Clinical approach to acute cellular rejection from the pediatric heart transplant society.

BACKGROUND: Early detection of cardiac allograft rejection is crucial for post-transplant graft survival. Despite the progress made in immunosuppression strategies, acute cellular rejection remains a serious complication during and after the first post-transplant year, and there is a continued lack of consensus regarding its treatment, especially in pediatric transplant patients. METHODS: An open request was placed via the listserv to the membership of the Pediatric Heart Transplant Society (PHTS). Along with a broad literature search, numerous institutional protocols were pooled, analyzed and consolidated. A clinical approach document was generated highlighting areas of consensus and practice variation. RESULTS: The clinical approach document divides cellular rejection by International Society for Heart and Lung Transplantation grades and provides management strategies for each, including persistent cellular rejection. CONCLUSIONS: Cellular rejection treatment can be tailored to the clinical status, graft function, and the grade of cellular rejection. A case of mild and asymptomatic rejection may not require treatment, whereas a higher-grade rejection or rejection with graft dysfunction or hemodynamic compromise may require aggressive intravenous therapies, changes to maintenance immunosuppression therapy and augmented surveillance.

Long-term outcomes of simultaneous heart and kidney transplantation in pediatric recipients.

Pediatric sHKTx has become an effective therapy for patients with combined cardiac and renal failure. Often, these patients develop human leukocyte antigen antibodies from their previous allografts and are therefore more difficult to re-transplant. We describe the largest case series of a predominantly sensitized pediatric sHKTx with emphasis on medical management and patient outcomes. Demographics, clinical characteristics, antibody, and biopsy data were retrospectively collected from University of California, Los Angeles database and correlated with short- and long-term patient and allograft outcomes of all sHKTx performed between 2002 and 2015. We identified seven pediatric patients who underwent sHKTx at our center. Mean age at time of sHKTx was 13.7 years and 85.7% were re-graft patients. 57.1% were sensitized with cPRA >50% and another 57.1% had preformed donor-specific antibody. Five-year renal allograft survival and patient survival was 85.7% for both end-points. The remaining six patients are all alive (mean follow-up 78.5 months) with good kidney and heart function. sHKTx in a population with increased immunological risk can be associated with good long-term outcomes and offers potential guidance to the pediatric transplant community where data are limited.

Initial Experience with Sildenafil, Bosentan, and Nitric Oxide for Pediatric Cardiomyopathy Patients with Elevated Pulmonary Vascular Resistance before and after Orthotopic Heart Transplantation.

Background. Although pulmonary hypertension complicating dilated cardiomyopathy has been shown to be a significant risk factor for graft failure after heart transplantation, the upper limits of pulmonary vascular resistance (PVR) that would contraindicate pediatric heart transplantation are not known. Methods. A retrospective review of all pediatric orthotopic heart transplant (OHT) performed at our institution from 2002 to 2007 was performed. Seven patients with PVR > 6 Wood's units (WU) prior to transplant were compared pre- and postoperatively with 20 matched controls with PVR < 6 WU. All pulmonary vasodilator therapies used are described as well as outcomes during the first year posttransplant. Results. The mean PVR prior to transplantation in the 7 study cases was 11.0 +/- 4.6 (range 6-22) WU, compared to mean PVR of 3.07 +/- 0.9 WU (0.56-4.5) in the controls (P = .27 x 10(-6)). All patients with elevated PVR were treated pre-OHT with either Sildenafil or Bosentan. Post-OHT, case patients received a combination of sildenafil, iloprost, and inhaled nitric oxide. All 7 case patients survived one year post-OHT, and there was no statistical difference between cases and controls for hospital stay, rejection/readmissions, or graft right ventricular failure. Mean PVR in the cases at one and three months post-OHT was not significantly different between the two groups. Only one of the cases required prolonged treatment with iloprost after OHT. Conclusions. A PVR above 6 WU should not be an absolute contraindication to heart transplantation in children.

Experience with the Cardiva Boomerang Catalyst system in pediatric cardiac catheterization.

