# Presentation: 743487

## 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

## 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.

## 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

## WHAT DOES THE AAP SAY?

- “Knowledge is good!”
- and
- “Children are _not_ little adults.”

## 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.)

## THE ULTIMATE COST IS THE CHILD’S 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

## 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

## 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.

## WHAT PEDIATRIC CARDIOLOGISTS WANT TO KNOW

- Are non-ionic contrast agents really that safe (or have I just been lucky...or 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?)

## WHY WOULDN’T YOU STUDY THESE AGENTS?

- Philosophical considerations
- Practical considerations
- “Fruits of FDAMA”

## Pediatric Exclusivity Statistics

- As of December 31, 2003

## 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.

## 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@utmem.edu