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Effect of erythromycin on ventricular arrhythmias and ventricular repolarization in idiopathic long QT syndrome
168
BRIEF REPORTS
Effect of Erythromycin on Ventricular Arrhythmias and Ventricular Repolarization in Idiopathic Long QT Syndrome ROGER A. FREEDMAN, MD KELLEY P. ANDERSON, MD LARRY S. GRF_EN,MD JAY W. MASON, MD
Patients with idiopathic long QT syndrome are subject to paroxysmal episodes of the torsades de pointes type of ventricular tachycardia. Torsades de pointes in these patients is frequently preceded by further prolongation of the QT interval, T-wave alternans and frequent ventricular premature complexes. Emotional upset, physical exertion, electrolyte disturbances and certain antiarrhythmic drugs may precipitate torsades de pointes. We report a patient with idiopathic long QT syndrome in whom erythromycin appeared to worsen repolarization abnormalities and precipitate arrhythmias.
~!'C:I:::,',F:li~:~t~::,;,,l~lll!lll~ t hl~l!lllltftt]l~t glT~il?t~!111~ll i
~:i!~'/i~:/!1' FIGURE
•'
I;:t~fi,I : ;t~: I:.!l'!' I i',{," }',[."~lt![!l"% ' '~]t!~I t' ':I .:I jt'.:~!7;l , ~ ' F % ~ i ~ . .
1. Torsedes de p o l n t e s
T
I n l U a t e d by an R-on-T ventrlcular
premature beat. The tracing is continuous and was recorded on the first hospital day.
II
'
V2
-~~~r--v~c-v-
lw-lw aVR
aV,
, v4
~
.
~ ,
,__J
1
sec
F I G U R E 2. Twelve-lead electrocardiogram before erythromycln ad-
A 29-year-old woman was transferred to the Uni- mlnlstraUon. The tracing shows sinus rhythm at 66/rain, prolonged versity of Utah Medical Center for control Of repeated QT I n t e r v a l ( 0 . 6 0 second), and widespread T-wave Inversion or episodes Of torsades de pointes. Since age 12 years the flattening. patient had had episodes of lighheadedness lasting 30 to 60 seconds. She had never lost consciousness and had never sought medical attention for these episodes. At the time of transfer, lidocaine and erythromycin Five days before transfer the patient started a course of erythromycin, 500 mg by mouth 4 times daily, pre- were discontinued, a transvenous pacemaker was poscribed for nonproductive cough. She was taking no sitioned in the right ventricular ape'x, and the episodes other medication. Three days later the patient had the of torsades de pointes were suppressed with pacing at first of several episodes of syncope. She presented 100 beats/rain, Because we suspected that erythromyto another hospital, where her electrocardiogram cin had precipitated the recent arrhythmias, we recshowed sinus rhythm at 70 beats/rain with frequent, ommended that the patient receive an infusion of short Salvos of polymorphic ventricular tachycar- erythromycin during electrocardiographic monitordia. The QT interval of the sinus beats was 0.56 ing for diagnostic purposes, and she agreed. On the third hospital day, the pacemaker was second. Serum potassium, magnesium and calcium levels were normal and remained normal for the rest turned off and the patient was observed in sinus of her course. Soon after admission the patient had rhythm. The sinus rate was 56beats/rain and QT inseveral prolonged episodes of torsades de pointes (Fig. terval was 0.60 second (Fig. 2). There were no ventric1), one of which degenerated into ventricular flutter ular premature beats or other rhythm abnormalities and required direct-current cardioversion for termi- daring 2 hours Of observation. The patient was then nation. Lidocaine was not effective in preventing told that she would be receiving intravenous infusions these arrhythmias, and the patient was transferred to of erythromycin and normal Saline solution placebo, the University of Utah Medical Center. The patient but was not told the order of administration. The first had no history of hearing loss. She reported that she infusion was normal saline solution, 100 ml adminishad never received erythromycin before the recent tered through a central venous catheter. No changes course. No family member was known to have long were noted in the 12-lead electrocardiogram and no arrhythmias were noted for 1 hour afterward. The QT syndrome. patient was then given an infusion of erythromycin lactobionate 250 mg in normal saline solution, 100 ml. Fourteen minutes later, T-wave alternans was noted From the Cardiology Division, Department of Medicine, University of Utah Medical Center, 50 North Medical Drive, Salt [Fig. 3). Frequent, multiform ventricular premature Lake City, Utah 84132. Manuscript received April 3, 1986; re- beats were noted shortly later (Fig. 4). The T-wave alternans and ventricular premature beats persisted vised manuscript receiving June 26, 1986, accepted July 2, 1986.
