sudden cardiac death in the pediatric population - sudden cardiac death … · 1. berger, s.,...

Sudden Cardiac Death in the Pediatric Population

Maggie Gray, MD

Department of Pediatric Cardiology

Palmetto Health/University of South Carolina School of Medicine

South Carolina AAP Meeting

August 2017

Objectives

• Describe the incidence of sudden cardiac death in the pediatric population

• Review the most common cardiac etiologies for sudden cardiac death

• Discuss the risk of sudden cardiac death in the young athlete

• Discuss the risk of sudden cardiac death in patients receiving stimulant medications

• Describe evidence-based primary prevention modalities

• Identify the role of the pediatrician in implementing secondary prevention measures

Incidence and Etiology

Background

• Abrupt and unexpected cardiac arrest

• Within 1 hour from onset of symptoms

• Devastating for family and community

Hugh D. Allen, et al. Moss and Adams' Heart Disease in Infants, Children, and Adolescents.

Prodrome Onset Arrest Death or Resuscitation

Incidence• 0.5 – 20 per 100,000 pt years1

• Up to 2x more frequent in athletes2

• 2-3x more frequent in males vs females3

• Most frequent in African American males

• Most frequent during basketball, swimming, football, cross country/track4

1. Berger, S., Sudden cardiac arrest and death in children.2. Corrado, D., et al., Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol.3. Maron, B.J., et al. Prevalence of sudden cardiac death during competitive sports activities in Minnesota high school athletes. J Am Coll Cardiol.4. Van Camp, S.P., et al., Nontraumatic sports death in high school and college athletes. Med Sci Sports Exerc.5. Harmon, K.G., et al., Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation.

Etiology

• Hypertrophic cardiomyopathy1-3

• Anomalous coronary artery

• Myocarditis

• Arrhythmogenic right ventricular cardiomyopathy

• Channelopathy• Long QT syndrome• Brugada syndrome

• Catecholaminergic polymorphic ventricular tachycardia

• Aortic dissection

• Aortic stenosis

1. Maron, B.J., et al., Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation.2. Hofman, N., et al., Contribution of inherited heart disease to sudden cardiac death in childhood. Pediatrics.3. Gajewski, K.K. and J.P. Saul, Sudden cardiac death in children and adolescents (excluding Sudden Infant Death Syndrome). Ann Pediatr Cardiol.

CHD

ArrhythmiaMyocarditis

SCD ≤2 years

CHD

HCM

LQTS

Arrhythmia

MVP

SCD 3-13 years

Arrhythmia

CHD

DCM

LQTS

Myocarditis HCM

SCD 14-24 years

HCMCoronary Anomaly

Myocarditis ARVC

ArrhythmiaOther

SCD Athletes

Hypertrophic Cardiomyopathy• 0.2-0.5% of general population1,2

• AD inheritance

• Pathophysiology• Thickened, nondilated LV• Disorganized myocytes arrhythmia and diastolic

dysfunction• 80% with abnormal coronary architecture ischemia and

scarring more arrhythmia and diastolic dysfunction• Dynamic LVOTO

• High Risk• Prior arrest or VT/VF• Family hx of SCD due to HCM• Syncope• LV wall ≥ 30 mm

1. Hugh D. Allen, et al. Moss and Adams' Heart Disease in Infants, Children, and Adolescents.2. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and

General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation.

Hypertrophic Cardiomyopathy

• Clinical features1

• Exam• Prominent apical impulse• Murmur – LLSB/apex medium pitch systolic murmur

• ECG• Abnormal in up to 90%• LVH, TWI, LAE, Q waves, LAD

• Echo• LV wall ≥ 15 mm anywhere• Systolic anterior motion of mitral valve• LVOTO

• Management2

• Beta blockers, myectomy, ICD• Sports restriction (class IA)


General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation..

Hugh D. Allen, R.E.S., Daniel J. Penny, Timothy F. Feltes, Frank Cetta, Moss and Adams' Heart Disease in Infants, Children, and Adolescents.

