- Email: [email protected]
Efficacy and safety of amiodarone in infants
1430
Shuler,
Case, and Gillette
Amermn
Heart
RCA
Fig. 3. Right internal mammary arteriogram in the left anterior oblique view and diagram outlining internal mammary-to-coronary artery communication. The slightly enlarged pericardial branch (P) of the right internal mammary artery (IMA) communicated with the right coronary artery CRC’A) (arrows) via retrograde filling of the sinus nodal branch (S’N) of the RCA.
Fig. 4. Myocardial perfusion imaging with ‘“‘TI-SPECT at rest. These images were obtained 5 days before the cardiac catheterization shown in Figs. 31 and 3. The orthopedic circumstances of this patient precluded exercise challenge. Vertical long-axis view (left side) and midventricular short-axis view (right side) are shown. Both the inferoposterior wall (arrows) and the upper half of the right ventricular wall (triangles) could be visualized as hypoperfused areas.
4. Singh RN. Radiographic anatomy of the internal mammary arteries. Cathet Cardiovasc Diagn 1981;7:373-86. 5. Zureikat HY. Collateral vessels between the coronary and bronchial arteries in patients with cvanotic congenital heart disease. Am J Cardioi 1983:45:599-60X. .. 6. Smith SC, Adams DF, Herman MV. Paulin S. Coronary to bronchial anastomoses: an in viva demonstration by selective coronary arteriographp. Radiology 1970;104:289-90.
Efficacy infants
and safety of amiodarone
Claudius Osborne Shuler, MD, Christopher L. Case, MD, and Paul C. Gillet,te, MD C’harlcston,
SC.
in
May 1993 Journal
Volume 125, Number 5, Part 1 American Heart Journal
Shuler,
the Medical University of South Carolina, Center, Division of Pediatric Cardiology.
South
Reprint requests: C. Osborne Shuler, MD, Medical Carolina, South Carolina Children’s Heart Center, Cardiology, 171 Ashley Ave., Charleston, SC 29425. AM HEART
University Division
Children’s of South of Pediatric
J 1993;125:1430-1432.
Copyright (c, 1993 0002.8703/93/$1.00
Table
Carolina
by Mosby-Year Book, + .lO 4/4/44903
1431
day for 7 days. The maintenancedosewas5 mglkg/day except in the two above-mentionedpatients, who received 10 mg/kg/day. The treatment protocol included monitoring thyroid function studies and liver enzymes before and 6 months after starting therapy. Results. Successof therapy was defined as significant improvement or completeelimination of the arrhythmia, as evaluated clinically by Holter monitoring. Failure of therapy was defined as worsening or no significant improvement of the arrhythmia. Amiodarone wasconsideredsuccessfulin 10of the 17 infants. In four casesamiodaronewas the only antiarrhythmic drug being used and in the remaining six casesa successfuloutcome ensued when amiodaronewasusedin combination with one or two other antiarrhythmic drugs. In the reentrant SVT subgroup, amiodaronewas successfulin only 3 of 10 cases.In the non-SVT subgroup, it was successfulin all seven infants. The two infants who were given a higher loading and maintenance dosehad junctional ectopic tachycardia and atria1ectopic tachycardia and were consideredtherapeutic successes. There were therapeutic failures in seven patients, all with reentrant SVT. Of the sevenpatients, three went on to have successfulradiofrequency ablation of an accessorypathway and four had successfulsurgical ablation of an accessorypathway. In two infants (patients No. 9 and lo), failure wasa result of SVT becomingincessant severaldays after the initiation of amiodarone.In both infants, the tachycardia frequency had decreasedwithin 2 days following discontinuation of amiodarone when the patients had successfulablation with radiofrequency catheterization. The other five patients failed to improve with amiodaronebecauseof poor control of SVT. The infants who failed to improve with amiodaronetherapy continued taking amiodarone for a mean of 20 days (range 5 to 35 days). Infants in whom therapy wassuccessfulremainedon
Amiodarone has been used in the treatment of children with serious cardiac arrhythmias for many years. Reports in general cite high success rates,l* 2 with varying frequency of side effects.3 Most references in the literature contain infants in the patient population but are dominated by older children.‘, 2,4 This study reviews our experience with the safety and efficacy of amiodarone exclusively in infants (<12 months) with life-threatening arrhythmias. Methods. Over a period of 4 years, 17 infants were treated with amiodarone, alone or in combination with other antiarrhythmic drugs (Table I). There were 7 females and 10 males, with a mean age of 2.6 months (range 0.5 to 7.6 months). There were 10 patients with reentrant supraventricular tachycardia (SVT) and seven with other arrhythmias. Fourteen of 17 infants had normal cardiac anatomy and function as diagnosed by echocardiography. Two infants with reentrant SVT had associated cardiomyopathies and one patient was status post surgical repair for anomalous left coronary artery. Fifteen infants had failed from one to four drug regimens before starting amiodarone, and two patients were started on amiodarone therapy as their primary antiarrhythmic drug. All patients were hospitalized with continuous telemetry monitoring during the loading period. Fifteen of 17 patients received a loading dose of 10 mg/kg/day for 7 to 10 days. One patient received 15 mg/kg/day for 7 days, while another received 20 mg/kg/ From Heart
Case,and Gillette
Inc.
