ORIGINAL CLINICAL SCIENCE
A longitudinal study of the course of asymptomatic
antibody-mediated rejection in heart transplantation
Abdallah G. Kfoury, MD,
a,b,e
Gregory L. Snow, PhD,
a
Deborah Budge, MD,
a,e
Rami A. Alharethi, MD,
a,e
Josef Stehlik, MD,
b,c,e
Melanie D. Everitt, MD,
d,e
Dylan V. Miller, MD,
a,e
Stavros G. Drakos, MD,
a,b,e
Bruce B. Reid, MD,
a,e
M. Patricia Revelo, MD,
b,e
Edward M. Gilbert, MD,
b,e
Craig H. Selzman, MD,
b,e
Feras M. Bader, MD,
b,e
Jennifer J. Connelly, FNP,
a,e
and
M. Elizabeth H. Hammond, MD
a,b,c,e
From the
a
Intermountain Medical Center and Intermountain Healthcare;
b
University of Utah School of Medicine;
c
George E. Wahlen
Veterans Affairs Medical Center;
d
Primary Children’s Medical Center; and
e
Utah Transplantation Affiliated hospitals (U.T.A.H.)
Cardiac Transplant Program, Salt Lake City, Utah.
BACKGROUND: Growing evidence suggests worse cardiac allograft vasculopathy and mortality in
patients with asymptomatic antibody-mediated rejection (AMR). Debate continues about whether
therapeutic intervention is warranted to avoid adverse outcomes. In this study we examine the course
of individual episodes of untreated asymptomatic AMR on follow-up endomyocardial biopsy (EMB).
METHODS: The U.T.A.H. Cardiac Transplant Program database was queried for transplant recipients
between 1985 and 2009 who survived beyond 1 year and had at least 1 episode of lone AMR with a
follow-up EMB. All EMBs were screened for AMR by immunofluorescence and graded for severity.
Data were analyzed based on time from transplant (early, 12 months; late, 12 months).
RESULTS: Nine hundred fifty-eight patients with a total of 15,448 biopsies qualified for the study.
Average age at transplant was 46.7 years; 13% of the patients were female. Within the first year
post-transplant, asymptomatic AMR was diagnosed in 13.6% of biopsies compared with 5.2% beyond
1 year. AMR resolved in 65% (early) vs 75% (late) on follow-up EMB. More severe AMR was less
likely to improve regardless of time from transplant. Furthermore, after an episode of AMR had
resolved, the recurrence rate at 3, 6 and 12 months was 44%, 50.1% and 56.2%, respectively.
CONCLUSIONS: The incidence of AMR is higher in the first year post-transplant and the likelihood of
resolution is less on follow-up EMB, especially when more severe. A small but significant number of
cases became worse or did not change. These new findings may be helpful in planning future studies
that test whether therapeutic interventions on asymptomatic AMR favorably impact outcomes.
J Heart Lung Transplant 2012;31:46 –51
© 2012 International Society for Heart and Lung Transplantation. All rights reserved.
KEYWORDS:
antibody-mediated
rejection;
asymptomatic;
course;
heart;
transplantation
Heart transplantation remains an excellent long-term
therapy that grants better quality of life and longevity for
select patients with end-stage heart failure.
1
Despite im-
proved efficacy and choices of combination immunosup-
pression over the years, allograft rejection continues to pose
a significant threat, especially early after transplantation.
Acute cellular rejection has been well described and studied,
and it is quite unusual nowadays for it to be fatal in a
compliant patient. On the other hand, antibody-mediated
rejection (AMR) of the cardiac allograft has been variably
defined and poorly understood, and contentious issues re-
main
2
: some skeptics still challenge whether it even exists,
and its 2005 defining diagnostic criteria had been at odds
Reprint requests: Abdallah G. Kfoury, MD, Heart Failure Prevention and
Treatment Program, Intermountain Medical Center, 5121 South Cottonwood
Street, Murray, UT 84107. Telephone: 801-507-4637. Fax: 801-507-4811.
E-mail address: akfoury@imail.org
http://www.jhltonline.org
1053-2498/$ -see front matter © 2012 International Society for Heart and Lung Transplantation. All rights reserved.
doi:10.1016/j.healun.2011.10.009