Julia K. Price

Association of Parvovirus B19 Genome in Children With Myocarditis and Cardiac Allograft Rejection Diagnosis Using the Polymerase Chain Reaction

BACKGROUND Inflammatory diseases of the heart, including myocarditis and cardiac transplant rejection, are important causes of morbidity and mortality in children. Although viral infection may be suspected in either of these clinical conditions, the definitive etiology is often difficult to ascertain. Furthermore, the histology is identical for both disorders. Coxsackievirus has long been considered the most common cause of viral myocarditis; however, we previously demonstrated by polymerase chain reaction (PCR) analysis that many different, and sometimes unexpected, viruses may be responsible for myocarditis and cardiac rejection. In this study, we describe the association of parvovirus genome identified through PCR analysis of cardiac tissue in the clinical setting of myocarditis and cardiac allograft rejection. METHODS AND RESULTS Myocardial tissue from endomyocardial biopsy, explant, or autopsy was analyzed for parvovirus B19 using primers designed to amplify a 699-base pair PCR product from the VP1 gene region. Samples tested included those obtained from patients with suspected myocarditis (n=360) or transplant rejection (n=200) or control subjects (n=250). Parvoviral genome was identified through PCR in 9 patients (3 myocarditis; 6 transplant) and no control patients. Of the 3 patients with myocarditis, 1 presented with cardiac arrest leading to death, 1 developed dilated cardiomyopathy, and the other gradually improved. Four of the 6 transplant patients had evidence of significant rejection on the basis of endomyocardial biopsy histology. All transplant patients survived the infection. CONCLUSIONS Parvovirus is associated with myocarditis in a small percentage of children and may be a potential contributor to cardiac transplant rejection. PCR may provide a rapid and sensitive method of diagnosis.

Intermediate follow-up of pediatric heart transplant recipients with elevated pulmonary vascular resistance index

OBJECTIVES This study examined perioperative and intermediate outcomes in pediatric cardiac transplant recipients who had elevated pulmonary vascular resistance indexes preoperatively. BACKGROUND Elevated pulmonary vascular resistance was associated with poor outcome in previous studies and constitutes a relative contraindication to transplantation. Few studies have evaluated this poor outcome risk factor in pediatric patients. METHODS To evaluate outcomes of nonneonatal transplant recipients, records were reviewed and divided into Group I (preoperative pulmonary vascular resistance index > or = 6 units.m2) and Group II (pulmonary vascular resistance index < 6 units.m2). Donor/recipient weight ratios, ischemic times, length of intensive care unit stay, posttransplantation infection rates, arrhythmia, response to pretransplantation vasodilator infusions and pulmonary vascular resistance indexes at the first and most recent posttransplantation biopsies were analyzed. RESULTS Group I (8 patients) had a mean (+/- SEM) pulmonary vascular resistance index of 11.5 +/- 3.5 units,m2; Group II (29 patients) had a mean pulmonary vascular resistance index of 2.3 +/- 0.4 units,m2 (p < 0.002). Pulmonary vascular resistance index decreased from 12.3 +/- 3.9 to 3.9 +/- 0.9 units.m2 (p < 0.05) in 7 Group I patients undergoing vasodilator infusion during pretransplantation catheterization. Thirty-six orthotopic heart transplantations were performed and one heterotopic transplantation. Donor weights exceeded recipient weights by 13% and 31% for Groups I and II, respectively (p > 0.25). Donor ischemic time was 215 min for Group I and 225 min for Group II (p > 0.75). Intensive care unit stay was 11.5 days in Group I and 15.1 days in Group II (p = 0.20). Infection rate was 38% in both groups (p > 0.80). Arrhythmias occurred in 90% of Group I and 42% in Group II (p < 0.03) patients. Pulmonary resistance index in Group I decreased from 11.5 +/- 3.5 to 3.3 +/- 1.2 units.m2 (p < 0.03) by the first posttransplantation biopsy and have not changed subsequently. During 2.3 years (range 0.3 to 8.5) of follow-up, the mortality rate was 25% and 21% for Groups I and II, respectively (p > 0.80). CONCLUSIONS Group I patients did not require significantly oversized donors, restricted donor locations or longer intensive care unit stays or have higher infection rates; however, arrhythmias were more frequent. Pulmonary resistance index normalized early after transplantation. Pulmonary vascular reactivity may be more important for survival than absolute resistance index.

Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric heart transplant recipients.

BACKGROUND Few reports document long-term results of pediatric cardiac transplantation in which triple therapy (cyclosporine, azathioprine, and corticosteroids) was the mainstay of immunosuppression. This report details a single centers pediatric transplant experience and analyzes the relative contributions of selected pre/posttransplant risk factors on long-term morbidity and mortality. METHODS Retrospective data were collected for all non-neonatal pediatric transplant recipients including: presenting diagnosis, cardiac hemodynamics (particularly pulmonary vascular resistance index), donor ischemic time, occurrence of postoperative infections, episodes of allograft rejection, incidence of posttransplant lymphoproliferative disease or coronary artery disease (CAD), and overall survival. Analysis of single variables and a Cox-proportional hazards model were utilized to determine the impact of pre/posttransplant risk factors on long-term survival. RESULTS From 1984 to 1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who had inoperable complex congenital heart disease, underwent cardiac transplantation and received triple-drug immunosuppression. Orthotopic transplantation was performed unless the pulmonary vascular resistance index remained >6 um2 (despite use of pulmonary vasodilator). One patient required heterotopic transplantation. Average donor ischemic time was 217 min. An average of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months). No patient developed posttransplant lymphoproliferative disease, but 22 patients (34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10 years, respectively. Of outcome variables analyzed, rejection frequency was significantly increased in patients who subsequently developed CAD, but the presence of CAD was not significantly correlated with mortality. CONCLUSION Triple-drug-based immunosuppressive maintenance therapy in pediatric heart transplant recipients results in good long-term graft survival.

Usefulness of routine surveillance biopsies in children more than one year after orthotopic heart transplantation

This retrospective study examines the usefulness of routine biopsies following the first year after transplant. This study found that routine biopsies detect few episodes of rejection in the first year after transplant and were less useful than nonroutine biopsies.