Coronary Artery Anomalies

• Abnormal origin of the coronary artery1,2

(0.2%)• MC is circumflex from right sinus

• No clinical significance

• LMCA from right sinus of Valsalva (1-3%)• Multiple possible courses

• Interarterial associated with SCD

• RCA from left sinus of Valsalva (30%)• Risk of SCD not well established

• Single coronary artery origin (5-20%)• Risk of SCD not well established



Coronary Artery Abnormalities

• Clinical features1

• Exam• Usually normal

• ECG • Usually normal

• Echo• Show coronary arteries by 2D and color• May require CTA confirmation

• Management2

• Surgical intervention• Sports restriction

• L from R – only class IA• R from L – sports ok if asymptomatic and EST negative• Return 3 months after surgery if asymptomatic and EST negative

1. Hugh D. Allen, et al. Moss and Adams' Heart Disease in Infants, Children, and Adolescents. 2. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and


Myocarditis

• Incidence between 4-5%

• Signs/symptoms• Nonspecific• Viral prodrome • Malaise, fatigue, pallor, diaphoresis,

dyspnea

• Chest x-ray• Cardiomegaly• Pulmonary vascular conestion

• ECG• Sinus tachycardia• T wave inversion• Q waves• PVCs, VT, SVT, AV block


Myocarditis• Echo

• Dilated LV

• Decreased function

• Pericardial effusion

• Biopsy (Dallas criteria)• Inflammatory infiltrate of the myocardium

• Necrosis/degeneration of myocytes

• Labs• +viral pcr

• Elevated BNP and cardiac enzymes


Myocarditis

• Management1

• Supportive care• Medication• Mechanical ventilation• ECMO

• IVIG, steroids debated• Heart failure management• Transplantation

• Sports Restriction2

• 3-6 months• No competitive sports if symptomatic

1. Hugh D. Allen, et al. Moss and Adams' Heart Disease in Infants, Children, and Adolescents. 2. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and


Arrythmogenic Right Ventricular Cardiomyopathy

• Incidence 1 in 50001,2

• AD inheritance

• Fibrofatty infiltration of the right ventricle• Thinning and dysfunction• Arrhythmia nidus

• Palpitations, syncope most common presenting symptoms

• ECG• T wave inversion in V1-V3• Epsilon wave

• Echo• RV dysfunction• RV dilation and thinning

1. Azaouagh, A., et al., Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol.2. Perez Diez D, Brugada J. Diagnosis and Management of Arrhythmogenic Right Ventricular Dysplasia: An article from the E-Journal of the ESC Council for

Cardiology Practice.

Arrythmogenic Right Ventricular Cardiomyopathy

• Management1

• ICD

• Antiarrhythmics

• Sports restriction2

• Consider class IA participation

1. Azaouagh, A., et al., Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol.2. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and


Long QT Syndrome

• Incidence 1 in 5000

• AD with variable penetrance• Mutation in sodium or potassium channels

• Leads to delayed repolarization

• Associated with deafness(Jervell Lange-Nielsen syndrome)

• Grey area with QTc

• Genetic testing important

Goldenberg, I. and A.J. Moss, Long QT syndrome. J Am Coll Cardiol.

Long QT Syndrome

• Management1

• Antiarrhythmic (beta blocker**)• ICD • Avoid QT prolonging medications

(sads.org)

• Sports restriction2

• No competitive sports• Gene +, pheno – ok after evaluation and

avoidance of triggers (AED)• Consider return if asymptomatic after

treatment• Participation ok with ICD if asymptomatic

1. Goldenberg, I., et al. Long QT syndrome. J Am Coll Cardiol. 2. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General

Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation.

Brugada Syndrome• First described in 19921

• 5 out of 10,000 (kids and adults)

• Characteristic ECG findings• Coved ST elevation • +/- T wave inversion• Right precordial leads

• AD inheritance (SCN5A mutation)

• Management2

• ICD • Sports Restriction

1. Antzelevitch, C., et al., Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation.

2. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation.