BRIEF REPORTS
January 1, 1987
THE AMERICAN JOURNAL OF CARDIOLOGY
Volume 59
169
li II aVL 1 sec FIGURE 4. Multiform ventricular premature depolarizations and
aVF
ventricular bigeminy after erythromycln administration. Shown is standard electrocardiographic lead li. The eighth beat Is an atrial premature depolarization. V6
1 sec FIGURE 3. T-wave alternans after erythromycln administration. AIternaUdn of T-wave morphology Is seen In each of the 6 standard
electrocardiographic leads shown. The QT Interval also alternates between 0.56 and 0.84 second.
for 40 minutes, after which time the electrocardiogram returned to baseline. The patient was subsequently started on propronoIol and the dose was increased to 160 mg by mouth every 6 hours. A left cervicothoracic sympathetic ganglionectomy 1 was performed on the ninth hospital day. No change in QTc was apparent after propronoIol therapy or the ganglionectomy. On the twelfth hospital day, infusion of erythromycin lactobionate was repeated, but it induced no T-wave changes or extrasystoles. No subsequent arrhythmias were observed by the thirteenth hospital day, and the patient was discharged. The patient has hod no further symptoms during 12 months of follow-up. Multiple electrocardiograms showing prolongation of the QT interval, including several when the patient was receiving no medications, establish the diagnosis of idiopathic long QT syndrome in this patient. Her recurrent, transient episodes of lightheadedness since adolescence are symptoms typically associated with nonsustained torsades de pointes in such patients. However, before the events immediately preceding hospitalization she had no symptoms indicative of a sustained arrhythmia. Two factors suggest that erythromycin exacerbated arrhythmias and repolarization abnormalities in this patient: (1) the close temporal association between oral erythromycin therapy and recurrent episodes of sustained torsades de pointes and (2) the T-wave alternans and ventricular ectopy after erythromycin infusion.
Erythromycin was associated with ventricular tachyarrhythmias and QT prolongation in 2 reports, 2,3 but the danger of administering erythromycin to patients with prolonged QT interval is not widely recognized. Furthermore, the patient described above is the first with idiopathic long QT syndrome in whom arrhythmia exacerbation with erythromycin has been reported. Our patient is also the first in whom the effect of erythromycin was shown to be abolished by interventions blocking the sympathetic nervous system. How erythromycin influences cardiac repolarization is unknown. Erythromycin causes myocardial potassium efflux and predisposes to ventricular arrhythmias in the anesthetized dog subjected to digitalis or ischemia.4 In our patient, the abolition of the erythromycin effect by propranolol therapy and left cervicothoracic sympathetic ganglionectomy suggests that the erythromycin effect was mediated by the sympathetic nervous system. How frequently erythromycin precipitates ventricular arrhythmias in patients with idiopathic long QT syndrome is unknown. Until the full scope of the relation between arrhythmias and erythromycin is clarified, caution is advised in administration of this drug to patients with prolongation of the QT interval. Further studies are warranted to establish the diagnostic value of erythromycin in patients with known or suspected long QT syndrome. 1. Moss A], McDonald ]. unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome. N Engl ] Med
1971;285:903-904. 2. McComb JM, Campbell NPS, Cleland ]. Recurrent ventricular tachycardia associated with QT prolongation after mitral valve replacement and its association with intravenous administration of erythromycin. Am J Cardiol
1984;54:922-923. 3. Gueugniaud PY, Guerin C, Mahul P, Due C, Robert D. Torsades de pointe induites par rassociation lidocaine-erythromycine et insuffisance hepatique. Presse Med 1985;14:896. 4. Regan T], Khan MI, Oldewnrtel HA, Passannante A]. Antibiotic effect on myocardial K+ transport and the production of ventricular tachycar-
dia. [ Clin Invest 1969;48:68a.
