Pediatr Cardiol (2014) 35:485–489 DOI 10.1007/s00246-013-0810-5
ORIGINAL ARTICLE
Attention Deficit Hyperactivity Disorder Screening Electrocardiograms: A Community-Based Perspective Shilpa A. Shahani • William N. Evans • Gary A. Mayman • Vincent C. Thomas
Received: 19 July 2013 / Accepted: 24 September 2013 / Published online: 19 October 2013 Ó Springer Science+Business Media New York 2013
Abstract Screening electrocardiograms (EKGs) for attention deficit hyperactivity disorder (ADHD) medication administration is controversial. We reviewed our experience as a community-based cardiology group. We reviewed all ADHD screening EKGs during a 2-year period. We evaluated whether screening EKGs resulted in further consultation and if management was altered. We also evaluated differences between patients on ADHD medications and those starting ADHD medications and further stratified the patients into stimulant versus nonstimulant groups. A total of 691 screening EKGs met our criteria. Forty-two patients (6.1 %) were recommended for further consultation. EKG findings requiring consultation included the following: left-ventricular hypertrophy, right atrial enlargement, arrhythmia, prolonged QT, and axis deviation. Studies performed during consultation included 39 echocardiograms, 2 stress tests, 2 Holter monitors, and 1 heart card. Five patients (0.72 %) were identified to have cardiac disease, one of whom decided against starting ADHD medications due to an arrhythmia, resulting in a change in management (0.14 %). Results comparing mean age, heart rate, and corrected QT interval between patients on medication and patients starting medications were as follows: 10.06 years, 82.87, bpm and 405.24 ms compared
S. A. Shahani W. N. Evans G. A. Mayman V. C. Thomas (&) Department of Pediatrics, University of Nevada School of Medicine, 2040 W. Charleston Blvd, Suite 402, Las Vegas, NV 89102, USA e-mail: [email protected] W. N. Evans G. A. Mayman V. C. Thomas Children’s Heart Center Nevada, 3006 S Maryland Pkwy #690, Las Vegas, NV 89109, USA
with 9.99 years, 80.05 bpm, and 405.82 ms, respectively (p = not significant [NS], p = 0.013 [NS], respectively). Results comparing mean age, heart rate, and corrected QT interval between patients on stimulant versus nonstimulant medications were as follows: 9.68 years, 83.10 bpm, and 403.04 ms compared with 9.81 years, 80.10 bpm, and 407.08 ms, respectively (p = NS for all). In our population, screening EKGs rarely resulted in management changes for patients taking or starting ADHD medications. Keywords
ADHD EKG Screening
Introduction Controversy persists over pretreatment screening electrocardiograms (EKGs) for attention deficit hyperactivity disorder (ADHD). In April 2008, the American Heart Association recommended routine screening EKGs for those who may need treatment with ADHD medications [18]. 25 days later, the American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry compiled a joint statement that conflicted with these recommendations, citing lack of evidence regarding the efficacy of screening EKGs for preventing sudden death in previously healthy patients [9]. In their 2009 joint position statement, the Canadian Cardiovascular Society, the Canadian Pediatric Society, and the Canadian Academy of Child and Adolescent Psychiatry did not support the recommendation for routine screening EKGs before ADHD medication. In addition, they recommended that the decision to initiate medication in patients with congenital heart disease should be made by an ADHD expert; however, the patient should continue to be monitored by a cardiologist [19].
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We hypothesized that the incidence of EKG abnormalities in children undergoing ADHD evaluation and treatment is low and that abnormal findings rarely affect management. The aims of this study were as follows: (1) to determine how many patients are referred for further evaluation based on screening EKG findings; (2) to describe the results of further consultation; (3) to identify how often cardiac evaluation led to a change in management; and (4) to evaluate for significant differences in heart rate and corrected QT interval (QTc) between patients on ADHD medications versus those before starting treatment. Differences were also evaluated between those on stimulant versus nonstimulant medications.
