Electrocardiographic Screening in Children With Attention-DeficitHyperactivity Disorder
ren rhouldowevsent swithtrocayearsultedgramere i
bjectsstudiposisyndect (nr subjtifyfor chardiaalueeningy diso99)
A recent American Heart Association (AHA) statementconcluded that screening with electrocardiogram may behetiotiocoreatheceipeintmithegraordticparesof
MethodsWith the approval of the institutional review board of
000doilpful to assess for cardiac disease in children with atten-n-deficit disorder who are treated with stimulant medica-n.1 This statement suggested that, It is reasonable tonsider adding an ECG [electrocardiogram], which is ofsonable cost, to the history and physical examination incardiovascular evaluation of children who need to re-
ve treatment with drugs for ADHD [attention-deficit hy-ractivity disorder]. Although these recommendations areriguing, to date it is unknown whether such a strategyght be successful in detecting occult cardiac disease. Inpresent study we analyzed the efficacy of electrocardio-phic screening in an attention-deficit hyperactivity dis-er population that resulted from changes in clinical prac-
e because of the AHA recommendations. In particular weid attention to the impact of false-positive studies thatult because of this strategy and report the economic costssuch an approach.
Childrens Healthcare of Atlanta (Atlanta, Georgia), weanalyzed data from a cohort of children who underwentelectrocardiography performed for the purpose of cardiacscreening for stimulant medication. The study populationincluded children 5 to 21 years of age who obtained anelectrocardiogram from April 21 to September 21, 2008. Astart date of April 21 was chosen because the AHA consen-sus guideline was published at that time. We assumed thatelectrocardiograms ordered after that date would represent aresponse to the AHA guidelines. Although the AHA state-ment did not explicitly recommend electrocardiographicscreening, many clinicians (psychiatrists and primary careproviders) began to refer children receiving or likely toreceive stimulants for this test.
Electrocardiograms from 3 major sources were included,namely outpatient cardiology practices, a hospital-basedlaboratory performing outpatient electrocardiography, andcommunity hospitals that perform the studies and then for-ward them to the Sibley Heart Center (Atlanta, Georgia).Those subjects who were identified as having attention-deficit hyperactivity disorder screening or stimulant medi-cation screening were included in the analysis.
Those subjects who were identified as having an abnormalinitial electrocardiogram were defined as positive screens.Findings that were considered variants of normal such assinus arrhythmia or early repolarization were consid-
aSibley Heart Center, Childrens Healthcare of Atlanta, and bDepart-nt of Pediatrics, Emory University School of Medicine, Atlanta, Geor-. Manuscript received April 29, 2009; revised manuscript received andepted June 19, 2009.*Corresponding author: Tel: 404-315-2672; fax: 404-325-6021.E-mail address: firstname.lastname@example.org (W.T. Mahle).
2-9149/09/$ see front matter 2009 Elsevier Inc. All rights reserved. www.AJConline.org:10.1016/j.amjcard.2009.06.052William T. Mahle, MDa,b,*, Camden Hebs
Some investigators have suggested that childage attention-deficit hyperactivity disorder sto identify asymptomatic cardiac disease. Hefficacy and costs of this strategy. In the preof electrocardiographic screening in childrenWe reviewed the clinical experience of elecattention-deficit hyperactivity disorder
1297Miscellaneous/Electrocardiographic Screening for Stimulant Medicationsd negative screens. Based on the AHA statement, thesedings would be classified as category 1 (normal or normalriants). The outcome for those with positive initial elec-cardiograms (AHA category II and III readings) wastermined.For those subjects with a positive initial screening elec-cardiogram who presented for further cardiology consul-ion, records were reviewed to determine results of repeatctrocardiogram if performed and physical examinationdings. Ancillary testing that was performed in the diag-stic work-up was also recorded. Final cardiac diagnosiss reported.To analyze the added cost of an electrocardiographiceening program for attention-deficit hyperactivity disor-r, we included the cost of the initial electrocardiogram.bsequent evaluation such as cardiology consultation,ocardiography, and stress testing were included in thedel. Costs for all tests were determined based on Currentcedural Terminology codes and 2008 Medicare reim-
rsement rates.2 The cost model assumed that the firstctrocardiogram did not result in any lost parental wages.e model did assume that follow-up cardiac consultationght result in lost wages.3The proportion of positive initial electrocardiographiceens was reported, as were 95% confidence intervals.e positive predictive value of electrocardiographic screens reported. Because the number of true-positive results inpopulation could not be determined, we were unable to
1st ECG NormalN=1351
1st ECG AbnormalN=119
2nd ECG PerformedN=97
2nd ECG Not PerformedN=22
2nd ECG AbnormalN=61
2nd ECG NormalN=36
ure 1. Results of electrocardiographic testing in study cohort. ECG trocardiogram.
