Tal Geva, MD

1
Food and Drug Administration Pediatric Advisory
Subcommittee Meeting February 3, 2004
Overview of Progress in Pediatric Cardiology
Tal Geva, MD Department of Cardiology Childrens
Hospital Boston
2
Outline

• Scope of congenital heart disease (CHD)
• Trends in CHD outcomes
• Trends in management
• Trends in imaging of pediatric and adult CHD
• Gaps in knowledge

Tal Geva 2/04
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Scope of Congenital Heart Disease

• AHA 8 per 1,000 live births (40,000/year),
  106 Americans currently living with CHD
• Hoffman and Kaplan (review of 62 studies
  published since 1955)
• 4 to 50 per 1,000 live births
• Incidence depends primarily on number of
  small VSDs included in series
• Moderate and severe CHD 6 per 1,000 without
  BAV and 19 per 1,000 with BAV

www.americanheart.org/presenter.jhtml?identifier
1477 JACC 2002391890-900
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Types of Congenital Heart Disease (median
incidence per 106 live births excluding
non-stenotic BAV and silent PDA)
Excluding tiny VSDs
Source JACC 2002391890-900
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Outcomes of CHD Mortality

• 1995-97 CHD contributed to 5822 deaths/year

Source Boneva et al. (CDC) Circulation
20011032376-81
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Outcomes of CHD Mortality

• 51 of deaths in infants 7 in 1-4 years
• 19 higher mortality in blacks compared with
  whites

Source Boneva et al. (CDC) Circulation
20011032376-81
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Childrens Hospital Boston CICU Mortality
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Despite an overall ? in mortality, some pockets
of resistance persist
Source Sadr et al. Am J Cardiol 200086577-9
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Outcomes of CHD Morbidity

• The majority of therapeutic interventions for CHD
  do not lead to cure
• Residual anatomic abnormalities
• Residual hemodynamic abnormalities
• Neurodevelopmental abnormalities
• Social and insurability issues

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As survival of patients with CHD improved,
attention shifted from getting patients out of
the hospital to improving their functional,
psychological, and social outcomes
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Neurodevelopmental Outcomes
D-TGA
Circulatory arrest v. low-flow CPB trial Wypij et
al. J Thorac Cardiovsc Surg 20031261397
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Neurodevelopmental Outcomes
S/p Fontan
Source Goldberg et al. J Ped 2000137646
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Neurodevelopmental Outcomes
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Dunbar-Masterson et al. Circulation 20011041138
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Outcomes of CHD Morbidity

• Residual anatomic abnormalities
• Residual hemodynamic abnormalities
• Neurodevelopmental abnormalities
• Social and insurability issues

Tal Geva 2/04
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Even when we think treatment leads to cure
22 year-old woman, s/p coarctation repair in
infancy
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Residual hemodynamic burden is common
S/p TOF repair
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Trends in Management of CHD
Tal Geva 2/04
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• Many variables account for the dramatic progress
  in outcomes of CHD
• Better understanding of anatomy, embryology,
  genetics, pathophysiology, and natural history
• Improved diagnosis
• Support technology (e.g., cardiorespiratory
  support and monitoring technology in the OR
  and CICU, ECMO, mechanical assist devices)
• Pharmacotherapy (e.g., pressors, ACE
  inhibitors, ?-blockers, NO, Sildenofil,
  Bosentan)
• Surgical techniques
• Transcatheter therapy

Tal Geva 2/04
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• Many variables account for the dramatic progress
  in outcomes of CHD
• Better understanding of anatomy, embryology,
  genetics, pathophysiology, natural history
• Improved diagnosis
• Support technology (e.g., cardiorespiratory
  support and monitoring technology in the OR
  and CICU, ECMO, mechanical assist devices)
• Pharmacotherapy (e.g., pressors, ACE
  inhibitors, ?-blockers, NO, Sildenofil,
  Bosentan)
• Surgical techniques
• Transcatheter therapy

Tal Geva 2/04
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Trends in Surgical Management of CHD
Staged palliative approach with emphasis on
Rx. of symptoms
Early anatomic repair with emphasis on
restoration of normal physiology

• Improved protection of vital organs
• Circulatory arrest v. low-flow bypass
• Improved myocardial protection
• Improved O2 delivery pH stat v. ? stat

• Minimally invasive surgery
• Video-assisted thoracoscopic surgery
• Robotic surgery

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Coarctation repair by robotic surgery
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• Many variables account for the dramatic progress
  in outcomes of CHD
• Better understanding of anatomy, embryology,
  genetics, pathophysiology, natural history
• Improved diagnosis
• Support technology (e.g., cardiorespiratory
  support and monitoring technology in the OR
  and CICU, ECMO, mechanical assist devices)
• Pharmacotherapy (e.g., pressors, ACE
  inhibitors, ? blockers, NO, Sildenofil,
  Bosentan)
• Surgical techniques
• Transcatheter therapy

