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Murmurs
Cardiac Monitoring for ADHD Medications
Kerry L. Rosen, MD, FACC, FAAP
Director, Outpatient Cardiology Services
Associate Professor of Clinical Pediatrics
The Ohio State University
Here is the problem …
Is it innocent ? …
Murmurs Murmurs Murmurs
Innocent Murmurs
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Newborn Murmurs
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Innocent Murmurs of Childhood
Murmur: Some Definitions
Classic 1983 college radio
album from R.E.M.
Murmur: Some Definitions
1. a half suppressed or muttered complaint
2. a low indistinct but often continuous sound
3. a soft or gentle utterance
4. an atypical sound of the heart typically
indicating a functional or structural abnormality
Therefore, a murmur is just a sound or a noise…
nothing is necessarily opening, closing,
blocking or leaking
… but, it may be …
Murmur: Some Definitions
s1
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s2
Systolic Ejection Murmur
“crescendo – decrescendo” type of murmur
“diamond” shaped murmur
typically related to outflow tract issue:
- LVOT turbulence or flow
- aortic or pulmonary valve stenosis
Murmur: Some Definitions
s1
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s2
Systolic Regurgitant Murmur
“pan-systolic” type of murmur
“flat” shaped murmur
typically related to:
- Tricuspid or Mitral valve regurgitation
- VSD shunt
* perimembranous type VSD
** small muscular VSDs
often “short” systolic murmur
Murmur: Some Definitions
s1
s2
• Continuous Murmur
• “machinery” type of murmur
• definition: “continues beyond the 2nd heart sound”
(+/- be heard “continuously” throughout the cardiac cycle)
• typically related to:
- Patent Ductus Arteriosus
- Aorto – pulmonary collateral
- Surgical shunt (aorta- pulmonary artery)
- Arteriovenous malformation (head/liver)
- Venous Hum (innocent murmur)
Murmur: Some Definitions
s1
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s2
Diastolic Murmur
Usually “decresendo”
Usually pathologic, if present
Timing with pulse, s1 and s2
typically related to:
- Aortic Valve regurgitation
- Pulmonary valve regurgitation
Common Newborn Murmurs
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“Transitional Murmurs”
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Pulmonary Artery Branch Flow Murmur
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Flow Murmurs
Newborn: Transitional Murmurs
1. Fetal to newborn transition
2. Tricuspid regurgitation ***
- low/medium pitched systolic regurgitant murmur
at the left sternal border – transient
3. Ductus arteriosus closing
- continuous … or … systolic regurgitant … or …
short systolic murmur – variable/ transient
Newborn: “PPS” or Branch
Pulmonary Artery Flow Murmur
• “PPS” – Peripheral Pulmonary “Stenosis”
• Birth to 2 weeks, especially premature babies
• Characteristic “I-III/VI short mid-systolic murmur
at the high left/right sternal border, radiating
well to the axilla and back”
• Turbulence  Murmur – due to relative acute angle
of the pulmonary artery bifurcation
• Murmur typically resolves by 6 months of life
• DDx: pulmonary valve stenosis, VSD, true branch PS
- Valve PS: more “harsh”, click present
- True Branch PS: persists beyond 6 months (*time to refer)
- True Branch PS: (William’s, Allagille’s, Rubella)
- VSD - more harsh, longer systolic sound, louder anteriorly
Newborn: “Flow Murmurs”
• Can have typical “Still’s murmur”
• Pulmonary flow murmur/
Left ventricular outflow murmur
• Characteristic “low/ medium pitched short
crescendo - decrescendo systolic murmur…
localized to the left sternal border”