le 1st common abnormalities on initial electrocardiogram
normality Subjects (%)t ventricular hypertrophy 34 (28.2%)ht ventricular hypertrophy 24 (20.5%)longed QT interval 22 (18.5%)ht bundle branch block 17 (14.2%)t-axis deviation 7 (5.9%)ht-axis deviation 7 (5.9%)t atrial enlargement 3 (2.5%)mature ventricular complexes 2 (1.7%)mature atrial complexes 2 (1.7%)ntricular pre-excitation 2 (1.7%)culate the sensitivity and specificity of electrocardio-phic screening.
During the 5-month study period 1,470 children hadctrocardiography performed for purposes of screeningattention-deficit hyperactivity disorder medications. Thean age of this population was 9.8 2.9 years. Thosedergoing electrocardiographic screening were primarilyys (1,237 of 1,470, 84%). The primary payers for childreneened with electrocardiogram were private payers in%, governmental in 44%, and self pay in 1%.Of the screened cohort of 1,470, there were 119 subjects1%) who were found to have an abnormal electrocar-gram. Electrocardiographic abnormalities were foundre commonly in children undergoing testing at commu-y hospitals than in pediatric cardiology offices or childrenspitals (11.2% vs 7.5%, respectively, p 0.04). The mostmmon abnormalities are listed in Table 1. The medianerval from first electrocardiogram to cardiology consul-ion was 11 days (range 1 to 49). Most subjects referred todiology evaluation (78 of 119, 65%) were already re-ving stimulant medications at the time of screening elec-cardiogram; the remaining subjects were referred in an-ipation of starting stimulant medications.Of the 119 with abnormal electrocardiograms, 97 sub-ts had a second electrocardiogram obtained at the time ofdiology consultation. More than 35% of subjects who
d repeat electrocardiography were thought to have a nor-l electrocardiogram when the study was repeated (FigureThe most common original diagnoses that were reinter-ted as normal were prolonged QT interval and left ven-ular hypertrophy, respectively.Physical examination performed by a cardiologist dem-strated abnormalities in 14 subjects. These abnormalitiesluded systolic ejection murmur (n 7), systolic ejectionck (n 3), irregular heart rhythm (n 5), and prominentcordial impulse (n 1). Seven subjects were thought to
ve an innocent heart murmur. Additional ancillary testingluded complete echocardiography in 63 subjects, Holternitoring in 9 subjects, and exercise stress testing in 5jects. Indications for echocardiograms were early sys-
ic ejection click in 2, heart murmur in 5, and abnormalctrocardiograms with a variety of findings (n 56), themost common being left ventricular hypertrophy, rightntricular hypertrophy, and right bundle branch block.ications for Holter monitors were prolonged QT interval5, ventricular pre-excitation in 2, and premature ventric-r complexes in 2. Indication for exercise stress testings prolonged QT interval in all 5 patients.Final diagnoses included no cardiac disease in 114, ven-ular pre-excitation syndrome in 2, bicuspid aortic valve2, and moderate secundum atrial septal defect in 1.erapeutic interventions undertaken because of new diag-ses included transcatheter closure of an atrial septal de-t (n 1) and ablation of an accessory pathway (n 2).erefore, the proportion of children with cardiac diseasentified with an electrocardiographic screening strategys 0.003 (95% confidence interval 0.001 to 0.008). Thesitive predictive value was 4.2%.Total cost for testing in the entire cohort of 1,470 chil-
n was $85,868. Therefore, the cost to screen a single
ild is $58. The calculated cost to identify a child with
1298 The American Journal of Cardiology (www.AJConline.org)e form of heart disease is $17,162. If one were toume that the additive risk of stimulant medication is
gligible in mild congenital heart lesions, such as bicuspidrtic valve and atrial septal defect, the cost to identify aild with complex congenital heart disease or potential-threatening arrhythmias is $42,904.
