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Survey of current practices in use of amiodarone and implantable cardioverter defibrillators in pediatric patients with end-stage heart failure
Survey of Current Practices in Use of Amiodarone and Implantable Cardioverter Defibrillators in Pediatric Patients With End-Stage Heart Failure Anne M. Dubin, MD, George F. Van Hare, MD, Kathryn K. Collins, Daniel Bernstein, MD, and David N. Rosenthal, MD tudies have shown that many adult patients still do not receive optimal heart failure management. S Thus, given the absence of pediatric-specific clinical 1
trails, it is possible that many of these new modalities are underutilized in pediatric patients with heart failure. We were interested as to whether these new approaches to diagnosis and therapy of adults with heart failure have been translated into pediatric practice in high-risk patients. To characterize current practice standards, we surveyed pediatric cardiologists at institutions involved in the care of children with endstage heart failure. •••
A survey on the use of implantable cardioverterdefibrillators (ICD), amiodarone therapy, and risk assessment for children with advanced heart failure was distributed to members of the Pediatric Heart Transplant Study Group and to members of the Pediatric Electrophysiology Society. A total of 44 institutions were surveyed. The questionnaire consisted of 13 questions that examined how pediatric cardiologists risk stratify and treat pediatric patients with arrhythmias and end-stage heart failure. Physicians were queried with regard to indications they employed for amiodarone and ICD therapy, the effect of patient age on these indications, and how many patients they treated. A total of 25 replies were received from 20 institutions, 18 of which were from electrophysiologists. Data routinely used for risk stratification in patients with end-stage heart failure was uniform among respondents with respect to use of electrocardiograms and Holter monitoring (96%) and exercise testing (80%), whereas the role of elecrophysiologic study was controversial (40% utilization). Use of heart rate variability analysis, QT dispersion measurement, or T-wave alternans was much less common, with only 6 respondents using any of these techniques. In patients with either syncope or resuscitated cardiac arrest, the use of electrophysiologic study was considerably higher (100% and 84%, respectively). Tilt-table testing was utilized in 11 of 25 respondents (44%) for patients with syncope. Of the survey respondents, 32% managed patients with failing congenital heart disease differently than those with pure From Stanford University, Stanford, California and University of California at San Francisco, San Francisco, California. Dr. Dubin’s address is: 750 Welch Rd., Suite 305, Palo Alto, California 94304. E-mail: [email protected]. Manuscript received January 12, 2001; revised manuscript received and accepted May 23, 2001. ©2001 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 88 October 1, 2001
MD,
cardiomyopathy and no structural abnormalities, usually in a more aggressive fashion. Intravenous amiodarone was used frequently by 15% of respondents, occasionally by 77%, and was never used by 8%. Oral amiodarone therapy was even more commonly used: 31% of respondents used it frequently, whereas 69% used it occasionally. The most common indications for amiodarone therapy are listed in Table 1. Utilization of amiodarone was not dependent upon patient age. ICD therapy was employed less frequently than amiodarone. ICDs were used frequently in pretransplant candidates by 4% of the respondents, occasionally by 81%, and never by 15%. In the 15% of respondents who did not use an ICD, 1 believed it was not a useful therapy, whereas 4 respondents had no patients whom they considered to be appropriate candidates. Most of the respondents (58%) were following between 1 and 5 patients with an ICD at the time of the survey, whereas 8% were following ⱖ11 with an ICD. ICDs were used in patients of various ages: 31% of respondents indicated that they had implanted an ICD in a patient ⬍2 years of age, whereas for 38%, the minimum age of implantation was 5 years. Most respondents believed that there was no age cutoff as to the appropriateness of an ICD (84%), whereas a minority of 16% would not place an ICD in a patient ⬍2 years old. No program had written guidelines for ICD implantation in this population. Most institutions decided on ICD therapy on a case-by-case basis. The most common indications for ICD implantation in children with advanced heart failure are listed in Table 1. Resuscitated cardiac arrest was an indication for ICD implantation for 23 of 25 respondents but was less commonly regarded as an indication for amiodarone therapy (17 of 25, p ⫽ 0.03). Documented ventricular tachycardia had the opposite response from the participants; it was an indication for ICD in only 17 of 25 respondents, whereas 23 of 25 respondents regarded it as an indication for amiodarone (p ⫽ 0.04). A positive electrophysiologic test was an indication for amiodarone more often than an indication for ICD (19 of 25 vs 14 of 25 respondents, p ⫽ 0.001). •••
