Murmurs Cardiac Monitoring for ADHD Medications Kerry L. Rosen, MD, FACC, FAAP Director, Outpatient Cardiology Services Associate Professor of Clinical

MurmursCardiac Monitoring for ADHD

Medications

MurmursCardiac Monitoring for ADHD

Medications

Kerry L. Rosen, MD, FACC, FAAPDirector, Outpatient Cardiology ServicesAssociate Professor of Clinical Pediatrics

The Ohio State University

Here is the problem … Here is the problem …

Is it innocent ? … Is it innocent ? …

Murmurs Murmurs MurmursInnocent Murmurs

Murmurs Murmurs MurmursInnocent Murmurs

• Newborn Murmurs

• Innocent Murmurs of Childhood

Murmur: Some DefinitionsMurmur: Some Definitions

Classic 1983 college radio album from R.E.M.


1. a half suppressed or muttered

complaint 2. a low indistinct but often continuous

sound3. 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 …


s1 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


s1 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


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)


s1 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 MurmursCommon Newborn Murmurs

• “Transitional Murmurs”

• Pulmonary Artery Branch Flow

Murmur

• Flow Murmurs

Newborn: Transitional 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

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”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”

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

So Far…Common Newborn Murmurs

• “Transitional Murmurs”

• Pulmonary Artery Branch Flow

Murmur

• Flow Murmurs

Next… Common Innocent Murmurs of Childhood

Next… Common Innocent Murmurs of Childhood

• Still’s Murmur

• Pulmonary Outflow Murmur

• Venous Hum

Still’s MurmurStill’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” shape5. Usually no radiation; occasionally radiates to the

upper sternal border or carotids6. 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 MurmurInnocent 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 MurmurStill’s vs. Pulmonary Flow Murmur

Innocent Murmur – Venous HumInnocent 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 … ? 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: long systolic murmur, “flat” in contour or “regurgitant”, higher pitched/ “harsh”

MR: long, flat, regurgitant murmur, mostly apex

HCM: SEM - typically does not decrease with standing, murmur can

actually increasePDA: continuous murmur…does not change

with head positional changes

Typically – no change with standing/positional changes

Innocent Murmurs – What You Can Do

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 ? 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 XRU.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/

dehydrationAug 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



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 Committee1999-2003 - 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 Committee1992-2005 - 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



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 problemsApril 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”



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

American Heart Association/ American College of Cardiology

Classification of Recommendation and Level of Evidence



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 PsychiatryThe Society for Developmental and Behavioral PediatricsThe National Initiative for Children’s Healthcare Quality

The National Association of Nurse PractitionersChildren 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”



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 ChildrenRisk of Sudden Cardiac Death in Children

• Hypertrophy cardiomyopathy• Long QT syndrome/ Brugada Syndrome• Other cardiomyopathies- arrhythmogenic right ventricular dysplasia• Coronary artery anomolies• Primary ventricular fibrillation/ tachycardia• Wolfe-Parkinson-White syndromePrevention 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 medicationsCV 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 ???????? 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: Patient History & Family History

Practice Tool: Physical ExaminationPractice Tool: Physical Examination

Practice Tool: ECG FindingsPractice Tool: ECG Findings



Ongoing assessment- patients being treated

Ongoing assessment- patients being treated

• 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

AAP summary/ recommendations

AHA Scientific Statement AHA Scientific Statement

Documents

Murmurs Cardiac Monitoring for ADHD Medications Kerry L. Rosen, MD, FACC, FAAP Director, Outpatient Cardiology Services Associate Professor of Clinical