“coved ST elevation”

Rounded/up sloping ST elevation in health athlete

“saddleback ST elevation”

Primary Prevention

Early identification of children at risk

for SCD

Genetic testing for family members

Pursue available medical therapy

Apply appropriate sports limitations

All while limiting adverse effects of screening and

treatment

Kaltman, J.R., et al., Screening for sudden cardiac death in the young: report from a national heart, lung, and blood institute working group.

Current Practices• AHA/AAP recommend1:

• Comprehensive PPE prior to participating in competitive sports• Not universal ECG screening• Cardiology referral for any red flags3

• Other recommendations2

• ESC PPE + ECG

• NCAA PPE +ECG

• NBA PPE, ECG, echo

• NFL PPE, EKG +/- echo

• SC State Law mandates PPE prior to sports enrollment• Can be done by physician, NP, or PA• Type of form used not specified• Does not YET include ECG screening

1. Mahle, W.T., et al. Key concepts in the evaluation of screening approaches for heart disease in children and adolescents: a science advisory from the AHA. Circ.2. Maron, B.J., et al., Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007

update: a scientific statement from the AHA Council on Nutrition, Physical Activity, and Metabolism: endorsed by the ACC Foundation. Circ.3. Fish, F.A., et al. Diagnosis and management of sudden death in children. Curr Opin Pediatr.

14 Point Screening Checklist

• Personal History• Exertional chest pain/tightness

• Palpitations

• Syncope or dizziness*

• Exertional fatigue/dyspnea*

• Prior history of a heart murmur

• Prior history of ↑BP

• Prior restriction from sports

• Prior cardiac testing

Drezner, J.A., et al., Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med, 2012. 25(4): p. 408-15.


• Family History• Death prior to age 50 due to cardiovascular causes

• Disability from heart disease prior to age 50

• HCM, DCM, Long QT syndrome (or other channelopathy), Marfan syndrome

Drezner, J.A., et al., Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med, 2012. 25(4): p. 408-15.


• Physical Exam• Heart murmur

• Femoral pulses

• Stigmata of Marfan Syndrome

• Brachial artery pressure (seated)

Giese, E.A., et al., The athletic preparticipation evaluation: cardiovascular assessment. Am Fam Physician.

Louder Softer

Standing Supine

Valsalva Squatting

Nitroglycerin Handgrip

HCM Murmur

AAP PPE Form

USAPPE only

ItalyPPE + ECG

IsraelPPE + ECG

JapanPPE + ECG for 1st, 7th, 10th graders

DenmarkNo universal

screening

Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation.

Universal ECG?• Estimated at $70-204,000 per quality year life added1,2

• Could avert up to 130 SCDs per million children

• $900,000 per averted SCD

• Positive predictive value impacted by incidence3

• Pilot studies in PA, IL, TX, NV, NC4

• 2-7% required additional testing

• 1-3% with “potentially serious conditions”

• PPE alone has not reduced mortality

1. Leslie, L.K., et al., Costs and benefits of targeted screening for causes of sudden cardiac death in children and adolescents. Circulation.2. Schoenbaum, M., et al., Economic evaluation of strategies to reduce sudden cardiac death in young athletes. Pediatrics.3. Friedman, R.A., Electrocardiographic screening should not be implemented for children and adolescents between ages 1 and 19 in the United States. Circulation.4. Vetter, V.L., Electrocardiographic screening of all infants, children, and teenagers should be performed. Circulation.

Universal ECG

• ECG abnormalities frequent among athletes

• Common training related changes• Increased QRS voltage

• Early repolarization in V3-V6

• Increased vagal tone

• Axis shift to -30˚ to 115˚

• First degree AV block

• Incomplete right bundle branch block

Uberoi, A., et al., Interpretation of the electrocardiogram of young athletes. Circulation..

Present in 50% of nonathletes and almost 90% of

athletes.