Materials and Methods We performed a retrospective chart review of all patients diagnosed with ADHD who presented to our institution for a screening EKG during a 2-year period from October 2009 to October 2011. For each visit, families filled out a standardized medical history form, which also included questions regarding the patient’s current medications. All EKGs were reviewed by a pediatric cardiologist. Abnormal EKGs triggered a pediatric cardiology consultation. Patients were excluded from analysis if they were (1) \18 years of age, (2) known to have congenital heart disease, (3) not an ADHD patient, (4) referred for reasons other than findings on a screening EKG, (5) on multiple medications that may affect EKG findings, or (6) on medications listed as ‘‘unknown.’’ Patients who met inclusion criteria, but who were evaluated more than once during this time period, were included in the analysis for their initial visit only. Data collected included age, sex, current medications, heart rate, and QTc. Patients were stratified into groups of patients currently on ADHD medications and those not yet started on ADHD medications. Those taking ADHD medication were further stratified into stimulant versus nonstimulant groups. Patients for whom stimulant versus nonstimulant were not clearly specified were excluded from the secondary analysis. If a consultation was recommended based on EKG findings, then the reason for consultation was recorded. We identified further tests performed, findings on consultation, and whether a change in ADHD management resulted from this screening process. Statistical Analysis Statistical analysis was performed using SPSS software (SPSS, Chicago, IL, USA). Continuous variables were evaluated between groups using an independent sample
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Student t test. Statistical significance was set at a = 0.05 for all analyses.
Results A total of 841 screening EKGs were performed at our institution during the study period. After eliminating those that met exclusion criteria, 691 ADHD screening EKGs remained. Demographic data included an overall mean age of 10 years (range 3–18) and 497 (72 %) males who met the inclusion criteria. Of the 691 screening EKGS, 42 (6.1 %) were abnormal and prompted a pediatric cardiology consultation. We display the breakdown of abnormal EKG findings in Fig. 1. Of patients categorized as ‘‘other,’’ findings included unusual Q waves, right-ventricular (RV) conduction delay, and low atrial rhythm. A breakdown of those with QRS axis deviations included two right axis, one left axis, and one superior axis. Four EKGs had a combination of findings, including two with RV and LV hypertrophy, one with RV hypertrophy and right-axis deviation, and one with PR prolongation, right QRS axis deviation, and RV hypertrophy. Of the 42 patients with abnormal EKGs, 25 (60.0 %) were on ADHD medications with 23 on stimulants. Of the 42 patients who underwent pediatric cardiology consultations, two were lost to follow-up. As part of the cardiology consultation, further testing included the following: echocardiograms, treadmill stress tests, 24-h Holter monitors, and a 30-day event monitor (Fig. 2). Five patients were determined to have cardiac disease and required continued follow-up. Identified structural conditions included a nonspecific aortic valve abnormality, small atrial septal defect, dilated ascending aorta, and mitral regurgitation (Table 1). One patient was discovered to have firstdegree atrioventricular conduction block, and the parent decided against starting ADHD medications. Although this decision was not based on the cardiologist’s recommendation, this was considered a change in management resulting from a screening EKG, for a total of 1 of 691 or 0.14 %. Analyses of age, heart rate and QTc of those on medication and those who had not been started on medication at the time of EKG are displayed in Table 2. The mean heart rate was statistically greater for patients on medication; however only a clinical difference of 2.82 beats per minute. The mean QTc was not significantly different between groups. After reviewing charts of those patients on medication, 223 patients specified the type of ADHD medication they were taking. Analyses of age, heart rate, and QTc for patients on stimulant versus nonstimulant ADHD medication at the time of the EKG are listed in Table 3. Differences did not meet statistical significance with respect to age, heart rate, or QTc.
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Fig. 1 EKG findings resulting in consultation. LAE left atrial enlargement, PAC premature atrial contraction, QTc prolonged corrected QT interval, AV delay first or second degree AV block, AXIS left, right or superior QRS axis deviation, RAE right atrial enlargement, LVH left ventricular hypertrophy by voltage, RVH right ventricular hypertrophy by voltage or RSR’ in precordial lead V1, OTHER unusual Q waves, right ventricular conduction delay, and low atrial rhythm
Fig. 2 Further testing performed during consultation
Table 1 Cardiac diagnosis with screening EKG Patient no.
Screening EKG finding
Cardiac diagnosis
On ADHD medication at time of EKG?
Change in management?