Newborn Murmurs: Infant with “CHF”
Infant with “CHF”- tachypnea, retractions
- poor feeding, failure to thrive
- cardiomegaly on chest radiograph
Don’t forget to listen to the head, listen to the liver
 Can diagnose: arteriovenous malformations (AVMs)
- large physiologic “left to right shunt”
- increased pulmonary blood flow
- cardiomegaly and “heart failure”
So Far…Common Newborn Murmurs
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“Transitional Murmurs”
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Pulmonary Artery Branch Flow Murmur
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Flow Murmurs
Next… Common Innocent Murmurs of
Childhood
• Still’s Murmur
• Pulmonary Outflow Murmur
• Venous Hum
Still’s Murmur
1. Can occur at any age, but most common in late preschool to early
school age
2. Low-pitched, I-III/VI: “musical, twanging- string, vibratory or
groaning quality”
3. Left sternal border and apex…
4. Systolic ejection murmur/ “crescendo-decrescendo” shape
5. Usually no radiation; occasionally radiates to the
upper sternal border or carotids
6. NO suprasternal notch thrill (seen in aortic stenosis)
7. Variable intensity: may or may not be heard…
or louder with exercise, fever, anemia or
any increased cardiac output state
8. *** Decreased intensity with standing or Valsalva maneuver
PE Key: Listen with patient SUPINE and STANDING – this
changes physiology - venous return to the heart
Innocent Pulmonary Flow Murmur
1. Second most common innocent murmur of childhood
2. Left upper sternal border, may radiate faintly to axilla
3. Characteristic:
I-III/VI “blowing, non-musical, low-medium pitched,
mid systolic crescendo - decrescendo murmur”
4. Increased intensity with exercise, fever, anemia
5. *** Decreased intensity with standing and inspiration ***
6. Caused by turbulence/ “vibration” in the pulmonary artery
7. No click (as seen in pulmonary valve stenosis)
8. Not “as harsh” as seen in pulmonary valve stenosis
PE Key: TOUCH the patient: suprasternal notch thrill
Precordial thrill: grade IV murmur
Still’s vs. Pulmonary Flow Murmur
Innocent Murmur – Venous Hum
1. Very common between ages 2 and 5 years
2. Soft, blowing, low/medium pitched, I-III/VI continuous murmur
3. Heard best at the right upper sternal border/
right infraclavicular area…occasionally heard in the
left infraclavicular area
4. Murmur disappears with supine position, positional
changes of the head … compressing the jugular vein !
5. Caused by turbulent flow in the jugular vein/ SVC
PE Key: Turn the head- “look at dad” “look at the door”
“look at the picture on the wall”
Innocent Murmur? Am I missing … ?
ASD:
fixed split S2, higher pitched murmur,
radiates to lungs – axilla and back
AS/PS: higher pitched, more “harsh,”
typically has systolic “click”
VSD:
MR:
HCM:
PDA:
long systolic murmur, “flat” in contour or
“regurgitant”, higher pitched/ “harsh”
long, flat, regurgitant murmur, mostly apex
SEM - typically does not decrease with
standing, murmur can actually increase
continuous murmur…does not change with
head positional changes
Typically – no change with standing/positional changes
Innocent Murmurs – What You Can Do
History:
prematurity
intermittent nature
normal growth and development
negative family history
Physical Exam:
characteristic qualities of innocent murmur - practice
second heart sound:
- inspiration- splits – “physiologic splitting”
- expiration- single – “physiologic splitting”
- no increased intensity, pounding or loud
- no click, no thrill (grade IV/VI murmur)
- no suprasternal notch thrill
- positional changes - supine and standing
Murmurs – When to Refer ?