Arrhythmia is a major cause of morbidity and mortality in pediatric patients with end-stage heart failure.2–9 In patients with dilated cardiomyopathy, between 50% and 63% of children who die have ventricular arrhythmias at presentation.2,3 We recently showed that in pediatric patients awaiting transplantation, 62% had life-threatening arrhythmias, most commonly ventricular tachycardia.10 0002-9149/01/$–see front matter PII S0002-9149(01)01860-4
809
TABLE 1 Indications for Therapy
Indications Missed sudden death Documented ventricular tachycardia Positive electrophysiologic Study Syncope
Respondents Reporting This Indication for Oral Amiodarone
Respondents Reporting This Indication for IV Amiodarone
Respondents Reporting This Indication for ICD Placement
14/25 (56%) 21/25 (85%)
12/25 (50%) 21/25 (81%)
22/25 (88%) 17/25 (68%)
17/25 (68%)
10/25 (40%)
14/25 (56%)
6/25 (24%)
9/25 (36%)
13/25 (52%)
There have been several advancements in risk stratification of adult patients with advanced heart failure over the past decade. Newer noninvasive technologies including QT dispersion, heart rate variability, and T-wave alternans have all been shown to have some benefit in the prediction of arrhythmia in this group of complicated patients, whereas the role of invasive electrophysiologic study remains controversial.11–16 The development of the ICD and of class III antiarrhythmics have improved survival in the adult population.17 Recent multicenter trials have shown that ICDs have conferred a greater survival benefit than pharmacotherapy in patients with ischemic cardiomyopathy as well as those with idiopathic cardiomyopathy.18,19 We found that these technologies are being utilized in pediatric practice but with several caveats. ICDs were commonly used in older patients with missed sudden death episodes but not as commonly used in younger patients or those with syncope. In the absence of randomized trials, this discrepancy most likely represents a clinical impression that missed sudden death episodes are associated with worse outcomes than syncope. The reasons for the overall lower utilization of ICDs in children were not explored in our survey, but may be related to technical difficulties in ICD implantation (small size, complex congenital heart disease) as well as to the increased risk of infection and complications in children as opposed to adults.20 As regards amiodarone therapy, it is commonly employed in children, although the selection of amiodarone versus ICD therapy appears to be idiosyncratic and arbitrary, as would be expected given the absence of clear trial data. In conclusion, this study reveals that consensus indications for ICD implantation in children with heart failure included older patients and missed sudden death episodes. Amiodarone therapy was used more often than ICDs, and oral amiodarone
810 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 88
more commonly than the intravenous form of the medication. The approach to risk stratification was more heterogenous. In particular, the utilization of electrophysiologic study was highly variable. 1. Brand DA, Newcomer LN, Freiburger A, Tian H. Cardiologists’ practices compared with practice guidelines: use of beta-blockade after acute myocardial infarction. J Am Coll Cardiol 1995;26:1432–1436. 2. Lewis AB, Chabot M. Outcome of infants and children with dilated cardiomyopathy. Am J Cardiol 1991; 68:365–369. 3. Griffin ML, Hernandez A, Martin TC, Goldring D, Bolman RM, Spray TL, Strauss AW. Dilated cardiomyopathy in infants and children. J Am Coll Cardiol
1988;11:129–144. 4. Friedman RA, Moak JP, Garson A. Clinical course of idiopathic dilated