I. Patient information
Patient NO.
No. of
Age (mo)l Sex
EP diagnosis
0.8/M 0.5/M 7.3/F
SVT SVTiWPW SVTIWPW
0 4 2
6.5 mo 25.5 mo >44 mo
4
1.0/F
5
0.5/M 6.4/F LO/M 0.5/M 0.5/M 2.7/F
SVT SVT/WPW SVT/WPW SVT SVT SVT SVT
1 3 2 3 4 2 4
20 days 22 days 28 days 35 days 21 days 12 days 5 days
0.5/M 6.5/M 3.8/F
VT VT SVTNT
1 2 1
16 mo 5.5 mo >3 mo
+ +lD +
2.2/M 2.2iF 7.6/M 5.5/F
AET AET
2 1
>13 >12 >38 >3
+/F
1 2 3
6 7 8 9 10 Other arrhythmias 11 12 13 14
15 16 17
AET, Atria1 ectopic tachwardia; radiofrequency ablation; syndrome; >, currently
AF JET
previous
drugs
0
2
Time on amiodarone
mo* mo mo mo*
Successl With
Outcome
+
+N +/D
-
RF
-
SA SA SA SA RF
RF -
+/F +/D, E +
AF, atria1 flutter; D, digoxin; E, encanide; EP, electrophysiologic; F, flecanide; JET, junctional SA, surgical ablation; SVT, reentrant supraventricular tachycardia; VT, ventricular tachycardia; WpW, taking amiodarone, *larger load and maintenance dose.
ectopic tachycardia; Wolff-Parkinson-White
RF,
my
1432
Singh et al.
Amrwcan
a regimen of amiodarone for a mean of 16.6 months (range 3 to 44 months), with six patients still taking amiodarone at the time of submission of this report. Side effects OI amiodarone therapy were limited only to proarrhythmic effects. Two patients with reentrant SVT had incessant episodes after the start of amiodarone. Comments. These data show that amiodarone was without side effects but exhibited variable efficacy in the infants studied. The success of amiodarone in medically resistant reentrant SVT was limited to 3 of 10 patients (30 I‘( ). though the drug does appear to be efficacious in the treatment of other arrhythmias including ventricular tachycardia, atria1 ectopic tachycardia, and junctional ect.opic tachycardia. The role of amiodarone in the treatment of infants has been controversial.” Given the increasing experience of radiofrequency catheter ablation in infancy,” the role of amiodarone in infants with reentrant SVT is likely to become less important. REFERENCES 1. 2.
3.
4.
5. 6.
Coumel P, Lucet V, Do Ngoc D. The use of amiodarone in children. PACE 1983;6:930-9. Guccione P, Paul T, Carson A Jr. Long-term follow-up ot amiodarone therapy in the young: continued efficacy, unimpaired growth, moderate side effects. .I Am Co11 Cardiol 1990;15:1118-24. Vrobel TR, Miller PE, Mostow ND, Rakita L. A general overview of amiodarone toxicity: its prevention, detection. and management. Prog Cardiovasc Dis 1989;31:393-426. Pongiglione G, Strasburger JF, Deal BJ, Benson DW Jr. Use of amiodarone for short-term and adjuvant therapy in young patients. Am J Cardiol 1991;68:603-8. Villain E. Surgery for Wolff-Parkinson-White syndrome in the very young. J Thorac Cardiovasc Surg 1992;103:388-9. Case CL, Gillette PC. Oslizlok PC. Knick BJ, Blair HI,. Radiofrequency catheter ablation of incessant, medically resistant supraventricular tachycardia in infants and small children. .J Am Co11 Cardiol 1992;20:1405-10.
