Gail Stendahl

Practical application of the virtual crossmatch.

Abstract:  Background: HLA antibody sensitization is a risk factor for morbidity and mortality following heart transplantation. We previously reported the results of our in vitro study demonstrating the predictive value of the Virtual Crossmatch (VXM) and have since applied it clinically for sensitized children listed for heart transplant at our center. The VXM utilizes the results of specific antibody screening via flow cytometry to predict acute incompatibility. This review examines the effect of the VXM on wait times and outcomes. Methods: The study population included all patients listed for heart transplantation at Childrens Hospital of Wisconsin. Antibody sensitization was defined as PRA > 10% and/or by the identification of HLA specific antibody using AHG‐CDC or flow cytometry. Categorical data was analyzed via Fishers exact test while continuous variables were compared via an unpaired t test. Results: There were a total of 111 listed patients between 7/91 – 9/06. The sensitization rate was 23% (25/111). 19 patients who went on to transplant, deterioration or death were divided into 3 groups depending on listing strategy; Group 1 were listed with a prospective crossmatch requirement, Group 2 with a VXM, and Group 3 with a retrospective cross match. 7/8 patients in group 1 died prior to transplant with median wait time of 119 days. 9/10 patients in group 2 were transplanted with 100% survival and median wait time of 65 days, Group 3 included 1 patient who received a graft after 54 days and died 3 months post transplant with humoral rejection. The VXM was highly concordant with the retrospective crossmatch. Conclusions: Use of a VXM can lead to shorter wait times and better outcomes as a listing strategy for sensitized children requiring cardiac transplantation. The VXM allows transplant physicians to risk stratify patients and consider an anticipated positive crossmatch as one additional factor in the risk‐benefit analysis inherent to any donor offer. This experience supports use of the VXM as an alternative to prospective crossmatch requirements. One should recognize that other era dependent improvements such as updated criteria for patient and donor selection along with newer therapies and bridging options may have contributed to superior outcomes seen in the more recent cohort of patients treated with the VXM approach.

Outcomes of children with restrictive cardiomyopathy listed for heart transplant: a multi-institutional study.

BACKGROUND Restrictive cardiomyopathy (RCM) in children often has a progressive nature, with a high risk of clinical deterioration and death. Heart transplantation (HTx) is a widely accepted therapy that offers long-term survival, but criteria for and outcomes after listing have not been well defined. METHODS A multi-institutional, prospective, event-driven data registry of 3,147 patients aged < 18 years listed for HTx from January 1993 to December 2006 was used to assess risk factors and survival of 145 listed RCM patients. RESULTS Mean age at listing was 8.1 years, with 44% listed as United Network of Organ Sharing status 1, 33% on inotropic support, 10% on a ventilator, and 5% on mechanical support. At 1 year, 82% of these patients survived to HTx, whereas 9% died waiting. Univariate risk factors for death while waiting included younger age (p < 0.001), ventilator dependence (p < 0.001), status 1 (p < 0.001), and inotrope usage (p < 0.001). Use of multiple support devices at listing (ventilator, extracorporeal membrane oxygenation, ventricular assist device, intraaortic balloon pump) was also an important risk factor for early phase death while waiting (relative risk; 9.01, p < 0.0001). Survival after listing was 63% at 10 years and compared favorably with survival for non-cardiomyopathy patients (p = 0.01). CONCLUSIONS Children with RCM awaiting HTx have a generally low waitlist mortality and reasonable overall survival. Children requiring mechanical support and infants had a significantly higher risk of death while waiting. Further study is warranted to identify factors important in determining the optimal timing of listing in children with RCM before the need for inotropic or mechanical support.

Pediatric Solid Organ Transplant Recipients: Transition to Home and Chronic Illness Care

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high‐level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self‐managing their childs complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty‐one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post‐discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post‐discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post‐discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self‐manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post‐discharge care.

Organizational structure and processes in pediatric heart transplantation: A survey of practices

Stendahl G, Bobay K, Berger S, Zangwill S. Organizational structure and processes in pediatric heart transplantation: A survey of practices.

MRI validated echocardiographic technique to measure total cardiac volume: a tool for donor-recipient size matching in pediatric heart transplantation.

Our aim is to develop and validate an accurate method for estimating TCV using standard echocardiographic imaging that can be easily employed to aid in donor–recipient size matching in pediatric heart transplantation. Thirty patients who underwent Echo and cardiac magnetic resonance imaging (cMRI) were identified. TCV was measured on cMRI. TCV was determined echocardiographically by two methods: a volume measurement using the modified Simpsons method on a four‐chamber view of the heart; and a calculated volume measurement which assumed a true‐elliptical shape of the heart. These two methods where compared with the value obtained by cMRI using the concordance correlation coefficient (CCC). TCV by method 1 correlated well with cMRI (CCC = 0.98%, CI = 0.97, 0.99). TCV by method 2 had a CCC = 0.90 (CI = 0.9464, 0.9716) when compared to cMRI. Left ventricular end‐diastolic volume (LVEDV) also correlated as a predictor of TCV in patients with structurally normal hearts and could be described by the equation: TCV = 6.6 (LVEDV) + 12 (R2 = 0.97). Echocardiographic assessment of TCV for recipients and their potential donors is a simple process and can be prospectively applied as part of donor evaluation.

Dual-axis rotational coronary angiography: a new technique for detecting graft coronary vasculopathy in pediatric heart transplant recipients.

Annual surveillance coronary angiograpyhy to screen for graft coronary vasculopathy is routine practice after orthotopic heart transplantation. Traditionally, this is performed with direct coronary angiography using static single-plane or biplane angiography. Recently, technological advances have made it possible to perform dual-axis rotational coronary angiography (RA). This technique differs from standard static single-plane or biplane angiography in that a single detector is preprogrammed to swing through a complex 80° arc during a single injection. It has the advantage of providing a perspective of the vessels from a full arc of images rather than from one or two static images per contrast injection. The current study evaluated two coronary angiography techniques used consecutively at a single center to evaluate pediatric heart transplant recipients for graft coronary vasculopathy. A total of 23 patients underwent routine coronary angiography using both biplane static coronary angiography (BiP) and RA techniques at the Children’s Hospital of Wisconsin from February 2009 to September 2010. Demographic and procedure data were collected from each procedure and analyzed for significance utilizing a Wilcoxon rank sum test. No significant demographic or procedural differences between the BiP and the RA procedures were noted. Specific measures of radiation dose including fluoroscopy time and dose area product were similar among the imaging techniques. The findings show that RA can be performed safely and reproducibly in pediatric heart transplant recipients. Compared with standard BiP, RA does not increase radiation exposure or contrast use and in our experience has provided superior angiographic imaging for the evaluation of graft coronary vasculopathy.

254 Highly Sensitive Transplant Rejection Surveillance Using Targeted Detection of Donor Specific Cell Free DNA

Provided herein are methods and computer-readable storage media related to cell-free DNA and uses thereof to determine risk of a condition, such as transplant rejection or cancer, in a subject.