Update on Pediatric Cardiac Transplantation

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Update on Pediatric Cardiac Transplantation

• Dr Jameel Al-ata
• Consultant Assistant Professor of Pediatrics
  Pediatric Cardiology
• Taif April 2007

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Introduction

• Orthotopic pediatric heart transplantation is
  well established for infants children with
  severe forms of CHD or cardiomyopathies.
• The one month , 1 y , 5 y , 10 y survival rate
  is 90 , 85 , 75 , 65 respective

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Indication

• Heart transplant is indicated when life
  expectancy is less than 1-2 y. OR unacceptable
  quality of sec to End-stage heart disease.
• CMP , CHD with ventricular failure are primary
  indications.
• HLHS , HIV , hepatitis are controversial
  indications.

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DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT
RECIPIENTS (Age lt 1 Year)
1988-1995
1/1996-6/2005
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DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT
RECIPIENTS (Age 1-10 Years)
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DIAGNOSIS IN PEDIATRIC HEART TRANSPLANT
RECIPIENTS (Age 11-17 Years)
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Pre-transplant considerations
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Pre-transplant medical considerations

• Malnutrition growth failure are common
  (anorexia , vomiting , mal-absorption ,
  hyper-metabolic state).
• Co-morbid conditions like PLE , renal chronic
  liver disease may be contributing to the poor
  nutritional state.

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Immunization

• Prior to transplantation Immunization records
  must be reviewed and vaccines given according to
  recommendations.
• Influenza vaccination should be yearly.
• Measles varicella vaccine should be given( if
  not immune ) titers checked 6-8 weeks.
• Hepatitis,B vaccine should also be given.
• Pneumococcal vaccine is recommended even over 2
  years of age.

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Waiting list

• Waiting time varies according to case severity ,
  blood type , recipient body WT.
• In the U.S. organ procurement transplantation
  network 2001 annual report the median time to
  transplantation for a 4 year old was 191 days
  when listed with 84 same age range. ( 190 days
  for less than 1 year old listed with 142 patients)

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Pre-transplant Surgical considerations

• Nearly 50 of refered cases are Coronary Heart
  Disease most of which undergone multiple
  palliations.
• In experienced centers , even those with
  pulmonary arteries stenosis , anomalies of system
  pulmonary venous drainage or atrial
  arrangement abnormalities have nearly comparable
  survival to cardiomyopathies.

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Surgical considerations

• High output failure may be sec to failure to
  recognize important aorto-pulmonary collateral
  circulation in transplanted cyanotic CHD patient.
• PLE , ch liver disease pulmonary. AVMs poses
  additional premorbid challenges to the failed
  fontan transplantation patient.
• Results of transplantation for ACHD are poor
  ( unclear reasons ).

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Surgical condition

• PVR less than 10 woods units is acceptable , but
  poses increased risk of acute RV failure (
  compared to less than 6 ).
• ECMO can be used to bridge infants and small
  children ( not more than 2 wks because of
  increased risk of complications ).
• Ventricular assist devices can a successfull
  bridge for the older child.

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AGE DISTRIBUTION OF PEDIATRIC HEART RECIPIENTS
(Transplants January 1996 - June 2005)
Number of Transplants
ISHLT
2006

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Survival after Pediatric Heart Transplantation

• 10 y actuarial survival rate between 1982 2001
  more than 50 ( ISHLT report ).
• Infants have higher mortality in first few months
  , with better outcome if they survive the 1st
  year.
• Adolescents have annual survival decrement rate
  of 4

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PEDIATRIC HEART TRANSPLANTATIONKaplan-Meier
Survival (1/1982-6/2004)
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PEDIATRIC HEART TRANSPLANTATION Kaplan-Meier
Survival by Era (1/1982-6/2004)
J Heart Lung Transplant 200625893-903
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Risk Factors
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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004)Risk
Factors For 1 Year Mortality
J Heart Lung Transplant 200625893-903
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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004)Border
line Significant Risk Factors For 1 Year Mortality
J Heart Lung Transplant 200625893-903
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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004)
Factors Not Significant for 1 Year Mortality

• Recipient Factors
• IV inotropes, sternotomy, thoracotomy, history of
  malignancy, height, recent infection, age, PA
  pressure, cardiac output, pulmonary vascular
  resistance.