Acceleration of atrioventricular conduction during corticosteroid
therapy
Rampaul G. Singh, MD, Mohammed Kassir, MD, Nancy Roistacher, MD, Bruce B. Lerman, MD, and Paul Kligfield, MD New Yorli, N.Y.
Anatomic, neurohumoral, and functional factors are known to affect the PR interval of the electrocardiogram (ECG),‘-I” but the potential effect of corticosteroids on atrioventricular (AV) conduction in the human heart has not been established. Classic reports have found steroid excess in paFrom the Division Hospital-Cornell Reprint Medical
of Cardiology, Medical Center.
Department
of Medicine.
The New
requests: Paul Kligfield, MD, The New York Hospital-Cornell Center, 525 East 68th St.. New York. NY 10021.
AM HEART
J 1993:125:1432-1434.
Copyright ” 1993 000%8703/93/$1.00
by Mosby-Year Book. + .lO 4/4/44899
Inc.
York
Heart
1993 Journal
tients with Gushing’s disease to be associated with shor! ened PR intervals” and steroid deficiency in patients with Addison’s disease to be associated with lengthened PR intervals.” Furt,her. we have observed short PR intervals to occur commonly in patients receiving combination chemotherapy regimens, and also ~JCCaSiond cases of otherwise unexplained rapid ventricular responses in patients with atria1 fibrillation who are taking steroids. Taken together. these report,s and observations suggest that corticosteroids might cause a clinically relevant acceleration of AV conduction. Accordingly, we examined the serial effects of transient pharmacologic doses of steroid, taken in conjunction with ot.herwise varied regimens of inpatient chemotherapy. on the PR interval of the ECG. Methods. The medical admission lists to the Memorial Hospital-Sloan Kettering Cancer Center (New York, N.Y.) between January 1, 1990, and April 1,1990, were reviewed daily to identify patients for study. Twenty-nine patients taking a course of steroids in conjunction with chemotherapy were selected from further review of their inpatient charts and pharmacy requisitions. Patients who had septicemia, who were otherwise infected, or who had clinical ev idence of intrinsic heart disease were excluded from consideration. Patients taking calcium channel blockers, &blockers, digoxin, or phenytoin were also excluded. There were 17 men (59’, ) and 12 women (41 ‘o ), whose mean age was 56 (range “4 to 80) years. Patients had a variety of different types of hematologic or solid malignancy (central nervous system in seven, leukemia in four, lymphoma in four, breast in three. and one different other type of malignancy each in the remaining patients). The mean daily dose of corticosteroids in this population, by standard estimates of drug equivalence, was 11:s mg of prednisone. Presteroid, steroid treatment. and poststeroid time periods were identified for each patient., and all ECGs obtained during each of these periods were examined. Where more than one tracing was available for each period, the tracing with the shortest PR interval was selected to represent the period: this selection factor governed the pre- and poststeroid data as well as the steroid treatment observations. By selection, all 29 patients had ECG data from the steroid treatment period. Paired data were available from presteroid and steroid therapy time periods in 2’7 patients, and from steroid therapy and postst.eroid time periods in 17 patients; data from all three time periods were available for 15 patients. The heart rat,e, PR interval, QRS duration, and QT interval were measured from computed ECG tracings, using digitized data from standard Hewlett-Packard recorders (Hewlett-Packard Co., Medical Products Group, Andover, Mass.) and analysis software in the Memorial Hospital heart st.ation. Rate-corrected QT intervals (QT,) were obtained from the standard Sazett relationship.‘” Dat.a were analyzed by paired t test for comparison of mean heart rate, PR, QT. and QT,. values bet,ween paired time periods for individual patients. Analysis of variance was used to further evaluate data that were available for patients studied during each of the three time periods, with post hoc comparison of treatment periods by the Scheff’e method. 4 p value of 0.0.5 was required for rejection of the null hypothesis.
