CONTRAST AGENTS AND RADIOPHARMACEUTICALS IN CHILDREN WITH CARDIAC DISEASE: SHOULD THEIR USE BE STUDI

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CONTRAST AGENTS AND RADIOPHARMACEUTICALS IN
CHILDREN WITH CARDIAC DISEASE SHOULD THEIR
USE BE STUDIED?

• John C. Ring, MD, FAAP, FACC
• Associate Professor of Pediatrics
• (Cardiology and Critical Care Medicine)
• University of Tennessee Health Science Center
• College of Medicine
• Member American Academy of Pediatrics Committee
  on Drugs
• United States Food and Drug Administration
• Center for Drug Evaluation and Research
• Pediatric Advisory Subcommittee Meeting
• February 3 4, 2004
• Rockville, Maryland

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WHAT WE KNOW ABOUT THIS QUESTION

• Congenital and acquired heart disease is common
  in children and of considerable clinical
  importance.
• Accurate diagnosis is central to effect a good
  outcome.
• The diagnostic use of intravascular contrast
  agents and radiopharmaceuticals is likely to
  increase in this patient population.
• Current use is guided by good intentions rather
  than data.

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WHAT DOES THE LITERATURE SAY?

• Key words utilized
• intravascular contrast agents and
  radiopharmaceuticals
• children
• cardiac disease
• complications
• Pertinent databases were exhaustively searched
• PubMed Medline 1950-Present
• BIOSIS Preview 1969-Present
• EMBASE Drugs and Pharmacology 1980-Present
• CINAHL 1982-Present
• Minimal information was found

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WHAT DOES THE AAP SAY?

• Knowledge is good!
• and
• Children are not little adults.

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CARDIAC DISEASE IMPACTS CHILDREN OF BOTH SEXES
AND EVERY ETHNICITY REGARDLESS OF AGE

• Reported frequency of CHD 2.03-8.56/1000
  (median 5.93) live births Confirmed cases
  2.03-4.30/1000 (median 3.99)
• ACHD 8,500 children with operated CHD reach
  adulthood annually
• (Am.J.Cardiol. 1982 50 560-568.)
• Inflammatory cardiac disease
• Kawasaki syndrome 3-3.5 x 103 new cases/year
  in the U.S.
• acute rheumatic fever incidence (U.S.)
  0.5-3.1/100,000 population
• myocarditis histopathology in 16-21 of
  children dying suddenly (JAMA. 1985 254
  13211325.)

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THE ULTIMATE COST IS THE CHILDS POTENTIAL LOST

• The AAP is committed to the attainment of
  optimal physical, mental, and social health and
  well-being for all infants, children,
  adolescents, and young adults.
• Mission Statement American Academy of
  Pediatrics
• Congenital anomalies are the 5th ranked cause of
  years of premature mortality in the U.S.
• (MMWR 1988 37 47-48.)
• structural CHD account for 6/15 most lethal
  congenital malformations

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OPTIMAL INTERVENTIONS DEPEND ON GOOD IMAGING

• Applies to both surgical and catheter-directed
  procedures
• Higher risk interventions reduce the acceptable
  margin of diagnostic error
• Different imaging modalities are complimentary
  rather than competitive

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USE OF THESE AGENTS IS LIKELY TO INCREASE

• The volume of interventional cardiac procedures
  performed in children is increasing rapidly.
• 35-60 of catheterizations include an
  intervention
• interventional procedures require
  more/different angiography
• The number of adult patients with congenital
  heart disease is burgeoning thus, the assessment
  of myocardial function and blood-flow becomes
  more important.
• Interventional radiology is increasingly applied
  to non-cardiac areas of pediatric practice, e.g.
  embolization of AVM in the CNS and
  catheter-directed thrombolysis.

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WHAT PEDIATRIC CARDIOLOGISTS WANT TO KNOW

• Are non-ionic contrast agents really that safe
  (or have I just been luckyor good)?
• Is there a maximum volume of contrast I can
  inject safely? Does that change with
• age
• lesion/co-morbidities
• program of injections?
• Is there an agent that will give me adequate
  opacification at lower volumes in large patients?
• (How can I earn as much as the internists do?)

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WHY WOULDNT YOU STUDY THESE AGENTS?

• Philosophical considerations
• Practical considerations
• Fruits of FDAMA

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Pediatric Exclusivity Statistics As of December
31, 2003
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RECOMMENDATIONS

• The FDA should exercise its authority to require
  that studies be performed regarding the use of
  intravascular contrast agents and
  radiopharmaceuticals in children with cardiac
  disease.
• Contrast studies should focus on dosing
  considerations, balancing safety concerns with
  imaging effectiveness.
• A different regulatory posture may need to be
  considered in order to study these agents.

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TO LEARN MORE CONTACT INFORMATION John C.
Ring, MD, FAAP, FACC Physician Office Building,
Suite P-215 777 Washington Ave. Memphis, TN
38105 901.572.3292 (voice) 901.572.5107
(FAX) jring_at_utmem.edu