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Transcatheter Management of CHD

• Valve and vessel stenosis
• balloon dilation
• stents
• radiofrequency energy

• Occlusion procedures
• ASD, VSD, PDA, collaterals, fistulae
• variety of occluding devices and coils

• Arrhythmia therapy (ablation)

• Fetal intervention

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Cardiac Catheterization Laboratory Annual Case
Volume
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• Many variables account for the dramatic progress
  in outcomes of CHD
• Better understanding of anatomy, embryology,
  genetics, pathophysiology, natural history
• Improved diagnosis
• Support technology (e.g., cardiorespiratory
  support and monitoring technology in the OR
  and CICU, ECMO, mechanical assist devices)
• Pharmacotherapy (e.g., pressors, ACE
  inhibitors, ? blockers, NO, Sildenofil,
  Bosentan)
• Surgical techniques
• Transcatheter therapy

Tal Geva 2/04
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Evolution of CHD Imaging
Cath X-rays
Diagnostic
Interventional
Nuclear Radioactive tracers
SPECT
99mTc
PET
Thallium
Radium
2D
Color
3D TDI
B?M-mode
Echo Ultrasound
CT X-rays
5 min/slice
400 msec/slice
MRI Magnetic fields and RF
Anatomy
Function
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Imaging Procedures Childrens Hospital Boston,
2003
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The excellent overall survival of patients with
CHD and the associated high rate of residual
anatomic and functional cardiovascular
impairments result in a rapidly growing
population of individuals with a life-long need
for surveillance that includes cardiac imaging
Tal Geva 2/04
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Echocardiography Laboratory Annual Case Volume
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Cardiovascular MRI Program Annual Case Volume
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Safety Issues in Pediatric Cardiac Imaging

• Sedation
• Inherent risks of invasive dx. procedures
• Ionizing radiation exposure
• Contrast agents
• Radiopharmaceuticals
• Auditory trauma
• Pharmacological testing
• Improper use of imaging technology, including
  an unfavorable risk/benefit ratio

Tal Geva 2/04
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Safety Issues in Pediatric Cardiac Imaging

• Sedation
• Inherent risks of invasive dx. procedures
• Ionizing radiation exposure (cath, CT)
• Contrast agents (cath, echo, CT, MRI)
• Radiopharmaceuticals (nuclear medicine)
• Auditory trauma (MRI)
• Pharmacological testing (cath, echo, MRI,
  nuclear)
• Proper use of imaging technology, including a
  favorable risk/benefit ratio

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Tal Geva 2/04
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Estimated Lifetime Attributable Risk of Fatal
Cancer in Pediatric CT
Risk
Age at CT Examination
Source Brenner. Pediatr Radiol 2002 32 228
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Brenner et al, 2003

• Above doses of 50-100mSv (protracted exposure)
  or 10-50 mSv (acute exposure), direct
  epidemiologic evidence from human populations
  demonstrate the exposure to ionizing radiation
  increases the risk of some cancer.

www.pnas.org/cgi/doi/10.1073/pnas.2235592100
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Cancer Following Cardiac Cath in Childhood Modan
et al. Int J of Epidemiology 200229424

• 674 children cath between 1950-1970
• 28.6 had gt1 cath mean age at cath 8.96
• Mean age at f/u 37.5 years
• Expected number of malignancies 4.75
• Observed number of malignancies 11.0
• Standardized incidence ratio 2.3
• (95 CI 1.2-4.1)
• Of the 11 malignancies, 4 were lymphomas and 3
  were melanomas

Tal Geva 2/04
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Summary

• Advances in diagnosis and management of CHD
  have led to a dramatic decline in mortality
  (lt3)
• Rapidly expanding population of patients with
  CHD (currently 1-2 million and growing)
• Patients rarely cured frequent anatomic and
  hemodynamic abnormalities requiring
  surveillance (e.g., imaging)
• ? use of transcatheter and minimally-invasive
  surgical interventions that rely on
  image-guidance

Tal Geva 2/04
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Summary

• Consequently, the number of cardiovascular
  imaging procedures in patients with CHD will
  continue to increase
• Urgent need for research in pediatric cardiac
  imaging
• safety and efficacy of radiopharmaceuticals
• cost-risk/benefit analysis of imaging
  strategies
• minimizing exposure to ionizing radiation

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Thank You
Tal Geva 2/04
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Nuclear Studies at CHB in 2003 N 515
Shunt and EF (n 3 0.5)
Myocardial perfusion (n 92 17.9)
Lung perfusion (n 420 82)
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Childrens Hospital Boston 2003
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