Preventing Pediatric Sudden Cardiac Death: In Reply

Robert M. Campbell and Stuart Berger

Pediatrics 2007;119;408-409
DOI: 10.1542/peds.2006-3170

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://www.pediatrics.org/cgi/content/full/119/2/408

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2007 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from www.pediatrics.org by on March 8, 2009

tims may be identified prospectively by obtaining a thor-
ough personal and family history. Even if accurate, I do
not believe that 40% would, by anyone’s criteria, define
an appropriate screening process. More importantly, I
believe that the number is probably overstated. In a
retrospective study of SCD among 134 trained athletes
(mean age: 17 years), Maron et al2 reported that only
3% might have been suspected on the basis of the stan-
dard preparticipation history and physical examination.
More recently, in a study of 241 cases of SCD among
young people,3 only 10% of the 70 patients who died
from a lethal arrhythmia had a positive family history,
although most deaths were probably related to an auto-
somal dominant genetic channelopathy.
In the United States, current screening practices rely
exclusively on the history and physical examination and
are based on recommendations that are a decade old.
During that time, there has been no demonstrable
change in the incidence of SCD among young people. In
distinction, since 1982, all competitive athletes (12–35
years old) in Italy have been required to obtain a 12-lead
ECG in addition to the usual preparticipation history and
physical examination.4 As a result of this change, the
annual incidence of SCD in young athletes in the Veneto
region of Italy decreased by 89%, from 3.6 in 100 000 to
0.4 in 100 000 per year.4 In the unscreened nonathletic
population, the SCD incidence did not change. More-
over, SCD from cardiomyopathies decreased 90% (from
1.5 to 0.15 in 100 000 per year), with the greatest de-
creases occurring in patients with hypertrophic cardio-
myopathy and arrhythmogenic right ventricular cardio-
myopathy.
A large proportion of anatomic and electrical diseases
that underlie SCD are detectable by ECG. I recognize the
considerable logistic and financial limitations to wide-
spread ECG screening. However, we universally screen
for numerous endocrine and metabolic disorders that
occur far less frequently than hypertrophic cardiomyop-
athy (1:500) which, in the United States, still accounts
for more SCD in young people than any other diagnosis.
Information acquired over the past decade has taught us
that many of the genetically determined entities that
predispose to SCD are clinically silent and are infre-
quently associated with a positive family history.
Steven M. Yabek, MD
Pediatric Cardiology Associates
Albuquerque, NM 87106
REFERENCES
1. Campbell RM, Berger S. Preventing pediatric sudden cardiac
death: where do we start? Pediatrics. 2006;118:802– 803
2. Maron BJ, Shirani J, Poliac LC, Mathenge R, Roberts WC, Muel-
ler FO. Sudden death in young competitive athletes: clinical,
demographic, and pathological profiles. JAMA. 1996;276:
199 –204
3. Puranik R, Chow CK, Duflou JA, Kilborn MJ, McGuire MA.
Sudden death in the young. Heart Rhythm. 2005;2:1277–1282
408 LETTERS TO THE EDITOR
Downloaded from www.pediatrics.org by on March 8, 2009
4. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G.
Trends in sudden cardiovascular death in young competitive
athletes after implementation of a preparticipation screening
program. JAMA. 2006;296:1593–1601
doi:10.1542/peds.2006-3083
In Reply.—
We thank Dr Yabek for his letter in response to our
recent commentary about pediatric sudden cardiac death
(SCD).1 To date, we are not aware of any prospective
evaluation of a standardized preparticipation-evaluation
form (such as currently proposed by the American Acad-
emy of Pediatrics) for screening of patients and families
at risk for SCD. Other studies in the literature2,3 have
been retrospective but reported a relatively high inci-
dence of patient symptoms and positive family history
for patients who suffered sudden cardiac arrest episodes.
We do not believe that the estimate of ⬃40% of pediatric
SCD victims being identified through comprehensive,
diligent personal and family history is unreasonable,
although it may represent the upper end of the spec-
trum. Remembering that many of the causes of pediatric
SCD are genetic, the identification of even the first af-
fected family member can help to unravel extensive
family involvement.
We endorse use of the American Academy of Pediat-
rics’ (or a similarly comprehensive standardized) prepar-
ticipation-evaluation form. For this approach to be suc-
cessful, the form must be used conscientiously and
consistently, and the data requested must be thorough.
The thoroughness of the data will require both family
and care provider input. Clearly the use of a less-than-
adequate questionnaire with poor attention to the
above-mentioned details will only result in less-than-
optimal outcome.
Although some have advocated the use of electrocar-
diogram and/or echocardiographic screening for ath-
letes, these are expensive tests that have not yet proven
to be truly cost-effective. The Italy experience4 is not
completely applicable in the United States, and we be-
lieve that a recent editorial by Thompson and Levine5
illustrated many of the shortcomings of the Italian effort.
Although we applaud any and all attempts to decrease
SCD in our athletes and/or all pediatric patients, we
must be realistic about cost and issues such as false-
positive and false-negative results. Because there is no
absolute gold standard for many of the rare diagnoses
that cause SCD, we do not actually know the true sen-
sitivity and/or specificity for electrocardiography or
echocardiography. A negative screen result does not ex-
clude diagnosis.
Although dealing exclusively with patients ⬎18 years
of age, a recent article from Müller et al6 raised the issue
that many episodes of adult SCD occur after a period of
typical warning symptoms. They question whether SCD
is actually sudden. An increased level of awareness of