Universal ECG?• Concerning findings1

• Q waves• QRS >120 ms• RVH• RAA or LAA• T wave inversion• ST depression• ≥2 premature ventricular contractions• QTc ≥440 ms in men and ≥460 ms in women• QTc <380 ms• Pre-excitation (PR <120 ms)• Type 1 Brugada (RBBB morphology with 2 mm ST elevation)

Chandra, N., et al., Prevalence of electrocardiographic anomalies in young individuals: relevance to a nationwide cardiac screening program. J Am Coll Cardiol.

Present in 20% of nonathletes and 30%

of athletes.

Evaluation of a High Risk Patient

• Referral to pediatric cardiology

• Treatment may include1,2:• Sports restriction (2015 AHA/ACC guidelines)

• Medication administration

• Medication avoidance

• ICD implantation

• Emergency preparedness

• Genetic Screening for family members

• Management of emotional distress

1. Pediatric sudden cardiac arrest. Policy Statement. Pediatrics.2. Pelliccia, A., et al. Bethesda Conference #36 and the European Society of Cardiology Consensus Recommendations revisited a comparison of U.S. and European

criteria for eligibility and disqualification of competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol.

Genetic Screening

• 49% of SCD due to potentially heritable condition1

• Allows further diagnosis when heart is structurally normal at autopsy2

• SCD is 1st manifestation in up to 50%

• Molecular autopsy and screening of first degree family members should be standard of care3

• Allows for better primary prevention

1. Winkel, B.G., et al., Sudden cardiac death in children (1-18 years): symptoms and causes of death in a nationwide setting. Eur Heart J.2. Miles, C.J. and E.R. Behr, The role of genetic testing in unexplained sudden death. Transl Res.3. Tester, D.J. and M.J. Ackerman, The molecular autopsy: should the evaluation continue after the funeral? Pediatr Cardiol.

ADHD and SCD• Stimulant medications1

• 70% efficacy• Generally accepted as safe2

• Mild increase in HR and BP (1-5bpm and 3-4 mmHG)• No significant change in QTc

• “Use caution in children with known structural heart disease, cardiomyopathy, or arrhythmia”

• AAP recommendations3,4

• Thorough patient and family history prior to Rx• Monitor heart rate and BP response• Increase research into risk factors for SCD

1. American Academy of Pediatrics/American Heart, A., American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD: May 16, 2008. J Dev Behav Pediatr.

2. Bange, F., et al., [Cardiovascular risks and management during Attention Deficit Hyperactivity Disorder treatment with methylphenidate]. Arch Pediatr.3. Silva, R.R., et al. Cardiovascular safety of stimulant medications for pediatric attention-deficit hyperactivity disorder. Clin Pediatr.4. Perrin, J.M., et al., Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics.

American Academy of Pediatrics/American Heart, A., American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD: May 16, 2008. J Dev Behav Pediatr.

ADHD and SCD• No increased risk of SCD compared to general population1,2

• Universal ECG not recommended

• Established increased risk of poor outcomes if ADHD not adequately treated3,4

• Injuries

• Academic underachievement

• Peer rejection

• Substance abuse

• Automobile accidents

• Antisocial behavior

1. Leslie, L.K., et al., Cardiac screening prior to stimulant treatment of ADHD: a survey of US-based pediatricians. Pediatrics.2. Wilens, T.E., et al., Stimulants and sudden death: what is a physician to do? Pediatrics.3. Berger, S., Cardiac evaluation of patients receiving pharmacotherapy for attention deficit hyperactivity disorder. UpToDate.4. Knight, M., Stimulant-drug therapy for attention-deficit disorder (with or without hyperactivity) and sudden cardiac death. Pediatrics.

Secondary Prevention

Widespread CPR and AED training

Engage emergency response plan

Prompt recognition of signs/symptoms

Access to AED

Berger, S., A Reflection on Pediatric Sudden Cardiac Arrest. American College of Cardiology.

Emergency Response

• Survival from pediatric OHCA is abysmal (<10%)1

• Survival increased when2:• Witnessed arrest

• Initial rhythm VT/VF

• Bystander CPR initiated

• Public location

• Significant reduction in mortality after compression only CPR introduced

1. Atkins, D.L., et al., Epidemiology and outcomes from out-of-hospital cardiac arrest in children: the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest.Circulation.