1
Right Ventricular hypertrophy
Nonspecific aortic valve abnormality
No
No
2
Biventricular hypertrophy
Small atrial septal defect
Yes
No
3
Borderline prolonged QTc
Dilated ascending aorta
Yes
No
4
Premature atrial contractions
Mitral regurgitation
Yes
No
5
Prolonged first-degree AV block
Structurally normal
No
Yes
Five patients were shown to have cardiac conditions that required further follow-up. In one patient there was a change in the management of ADHD due to parental objection to start medications
Discussion ADHD is a neurobehavioral disorder characterized by impulsivity, inattentiveness, and hyperactivity that impairs school- or work-related performance. Approved medication options are divided between stimulants—such as methylphenidate, dexmethylphenidate HCl, dextroamphetamine
sulfate, lisdexamfetamine dimesylate, methamphetamine, and amphetamine mixed salts—and nonstimulants, such as atomoxetine and guanfacine. Although these medications are highly effective at controlling symptoms and improving quality of life for patients and their families, safety concerns began to surface regarding their use in the pediatric population.
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Table 2 Age, heart rate, and QTc for patients on ADHD medication versus those before treatment Factor
On medication (n = 350)
No medication (n = 341)
p
Age (year)
10.06 ± 3.11
9.99 ± 3.92
Heart rate (bpm)
82.87 ± 14.53
80.05 ± 15.24
0.013
405.24 ± 21.23
405.82 ± 20.77
0.718
QTc (ms)a
0.781
a
Four EKGs were performed without report of QTc, yielding n = 349 for ‘‘on medication’’ and n = 338 for ‘‘no medication’’ categories
Table 3 Age, heart rate, and QTc for patients on stimulant versus nonstimulant ADHD medication Factor Age (year) Heart rate (bpm) QTc (ms)a
Stimulant (n = 202)
Nonstimulant (n = 21)
p
9.68 ± 3.02
9.81 ± 3.25
83.10 ± 14.17
80.10 ± 16.26
0.861 0.423
403.04 ± 20.45
407.08 ± 23.03
0.405
a
One EKG was performed without report of QTc on a patient taking stimulant medication, yielding n = 20 for that category
Initial case reports included stroke in a pediatric patient after long-term use of methylphenidate, acute myocardial infarction in an adolescent, and cardiac arrest in another adolescent who had previously showed a normal baseline EKG [3, 5, 13]. The Food and Drug Administration’s (FDA) Adverse Event Reporting System recorded of 11 cases of sudden death among pediatric patients on methylphenidate from January 1992 to February 2005 [14]. In August 2005, the FDA placed a warning label on amphetamine mixed salts [14]. They revisited the issue with advising for a black-box warning in February 2006 [8], which the FDA’s Pediatric Psychopharmacology Advisory Panel did not support in their meeting 1 month later [16]. The FDA then recommended in 2007 that drug manufactures prepare patient medication guidelines and alert them of cardiovascular risk and sudden death in those with pre-existing heart conditions [15]. This was followed by the recommendation for screening EKGs by the American Heart Association in 2008, which was later rebutted by the American Academy of Pediatrics just days later. With conflicting recommendations from guiding bodies and individual case reports raising concern for ADHD medication-related morbidity and mortality, clinicians are left without clear, evidence-based practice parameters resulting in significant variations in clinical practices. Studies in the United States and Canada found that general practitioners significantly increased their use of screening EKGs and decreased their willingness to prescribe ADHD medications for those with congenital heart disease. In
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contrast, pediatric cardiologists had a high baseline use of screening EKGs and continued to recommend ADHD medications even in patients with congenital heart disease [1, 2]. The evidence collected since the guidelines were issued has also been conflicting. Some studies have identified greater rates of sudden unexplained death or emergency visits among patients taking stimulant medications for ADHD [6, 21]. Still others, including one study performed by the FDA, have not found an increased risk of mortality or morbidity compared with baseline [7, 12]. The FDA has since updated their safety review for ADHD medications; however, they continue to recommend that ‘‘stimulant products and atomoxetine should generally not be used in patients with serious heart problems, or for whom an increase in blood pressure or heart rate would be problematic’’ [17]. Our observational findings suggest that primary care providers continue to use screening EKGs before or concomitant with ADHD medications. In our experience, only small percentages (6.1 %) of these screening EKGs have significant findings requiring further evaluation and followup. Interestingly, the rare instance of structural heart disease identified on consultation was not always congruent with the EKG findings. Few patients had cardiac abnormalities; furthermore, fewer still (0.14 %) had an alteration in ADHD medical management. This was consistent with ADHD medication recommendations among pediatric cardiologists previously reported [1, 2]. Less controversial is the evidence behind vital sign changes. Although studies have shown a statistically significant change in blood pressure in patients on ADHD medication, the absolute difference amounted to an approximately 4 mm Hg increase in diastolic blood pressure [11, 20]. Heart rate changes have also been found, B11 bpm, with evidence of tolerance developing after continued use for a persistent increase of 4 bpm [4, 10]. In addition, significant differences in the frequency of EKG irregularities among patients on methylphenidate versus nonusers have not been found. Our findings are consistent with the medical literature with statistically significant, although small, absolute changes in heart rate among patients on ADHD medications versus nonusers. In addition, the lack of significant difference in heart rate among those taking stimulant versus nonstimulant medications is consistent. We recognize several limitations in our study. First, the retrospective, observational nature of our study is an inherent limitation. EKG interpretations can vary widely between physicians, but all EKGs were interpreted by pediatric cardiologists. In addition, decisions as to what further tests needed to be performed and interpretations of those tests certainly lack standardization among pediatric
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cardiologists, even among members within the same group. The number of patients identified as having nonstimulant medications was small, which may have affected our ability to detect statistical differences. Given that we are a referral center, there may be a selection bias in that patients who had normal screening EKGs, as interpreted by their general practitioners, may not have been referred. Therefore, our findings may be difficult to generalize. As the sole pediatric cardiology provider in Nevada, we have the unique perspective of a community-based practice. Our study reflects continued use of screening EKG in the community for patients on or starting ADHD medications. Interestingly, few patients are referred for further consultation with even fewer showing true cardiac disease. Rarely did screening EKGs or cardiac consultation result in changes in the management of ADHD medications. These observational findings would suggest that the utility of ADHD screening EKGs is low. However, the burden of determining the safety of using ADHD medication lies in the hands of the prescribing provider. Although our results may not support the routine use of EKG screening, the prescribing provider must feel comfortable with the decision to treat. Further study regarding the safety of ADHD medications in cardiac patients is warranted.
References 1. Batra AS, Alexander ME, Silka MJ (2012) Attention-deficit/ hyperactivity disorder, stimulant therapy, and the patient with congenital heart disease: evidence and reason. Pediatr Cardiol 33(3):394–401 2. Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC et al (2011) ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 365(20):1896–1904 3. Daly MW, Custer G, McLeay PD (2008) Cardiac arrest with pulseless electrical activity associated with methylphenidate in an adolescent with a normal baseline echocardiogram. Pharmacotherapy 28(11):1408–1412 4. Findling RL, Short EJ, Manos MJ (2001) Short-term cardiovascular effects of methylphenidate and adderall. J Am Acad Child Adolesc Psychiatry 40(5):525–529 5. George AK, Kunwar AR, Awasthi A (2005) Acute myocardial infarction in a young male on methylphenidate, bupropion, and erythromycin. J Child Adolesc Psychopharmacol 15(4):693–695 6. Gould MS, Walsh BT, Munfakh JL, Kleinman M, Duan N, Olfson M et al (2009) Sudden death and use of stimulant medications in youths. Am J Psychiatry 166(9):992–1001 7. McCarthy S, Cranswick N, Potts L, Taylor E, Wong IC (2009) Mortality associated with attention-deficit hyperactivity disorder (ADHD) drug treatment: a retrospective cohort study of children, adolescents and young adults using the general practice research database. Drug Saf 32(11):1089–1096
489 8. Nissen SE (2006) ADHD drugs and cardiovascular risk. N Engl J Med 354(14):1445–1448 9. Perrin JM, Friedman RA, Knilans TK (2008) Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics 122(2):451–453 10. Safer DJ (1992) Relative cardiovascular safety of psychostimulants used to treat attention-deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2(4):279–290 11. Samuels JA, Franco K, Wan F, Sorof JM (2006) Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial. Pediatr Nephrol 21(1):92–95 12. Schelleman H, Bilker WB, Strom BL, Kimmel SE, Newcomb C, Guevara JP et al (2011) Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics 127(6):1102–1110 13. Trugman JM (1988) Cerebral arteritis and oral methylphenidate. Lancet 1(8585):584–585 14. United States Food and Drug Administration (2005) Detailed view: safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER). Available at: http://www.fda. gov/medwatch/safety/2005/aug05.htm. Accessed 12 Sept 2011 15. United States Food and Drug Administration (2007) FDA directs ADHD drug manufacturers to notify patients about cardiovascular adverse events and