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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2004)
Factors Not Significant for 1 Year Mortality

• Donor Factors
• Gender, history of hypertension, height, clinical
  infection, history of diabetes
• Transplant Factors
• CMV mismatch, ABO identical/compatible, ischemia
  time, HLA mismatch, transplant center volume

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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000)Risk
Factors For 5 Year Mortality Conditional on 1
Year Survival
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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000)
Factors Not Significant for Conditional 5 Year
Mortality

• Recipient Factors
• History of malignancy, recent infection,
  hospitalized at time of transplant, bilirubin,
  creatinine, cardiac output, pulmonary vascular
  resistance, PRA, sternotomy, ventilator, VAD,
  age, PA pressures

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PEDIATRIC HEART TRANSPLANTS (1/1995-6/2000)
Factors Not Significant for Conditional 5 Year
Mortality

• Donor Factors
• Cause of death, history of hypertension, weight,
  height, age, gender, clinical infection at
  donation
• Transplant Factors
• Donor/recipient weight ratio, year of transplant,
  CMV mismatch, transplant center volume, induction
  use, treated for infection prior to discharge,
  dialysis prior to discharge

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Long term management post Pediatric Heart
Transplantation
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PEDIATRIC HEART RECIPIENTS Functional Status of
Surviving Recipients (Follow-ups April 1994 -
June 2005)
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Early issues

• Immunosuppressive therapy needed for life of the
  graft.
• To prevent host immune response to donor antigens
  minimize toxicity
• ( nephrotoxicity , bone marrow suppression ,
  hyperlipidemia , diabetes ..etc ).

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Immunosuppressive agents

• Triple protocol ( calcineurin inhibitro e.g.
  cyclosporine or tacrolimus plus MMF ( replacing
  azathiop ) and steroids ( weaned within 1st year
  ).
• Rapamycin as rescue therapy for acute rejection.

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PEDIATRIC HEART RECIPIENTS Induction
Immunosuppression (Transplants January 2001 -
June 2005)
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PEDIATRIC HEART RECIPIENTS Maintenance
Immunosuppression at Time of Follow-up(Follow-ups
January 2001 - June 2005)
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Morbidity
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POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS
Cumulative Prevalence in Survivors within 1 Year
Post-Transplant (Follow-ups April 1994 - June
2005)
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POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS
Cumulative Prevalence in Survivors within 5
Years Post-Transplant (Follow-ups April 1994 -
June 2005)
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POST-HEART TRANSPLANT MORBIDITY FOR PEDIATRICS
Cumulative Prevalence in Survivors within 8
Years Post-Transplant (Follow-ups April 1994 -
June 2005)
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FREEDOM FROM CORONARY ARTERY VASCULOPATHY For
Pediatric Heart Recipients (Follow-ups April
1994 - June 2005)
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Renal Dysfunction Sys Hypertension

• 73 n. renal function at 5 y
• Factors for decreased renal function include low
  COP, ischemia/ repefusion calcineurin
  inhibitant.
• 2/5 have decreased glomerular filtration at long
  term follow up.
• Aggressive high blood pressure therapy and use of
  non nephrotoxic agents ( mmf ) promotes renal
  function preservation
• A small number may need renal transplant
• 60 at 5 y will need at least 1 antihypertensive

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FREEDOM FROM SEVERE RENAL DYSFUNCTIONFor
Pediatric Heart Recipients (Follow-ups April
1994 - June 2005)
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Rejection

• 2 /3 recipients are free at 1 m. , but lt 1/3 at 1
  year.
• Risk factors include older age at transplant ,
  af-am race CMV previous rejection.
• Usually no symptoms.
• Mild to moderate rejection DX. At surv.
  Endomyocardial biopsies.

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S S of rejection

• Fatigue , decreased appetite,nausea,abdominal
  pain, rapid including in weight., fussiness
  poor feeding.
• Tachycardia, irregular rhythm,fever,gallop
  hepatomegally.

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Chronic rejection( graft vasculopathy)

• Accelerated coronary vasculopathy is the leading
  cause of death in late survivors.
• Is due to myointimal prolifration involving the
  entire vessel including intra myo.branch
• Angiography is not sensitive for mild forms.
• 75 overall prevalence by IVUS. AT 5 Y.
• Ectopy, pre-syncope, syncope, interm oedema, ex
  intolerance rarely chest pain are some
  symptoms.
• Rapamycin prevents it in animals.

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Cause of Death

• Acute allograft failure 1st 30 days
• Acute cellular rejection infections 1-5 y
• Chronic rejection causing heart or pt. Loss
  beyond 5 y.

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Other issues

• Growth
• Osteoporosis
• Exercise
• Psychosocial
• Noncompliance

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Summary

• Pediatric heart transplantation is effective
• Multidisciplinary approach is needed
• Vasculopathy is a major obstacle
• Much needed in KSA.

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THANK YOU