Cardiac Transplantation - NCBI

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study period, no patient received FK506 (tacroli- mus). Statistical Analysis. .... month after transplantation) averaged 0.32 ± 0.6 epi- sodes for patients with ...
Clinical Investigation

Cardiac Transplantation for Pediatric Patients with Inoperable Congenital Heart Disease

Kenneth M. Shaffer, MD Susan W. Denfield, MD, FACC Kenneth 0. Schowengerdt, MD, FACC Jeffery A. Towbin, MD Branislav Radovan6evi6, MD O.H. Frazier, MD Julia K. Price, RN Robert J. Gajarski, MD

Recent studies have reported the expanding use of transplantation as the definitive option for pediatric patients with inoperable congenital heart disease. This study compares perioperative risk factors and outcomes in pediatric patients who received heart transplants for congenital heart disease with those in pediatric patients who received heart transplants for cardiomyopathy. Retrospective data collected on 40 consecutive pediatric patients undergoing cardiac transplantation from 1 January 1990 through 31 January 1995 provided the following results: 26 patients with cardiomyopathy (mean age, 7.6 years) and 14 patients with congenital heart disease (mean age, 7.2 years) underwent heart transplantation. Between groups, no significant difference was detected in waiting time for a donor heart (cardiomyopathy = 85 days, range = 2 to 409; congenital heart disease = 126 days, range = 9 to 396; P=NS); in donor/recipient weight ratio (1.27 + 0.34 vs 1.27 ± 0.28, P=NS); or in ischemic times (209 ± 92 minutes vs 248 ± 70 minutes, P=NS). Cardiopulmonary bypass times accounted for the only significant difference (73 ± 21 minutes vs 102 ± 29 minutes, P=0.003). No significant difference was found in the number of infection episodes, total days hospitalized, rejection episodes, or incidence of transplant coronary artery disease. Forty-month actuarial survival was 88% + 6% and 92% ± 7% for cardiomyopathy and congenital heart disease transplant recipients, respectively (P=NS). We conclude that post-transplantation morbidity and mortality in patients with previous congenital heart disease are not significantly different from morbidity and mortality in patients with cardiomyopathy. Transplantation should be considered an acceptable therapeutic option for patients with congenital heart disease when surgical repair of the native heart is not possible. (Tex Heart Inst J 1998;25:57-63)

Key words: Heart transplantation; cardiomyopathy, congestive; cardiomyopathy, hypertrophic; cardiomyopathy, restrictive; heart defects, congenital; pediatrics

istorically, physicians have been hesitant to perform cardiac transplantation in pediatric patients with congenital heart disease." 2 Many of these patients have had complex anatomical anomalies that challenged standard implantation techniques and increased the technical difficulty of the surgery,3 while other patients have undergone palliative surgical procedures that further increased surgical risk.4 These factors have prolonged allograft ischemic times, and initial reports of post-transplant morbidity and mortality were discouraging: perioperative mortality rates of 64% were cited in patients with congenital heart disease.',5 In addition, many patients who have undergone surgical palliations for congenital heart disease have received multiple blood-product transfusions, which may induce production of minor-blood-group antigens and "non-self" HLA (human leukocyte antigen) antibodies. It has been suggested that the persistence of these antibodies and the consequent presence of an upregulated immune system increase the post-transplantation risk of acute and chronic allograft rejection and coronary arteriopathy. Cardiac transplantation has been the accepted treatment for end-stage cardiomyopathy in children since the 1980s. In 1990, the International Society for Heart Transplantation noted an increase in cardiac transplantation for congenital heart disease.6 Subsequent reports by the same collaborative body have recorded that the pre-transplant diagnosis of congenital heart disease now accounts for nearly 50% of all children who are awaiting transplantation or have undergone it.7 A similar trend has been noted in our institution. To investigate the appropriateness of transplantation as a viable option for pediatric patients with inoperable congenital heart disease, we compared perioperative risk factors and outcomes of these patients with risk factors and outcomes of pediatric patients who had undergone transplantation for cardiomyopathy.