• If you are not sure
• If you are worried something is pathologic
• If you are not worried, but want reassurance
ALL are OK reasons to refer a murmur
• Really Sick Baby: blue, shock, respiratory distress
 Transfer or NICU care with cardiology available
• Loud murmur, but baby is stable…
 Get data to be reassured:
- RA/ leg BP, pulse Ox, CXR, ECG
- can “DC” baby and have seen in a few days
• Murmur – not so bad/loud/ stable (+/- extra data)
 “Routine” cardiology evaluation- 1-3 weeks
Cardiovascular Monitoring/ ADHD Medications
Feb 2005: Health Canada/ Adderall XR
U.S Post marketing reports sudden death (SD) in pediatric patients
 Health Canada (FDA equivalent) suspends sales of Adderall XR
 US FDA “Public Heath Advisory for Adderall and Adderal XR”
- FDA was aware of SD reports
- Factors potentially associated with SD include:
structural abnormalities- coronary artery, HCM, BAV &
cardiac hypertrophy; increased or toxic levels,
family hx (FH) of ventricular arrhythmias & extreme exercise/ dehydration
Aug 2005: FDA adds warning to Adderall labeling:
“Sudden Death and Preexisting Structural Cardiac Abnormalities”
- “SD has been reported… misuse may cause SD…”
- “Adderall XR generally should not be used in children or adults
with structural cardiac abnormalities”
Aug 2005: Health Canada reinstates Adderall XR with above warning
Cardiovascular Monitoring/ ADHD Medications
June 2005: FDA Pediatric Advisory Committee
- Review post marketing reports for methylphenidate/ amphetamines
- Could not determine whether adverse CV events were “causally associated
with the treatment”
Feb 2006: FDA Drug Safety & Risk Management Advisory Committee
1999-2003 - 25 people (19 children) taking ADHD meds died suddenly
- 43 people (26 children) CV events- stroke, arrest, palpitations
- BLACK BOX WARNING (8 to 7 vote)
- “stimulant medications”
- REC- clinicians continue to follow AAP guidelines re: assess/mgt of ADHD
March 2006: FDA Pediatric Advisory Committee
1992-2005 - 11 SD methylphenidates, 13 SD amphetamines
- 3 sudden deaths associated with atomoxetine (2003-2005)
“Highlight section/ new labeling format”: “children with structural heart defects,
cardiomyopathy, or heart-rhythm disturbances may be at risk for adverse
cardiac events, including sudden death”
 develop booklet re: risk/benefit/adverse events
Cardiovascular Monitoring/ ADHD Medications
Feb 2007: FDA Press Release: “FDA Directs ADHD Drug Manufacturers
To Notify Patients About CV Adverse Events & Psychiatric Adverse Events”
- Develop Patient Medication Guides
- Patients being considered for Rx with ADHD medications… develop treatment plan
that includes a careful health history and evaluation of current status, particularly
cardiovascular and psychiatric problems (including assessment for a family history
of such problems)
- All mention risk of sudden death in patients who have heart problems/defects or
family history of heart problems
April 2008: AHA Scientific Statement: Cardiovascular Monitoring of
Children and Adolescents with Heart Disease Receiving Medications
for ADHD in the AHA journal, Circulation
”The use of selective ECG screening in this population is thought to be
medically indicated and of reasonable cost”
Cardiovascular Monitoring/ ADHD Medications
April 2008: AHA Scientific Statement: Cardiovascular Monitoring of
Children and Adolescents with Heart Disease Receiving Medications
for ADHD in the AHA journal, Circulation
”the consensus of the committee is that is reasonable and useful to obtain
ECGs as part to the evaluation of children being considered for stimulant drug
therapy” (class I: evidence and/or agreement that given procedure/treatment
is beneficial, useful, effective and should be performed. Benefit >>> Risk,
AHA, ACC)
The above should NOT have been stated as a class I recommendation,
The recommendation should be/ is a class II recommendation
American Heart Association/ American College of Cardiology
Classification of Recommendation and Level of Evidence
Cardiovascular Monitoring/ ADHD Medications
Class II Recommendation: Condition for which there is conflicting
evidence and/or a divergence of opinion about the usefulness/
efficacy of a procedure or treatment
June-Aug 2008: AAP Statement: AAP does NOT recommend routine
use of ECGs before initiating stimulant therapy for ADHD
American Academy of Pediatrics
American Academy of Child and Adolescent Psychiatry
The Society for Developmental and Behavioral Pediatrics