BRIEF REPORTS
Effect of Erythromycin on Ventricular Arrhythmias and Ventricular Repolarization in Idiopathic Long QT Syndrome ROGER A. FREEDMAN, MD KELLEY P. ANDERSON, MD LARRY S. GRF_EN,MD JAY W. MASON, MD
Patients with idiopathic long QT syndrome are subject to paroxysmal episodes of the torsades de pointes type of ventricular tachycardia. Torsades de pointes in these patients is frequently preceded by further prolongation of the QT interval, T-wave alternans and frequent ventricular premature complexes. Emotional upset, physical exertion, electrolyte disturbances and certain antiarrhythmic drugs may precipitate torsades de pointes. We report a patient with idiopathic long QT syndrome in whom erythromycin appeared to worsen repolarization abnormalities and precipitate arrhythmias.
~!'C:I:::,',F:li~:~t~::,;,,l~lll!lll~ t hl~l!lllltftt]l~t glT~il?t~!111~ll i
~:i!~'/i~:/!1' FIGURE
•'
I;:t~fi,I : ;t~: I:.!l'!' I i',{," }',[."~lt![!l"% ' '~]t!~I t' ':I .:I jt'.:~!7;l , ~ ' F % ~ i ~ . .
1. Torsedes de p o l n t e s
T
I n l U a t e d by an R-on-T ventrlcular
premature beat. The tracing is continuous and was recorded on the first hospital day.
II
'
V2
-~~~r--v~c-v-
lw-lw aVR
aV,
, v4
~
.
~ ,
,__J
1
sec
F I G U R E 2. Twelve-lead electrocardiogram before erythromycln ad-
A 29-year-old woman was transferred to the Uni- mlnlstraUon. The tracing shows sinus rhythm at 66/rain, prolonged versity of Utah Medical Center for control Of repeated QT I n t e r v a l ( 0 . 6 0 second), and widespread T-wave Inversion or episodes Of torsades de pointes. Since age 12 years the flattening. patient had had episodes of lighheadedness lasting 30 to 60 seconds. She had never lost consciousness and had never sought medical attention for these episodes. At the time of transfer, lidocaine and erythromycin Five days before transfer the patient started a course of erythromycin, 500 mg by mouth 4 times daily, pre- were discontinued, a transvenous pacemaker was poscribed for nonproductive cough. She was taking no sitioned in the right ventricular ape'x, and the episodes other medication. Three days later the patient had the of torsades de pointes were suppressed with pacing at first of several episodes of syncope. She presented 100 beats/rain, Because we suspected that erythromyto another hospital, where her electrocardiogram cin had precipitated the recent arrhythmias, we recshowed sinus rhythm at 70 beats/rain with frequent, ommended that the patient receive an infusion of short Salvos of polymorphic ventricular tachycar- erythromycin during electrocardiographic monitordia. The QT interval of the sinus beats was 0.56 ing for diagnostic purposes, and she agreed. On the third hospital day, the pacemaker was second. Serum potassium, magnesium and calcium levels were normal and remained normal for the rest turned off and the patient was observed in sinus of her course. Soon after admission the patient had rhythm. The sinus rate was 56beats/rain and QT inseveral prolonged episodes of torsades de pointes (Fig. terval was 0.60 second (Fig. 2). There were no ventric1), one of which degenerated into ventricular flutter ular premature beats or other rhythm abnormalities and required direct-current cardioversion for termi- daring 2 hours Of observation. The patient was then nation. Lidocaine was not effective in preventing told that she would be receiving intravenous infusions these arrhythmias, and the patient was transferred to of erythromycin and normal Saline solution placebo, the University of Utah Medical Center. The patient but was not told the order of administration. The first had no history of hearing loss. She reported that she infusion was normal saline solution, 100 ml adminishad never received erythromycin before the recent tered through a central venous catheter. No changes course. No family member was known to have long were noted in the 12-lead electrocardiogram and no arrhythmias were noted for 1 hour afterward. The QT syndrome. patient was then given an infusion of erythromycin lactobionate 250 mg in normal saline solution, 100 ml. Fourteen minutes later, T-wave alternans was noted From the Cardiology Division, Department of Medicine, University of Utah Medical Center, 50 North Medical Drive, Salt [Fig. 3). Frequent, multiform ventricular premature Lake City, Utah 84132. Manuscript received April 3, 1986; re- beats were noted shortly later (Fig. 4). The T-wave alternans and ventricular premature beats persisted vised manuscript receiving June 26, 1986, accepted July 2, 1986.