From: The Lillie Frank Abercrombie Section of Cardiology of the Department of Pediatrics, Baylor College of Medicine (Drs. Shaffer, Denfield, Schowengerdt, Towbin, and Gajarski; and Ms Price); the

Cardiology Department at Texas Children's Hospital (Drs. Shaffer, Denfield, Schowengerdt, Towbin, and Gajarski); and the Department of Cardiovascular Surgery (Drs. Radovandevi6 and Frazier), Texas Heart Institute, Houston, Texas 77030 Address for reprints: Robert J. Gajarski, MD, Department of Pediatric Cardiology, Texas Children's Hospital, MC 2-2280, 6621 Fannin Street, Houston, TX 77030 Texas Heart Instituteiournal

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Patients and Methods Patient Population. We retrospectively reviewed the cases of 40 pediatric patients who had undergone cardiac transplantation at our institution during the period from 1 January 1990 through 31 January 1995. As the indication for transplantation, 26 of these patients had a pretransplant diagnosis of end-stage cardiomyopathy and the other 14 had a diagnosis of non-neonatal congenital heart disease. The 26 patients with cardiomyopathy comprised 17 males and 9 females. The group with congenital heart disease comprised 9 males and 5 females, all beyond the neonatal period. The mean age at transplantation was 7.6 ± 6.1 years (range: 1 to 20 years) and 7.2 ± 7.5 years (range: 1 to 19 years), respectively (P=NS). The length of follow-up was 24 + 19 months for the cardiomyopathy group and 32 ± 17 months for the congenital heart disease group (P=NS). See Table I for details on presenting diagnoses and prior surgical procedures. Thirteen of the 14 patients with congenital heart disease had prior surgical procedures. Systemic-topulmonary artery shunts with or without pulmonary artery bands were the most common palliation. One coarctation repair, 1 tricuspid valvuloplasty, and 1 cavo-pulmonary anastomosis (Fontan) were also performed in this group of patients. One patient had undergone no prior surgical procedures, although as an infant he had undergone balloon angioplasty of his coarctation of the aorta. Eleven of 14 patients (79%) had received at least 1 blood product transfusion prior to transplant evaluation and United Network for Organ Sharing (UNOS) listing. To our knowledge, only 1 patient with cardiomyopathy had received blood products before transplantation. Panel reactive antibody screens demonstrated less than 10% reactivity in all patients. Data Collected. We recorded the pretransplant diagnosis, the age at transplantation, the sex, the results of panel reactive antibody (PRA) screens, and any prior palliative surgical procedures-in which event we recorded the blood-product exposures. Other collected data included the number of days the patient was on the UNOS waiting list; the donor's weight; the recipient's weight; the total ischemic time for the donor organ (from aortic cross-clamping of the donor to release of the recipient's cross-clamp); and the cardiopulmonary bypass time. Episodes of viral and bacterial infections requiring medical intervention were categorized as having occurred early (within the 1st 30 days after transplantation) or late (more than 30 days after transplantation). We also recorded the number of hospital days, the number of rejection episodes per patient month, and the presence of coronary arteriopathy. Immunosuppression and Rejection. All children routinely received immunosuppression with cyclo58

Transplantation for Inoperable Congenital Heart Disease

sporine, azathioprine, and prednisone. Patients initially received 4 mg/kg azathioprine perioperatively, by mouth or intravenously. Methylprednisolone was administered intraoperatively at 10 mg/kg. Postoperative therapy included cyclosporine at an initial intravenous dose of 1 mg/kg/day, beginning 24 to 72 hours after transplantation. Subsequent oral dosing was adjusted to maintain levels between 250 ng/ dL and 500 ng/dL during the 1st 30 days after transplantation. Azathioprine was administered at approximately 2 mg/kg and adjusted to maintain the white blood cell count above 5000/cc. The dosage of steroids was tapered over the 1st 15 days, from approximately 15 mg/kg/day to approximately 0.25 mg/kg/day. Rejection was diagnosed by histologic analysis of right ventricular endomyocardial biopsy specimens. Histologic rejection grades were assigned in accordance with the Texas Heart Institute (THI) and the International Society for Heart and Lung Transplantation (ISHLT) scales. A rejection grade greater than 5 on the THI scale or greater than early 3a on the ISHLT scale indicated that anti-rejection therapy was required. Acute rejection was treated by a steroid pulse and by adjusting baseline immunosuppression. Refractory episodes or rejection accompanied by hemodynamic compromise regardless of biopsy grade were treated with rabbit antithymocyte globulin (ATG) or with a murine-derived monoclonal CD3 receptor antibody preparation (OKT3). During the study period, no patient received FK506 (tacrolimus). Statistical Analysis. Numerical results are expressed as mean values ± standard deviation. Data from the congenital heart disease group were compared with data from the cardiomyopathy group by means of unpaired t-tests. Comparisons became statistically significant at P