The National Initiative for Children’s Healthcare Quality
The National Association of Nurse Practitioners
Children and Adults with Attention Deficit/ Hyperactivity Disorder
June-Aug 2008: AHA Scientific Statement is revised (level II rec for ECG)
- “it is reasonable to consider adding an ECG, which is of reasonable
cost, to the history and physical examination in the CV evaluation of
children who need to received treatment with drugs for ADHD”
Cardiovascular Monitoring/ ADHD Medications
AHA Scientific Statement: Cardiovascular Monitoring of Children
and Adolescents with Heart Disease Receiving Medications for ADHD
”The use of selective ECG screening in this population is thought to be
medically indicated and of reasonable cost” (initial recommendation)
VERSUS
“it is reasonable to consider adding an ECG, which is of reasonable cost, to the
history and physical examination in the CV evaluation of children who need to
receive treatment with drugs for ADHD” (final/ revised recommendation)
Risk of Sudden Cardiac Death in Children
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Hypertrophy cardiomyopathy
Long QT syndrome/ Brugada Syndrome
Other cardiomyopathies- arrhythmogenic right ventricular dysplasia
Coronary artery anomolies
Primary ventricular fibrillation/ tachycardia
Wolfe-Parkinson-White syndrome
Prevention of Sudden Cardiac Death
• Secondary Prevention- Defibrillation/ Automated External Defibrillators (AED)
• Primary Prevention (mass ECG screening)
- very controversial
- Europe, Italy, Japan vs. US recommendations
- cost-effectiveness, feasibility issues, medical-legal implications
- US AHA Athletic Screening Statement, 2007- include personal
and family medical history and physical examination (no ECG)
CV side effects of ADHD medications
• Tachycardia- increase in HR ~ 1-2 bpm
• BP- increase in systolic and diastolic BP ~ 3-4 mmHg
• No study has demonstrated a significant change in QT or QTc intervals
(exception: imipramine, TCAs- rarely used in ADHD)
• Because the risk of sudden death in the population of patients pharmacologically
treated for ADHD is no higher than that in the general population, performance of
screening tests would not seem to be any more indicated than in the general
population, and the AHA, along with the AAP, does not recommend routine
screening for children and adolescents because of problems with the sensitivity
and specificity of the ECG as a general screening test (AAP, Pediatrics statement)
• There does not seem to be compelling findings of a medication- specific risk
necessitating changes in our stimulant treatment of children and adolescents with
ADHD (AAP, Pediatrics statement)
???? So… What IS recommended ????
After ADHD diagnosis is made, but before ADHD medication is initiated:
• Patient History- symptoms
• Review of all medications
• Complete Family History
• Thorough Physical Examination
• It is reasonable to consider adding an ECG, which is of reasonable cost,
to the history and physical examination in the CV evaluation of children
who need to receive treatment with drugs for ADHD
• If possible, ECGs should be read by a pediatric cardiologist or a
cardiologist or physician with expertise in reading pediatric ECGs
• Pediatric Cardiology Consultation should be obtained before starting
ADHD medication if there are significant findings on history, FH, PE or
ECG
• If ECG obtained before age 12 years, a repeat ECG may be useful after
child is > 12 years; also, repeat ECG may be useful with change in
patient symptoms or change in family history
Practice Tool: Patient History & Family History
Practice Tool: Physical Examination
Practice Tool: ECG Findings
Practice Tool: ECG Findings
Practice Tool: ECG Findings
Ongoing assessment- patients being treated
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Review of symptoms and family history
BP & pulse- 1-3 months, then every 6-12 months
Any cardiac symptoms- referral and evaluation
ECG- reasonable to consider
Patients with Structural Heart Disease
• NO clinical studies or data indicating that children with most types of CHD are at
significant risk while on these medications
• Reasonable to use medications with caution
• Careful monitoring should be performed after initiation of medication
• If arrhythmias are treated and controlled, on approval of a pediatric cardiologist,
patient can be restarted on medication
AAP summary/ recommendations
AHA Scientific Statement