2. Meyer, L., et al., Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age: a 30-year review. Circulation.

Emergency Response• 83% of US high schools have a plan1

• 40% practice and review annually

• SC bill passed in 2016 mandates CPR/AED training for high school students (“Ronald Rouse Law”)• Requires training in CPR (including compression

only) and AED use• Begins 2017-2018 school year

• SC bill passed in 2008 requiring an AED on school grounds• Does not provide funding• Does not require at sporting events• Does not mandate emergency response plan

http://cpr.heart.org/AHAECC/CPRAndECC/Programs/CPRInSchools/UCM_475820_CPR-in-Schools-Legislation-Map.jsp

Drezner, J.A., et al., Effectiveness of emergency response planning for sudden cardiac arrest in United States high schools with automated external defibrillators.Circulation.

National Registry

• No national mandatory registry

• Better understanding of SCD events may improve prevention

• Attempts to quantify and study SCD rely on piecemeal data sets

• National Center for the Review and Prevention of Child Deaths1

• Reviews deaths age 0-21 years

• 35 states involved (SC included)

• State specific review teams

• Traditionally aimed at injuries, abuse, neglect, homicide

Vetter, V.L., et al., Development of a data set of national cardiovascular deaths in the young. Am Heart J.

In Summary – The AAP Stance

• Standardize the PPE• Perform thorough CV family history

• Refer to cardiology for any red flags

• Autopsy (including genetics) for SCD patients

• Comprehensive cardiology evaluation (including genetics) for SCD survivors

• Recognize signs and symptoms of SCD

• Promote education for CPR and AED

• Promote school emergency response plan

• Support nationwide registry

• Encourage EBM review of screening modalities

Pediatric sudden cardiac arrest. Policy Statement. Pediatrics.

Works Cited1. Hugh D. Allen, et al. Moss and Adams' Heart Disease in Infants, Children, and Adolescents. 9 ed. 2016: LWW.

2. Berger, S., Sudden cardiac arrest and death in children. UpToDate, 2015.

3. Corrado, D., et al., Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol, 2003. 42(11): p. 1959-63.

4. Maron, B.J., T.E. Gohman, and D. Aeppli, Prevalence of sudden cardiac death during competitive sports activities in Minnesota high school athletes. J Am Coll Cardiol, 1998. 32(7): p. 1881-4.

5. Van Camp, S.P., et al., Nontraumatic sports death in high school and college athletes. Med Sci Sports Exerc, 1995. 27(5): p. 641-7.

6. Harmon, K.G., et al., Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation, 2011. 123(15): p. 1594-600.

7. Maron, B.J., et al., Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation, 2009. 119(8): p. 1085-92.

8. Hofman, N., et al., Contribution of inherited heart disease to sudden cardiac death in childhood. Pediatrics, 2007. 120(4): p. e967-73.

9. Gajewski, K.K. and J.P. Saul, Sudden cardiac death in children and adolescents (excluding Sudden Infant Death Syndrome). Ann Pediatr Cardiol, 2010. 3(2): p. 107-12.

10. Antzelevitch, C., et al., Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation, 2005. 111(5): p. 659-70.

11. Azaouagh, A., et al., Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol, 2011. 100(5): p. 383-94.

12. Perez Diez D, Brugada J. Diagnosis and Management of Arrhythmogenic Right Ventricular Dysplasia: An article from the E-Journal of the ESC Council for Cardiology Practice, European Society of Cardiology 2008

13. Goldenberg, I. and A.J. Moss, Long QT syndrome. J Am Coll Cardiol, 2008. 51(24): p. 2291-300.

14. Kaltman, J.R., et al., Screening for sudden cardiac death in the young: report from a national heart, lung, and blood institute working group. Circulation, 2011. 123(17): p. 1911-8.

15. Mahle, W.T., et al., Key concepts in the evaluation of screening approaches for heart disease in children and adolescents: a science advisory from the American Heart Association. Circulation, 2012. 125(22): p. 2796-801.