Shuler,
Case, and Gillette
Amermn
Heart
RCA
Fig. 3. Right internal mammary arteriogram in the left anterior oblique view and diagram outlining internal mammary-to-coronary artery communication. The slightly enlarged pericardial branch (P) of the right internal mammary artery (IMA) communicated with the right coronary artery CRC’A) (arrows) via retrograde filling of the sinus nodal branch (S’N) of the RCA.
Fig. 4. Myocardial perfusion imaging with ‘“‘TI-SPECT at rest. These images were obtained 5 days before the cardiac catheterization shown in Figs. 31 and 3. The orthopedic circumstances of this patient precluded exercise challenge. Vertical long-axis view (left side) and midventricular short-axis view (right side) are shown. Both the inferoposterior wall (arrows) and the upper half of the right ventricular wall (triangles) could be visualized as hypoperfused areas.
4. Singh RN. Radiographic anatomy of the internal mammary arteries. Cathet Cardiovasc Diagn 1981;7:373-86. 5. Zureikat HY. Collateral vessels between the coronary and bronchial arteries in patients with cvanotic congenital heart disease. Am J Cardioi 1983:45:599-60X. .. 6. Smith SC, Adams DF, Herman MV. Paulin S. Coronary to bronchial anastomoses: an in viva demonstration by selective coronary arteriographp. Radiology 1970;104:289-90.
Efficacy infants
and safety of amiodarone
Claudius Osborne Shuler, MD, Christopher L. Case, MD, and Paul C. Gillet,te, MD C’harlcston,
SC.
in
May 1993 Journal
Volume 125, Number 5, Part 1 American Heart Journal
Shuler,
the Medical University of South Carolina, Center, Division of Pediatric Cardiology.
South
Reprint requests: C. Osborne Shuler, MD, Medical Carolina, South Carolina Children’s Heart Center, Cardiology, 171 Ashley Ave., Charleston, SC 29425. AM HEART
University Division
Children’s of South of Pediatric
J 1993;125:1430-1432.
Copyright (c, 1993 0002.8703/93/$1.00
Table
Carolina
by Mosby-Year Book, + .lO 4/4/44903
1431
day for 7 days. The maintenancedosewas5 mglkg/day except in the two above-mentionedpatients, who received 10 mg/kg/day. The treatment protocol included monitoring thyroid function studies and liver enzymes before and 6 months after starting therapy. Results. Successof therapy was defined as significant improvement or completeelimination of the arrhythmia, as evaluated clinically by Holter monitoring. Failure of therapy was defined as worsening or no significant improvement of the arrhythmia. Amiodarone wasconsideredsuccessfulin 10of the 17 infants. In four casesamiodaronewas the only antiarrhythmic drug being used and in the remaining six casesa successfuloutcome ensued when amiodaronewasusedin combination with one or two other antiarrhythmic drugs. In the reentrant SVT subgroup, amiodaronewas successfulin only 3 of 10 cases.In the non-SVT subgroup, it was successfulin all seven infants. The two infants who were given a higher loading and maintenance dosehad junctional ectopic tachycardia and atria1ectopic tachycardia and were consideredtherapeutic successes. There were therapeutic failures in seven patients, all with reentrant SVT. Of the sevenpatients, three went on to have successfulradiofrequency ablation of an accessorypathway and four had successfulsurgical ablation of an accessorypathway. In two infants (patients No. 9 and lo), failure wasa result of SVT becomingincessant severaldays after the initiation of amiodarone.In both infants, the tachycardia frequency had decreasedwithin 2 days following discontinuation of amiodarone when the patients had successfulablation with radiofrequency catheterization. The other five patients failed to improve with amiodaronebecauseof poor control of SVT. The infants who failed to improve with amiodaronetherapy continued taking amiodarone for a mean of 20 days (range 5 to 35 days). Infants in whom therapy wassuccessfulremainedon
Amiodarone has been used in the treatment of children with serious cardiac arrhythmias for many years. Reports in general cite high success rates,l* 2 with varying frequency of side effects.3 Most references in the literature contain infants in the patient population but are dominated by older children.‘, 2,4 This study reviews our experience with the safety and efficacy of amiodarone exclusively in infants (<12 months) with life-threatening arrhythmias. Methods. Over a period of 4 years, 17 infants were treated with amiodarone, alone or in combination with other antiarrhythmic drugs (Table I). There were 7 females and 10 males, with a mean age of 2.6 months (range 0.5 to 7.6 months). There were 10 patients with reentrant supraventricular tachycardia (SVT) and seven with other arrhythmias. Fourteen of 17 infants had normal cardiac anatomy and function as diagnosed by echocardiography. Two infants with reentrant SVT had associated cardiomyopathies and one patient was status post surgical repair for anomalous left coronary artery. Fifteen infants had failed from one to four drug regimens before starting amiodarone, and two patients were started on amiodarone therapy as their primary antiarrhythmic drug. All patients were hospitalized with continuous telemetry monitoring during the loading period. Fifteen of 17 patients received a loading dose of 10 mg/kg/day for 7 to 10 days. One patient received 15 mg/kg/day for 7 days, while another received 20 mg/kg/ From Heart
Case,and Gillette
Inc.