OBJECTIVES: We studied the safety and efficacy of the Cardiva Boomerang Catalyst vascular closure system in pediatric patients after cardiac catheterization with access in femoral and internal jugular vessels. BACKGROUND: Recurrent catheterization and advances in pediatric interventions increase the need for easy hemostasis without a residual foreign body that may prevent re-accessing the vessel. The Boomerang can be deployed in sheaths as small as 4Fr without residual foreign body, with minimal orientation needed, and few complications reported. METHODS: In a two-month period, all patients between 18 months and 21 years old catheterized with 4-8Fr sheaths less than 15 cm long were eligible for Boomerang placement. These were compared retrospectively with control patients with manual hemostasis. Anthropomorphic measurements, procedure type, activated clotting time, and sheath size as well as total times of cases, intubation, hemostasis, and extubation were compared between the two groups. RESULTS: Forty-six Boomerangs were deployed in 31 patients and compared with 40 patients with manual hemostasis. Boomerangs were deployed in femoral vessels and the internal jugular vein. Device success with hemostasis was achieved in 39 patients (85%). There were no significant differences in time to hemostasis or extubation between the two groups. No major complications or operator error occurred, including hematoma, transfusion, retroperitoneal bleed, infection, vessel occlusion, or need for surgery. CONCLUSIONS: The Boomerang is a safe and easy means of achieving hemostasis in the pediatric population, in femoral vessels as well as internal jugular veins. Its times to hemostasis and extubation were not significantly different from manual hold.

Clinico-pathologic findings in end-stage pediatric heart transplant grafts.

The pathologic patterns existing in end-stage pediatric heart transplant grafts may help explain the symptoms and changes seen by echocardiography and angiography in these children. Retrospective chart review and pathologic study of explanted heart grafts was performed on 12 patients that had undergone 14 heart re-transplantations. Clinical status, echocardiographic and catheterization data at the time of transplantation were correlated to the pathologic findings. At re-OHT, eight were inpatients with heart failure symptoms and/or inotropic support requirements. Echocardiograms were abnormal in all prior to re-OHT with significant diastolic dysfunction, but LVEF >40% in all but one. There was significant epicardial fibrosis in all grafts, and all had severe CAV of epicardial arteries. However, intramyocardial coronary disease was mild in nine (64%) grafts. Moderate or severe interstitial fibrosis occurred in only three grafts, and in a perivascular distribution in eight. End-stage pediatric heart allografts have severe epicardial CAV and epicardial fibrosis, with relative sparing of the myocardium. Epicardial disease with sparing of the myocardium may explain the restrictive hemodynamics and relatively preserved systolic function present in these grafts at the time of re-OHT.

Screening for rejection in symptomatic pediatric heart transplant recipients: the sensitivity of BNP.

As the pediatric OHT population expands, there is increasing demand for convenient, yet sensitive screening techniques to identify children with acute rejection when they present to acute care facilities. In children, symptoms of acute rejection or other causes of graft dysfunction are often non-specific and can mimic other childhood illnesses. The aim of this study was to assess the utility of BNP as a biomarker to assist providers in clinical decision-making when evaluating symptomatic pediatric heart transplant patients. One hundred twenty-two urgent care and emergency room visits from 53 symptomatic pediatric OHT patients were retrospectively reviewed to evaluate the relationship between BNP levels, symptoms, and clinical diagnosis at these visits. An ROC curve was generated to determine the accuracy of BNP as a screening tool for acute rejection in this patient population. In this group of patients, a BNP value of >700 pg/mL was 100% sensitive and 92% specific for detecting allograft acute rejection (NPV of 100%). We concluded that BNP is a highly sensitive screening test for acute rejection in symptomatic pediatric heart transplant patients.

Muronomab-CD3 for pediatric acute myocarditis.

The treatment of pediatric acute myocarditis that is hemodynamically significant often includes immune modulation with intravenous immunoglobulin (IVIG) and steroids, and supportive measures. In this population, published outcomes include recovery of ventricular function from 6 months to years, transplantation, or death. We studied the effect of the immunosuppressive agent muronomab-CD3 (OKT3) on recovery of heart failure in the treatment of pediatric myocarditis. A retrospective chart review was performed identifying 15 pediatric patients diagnosed with acute myocarditis and depressed left ventricular ejection fraction (LVEF) or arrhythmias to which OKT3 was added to the immunosuppressive regimen. All patients were treated with supportive care, intravenous immunoglobulin, and steroids. LVEF by echocardiogram was plotted for each patient versus time. Outcomes included recovery of left ventricular function (as defined by an LVEF > or = 45%), death, or listing for transplant. The diagnosis of acute myocarditis was made by a positive endomyocardial biopsy in 8 patients. Nine patients required extracorporeal membrane oxygenation (ECMO) or LV assist device. After treatment with OKT3, 9 patients made a significant recovery of LVEF within 17 days, and 1 recovered by 60 days. Six of the patients requiring mechanical assistance recovered within this time period. There were 4 deaths--3 due to ECMO complications and 1 due to underlying gastrointestinal illness. One patient diagnosed with chronic myocarditis on biopsy underwent transplantation. No significant side effects attributable to OKT3 occurred. By decreasing the autoimmune inflammatory response, OKT3 may hasten recovery of ventricular function and be a useful adjunct therapy for hemodynamically significant acute pediatric myocarditis.