psychiatric adverse events. Available at: http://www.fda.gov/bbs/topics/news/2007/new01568.html. Accessed 12 Sept 2011 16. United States Food and Drug Administration (2006) Minutes of the Pediatric Advisory Committee March 22, 2006. Available at: http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4210m_ minutes%20pac%20march%2022%202006.pdf. Accessed 12 Sept 2011 17. U.S. Food and Drug Administration (2011) FDA drug safety communication: Safety review update of medications used to treat attention-deficit/hyperactivity disorder (ADHD) in children and young adults. Available at: http://www.fda.gov/drugs/ drugsafety/ucm277770.htm. Accessed 3 April 2013 18. Vetter VL, Elia J, Erickson C, Berger S, Blum N, Uzark K et al (2008) Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/ hyperactivity disorder [corrected]: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation 117(18):2407– 2423 19. Warren AE, Hamilton RM, Belanger SA, Gray C, Gow RM, Sanatani S et al (2009) Cardiac risk assessment before the use of stimulant medications in children and youth: a joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society, and the Canadian Academy of Child and Adolescent Psychiatry. Can J Cardiol 25(11):625–630 20. Wilens TE, Hammerness PG, Biederman J, Kwon A, Spencer TJ, Clark S et al (2005) Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry 66(2):253–259 21. Winterstein AG, Gerhard T, Shuster J, Johnson M, Zito JM, Saidi A (2007) Cardiac safety of central nervous system stimulants in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 120(6):e1494–e1501
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ORIGINAL ARTICLE
Attention Deficit Hyperactivity Disorder Screening Electrocardiograms: A Community-Based Perspective Shilpa A. Shahani • William N. Evans • Gary A. Mayman • Vincent C. Thomas
Received: 19 July 2013 / Accepted: 24 September 2013 / Published online: 19 October 2013 Ó Springer Science+Business Media New York 2013
Abstract Screening electrocardiograms (EKGs) for attention deficit hyperactivity disorder (ADHD) medication administration is controversial. We reviewed our experience as a community-based cardiology group. We reviewed all ADHD screening EKGs during a 2-year period. We evaluated whether screening EKGs resulted in further consultation and if management was altered. We also evaluated differences between patients on ADHD medications and those starting ADHD medications and further stratified the patients into stimulant versus nonstimulant groups. A total of 691 screening EKGs met our criteria. Forty-two patients (6.1 %) were recommended for further consultation. EKG findings requiring consultation included the following: left-ventricular hypertrophy, right atrial enlargement, arrhythmia, prolonged QT, and axis deviation. Studies performed during consultation included 39 echocardiograms, 2 stress tests, 2 Holter monitors, and 1 heart card. Five patients (0.72 %) were identified to have cardiac disease, one of whom decided against starting ADHD medications due to an arrhythmia, resulting in a change in management (0.14 %). Results comparing mean age, heart rate, and corrected QT interval between patients on medication and patients starting medications were as follows: 10.06 years, 82.87, bpm and 405.24 ms compared
S. A. Shahani W. N. Evans G. A. Mayman V. C. Thomas (&) Department of Pediatrics, University of Nevada School of Medicine, 2040 W. Charleston Blvd, Suite 402, Las Vegas, NV 89102, USA e-mail: [email protected] W. N. Evans G. A. Mayman V. C. Thomas Children’s Heart Center Nevada, 3006 S Maryland Pkwy #690, Las Vegas, NV 89109, USA
with 9.99 years, 80.05 bpm, and 405.82 ms, respectively (p = not significant [NS], p = 0.013 [NS], respectively). Results comparing mean age, heart rate, and corrected QT interval between patients on stimulant versus nonstimulant medications were as follows: 9.68 years, 83.10 bpm, and 403.04 ms compared with 9.81 years, 80.10 bpm, and 407.08 ms, respectively (p = NS for all). In our population, screening EKGs rarely resulted in management changes for patients taking or starting ADHD medications. Keywords
ADHD EKG Screening
Introduction Controversy persists over pretreatment screening electrocardiograms (EKGs) for attention deficit hyperactivity disorder (ADHD). In April 2008, the American Heart Association recommended routine screening EKGs for those who may need treatment with ADHD medications [18]. 25 days later, the American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry compiled a joint statement that conflicted with these recommendations, citing lack of evidence regarding the efficacy of screening EKGs for preventing sudden death in previously healthy patients [9]. In their 2009 joint position statement, the Canadian Cardiovascular Society, the Canadian Pediatric Society, and the Canadian Academy of Child and Adolescent Psychiatry did not support the recommendation for routine screening EKGs before ADHD medication. In addition, they recommended that the decision to initiate medication in patients with congenital heart disease should be made by an ADHD expert; however, the patient should continue to be monitored by a cardiologist [19].