cardiomyopathy in children. J Am Coll Cardiol 1991;18:152–156. 5. Muller G, Ulmer HE, Hagel KJ, Wolf D. Cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy. Pediatr Cardiol 1995; 16:56–60. 6. Duster MC, Bink-Boelkens MTE, Wampler D, Gillette PC, McNamara DG, Cooley DA. Long-term follow-up of dysrhythmias following the Mustard procedure. Am Heart J 1985;109:1323–1326. 7. Hayes CJ, Gersony WM. Arrhythmias after the Mustard operation for transposition of the great arteries: a long-term study. J Am Coll Cardiol 1986;7:133– 137. 8. Garson A, Randall DC, Gillette PC, Smith RT, Moak JP, McVey P, McNamara DG. Prevention of sudden death after repair of tetralogy of Fallot: treatment of ventricular arrhythmias. J Am Coll Cardiol 1985;6:221–227. 9. Gillette PC, Yeoman MA, Mullins CE, McNamara DG. Sudden death after repair of tetralogy of Fallot electrocardiographic and electrophysiologic abnormalities. Circulation 1977;56:566–571. 10. Rosenthal DN, Dubin AM, Chin C, Falco D, Gamberg P, Bernstein D. Outcome while awaiting transplantation in children: a comparison of congenital heart disease and cardiomyopathy. J Heart Lung Transplant 2000;19:751–755. 11. Anastasiou-Nana MI, Nanas JN, Karangounis LA, Tsagalou EP, Alecopoulos GE, Toumanidis S, Gerali S, Stamatelopoulos SF, Moulopoulos SD. Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality. Am J Cardiol 2000;85:1212–1217. 12. Dubin AM, Rosenthal DN, Chin C, Bernstein DE. QT dispersion predicts ventricular arrhythmia in pediatric cardiomyhopathy patients referred for heart transplantation. J Heart Lung Transplant 1999;18:781–785. 13. Grimm W, Hoffman J, Menz V, Muller HH, Maisch B. Prediction of major arrhythmic events and sudden cardiac death in dilated cardiomyopathy. The Marburg Cardiomyopathy Study design and description of baseline clinical characteristics. Herz 2000;25:189–199. 14. Hohnloser S, Cohen RJ. T wave alternans and left ventricular ejection fraction but not QT variability index, predict appropriate ICD discharge. J Cardiovasc Electrophysiol 1999;10:626–627. 15. Bonaduce D, Petretta M, Marciano F, Vacario ML, Apicella C, Rao MA, Nicolai E, Volpe M. Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure. Am Heart J 1999;128:273–284. 16. Turitto G, Ahuja RK, Caref EB, El-Sherif N. Risk stratification for arrhythmic events in patients with nonischemic dilated cardiomyopathy and nonsustained ventircular tachycardia: role of programmed ventricular stimulation and the signal-averaged electrocardiogram. J Am Coll Cardiol 1994;24:1523–1528. 17. Fogoros RN. The effect of the implantable cardioverter defibrillator on sudden death and on total survival. PACE 1993;16:506–510. 18. Moss AJ, Hall WJ, Cannon DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933–1940. 19. The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576–1583. 20. Link MS, Hill SL, Cliff DL, Swygman CA, Foote CB, Homoud MK, Wang PJ, Estes NAM, Berul CI. Comparison of frequency of complications of implantable cardioverter-defibrillators in children versus adults. Am J Cardiol 1999;83: 263–266.
OCTOBER 1, 2001
trails, it is possible that many of these new modalities are underutilized in pediatric patients with heart failure. We were interested as to whether these new approaches to diagnosis and therapy of adults with heart failure have been translated into pediatric practice in high-risk patients. To characterize current practice standards, we surveyed pediatric cardiologists at institutions involved in the care of children with endstage heart failure. •••
A survey on the use of implantable cardioverterdefibrillators (ICD), amiodarone therapy, and risk assessment for children with advanced heart failure was distributed to members of the Pediatric Heart Transplant Study Group and to members of the Pediatric Electrophysiology Society. A total of 44 institutions were surveyed. The questionnaire consisted of 13 questions that examined how pediatric cardiologists risk stratify and treat pediatric patients with arrhythmias and end-stage heart failure. Physicians were queried with regard to indications they employed for amiodarone and ICD therapy, the effect of patient age on these indications, and how many patients they treated. A total of 25 replies were received from 20 institutions, 18 of which were from electrophysiologists. Data routinely used for risk stratification in patients with end-stage heart failure was uniform among respondents with respect to use of electrocardiograms and Holter monitoring (96%) and exercise testing (80%), whereas the role of elecrophysiologic study was controversial (40% utilization). Use of heart rate variability analysis, QT dispersion measurement, or T-wave alternans was much less common, with only 6 respondents using any of these techniques. In patients with either syncope or resuscitated cardiac arrest, the use of electrophysiologic study was considerably higher (100% and 84%, respectively). Tilt-table testing was utilized in 11 of 25 respondents (44%) for patients with syncope. Of the survey respondents, 32% managed patients with failing congenital heart disease differently than those with pure From Stanford University, Stanford, California and University of California at San Francisco, San Francisco, California. Dr. Dubin’s address is: 750 Welch Rd., Suite 305, Palo Alto, California 94304. E-mail: [email protected]. Manuscript received January 12, 2001; revised manuscript received and accepted May 23, 2001. ©2001 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 88 October 1, 2001
