I have no relevant financial
relationships to disclose.
Congenital Heart Defects & ADHD
Russell Schachar
Russell Schachar
Department of Psychiatry
Neurosciences and Mental Health
Toronto Dominion Bank Chair in Child and Adolescent Psychiatry
russell.schachar@sickkids.ca
Every child deserves a healthy start, a strong mind, and a bright future.
Outline
Every child deserves a healthy start, a strong mind, and a bright future.
What is ADHD?
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Symptoms of inattentiveness and/or hyperactivity‐impulsivity
• Brief introduction to ADHD
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≥6 months
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Onset before 12 years
• ADHD and congenital heart defects
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Pervasive and impairing
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Not only in the context of psychosis or another mental disorder
Not only in the context of psychosis or another mental disorder
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7.8% ages 4 ‐17 years or 4.42 million children
• Treatment lessons and strategies
Every child deserves a healthy start, a strong mind, and a bright future.
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4.3% were taking medication, or 2.47 million
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Boys > girls
Every child deserves a healthy start, a strong mind, and a bright future.
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Co‐existing conditions
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Opposition disorder
Conduct disorder
Anxiety disorder
Mood disorder
Reading/learning disability Impairment
20%
15%
25%
15%
25%
Every child deserves a healthy start, a strong mind, and a bright future.
• Adolescence
- Persists in 50% of individuals - Impaired over and above comorbidity - School failure
- Unemployment, quit jobs, perform poorly at work
(
g)
- Antisocial behavior, substance use (smoking)
- More accidents and injuries - Trouble with the law
• Adulthood
- Adverse impact across generations
Every child deserves a healthy start, a strong mind, and a bright future.
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Academic underachievement and educational services
Social difficulties (peers and family)
Health services
Head injury and burns
Head injury and burns Every child deserves a healthy start, a strong mind, and a bright future.
Cognitive problems
• Lower achievement • Learning problems • Poor neuropsychological performance
Every child deserves a healthy start, a strong mind, and a bright future.
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Environmental effects
Genetics of ADHD
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• Family studies
• Twin studies
• Molecular genetic studies
- Common and rare variants
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Every child deserves a healthy start, a strong mind, and a bright future.
Every child deserves a healthy start, a strong mind, and a bright future.
Medication
Treatment
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Medication
Behavioral Combined
C
Core symptoms
- MED = COMB > BEH = CC
• Parent satisfaction
- COMB = BEH > MED
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Every child deserves a healthy start, a strong mind, and a bright future.
Perinatal
– Prematurity
– Low birth weight
– Severe emotional distress
– Prenatal exposure to smoking
– Prenatal alcohol exposure
Prenatal alcohol exposure
– Perinatal complications and hypoxia
Post natal
– Closed head injury
– Infection
– Autoimmune disorders
– Toxic exposures
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Methylphenidate and dextroamphetamine
- Blocks DA reuptake
- 54 – 75 % respond
Atomoxetine
Blocks noradrenergic
- Blocks noradrenergic reuptake - 40% respond
Α‐2 agonists
– Clonidine, guanfacine
Antidepressants
– Tricyclics
- Bupropion
Every child deserves a healthy start, a strong mind, and a bright future.
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Stimulant side effects
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At least 1 side effect 90%
Majority are mild (63% to 69%) or moderate (28% to 34%)
4% report severe side effects 15% withdraw Decreased growth rate after long‐term stimulant treatment
Increase in heart rate of 1 to 2 bpm
Increase in systolic and diastolic BP of 3 to 4 mm Hg
No study has demonstrated a significant change in the QT or QTc intervals
Every child deserves a healthy start, a strong mind, and a bright future.
Congenital heart disease
• Genetic and environmental influences
Every child deserves a healthy start, a strong mind, and a bright future.
Brain effects of CHD
• Fetal brain dysmaturation
• Reduction in brain growth/maturation during 3rd
trimester (Limperopoulos et al., 2010)
• Link with reduced cerebral oxygenation
Li k i h d d
b l
i
- 15% reduction in cerebral oxygen delivery and 32% reduction cerebral VO2 in CHD fetuses associated with 13% reduction in fetal brain volume
• Grey and white matter effects
– 21% of adolescents who had open‐heart surgery for CHD
 von Rhein et al. (2011); Snookes et al. (2010) – The
The risk of white matter injury is greatest during the first risk of white matter injury is greatest during the first
weeks of postnatal life, during the most active period of synaptogenesis and myelination
 Kaltman et al. (2005)
 Dimitropoulos et al. (2013)
 Sun et al. (2015)
Every child deserves a healthy start, a strong mind, and a bright future.
Every child deserves a healthy start, a strong mind, and a bright future.
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General health outcomes
• Worse health
• > 10 days of school/daycare missed in previous year
• Higher rates of ER and doctors’ office visits
Neurodevelopmental Outcomes
1) Cognitive deficits
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Long‐term memory
Executive performance
Processing speed
Visual attention span
Visual attention span