signs and symptoms may help to prevent pediatric SCD
episodes. Likewise, we would suggest that more atten-
tion to the details of a careful and thorough patient and
family history may yield better screening than we have
seen by previous retrospective studies. This is an inex-
pensive approach that can be widely applied (any pro-
vider, any patient, any time, any setting). Perhaps a
controlled multicenter trial to assess the efficacy of this
approach is indicated.
Robert M. Campbell, MD
Sibley Heart Center
Children’s Healthcare of Atlanta
Emory University School of Medicine
Atlanta, GA 30341
Stuart Berger, MD
Herma Heart Center
Children’s Hospital of Wisconsin
Milwaukee, WI 53201-1997
REFERENCES
1. Campbell RM, Berger S. Preventing pediatric sudden cardiac
death: where do we start? Pediatrics. 2006;118:802– 804
2. Wisten A, Messner T. Symptoms preceding sudden cardiac death
in the young are common but often misinterpreted. Scand Car-
diovasc J. 2005;39:143–149
3. Basso C, Maron BJ, Corrado D, Thiene G. Clinical profile of
congenital coronary artery anomalies with origin from the
wrong aortic sinus leading to sudden death in young competi-
tive athletes. J Am Coll Cardiol. 2000;35:1493–1501
4. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G.
Trends in sudden cardiovascular death in young competitive
athletes after implementation of a preparticipation screening
program. JAMA. 2006;296:1593–1601
5. Thompson PD, Levine BD. Protecting athletes from sudden car-
diac death. JAMA. 2006;296:1648 –1650
6. Müller D, Agrawal R, Arntz H. How sudden is sudden cardiac
death? Circulation. 2006;114:1146 –1150
doi:10.1542/peds.2006-3170
Stimulants and Sudden Death:
What Is the Real Risk?
To the Editor.—
The special article in Pediatrics entitled “Stimulants and
Sudden Death: What Is a Physician to Do?”1 concludes
that the risk of sudden death in children and adolescents
treated with stimulants is no different from the risk of
sudden death in the general population. Although it is
possible that this is correct, the available evidence does
not substantiate the authors’ conclusion, and readers
need to be aware of the possibility of author bias.
Data from the Adverse Events Reporting System
(AERS) of the Food and Drug Administration reveal 19
reported cases of sudden death in children/adolescents
who were receiving stimulant medications (12 received
amphetamines and 7 received methylphenidate). It is
generally agreed that only 1% to 10% of actual serious
Downloaded from www.pediatrics.org by on March 8, 2009
adverse events are reported to AERS; thus, comparisons
to population rates of sudden death among either all
children/adolescents or those receiving stimulants are
not possible.2 Many children currently receive stimulant
medications (⬃2 million prescriptions are written per
month).3 Given biological plausibility (ie, stimulants in-
crease heart rate and blood pressure), it is likely that
amphetamines and methylphenidate are not safe in chil-
dren/adolescents with a variety of underlying undiag-
nosed cardiac conditions.4 The solution to this dilemma
is not clear, but we cannot simply wish away the AERS
data.
The authors of the article provided financial-disclo-
sure data. In order of authorship, they receive 8, 3, 7,
and 11 pharmaceutical sponsorships each (if I have
counted correctly), via consulting, speaker’s bureau, or
sponsored research funds. These pharmaceutical compa-
nies produce attention-deficit/hyperactivity disorder
medications including amphetamines and methylpheni-
date. Readers should include this information in their
evaluation of the authors’ conclusions.
Lydia Furman, MD
Department of Pediatrics
Rainbow Babies & Children’s Hospital
Cleveland, OH 44106
REFERENCES
1. Wilens TE, Prince JB, Spencer TJ, Biederman J. Stimulants and
sudden death: what is a physician to do? Pediatrics. 2006;118:
1215–1219
2. Musholder AD, Pamer CA. Postmarketing surveillance of sui-
cidal adverse events with pediatric use of antidepressants. J Child
Adolesc Psychopharmacol. 2006;16:33–36
3. Rusk J. FDA’s Pediatric Advisory Committee does not back black
box for ADHD drugs. Available at: www.idinchildren.com/
200604/frameset.asp?article⫽box.asp. Accessed December 1,
2006
4. Nissen SE. ADHD drugs and cardiovascular risk. N Engl J Med.
2006;354:1445–1448
doi:10.1542/peds.2006-3029
In Reply.—
Dr Furman questions whether the actual rates of cata-
strophic events of children/adolescents on stimulants
was a massive underestimate (eg, 90%–99% underesti-
mate) and concludes that, given biological plausibility,
there is likely an elevated risk for sudden death associ-
ated with stimulants, particularly with underlying undi-
agnosed cardiovascular deficits. Although Dr Furman
uses as basis for her argument the rates of underreport-
ing associated with medications used for depression, sui-
cidality as the adverse event in a disorder in which
suicidality is also a symptom seems to be an overinter-
pretation. In fact, in our estimates of the risk for sudden
death associated with stimulants, we used the estab-
lished rate of underreporting of serious adverse medical
events that was derived from a systematic study pub-
PEDIATRICS Volume 119, Number 2, February 2007 409
 Preventing Pediatric Sudden Cardiac Death: In Reply
Robert M. Campbell and Stuart Berger
Pediatrics 2007;119;408-409
DOI: 10.1542/peds.2006-3170
Updated Information including high-resolution figures, can be found at:
& Services http://www.pediatrics.org/cgi/content/full/119/2/408
References This article cites 6 articles, 5 of which you can access for free at:

Subspecialty Collections
Permissions & Licensing
Reprints
http://www.pediatrics.org/cgi/content/full/119/2/408#BIBL
This article, along with others on similar topics, appears in the
following collection(s):
Heart & Blood Vessels
http://www.pediatrics.org/cgi/collection/heart_and_blood_vessel
s
Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
http://www.pediatrics.org/misc/Permissions.shtml
Information about ordering reprints can be found online:
http://www.pediatrics.org/misc/reprints.shtml

Downloaded from www.pediatrics.org by on March 8, 2009