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We hypothesized that the incidence of EKG abnormalities in children undergoing ADHD evaluation and treatment is low and that abnormal findings rarely affect management. The aims of this study were as follows: (1) to determine how many patients are referred for further evaluation based on screening EKG findings; (2) to describe the results of further consultation; (3) to identify how often cardiac evaluation led to a change in management; and (4) to evaluate for significant differences in heart rate and corrected QT interval (QTc) between patients on ADHD medications versus those before starting treatment. Differences were also evaluated between those on stimulant versus nonstimulant medications.
Materials and Methods We performed a retrospective chart review of all patients diagnosed with ADHD who presented to our institution for a screening EKG during a 2-year period from October 2009 to October 2011. For each visit, families filled out a standardized medical history form, which also included questions regarding the patient’s current medications. All EKGs were reviewed by a pediatric cardiologist. Abnormal EKGs triggered a pediatric cardiology consultation. Patients were excluded from analysis if they were (1) \18 years of age, (2) known to have congenital heart disease, (3) not an ADHD patient, (4) referred for reasons other than findings on a screening EKG, (5) on multiple medications that may affect EKG findings, or (6) on medications listed as ‘‘unknown.’’ Patients who met inclusion criteria, but who were evaluated more than once during this time period, were included in the analysis for their initial visit only. Data collected included age, sex, current medications, heart rate, and QTc. Patients were stratified into groups of patients currently on ADHD medications and those not yet started on ADHD medications. Those taking ADHD medication were further stratified into stimulant versus nonstimulant groups. Patients for whom stimulant versus nonstimulant were not clearly specified were excluded from the secondary analysis. If a consultation was recommended based on EKG findings, then the reason for consultation was recorded. We identified further tests performed, findings on consultation, and whether a change in ADHD management resulted from this screening process. Statistical Analysis Statistical analysis was performed using SPSS software (SPSS, Chicago, IL, USA). Continuous variables were evaluated between groups using an independent sample
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Student t test. Statistical significance was set at a = 0.05 for all analyses.