MD,
cardiomyopathy and no structural abnormalities, usually in a more aggressive fashion. Intravenous amiodarone was used frequently by 15% of respondents, occasionally by 77%, and was never used by 8%. Oral amiodarone therapy was even more commonly used: 31% of respondents used it frequently, whereas 69% used it occasionally. The most common indications for amiodarone therapy are listed in Table 1. Utilization of amiodarone was not dependent upon patient age. ICD therapy was employed less frequently than amiodarone. ICDs were used frequently in pretransplant candidates by 4% of the respondents, occasionally by 81%, and never by 15%. In the 15% of respondents who did not use an ICD, 1 believed it was not a useful therapy, whereas 4 respondents had no patients whom they considered to be appropriate candidates. Most of the respondents (58%) were following between 1 and 5 patients with an ICD at the time of the survey, whereas 8% were following ⱖ11 with an ICD. ICDs were used in patients of various ages: 31% of respondents indicated that they had implanted an ICD in a patient ⬍2 years of age, whereas for 38%, the minimum age of implantation was 5 years. Most respondents believed that there was no age cutoff as to the appropriateness of an ICD (84%), whereas a minority of 16% would not place an ICD in a patient ⬍2 years old. No program had written guidelines for ICD implantation in this population. Most institutions decided on ICD therapy on a case-by-case basis. The most common indications for ICD implantation in children with advanced heart failure are listed in Table 1. Resuscitated cardiac arrest was an indication for ICD implantation for 23 of 25 respondents but was less commonly regarded as an indication for amiodarone therapy (17 of 25, p ⫽ 0.03). Documented ventricular tachycardia had the opposite response from the participants; it was an indication for ICD in only 17 of 25 respondents, whereas 23 of 25 respondents regarded it as an indication for amiodarone (p ⫽ 0.04). A positive electrophysiologic test was an indication for amiodarone more often than an indication for ICD (19 of 25 vs 14 of 25 respondents, p ⫽ 0.001). •••
Arrhythmia is a major cause of morbidity and mortality in pediatric patients with end-stage heart failure.2–9 In patients with dilated cardiomyopathy, between 50% and 63% of children who die have ventricular arrhythmias at presentation.2,3 We recently showed that in pediatric patients awaiting transplantation, 62% had life-threatening arrhythmias, most commonly ventricular tachycardia.10 0002-9149/01/$–see front matter PII S0002-9149(01)01860-4
809
TABLE 1 Indications for Therapy
Indications Missed sudden death Documented ventricular tachycardia Positive electrophysiologic Study Syncope
Respondents Reporting This Indication for Oral Amiodarone
Respondents Reporting This Indication for IV Amiodarone
Respondents Reporting This Indication for ICD Placement
14/25 (56%) 21/25 (85%)
12/25 (50%) 21/25 (81%)
22/25 (88%) 17/25 (68%)
17/25 (68%)
10/25 (40%)
14/25 (56%)
6/25 (24%)
9/25 (36%)
13/25 (52%)
There have been several advancements in risk stratification of adult patients with advanced heart failure over the past decade. Newer noninvasive technologies including QT dispersion, heart rate variability, and T-wave alternans have all been shown to have some benefit in the prediction of arrhythmia in this group of complicated patients, whereas the role of invasive electrophysiologic study remains controversial.11–16 The development of the ICD and of class III antiarrhythmics have improved survival in the adult population.17 Recent multicenter trials have shown that ICDs have conferred a greater survival benefit than pharmacotherapy in patients with ischemic cardiomyopathy as well as those with idiopathic cardiomyopathy.18,19 We found that these technologies are being utilized in pediatric practice but with several caveats. ICDs were commonly used in older patients with missed sudden death episodes but not as commonly used in younger patients or those with syncope. In the absence of randomized trials, this discrepancy most likely represents a clinical impression that missed sudden death episodes are associated with worse outcomes than syncope. The reasons