16. Fish, F.A. and P.J. Kannankeril, Diagnosis and management of sudden death in children. Curr Opin Pediatr, 2012. 24(5): p. 592-602.

17. Maron, B.J., et al., Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation, 2007. 115(12): p. 1643-455.

18. Drezner, J.A., et al., Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med, 2012. 25(4): p. 408-15.

19. Giese, E.A., et al., The athletic preparticipation evaluation: cardiovascular assessment. Am Fam Physician, 2007. 75(7): p. 1008-14. Maron, B.J., et al., Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation, 2015. 132(22): p. e256-61.

20. Pediatric sudden cardiac arrest. Policy Statement. Pediatrics, 2012. 129(4): p. e1094-102.

21. Pelliccia, A., D.P. Zipes, and B.J. Maron, Bethesda Conference #36 and the European Society of Cardiology Consensus Recommendations revisited a comparison of U.S. and European criteria for eligibility and disqualification of competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol, 2008. 52(24): p. 1990-6

22. Leslie, L.K., et al., Costs and benefits of targeted screening for causes of sudden cardiac death in children and adolescents. Circulation, 2012. 125(21): p. 2621-9.

http://www.aafp.org/afp/2006/0415/p1391.html

Works Cited23. Schoenbaum, M., et al., Economic evaluation of strategies to reduce sudden cardiac death in young athletes. Pediatrics, 2012. 130(2): p. e380-9.

24. Friedman, R.A., Electrocardiographic screening should not be implemented for children and adolescents between ages 1 and 19 in the United States. Circulation, 2014. 130(8): p. 698-702; discussion 702.

25. Vetter, V.L., Electrocardiographic screening of all infants, children, and teenagers should be performed. Circulation, 2014. 130(8): p. 688-97; discussion 697.

26. Winkel, B.G., et al., Sudden cardiac death in children (1-18 years): symptoms and causes of death in a nationwide setting. Eur Heart J, 2014. 35(13): p. 868-75.

27. Miles, C.J. and E.R. Behr, The role of genetic testing in unexplained sudden death. Transl Res, 2016. 168: p. 59-73.

28. Tester, D.J. and M.J. Ackerman, The molecular autopsy: should the evaluation continue after the funeral? Pediatr Cardiol, 2012. 33(3): p. 461-70.

29. American Academy of Pediatrics/American Heart, A., American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD: May 16, 2008. J Dev Behav Pediatr, 2008. 29(4): p. 335.

30. Bange, F., et al., [Cardiovascular risks and management during Attention Deficit Hyperactivity Disorder treatment with methylphenidate]. Arch Pediatr, 2014. 21(1): p. 108-12.

31. Silva, R.R., J.W. Skimming, and R. Muniz, Cardiovascular safety of stimulant medications for pediatric attention-deficit hyperactivity disorder. Clin Pediatr (Phila), 2010. 49(9): p. 840-51.

32. Perrin, J.M., et al., Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics, 2008. 122(2): p. 451-3.

33. Leslie, L.K., et al., Cardiac screening prior to stimulant treatment of ADHD: a survey of US-based pediatricians. Pediatrics, 2012. 129(2): p. 222-30.

34. Wilens, T.E., et al., Stimulants and sudden death: what is a physician to do? Pediatrics, 2006. 118(3): p. 1215-9.

35. Berger, S., Cardiac evaluation of patients receiving pharmacotherapy for attention deficit hyperactivity disorder. UpToDate, 2016.

36. Knight, M., Stimulant-drug therapy for attention-deficit disorder (with or without hyperactivity) and sudden cardiac death. Pediatrics, 2007. 119(1): p. 154-5.

37. Berger, S., A Reflection on Pediatric Sudden Cardiac Arrest. American College of Cardiology, 2015.

38. Drezner, J.A., et al., Effectiveness of emergency response planning for sudden cardiac arrest in United States high schools with automated external defibrillators. Circulation, 2009. 120(6): p. 518-25.

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