Results A total of 841 screening EKGs were performed at our institution during the study period. After eliminating those that met exclusion criteria, 691 ADHD screening EKGs remained. Demographic data included an overall mean age of 10 years (range 3–18) and 497 (72 %) males who met the inclusion criteria. Of the 691 screening EKGS, 42 (6.1 %) were abnormal and prompted a pediatric cardiology consultation. We display the breakdown of abnormal EKG findings in Fig. 1. Of patients categorized as ‘‘other,’’ findings included unusual Q waves, right-ventricular (RV) conduction delay, and low atrial rhythm. A breakdown of those with QRS axis deviations included two right axis, one left axis, and one superior axis. Four EKGs had a combination of findings, including two with RV and LV hypertrophy, one with RV hypertrophy and right-axis deviation, and one with PR prolongation, right QRS axis deviation, and RV hypertrophy. Of the 42 patients with abnormal EKGs, 25 (60.0 %) were on ADHD medications with 23 on stimulants. Of the 42 patients who underwent pediatric cardiology consultations, two were lost to follow-up. As part of the cardiology consultation, further testing included the following: echocardiograms, treadmill stress tests, 24-h Holter monitors, and a 30-day event monitor (Fig. 2). Five patients were determined to have cardiac disease and required continued follow-up. Identified structural conditions included a nonspecific aortic valve abnormality, small atrial septal defect, dilated ascending aorta, and mitral regurgitation (Table 1). One patient was discovered to have firstdegree atrioventricular conduction block, and the parent decided against starting ADHD medications. Although this decision was not based on the cardiologist’s recommendation, this was considered a change in management resulting from a screening EKG, for a total of 1 of 691 or 0.14 %. Analyses of age, heart rate and QTc of those on medication and those who had not been started on medication at the time of EKG are displayed in Table 2. The mean heart rate was statistically greater for patients on medication; however only a clinical difference of 2.82 beats per minute. The mean QTc was not significantly different between groups. After reviewing charts of those patients on medication, 223 patients specified the type of ADHD medication they were taking. Analyses of age, heart rate, and QTc for patients on stimulant versus nonstimulant ADHD medication at the time of the EKG are listed in Table 3. Differences did not meet statistical significance with respect to age, heart rate, or QTc.
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Fig. 1 EKG findings resulting in consultation. LAE left atrial enlargement, PAC premature atrial contraction, QTc prolonged corrected QT interval, AV delay first or second degree AV block, AXIS left, right or superior QRS axis deviation, RAE right atrial enlargement, LVH left ventricular hypertrophy by voltage, RVH right ventricular hypertrophy by voltage or RSR’ in precordial lead V1, OTHER unusual Q waves, right ventricular conduction delay, and low atrial rhythm
Fig. 2 Further testing performed during consultation
Table 1 Cardiac diagnosis with screening EKG Patient no.
Screening EKG finding
Cardiac diagnosis
On ADHD medication at time of EKG?
Change in management?
1
Right Ventricular hypertrophy
Nonspecific aortic valve abnormality
No
No
2
Biventricular hypertrophy
Small atrial septal defect
Yes
No
3
Borderline prolonged QTc
Dilated ascending aorta
Yes
No
4
Premature atrial contractions
Mitral regurgitation
Yes
No
5
Prolonged first-degree AV block
Structurally normal
No
Yes
Five patients were shown to have cardiac conditions that required further follow-up. In one patient there was a change in the management of ADHD due to parental objection to start medications
Discussion ADHD is a neurobehavioral disorder characterized by impulsivity, inattentiveness, and hyperactivity that impairs school- or work-related performance. Approved medication options are divided between stimulants—such as methylphenidate, dexmethylphenidate HCl, dextroamphetamine
sulfate, lisdexamfetamine dimesylate, methamphetamine, and amphetamine mixed salts—and nonstimulants, such as atomoxetine and guanfacine. Although these medications are highly effective at controlling symptoms and improving quality of life for patients and their families, safety concerns began to surface regarding their use in the pediatric population.
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Table 2 Age, heart rate, and QTc for patients on ADHD medication versus those before treatment Factor
On medication (n = 350)
No medication (n = 341)
p
Age (year)
10.06 ± 3.11
9.99 ± 3.92
Heart rate (bpm)
82.87 ± 14.53
80.05 ± 15.24
0.013
405.24 ± 21.23
405.82 ± 20.77
0.718
QTc (ms)a
0.781
a
Four EKGs were performed without report of QTc, yielding n = 349 for ‘‘on medication’’ and n = 338 for ‘‘no medication’’ categories
Table 3 Age, heart rate, and QTc for patients on stimulant versus nonstimulant ADHD medication Factor Age (year) Heart rate (bpm) QTc (ms)a
Stimulant (n = 202)
Nonstimulant (n = 21)
p
9.68 ± 3.02
9.81 ± 3.25
83.10 ± 14.17
80.10 ± 16.26
0.861 0.423
403.04 ± 20.45
407.08 ± 23.03
0.405
a
One EKG was performed without report of QTc on a patient taking stimulant medication, yielding n = 20 for that category