for the overall lower utilization of ICDs in children were not explored in our survey, but may be related to technical difficulties in ICD implantation (small size, complex congenital heart disease) as well as to the increased risk of infection and complications in children as opposed to adults.20 As regards amiodarone therapy, it is commonly employed in children, although the selection of amiodarone versus ICD therapy appears to be idiosyncratic and arbitrary, as would be expected given the absence of clear trial data. In conclusion, this study reveals that consensus indications for ICD implantation in children with heart failure included older patients and missed sudden death episodes. Amiodarone therapy was used more often than ICDs, and oral amiodarone
810 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 88
more commonly than the intravenous form of the medication. The approach to risk stratification was more heterogenous. In particular, the utilization of electrophysiologic study was highly variable. 1. Brand DA, Newcomer LN, Freiburger A, Tian H. Cardiologists’ practices compared with practice guidelines: use of beta-blockade after acute myocardial infarction. J Am Coll Cardiol 1995;26:1432–1436. 2. Lewis AB, Chabot M. Outcome of infants and children with dilated cardiomyopathy. Am J Cardiol 1991; 68:365–369. 3. Griffin ML, Hernandez A, Martin TC, Goldring D, Bolman RM, Spray TL, Strauss AW. Dilated cardiomyopathy in infants and children. J Am Coll Cardiol
1988;11:129–144. 4. Friedman RA, Moak JP, Garson A. Clinical course of idiopathic dilated
cardiomyopathy in children. J Am Coll Cardiol 1991;18:152–156. 5. Muller G, Ulmer HE, Hagel KJ, Wolf D. Cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy. Pediatr Cardiol 1995; 16:56–60. 6. Duster MC, Bink-Boelkens MTE, Wampler D, Gillette PC, McNamara DG, Cooley DA. Long-term follow-up of dysrhythmias following the Mustard procedure. Am Heart J 1985;109:1323–1326. 7. Hayes CJ, Gersony WM. Arrhythmias after the Mustard operation for transposition of the great arteries: a long-term study. J Am Coll Cardiol 1986;7:133– 137. 8. Garson A, Randall DC, Gillette PC, Smith RT, Moak JP, McVey P, McNamara DG. Prevention of sudden death after repair of tetralogy of Fallot: treatment of ventricular arrhythmias. J Am Coll Cardiol 1985;6:221–227. 9. Gillette PC, Yeoman MA, Mullins CE, McNamara DG. Sudden death after repair of tetralogy of Fallot electrocardiographic and electrophysiologic abnormalities. Circulation 1977;56:566–571. 10. Rosenthal DN, Dubin AM, Chin C, Falco D, Gamberg P, Bernstein D. Outcome while awaiting transplantation in children: a comparison of congenital heart disease and cardiomyopathy. J Heart Lung Transplant 2000;19:751–755. 11. Anastasiou-Nana MI, Nanas JN, Karangounis LA, Tsagalou EP, Alecopoulos GE, Toumanidis S, Gerali S, Stamatelopoulos SF, Moulopoulos SD. Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality. Am J Cardiol 2000;85:1212–1217. 12. Dubin AM, Rosenthal DN, Chin C, Bernstein DE. QT dispersion predicts ventricular arrhythmia in pediatric cardiomyhopathy patients referred for heart transplantation. J Heart Lung Transplant 1999;18:781–785. 13. Grimm W, Hoffman J, Menz V, Muller HH, Maisch B. Prediction of major arrhythmic events and sudden cardiac death in dilated cardiomyopathy. The Marburg Cardiomyopathy Study design and description of baseline clinical characteristics. Herz 2000;25:189–199. 14. Hohnloser S, Cohen RJ. T wave alternans and left ventricular ejection fraction but not QT variability index, predict appropriate ICD discharge. J Cardiovasc Electrophysiol 1999;10:626–627. 15. Bonaduce D, Petretta M, Marciano F, Vacario ML, Apicella C, Rao MA, Nicolai E, Volpe M. Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure. Am Heart J 1999;128:273–284. 16. Turitto G, Ahuja RK, Caref EB, El-Sherif N. Risk stratification for arrhythmic events in patients with nonischemic dilated cardiomyopathy and nonsustained ventircular tachycardia: role of programmed ventricular stimulation and the signal-averaged electrocardiogram. J Am Coll Cardiol 1994;24:1523–1528. 17. Fogoros RN. The effect of the implantable cardioverter defibrillator on sudden death and on total survival. PACE 1993;16:506–510. 18. Moss AJ, Hall WJ, Cannon DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933–1940. 19. The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576–1583. 20. Link MS, Hill SL, Cliff DL, Swygman CA, Foote CB, Homoud MK, Wang PJ, Estes NAM, Berul CI. Comparison of frequency of complications of implantable cardioverter-defibrillators in children versus adults. Am J Cardiol 1999;83: 263–266.
OCTOBER 1, 2001