Bergemann et al. (2015) - Social cognition
- Low IQ - 1/3 special education
- 18% had mental retardation

Every child deserves a healthy start, a strong mind, and a bright future.
2) Neurodevelopmental disabilities – 41% had abnormal neurologic examinations
Mental health outcomes
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– 42% gross and/or fine motor delays
– 23% global developmental delay

Mahle et al. (2000) Razzaghi et al. (2015)
Every child deserves a healthy start, a strong mind, and a bright future.
Behavioral difficulties common (27.1%)
• Functional limitations in socialization, daily living skills, communication and adaptive behavior in 11‐17% children
 Majnemer et al. (2008)  Bellinger (2008)
Limperopoulos et al (2002)
Limperopoulos et al. (2002) •
20‐30% ADHD
 Yamada et al. (2013) Sistino et al. (2015) Shillingford et al. (2008) Hansen et al. (2012) Davidson et al. (2015) Brosig et al. (2007) •
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Every child deserves a healthy start, a strong mind, and a bright future.
Anxiety and depression
Autism spectrum disorder (4‐5x)
Every child deserves a healthy start, a strong mind, and a bright future.
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Predictors
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Cerebral oxygen saturation and cyanosis
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Low birth weight
Subtle brain injury from circulator arrest or cardiopulmonary bypass during the neonatal period
t l
i d
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Type of CHD
- Hypoplastic left heart syndrome < Tetralogy of Fallot 


Hoffman et al. (2013) Wray & Sensky (1999)
Treating CHD in face of black box warning
• “serious structural cardiac abnormalities, cardiomyopathy, heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug ”
the sympathomimetic effects of a stimulant drug.
Batra et al. (2012)
– Brosig et al. (2007), Davidson et al. (2015) Every child deserves a healthy start, a strong mind, and a bright future.
Every child deserves a healthy start, a strong mind, and a bright future.
Drug risks in ADHD and CHD?
Sudden Cardiac Death
• Between 1999 and 2003, 25 people (19 children) taking ADHD medications died suddenly and 43 people (26 children) experienced cardiovascular events such as strokes cardiac arrest and heart palpitations
strokes, cardiac arrest, and heart palpitations.
• Risk is not clear
• Screening has low sensitivity and cost‐effectiveness
• Does it vary with pre‐existing heart disease or risk?
• How does one establish presence of pre‐existing CHD
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1000 to 7000 children and adolescents each year in the United States, accounting for 5% to 10% of all childhood deaths annually, with an incidence of 0.8 to 6.2 per 100 000.
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Most common causes of SCD in the United States are
– hypertrophic cardiomyopathy (HCM; 33% to 50%);
– long‐QT syndrome (LQTS; 15% to 25%); – other cardiomyopathies, including arrhythmogenic right ventricular dysplasia and dilated cardiomyopathy (10% to 20%); coronary artery anomalies (10% to 20%); – primary ventricular fibrillation or tachycardia (10% to 15%); – Wolff‐Parkinson‐White syndrome (WPW; 3% to 5%); – others, including aortic rupture (5%)
Every child deserves a healthy start, a strong mind, and a bright future.
Every child deserves a healthy start, a strong mind, and a bright future.
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Can stimulants be used in CHD?
• No systematically collected data to indicate that “structural heart disease” broadly should be a reason to avoid these medications
• No data to identify the actual risks of stimulant medication N d
id if h
l ik f i l
di i
in children with congenital heart disease.
• Tricyclics have more cardiac side‐effects
Every child deserves a healthy start, a strong mind, and a bright future.
Suggested Pharmacological Algorithm for ADHD and CHD
1.
2.
3.
3
4.
Stimulants* (try methylphenidate and at least one amphetamine before moving on)
Atomoxetine*
α‐2
α
2 agonists (guanfacine
agonists (guanfacine* & clonidine
& clonidine**))
Bupropion
*Only stimulants, atomoxetine, and guanfacine XR are approved by Health Canada for the
treatment of ADHD
**Clonidine XR is approved by the FDA for the treatment of ADHD, but it is not available in
Canada
Every child deserves a healthy start, a strong mind, and a bright future.
Minimizing risk of SCD
• History
– Assess for palpitations, syncope
– Including family history
• Cardiology consult
Cardiology consult
– Known structural heart disease, arrhythmias, or a family history of SCD in members 35 years of age
• Baseline ECG, echocardiograms, and cardiac MRI
• Regular monitoring during use
Every child deserves a healthy start, a strong mind, and a bright future.
Conclusion
• CHD is a complex and multifactorial disease
• Outcome varies with type and treatment
• ADHD and other mental health issues are common
- Hypoxia and shared genetic risk
• Screening and management of these outcomes is necessary
• ADHD medications play a role
• Careful monitoring is recommended
Every child deserves a healthy start, a strong mind, and a bright future.
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Schachar lab website
http://www.sickkids.ca/Research/schachar-lab/index.html
(Circulation. 2008;117:2407-2423.)
Every child deserves a healthy start, a strong mind, and a bright future.
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