BRIEF REPORTS
January 1, 1987
THE AMERICAN JOURNAL OF CARDIOLOGY
Volume 59
169
li II aVL 1 sec FIGURE 4. Multiform ventricular premature depolarizations and
aVF
ventricular bigeminy after erythromycln administration. Shown is standard electrocardiographic lead li. The eighth beat Is an atrial premature depolarization. V6
1 sec FIGURE 3. T-wave alternans after erythromycln administration. AIternaUdn of T-wave morphology Is seen In each of the 6 standard
electrocardiographic leads shown. The QT Interval also alternates between 0.56 and 0.84 second.
for 40 minutes, after which time the electrocardiogram returned to baseline. The patient was subsequently started on propronoIol and the dose was increased to 160 mg by mouth every 6 hours. A left cervicothoracic sympathetic ganglionectomy 1 was performed on the ninth hospital day. No change in QTc was apparent after propronoIol therapy or the ganglionectomy. On the twelfth hospital day, infusion of erythromycin lactobionate was repeated, but it induced no T-wave changes or extrasystoles. No subsequent arrhythmias were observed by the thirteenth hospital day, and the patient was discharged. The patient has hod no further symptoms during 12 months of follow-up. Multiple electrocardiograms showing prolongation of the QT interval, including several when the patient was receiving no medications, establish the diagnosis of idiopathic long QT syndrome in this patient. Her recurrent, transient episodes of lightheadedness since adolescence are symptoms typically associated with nonsustained torsades de pointes in such patients. However, before the events immediately preceding hospitalization she had no symptoms indicative of a sustained arrhythmia. Two factors suggest that erythromycin exacerbated arrhythmias and repolarization abnormalities in this patient: (1) the close temporal association between oral erythromycin therapy and recurrent episodes of sustained torsades de pointes and (2) the T-wave alternans and ventricular ectopy after erythromycin infusion.
Erythromycin was associated with ventricular tachyarrhythmias and QT prolongation in 2 reports, 2,3 but the danger of administering erythromycin to patients with prolonged QT interval is not widely recognized. Furthermore, the patient described above is the first with idiopathic long QT syndrome in whom arrhythmia exacerbation with erythromycin has been reported. Our patient is also the first in whom the effect of erythromycin was shown to be abolished by interventions blocking the sympathetic nervous system. How erythromycin influences cardiac repolarization is unknown. Erythromycin causes myocardial potassium efflux and predisposes to ventricular arrhythmias in the anesthetized dog subjected to digitalis or ischemia.4 In our patient, the abolition of the erythromycin effect by propranolol therapy and left cervicothoracic sympathetic ganglionectomy suggests that the erythromycin effect was mediated by the sympathetic nervous system. How frequently erythromycin precipitates ventricular arrhythmias in patients with idiopathic long QT syndrome is unknown. Until the full scope of the relation between arrhythmias and erythromycin is clarified, caution is advised in administration of this drug to patients with prolongation of the QT interval. Further studies are warranted to establish the diagnostic value of erythromycin in patients with known or suspected long QT syndrome. 1. Moss A], McDonald ]. unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome. N Engl ] Med
1971;285:903-904. 2. McComb JM, Campbell NPS, Cleland ]. Recurrent ventricular tachycardia associated with QT prolongation after mitral valve replacement and its association with intravenous administration of erythromycin. Am J Cardiol
1984;54:922-923. 3. Gueugniaud PY, Guerin C, Mahul P, Due C, Robert D. Torsades de pointe induites par rassociation lidocaine-erythromycine et insuffisance hepatique. Presse Med 1985;14:896. 4. Regan T], Khan MI, Oldewnrtel HA, Passannante A]. Antibiotic effect on myocardial K+ transport and the production of ventricular tachycar-
dia. [ Clin Invest 1969;48:68a.