I. Patient information
Patient NO.
No. of
Age (mo)l Sex
EP diagnosis
0.8/M 0.5/M 7.3/F
SVT SVTiWPW SVTIWPW
0 4 2
6.5 mo 25.5 mo >44 mo
4
1.0/F
5
0.5/M 6.4/F LO/M 0.5/M 0.5/M 2.7/F
SVT SVT/WPW SVT/WPW SVT SVT SVT SVT
1 3 2 3 4 2 4
20 days 22 days 28 days 35 days 21 days 12 days 5 days
0.5/M 6.5/M 3.8/F
VT VT SVTNT
1 2 1
16 mo 5.5 mo >3 mo
+ +lD +
2.2/M 2.2iF 7.6/M 5.5/F
AET AET
2 1
>13 >12 >38 >3
+/F
1 2 3
6 7 8 9 10 Other arrhythmias 11 12 13 14
15 16 17
AET, Atria1 ectopic tachwardia; radiofrequency ablation; syndrome; >, currently
AF JET
previous
drugs
0
2
Time on amiodarone
mo* mo mo mo*
Successl With
Outcome
+
+N +/D
-
RF
-
SA SA SA SA RF
RF -
+/F +/D, E +
AF, atria1 flutter; D, digoxin; E, encanide; EP, electrophysiologic; F, flecanide; JET, junctional SA, surgical ablation; SVT, reentrant supraventricular tachycardia; VT, ventricular tachycardia; WpW, taking amiodarone, *larger load and maintenance dose.
ectopic tachycardia; Wolff-Parkinson-White
RF,
my
1432
Singh et al.
Amrwcan
a regimen of amiodarone for a mean of 16.6 months (range 3 to 44 months), with six patients still taking amiodarone at the time of submission of this report. Side effects OI amiodarone therapy were limited only to proarrhythmic effects. Two patients with reentrant SVT had incessant episodes after the start of amiodarone. Comments. These data show that amiodarone was without side effects but exhibited variable efficacy in the infants studied. The success of amiodarone in medically resistant reentrant SVT was limited to 3 of 10 patients (30 I‘( ). though the drug does appear to be efficacious in the treatment of other arrhythmias including ventricular tachycardia, atria1 ectopic tachycardia, and junctional ect.opic tachycardia. The role of amiodarone in the treatment of infants has been controversial.” Given the increasing experience of radiofrequency catheter ablation in infancy,” the role of amiodarone in infants with reentrant SVT is likely to become less important. REFERENCES 1. 2.
3.
4.
5. 6.
Coumel P, Lucet V, Do Ngoc D. The use of amiodarone in children. PACE 1983;6:930-9. Guccione P, Paul T, Carson A Jr. Long-term follow-up ot amiodarone therapy in the young: continued efficacy, unimpaired growth, moderate side effects. .I Am Co11 Cardiol 1990;15:1118-24. Vrobel TR, Miller PE, Mostow ND, Rakita L. A general overview of amiodarone toxicity: its prevention, detection. and management. Prog Cardiovasc Dis 1989;31:393-426. Pongiglione G, Strasburger JF, Deal BJ, Benson DW Jr. Use of amiodarone for short-term and adjuvant therapy in young patients. Am J Cardiol 1991;68:603-8. Villain E. Surgery for Wolff-Parkinson-White syndrome in the very young. J Thorac Cardiovasc Surg 1992;103:388-9. Case CL, Gillette PC. Oslizlok PC. Knick BJ, Blair HI,. Radiofrequency catheter ablation of incessant, medically resistant supraventricular tachycardia in infants and small children. .J Am Co11 Cardiol 1992;20:1405-10.
