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J Am Coll Cardiol, 2001; 37:243-250
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY: PEDIATRIC CARDIOLOGY

Late rejection is a predictor of transplant coronary artery disease in children

Neda F. Mulla, MD, FACC*, Joyce K. Johnston, RN{dagger}, Laura Vander Dussen, RN{dagger}, W. Lawrence Beeson, MSPH*, Richard E. Chinnock, MD*, Leonard L. Bailey, MD, FACC{ddagger} and Ranae L. Larsen, MD, FACC*

* Department of Pediatrics, Loma Linda University Children’s Hospital, Loma Linda, California, USA
{dagger} Department of Nursing, Loma Linda University Children’s Hospital, Loma Linda, California, USA
{ddagger} Department of Surgery, Loma Linda University Children’s Hospital, Loma Linda, California, USA

Manuscript received April 16, 1999; revised manuscript received June 28, 2000, accepted September 7, 2000.

Reprint requests and correspondence: Dr. Neda F. Mulla, 11234 Anderson St., Room 4433, Loma Linda, California 92354
Nmulla{at}ahs.llumc.edu

OBJECTIVES

The study objectives were to determine posttransplant coronary artery disease (TxCAD) incidence, predisposing factors and optimal timing for retransplantation (re-Tx) in pediatric heart transplantation (Tx) recipients.

BACKGROUND

The TxCAD limits long-term survival following heart Tx, with re-Tx being the primary therapy. Information on risk factors and timing of listing for re-Tx is limited in children.

METHODS

The records of children who survived >1 year post-Tx at Loma Linda University were reviewed. Nonimmune and immune risk factors were analyzed.

RESULTS

TxCAD was documented in 24 of 210 children. Freedom from TxCAD was 92 ± 2% and 75 ± 5% at 5 and 10 years’ post-Tx, respectively. The TxCAD diagnosis was established at autopsy in 10 asymptomatic patients who died suddenly within nine months following the most recent negative angiograms. The remaining 14 children had angiographic diagnoses of TxCAD and had symptoms and/or graft dysfunction (n = 10) or positive stress studies (n = 4). Three of 14 died within three months after the diagnosis was made. Eleven patients underwent re-Tx within seven months of diagnosis; nine survived. Univariate and multivariate analyses showed that only late rejection (>1 year posttransplant) frequency (p = 0.025) and severity (hemodynamically compromising) (p < 0.01) were independent predictors of TxCAD development. Freedom from TxCAD after severe late rejection was 78 ± 8% one year postevent and 55 ± 10% by two years.

CONCLUSIONS

Late rejection is an independent predictor of TxCAD. Patients suffering severe late rejection develop angiographically apparent TxCAD rapidly and must be monitored aggressively. Both TxCAD mortality and morbidity occur early; therefore, we recommend immediate listing for re-Tx upon diagnosis.

Abbreviations and Acronyms
  CMV = cytomegalovirus
  DSE = dobutamine stress echocardiography
  ECG = electrocardiogram/electrocardiographic
  re-Tx = retransplantation
  Tx = transplantation
  TxCAD = posttransplant coronary artery disease




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