Initial case reports included stroke in a pediatric patient after long-term use of methylphenidate, acute myocardial infarction in an adolescent, and cardiac arrest in another adolescent who had previously showed a normal baseline EKG [3, 5, 13]. The Food and Drug Administration’s (FDA) Adverse Event Reporting System recorded of 11 cases of sudden death among pediatric patients on methylphenidate from January 1992 to February 2005 [14]. In August 2005, the FDA placed a warning label on amphetamine mixed salts [14]. They revisited the issue with advising for a black-box warning in February 2006 [8], which the FDA’s Pediatric Psychopharmacology Advisory Panel did not support in their meeting 1 month later [16]. The FDA then recommended in 2007 that drug manufactures prepare patient medication guidelines and alert them of cardiovascular risk and sudden death in those with pre-existing heart conditions [15]. This was followed by the recommendation for screening EKGs by the American Heart Association in 2008, which was later rebutted by the American Academy of Pediatrics just days later. With conflicting recommendations from guiding bodies and individual case reports raising concern for ADHD medication-related morbidity and mortality, clinicians are left without clear, evidence-based practice parameters resulting in significant variations in clinical practices. Studies in the United States and Canada found that general practitioners significantly increased their use of screening EKGs and decreased their willingness to prescribe ADHD medications for those with congenital heart disease. In
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contrast, pediatric cardiologists had a high baseline use of screening EKGs and continued to recommend ADHD medications even in patients with congenital heart disease [1, 2]. The evidence collected since the guidelines were issued has also been conflicting. Some studies have identified greater rates of sudden unexplained death or emergency visits among patients taking stimulant medications for ADHD [6, 21]. Still others, including one study performed by the FDA, have not found an increased risk of mortality or morbidity compared with baseline [7, 12]. The FDA has since updated their safety review for ADHD medications; however, they continue to recommend that ‘‘stimulant products and atomoxetine should generally not be used in patients with serious heart problems, or for whom an increase in blood pressure or heart rate would be problematic’’ [17]. Our observational findings suggest that primary care providers continue to use screening EKGs before or concomitant with ADHD medications. In our experience, only small percentages (6.1 %) of these screening EKGs have significant findings requiring further evaluation and followup. Interestingly, the rare instance of structural heart disease identified on consultation was not always congruent with the EKG findings. Few patients had cardiac abnormalities; furthermore, fewer still (0.14 %) had an alteration in ADHD medical management. This was consistent with ADHD medication recommendations among pediatric cardiologists previously reported [1, 2]. Less controversial is the evidence behind vital sign changes. Although studies have shown a statistically significant change in blood pressure in patients on ADHD medication, the absolute difference amounted to an approximately 4 mm Hg increase in diastolic blood pressure [11, 20]. Heart rate changes have also been found, B11 bpm, with evidence of tolerance developing after continued use for a persistent increase of 4 bpm [4, 10]. In addition, significant differences in the frequency of EKG irregularities among patients on methylphenidate versus nonusers have not been found. Our findings are consistent with the medical literature with statistically significant, although small, absolute changes in heart rate among patients on ADHD medications versus nonusers. In addition, the lack of significant difference in heart rate among those taking stimulant versus nonstimulant medications is consistent. We recognize several limitations in our study. First, the retrospective, observational nature of our study is an inherent limitation. EKG interpretations can vary widely between physicians, but all EKGs were interpreted by pediatric cardiologists. In addition, decisions as to what further tests needed to be performed and interpretations of those tests certainly lack standardization among pediatric
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cardiologists, even among members within the same group. The number of patients identified as having nonstimulant medications was small, which may have affected our ability to detect statistical differences. Given that we are a referral center, there may be a selection bias in that patients who had normal screening EKGs, as interpreted by their general practitioners, may not have been referred. Therefore, our findings may be difficult to generalize. As the sole pediatric cardiology provider in Nevada, we have the unique perspective of a community-based practice. Our study reflects continued use of screening EKG in the community for patients on or starting ADHD medications. Interestingly, few patients are referred for further consultation with even fewer showing true cardiac disease. Rarely did screening EKGs or cardiac consultation result in changes in the management of ADHD medications. These observational findings would suggest that the utility of ADHD screening EKGs is low. However, the burden of determining the safety of using ADHD medication lies in the hands of the prescribing provider. Although our results may not support the routine use of EKG screening, the prescribing provider must feel comfortable with the decision to treat. Further study regarding the safety of ADHD medications in cardiac patients is warranted.
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