Acceleration of atrioventricular conduction during corticosteroid
therapy
Rampaul G. Singh, MD, Mohammed Kassir, MD, Nancy Roistacher, MD, Bruce B. Lerman, MD, and Paul Kligfield, MD New Yorli, N.Y.
Anatomic, neurohumoral, and functional factors are known to affect the PR interval of the electrocardiogram (ECG),‘-I” but the potential effect of corticosteroids on atrioventricular (AV) conduction in the human heart has not been established. Classic reports have found steroid excess in paFrom the Division Hospital-Cornell Reprint Medical
of Cardiology, Medical Center.
Department
of Medicine.
The New
requests: Paul Kligfield, MD, The New York Hospital-Cornell Center, 525 East 68th St.. New York. NY 10021.
AM HEART
J 1993:125:1432-1434.
Copyright ” 1993 000%8703/93/$1.00
by Mosby-Year Book. + .lO 4/4/44899
Inc.
York
Heart
1993 Journal
tients with Gushing’s disease to be associated with shor! ened PR intervals” and steroid deficiency in patients with Addison’s disease to be associated with lengthened PR intervals.” Furt,her. we have observed short PR intervals to occur commonly in patients receiving combination chemotherapy regimens, and also ~JCCaSiond cases of otherwise unexplained rapid ventricular responses in patients with atria1 fibrillation who are taking steroids. Taken together. these report,s and observations suggest that corticosteroids might cause a clinically relevant acceleration of AV conduction. Accordingly, we examined the serial effects of transient pharmacologic doses of steroid, taken in conjunction with ot.herwise varied regimens of inpatient chemotherapy. on the PR interval of the ECG. Methods. The medical admission lists to the Memorial Hospital-Sloan Kettering Cancer Center (New York, N.Y.) between January 1, 1990, and April 1,1990, were reviewed daily to identify patients for study. Twenty-nine patients taking a course of steroids in conjunction with chemotherapy were selected from further review of their inpatient charts and pharmacy requisitions. Patients who had septicemia, who were otherwise infected, or who had clinical ev idence of intrinsic heart disease were excluded from consideration. Patients taking calcium channel blockers, &blockers, digoxin, or phenytoin were also excluded. There were 17 men (59’, ) and 12 women (41 ‘o ), whose mean age was 56 (range “4 to 80) years. Patients had a variety of different types of hematologic or solid malignancy (central nervous system in seven, leukemia in four, lymphoma in four, breast in three. and one different other type of malignancy each in the remaining patients). The mean daily dose of corticosteroids in this population, by standard estimates of drug equivalence, was 11:s mg of prednisone. Presteroid, steroid treatment. and poststeroid time periods were identified for each patient., and all ECGs obtained during each of these periods were examined. Where more than one tracing was available for each period, the tracing with the shortest PR interval was selected to represent the period: this selection factor governed the pre- and poststeroid data as well as the steroid treatment observations. By selection, all 29 patients had ECG data from the steroid treatment period. Paired data were available from presteroid and steroid therapy time periods in 2’7 patients, and from steroid therapy and postst.eroid time periods in 17 patients; data from all three time periods were available for 15 patients. The heart rat,e, PR interval, QRS duration, and QT interval were measured from computed ECG tracings, using digitized data from standard Hewlett-Packard recorders (Hewlett-Packard Co., Medical Products Group, Andover, Mass.) and analysis software in the Memorial Hospital heart st.ation. Rate-corrected QT intervals (QT,) were obtained from the standard Sazett relationship.‘” Dat.a were analyzed by paired t test for comparison of mean heart rate, PR, QT. and QT,. values bet,ween paired time periods for individual patients. Analysis of variance was used to further evaluate data that were available for patients studied during each of the three time periods, with post hoc comparison of treatment periods by the Scheff’e method. 4 p value of 0.0.5 was required for rejection of the null hypothesis.