238
made to develop noninvasive methods of
detecting allograft rejection,
1-4
but the
gold standard for detection of rejection
remains the endomyocardial biopsy.
5
Most pediatric heart transplant centers
have continued to rely on the endomy-
ocardial biopsy for routine surveillance.
There has been a push to abandon or se-
verely limit the frequency of routine biop-
sies after 1 year after transplant in the
adult population.
6,7
This approach has
not been adequately addressed in a large
pediatric population with long-term fol-
low-up. Differences between pediatric
and adult patients include rapid growth
spurts and a changing metabolic and hor-
monal milieu that can alter the functional
level of immunosuppression. The pur-
pose of this study was to assess the utility
and safety of the routine surveillance
biopsy in infants and children at least 2
years after transplantation.
S TUDY D ESIGN
Patient Population
Fifty-six pediatric patients at Stanford
University were entered in this study
during the period from September 1985
to J une 1997. Indications for transplan-
tation were dilated cardiomyopathy (n =
39), hypoplastic left heart syndrome (n =
7), hypertrophic cardiomyopathy (n =
2), postoperative complex congenital
heart disease with refractory ventricular
failure (n = 6), and anomalous origin of
the left coronary artery from the pul-
S
S afety and utility of the routine surveillance biopsy
in pediatric patients 2 years after heart
transplantation
Clifford Chin, MD, Mustansar J. Akhtar, MD, David N. Rosenthal, MD, and Daniel Bernstein, MD
Heart transplantation is a well-accepted
treatment for end-stage cardiac disease in
children. Short- and long-term survival is
excellent because of improvement in
organ preservation, immunosuppression
strategies, and care of the immunosup-
pressed individual. Allograft rejection,
however, still remains a leading cause of
morbidity and mortality after heart trans-
plantation. Many attempts have been
From the Division of Pediatric Cardiology, Stanford
University, Stanford, California.
Submitted for publication Nov 23, 1998; revi-
sions received Mar 9, 1999, and J uly 7, 1999;
accepted Sept 21, 1999.
Reprint requests: Clifford Chin, MD, Assis-
tant Professor of Pediatrics, Division of Pedi-
atric Cardiology, 750 Welch Rd, Suite 305,
Palo Alto, CA 94304.
Copyright © 2000 by Mosby, Inc.
0022-3476/2000/$12.00 + 0 9/21/103362
G3+ Grade 3-4 rejection
ISH LT International Society of H ear t and Lung
Transplantation
Objectives: The standard for diagnosing allograft rejection after heart
transplantation is the endomyocardial biopsy, but the value of routine sur-
veillance biopsies after 2 years after transplant is controversial. The objec-
tive of this study was to determine the necessity and safety of surveillance
biopsies and to correlate rejection with signs and symptoms beyond the sec-
ond post-transplant anniversary in pediatric patients.
Study design: We reviewed the results of 899 biopsies and coincident clini-
cal histories in 56 pediatric patients, comprising 314 patient-years of follow-
up. Patients were classified as having symptoms or not based on a blinded
review of their clinical status and echocardiograms. Biopsies were classified
as negative or positive with established criteria.
Results: After biopsies performed less than 2 years after transplant or as a
follow-up for a positive biopsy were excluded, 481 biopsies were available
for analysis, of which 20 (4%) were positive. Positive biopsies were found
in 15 (3%) of 456 biopsies in patients without symptoms compared with 5
(20%) of 25 biopsies in patients with symptoms. Patients with symptoms
were 6 times more likely to have a positive biopsy compared with patients
without symptoms. Of the positive rejection episodes, 75% occurred in pa-
tients without symptoms.
Conclusion: Although rejection is uncommon in pediatric patients greater
than 2 years after transplant, episodes of treatable allograft rejection can
occur in the absence of clinical signs and symptoms. This study emphasizes
the safety of and the need to continue to perform routine surveillance biop-
sies in patients without symptoms, even after the second post-transplant
year. (J Pediatr 2000;136:238-42)