scussionThis study in a small, contemporary cohort of childreneiving stimulant medications demonstrates electrocardio-phic screening can identify otherwise asymptomatic
art disease. Electrocardiographic screening can promptditional testing and ultimately diagnosis of cardiac dis-e that might be life-threatening and that may represent a
ntraindication to the administration of stimulant medica-ns. Conversely, the positive predictive value of electro-diographic screening is low, meaning that a significantmber of children without heart disease will likely bejected to additional testing.Recent recommendations from the AHA have engen-
red considerable controversy. The American Academy ofdiatrics writing group stated that, the harm outweighs theefit of recommending routine ECGs [electrocardiograms]healthy children starting stimulant medication for ADHD
tention-deficit hyperactivity disorder].4 These investiga-s raised concerns about the sensitivity and specificity of thectrocardiogram as a general screening test. Much of theistance to routine electrocardiographic screening relates toconcern that this strategy will produce many false-positiveults. Studies of electrocardiographic screening in otherpulations have generally reported that 5% to 10% ofildren will have an abnormal electrocardiogram ontial testing.5,6 Findings from our analysis are verych in agreement with these previous publications be-se we reported that 8.1% had an abnormal screen ont examination.Many quality initiatives could decrease the number ofse-positive results. For example, we found that electro-diograms obtained in community hospitals generally hadigher rate of abnormalities than those obtained in pedi-ic cardiology clinics and childrens hospitals. This mayult from improper lead placement in centers that care formarily for adults.7 Also, there may be significant incon-tencies among interpretations by pediatric cardiologists.8vious investigators have suggested that there is con-erable variability in the interpretation of QT intervalpediatric cardiologists and that reinterpretation by spe-lists at large referral centers can demonstrate 30%cordance.9A key assumption of any screening strategy is that early
tection of the disorder might improve outcome. To date,wever, the link between stimulant medications used toat attention-deficit disorder and an increased cardiovas-lar risk is tenuous. The original Health Canada warninggested a possible association between congenital heart
fectseven mild defects such as bicuspid aortic valved sudden death while receiving Adderall XR (Shire US,., Florence, Kentucky).10 Therefore, the discovery ofngenital heart disease with minimal or mild hemody-mic significance may be a valuable finding of electrocar- begraphic screening. However, it should be recognized thatthe 2 subjects with bicuspid aortic valve identified in thisies, the minor electrocardiographic abnormalities weret thought to be related to valvar disease.The balance of risks and benefits of stimulants in chil-n with heart disease and attention-deficit hyperactivityorder continues to be evaluated by the Food and Drugministration and other organizations. However, use of
mulant medications in children with known structuralart disease is controversial. Even with more complexuctural heart lesions, practitioners may believe that thenefits of medical management of attention-deficit hyper-ivity disorder may outweigh any cardiovascular risks. Ash, the advantage of identification of these predominantly
ld forms of congenital heart disease through electrocar-graphic screening remains speculative.In contrast, many cardiologists would likely agree that
mulant medications may pose a risk in children withtentially life-threatening arrhythmias such as supraven-ular tachycardia, long QT syndrome, and hypertrophicdiomyopathy.11,12 Importantly, with diseases such as
olff-Parkinson-White syndrome (or ventricular pre-exci-ion), ablation procedures can effectively treat the disorderd decrease any potential risk. For other entities that can-t be cured, such as long QT syndrome, further diag-stic testing and risk stratification might allow clinicians toigh the risks and benefits of stimulant medications.With any screening strategy cost-effectiveness is an im-rtant issue. To calculate cost-effectiveness one needs toable to quantify the economic benefits of early detection,h quantifiable decrease in morbidity or mortality. Givenvery limitedand controversialdata regarding the
k of sudden death related to the use of stimulant medi-ions, one cannot say with certainty whether an electro-diographic screening program has the potential of saving
y lives. The cost of a single electrocardiogram is rela-ely lowapproximately $22. However, one must con-er the additional costs incurred from added testing. Thest per subject increased approximately threefold due to theed diagnostic work-up that is required when the initial
ctrocardiogram is abnormal. Assuming that in the Unitedtes approximately 2.5 million children receive stimulantdication for attention-deficit hyperactivity disorder, the totalt of a screening electrocardiographic...