Patient 7. A, before isoproterenol administration coronary sinus pacing with a basic cycle length of 600 msec shows that the anterograde refractory period of the accessory pathway measures 500 ms. B, premature beats given with shorter coupling intervals initiate a circus movement tachycardia with anterograde conduction over the atrioventricular node and ventriculoatrial conduction over a left lateral accessory pathway. Leads 1, II, Ill, VI, Vs, a high right atrial lead (HRA), a distal coronary sinus lead (CSd) and a His bundle electrogram were recorded simultaneously.
182
July 1982
The American
Journal of CARDIOLOGY
Volume 50
ISOPROTERENOL
duration of the anterograde refractory period of the accessory pathway before and during isoproterenol administration, we believe that our observations explain why, in some patients, the shortest R-R interval during atria1 fibrillation is less than the measured anterograde refractory period of the accessory pathway using the single test stimulation technique at rest. Sympathetic discharge after the onset of atria1 fibrillation may shorten the anterograde refractory period of the accessory pathway, leading to high ventricular rates resulting in serious hemodynamic consequences. The abbreviation of the anterograde refractory period of the accessory pathway during sympathetic stimulation may theoretically result in such rapid ventricular rates during atria1 fibrillation that deterioration in ventricular fibrillation occurs. Denes et a1.8reported that beta adrenergic blockade by propranolol had little effect on the duration of the anterograde refractory period of the accessory pathway as assessed with the single test stimulus technique. In their patients measurements were made at rest suggesting a normal level of sympathetic activity. It would be of interest to study the effect of beta adren-
IN WOLFF-PARKINSON-WHITE
SYNDROME--WELLENS
ET AL.
ergic blockade during atria1 fibrillation in patients with the Wolff-Parkinson-White syndrome, especially during exercise. Effect of amiodarone: Amiodarone is the drug that most consistently lengthens the duration of the anterograde refractory period of the accessory pathway.gJO However, our observations suggest that the drug does not protect against the abbreviation of the anterograde refractory period of the accessory pathway after beta adrenergic stimulation. This can be of clinical importance. Although our experience indicates that in patients with the Wolff-Parkinson-White syndrome and documented atria1 fibrillation the incidence of atria1 fibrillation diminishes after amiodarone administration, episodes of atria1 fibrillation may still occur. When accompanied by sympathetic stimulation as during exercise or anxiety the ventricular rate during the arrhythmia may still be life-threatening. Therapeutic implications: We believe that the results of our study with isoproterenol should influence the approach to patients with the Wolff-ParkinsonWhite syndrome. They suggest that in patients with this syndrome suffering from arrhythmias the effect of beta
ISOPROTERENOL
FIGURE 2. Same patient. A, during isoproterenol administration the anterograde refractory period of the accessory pathway shortens to 320 ms. B, again at shorter premature beat intervals a circus movement tachycardia is initiated. Note that the R-R interval of the tachycardia has decreased from 430 (Fig. 1) to 360 ms. This shortening is the result of abbreviation of the A-H interval during isoproterenol administration. Comparison between Figures 1 and 2 suggests a shortening in intraatrial conduction time after isoproterenol. We are reluctant to accept this as proved, however, because of (1) a possible change in catheter positions, and (2) a possible decrease in atrial dimensions because of beta adrenergic stimulation by isoproterenol.
July 1982
The American Journal of CARDIOLOGY
Volume 50
183
ISOPROTERENOL IN WOLFF-PARKINSON-WHITE
SYNDROMEPWELLENS
ET AL
adrenergic stimulation on the anterograde refractory period of the accessory pathway should be evaluated. If marked abbreviation of the refractory period results, the changes in R-R interval during pacing-induced atria1 fibrillation should be studied while the patient is receiving isoproterenol. When isoproterenol administration results in R-R intervals during atria1 fibrillation of 220 ms or less the value of adding a beta adrenergic blocking agent to the antiarrhythmic drug regimen should be evaluated. Przybylski et a1.4showed that, in some patients with prior electrocardiographic documentation of anterograde conduction over an accessory A-V pathway but not showing A-V conduction over this structure during sinus rhythm in current electrocardiograms, anterograde A-V conduction over the accessory pathway could be reinstituted during vagal stimulation or intravenous
isoproterenol administration. Although these patients are different from ours, because our patients always had anterograde conduction over the accessory pathway during sinus rhythm, their observations and ours indicate that the electrophysiologic properties of accessory pathways in the Wolff-Parkinson-White syndrome are not constant. In patients with intermediate values for the duration of the anterograde refractory period of the accessory pathway, sympathetic stimulation may possibly have life-threatening consequences if atria1 fibrillation supervenes. These considerations and the impressive results from the group at Duke University” suggest that surgical interruption of the accessory pathway should play an increasingly important role in the management of patients with the Wolff-Parkinson-White syndrome.
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drome. In: Bircks W, Loogen F, Schulte HD, Seipel L, eds. Medical and Surgical Management of Tachyarrhythmias. Berlin: Springer Verlag, 1980:94-105. Sherf L, Neufeld H. The Pre-excitation Syndrome: Facts and Theories. New York: Yorke, 1978:92-l 10. Denes P, Cummings JM, Slmpson R, et al. Effects of propranolol on anomalous pathway refractoriness and circus movement tachycardias in patients with pre-excitation. Am J Cardiol 1978; 41:1061-7. Wellens HJJ, Lie K, B&r FW, et al. Effects of amiodarone in the Wolff-Parkinson-White syndrome. Am J Cardiol 1976;38:18994. Wellens HJJ, Bar FW, Dassen WRM, Brugada P, Vanagt EJ, Farre J. Effects of drugs in the Wolff-Parkinson-White syndrome. Am J Cardiol 1980;46:665-9. Gallagher JJ, Sealy WC, Kasell JH. Intra-operative localization and division of accessory pathways associated with the WolffParkinson-White syndrome. In Ref 6, 114-37.