Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

Background: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection.

Methods: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements.

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults.

Objectives: Donor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.

Methods: Pediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies.

Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

Background: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest.

Methods: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies.

Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients.

Background: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored.

Objective: Explore the relationship between ncfDNA and clinical events in heart transplant recipients.

Total Cell-Free DNA Predicts Death and Infection Following Pediatric and Adult Heart Transplantation.

Background: Elevated total cell-free DNA (TCF) concentration has been associated with critical illness in adults and elevated donor fraction (DF), the ratio of donor specific cell-free DNA to total cell-free DNA present in the recipient's plasma, is associated with rejection following cardiac transplantation. This study investigates relationships between TCF and clinical outcomes after heart transplantation.

Methods: A prospective, blinded, observational study of 87 heart transplantation recipients was performed.

Volumetrics and fit assessments for donor to recipient size matching in pediatric heart transplantation: Is it time for a new paradigm?

Pediatric heart transplant patients face the highest waitlist mortality in solid organ transplantation. Given the relatively fixed number of donor organs becoming available each year, improving donor organ utilization could potentially have significant impact on reducing waitlist mortality. Donor to recipient weight ratio has historically been used to identify suitable donors; however, this method does not take into account the potential for significant variance in heart size due to complex congenital heart disease or underlying cardiomyopathy.

Donor fraction cell-free DNA and rejection in adult and pediatric heart transplantation.

Background: Endomyocardial biopsy (EMB) is the current standard for rejection surveillance in heart transplant recipients. The quantification of donor-specific cell-free DNA (cfDNA) may be an appropriate biomarker for non-invasive rejection surveillance. A multicenter prospective blinded study (DNA-Based Transplant Rejection Test, DTRT) investigated the value of donor fraction (DF), defined as the ratio of cfDNA specific to the transplanted organ to the total amount of cfDNA present in a blood sample.

Early changes in cell-free DNA levels in newly transplanted heart transplant patients.

Heart transplantation is a well-established therapy for end-stage heart failure in children and young adults. The highest risk of graft loss occurs in the first 60 days post-transplant. Donor fraction of cell-free DNA is a highly sensitive marker of graft injury.

Alternative methods for virtual heart transplant-Size matching for pediatric heart transplantation with and without donor medical images available.

Background: Listed pediatric heart transplant patients have the highest solid-organ waitlist mortality rate. The donor-recipient body weight (DRBW) ratio is the clinical standard for allograft size matching but may unnecessarily limit a patient's donor pool. To overcome DRBW ratio limitations, two methods of performing virtual heart transplant fit assessments were developed that account for patient-specific nuances.

Ventricular Assist Device in Single-Ventricle Heart Disease and a Superior Cavopulmonary Anastomosis.

Our objective is to describe the use of a ventricular assist device (VAD) in single-ventricle patients with circulatory failure following superior cavopulmonary anastomosis (SCPA). We performed a retrospective chart review of all single-ventricle patients supported with a VAD following SCPA. Implantation techniques, physiologic parameters while supported, medical and surgical interventions postimplant, and outcomes were reviewed.

Incidence and outcome of pediatric patients with intracranial hemorrhage while supported on ventricular assist devices.

Pediatric patients supported on ventricular assist devices (VADs) require systemic anticoagulation and are at risk for intracranial hemorrhage (ICH). Little is known about the incidence or outcomes of pediatric patients with ICH while supported on a VAD. A retrospective chart review of all patients receiving VAD support was completed.

The spectrum of congenital heart disease and outcomes after surgical repair among children with Turner syndrome: a single-center review.

Turner syndrome (TS), a genetic abnormality affecting 1 in 2,500 people, is commonly associated with congenital heart disease (CHD). However, the surgical outcomes for TS patients have not been well described. This study reviewed the spectrum of CHD in TS at the authors' center.

Comparison of risk factors and outcomes for pediatric patients listed for heart transplantation after bidirectional Glenn and after Fontan: an analysis from the Pediatric Heart Transplant Study.

Background: Patients listed for transplant after the bidirectional Glenn (BDG) may have better outcomes than patients listed after Fontan. This study examined and compared outcomes after listing for BDG and Fontan patients.

Methods: All patients listed for transplant after the BDG in the Pediatric Heart Transplant Study between January 1993 and December 2008 were evaluated.

Near infrared spectroscopy: guided tilt table testing for syncope.

Syncope is transient loss of consciousness. Neurocardiogenic syncope (NCS) is the most common cause of syncope. Head-up tilt-table test (HUTT) has been used to demonstrate physiologic events during graded orthostatic challenge in individuals with significant handicap from NCS.

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.

Marfan syndrome type II: there is more to Marfan syndrome than fibrillin 1.

Marfan syndrome is a well-described autosomal dominant syndrome with widely variable clinical manifestations. Cardiovascular complications include mitral valve prolapse with or without associated mitral valve insufficiency, aortic root dilatation, and most importantly the occasional development of aortic aneurysms or rupture. Given the inconsistent phenotype along with the potentially life-threatening implications, clinicians are increasingly turning to genetic testing for definitive diagnostic confirmation.

Rosiglitazone antagonizes vascular endothelial growth factor signaling and nuclear factor of activated T cells activation in cardiac valve endothelium.

Nuclear factor of activated T cells, Cytoplasmic 1 (NFATc1) is required for heart valve formation. Vascular endothelial growth factor (VEGF) signaling, mediated by NFATc1 activation, positively regulates growth of valvular endothelial cells. However, regulators of VEGF/NFATc1 signaling in valve endothelium are poorly understood.

Commotio cordis.

Commotio cordis is ventricular fibrillation that results from blunt chest trauma and is a life threatening condition; early resuscitation and defibrillation are critical. This may occur during sporting events or from child abuse and most patients are boys who are younger than 16 years. Commotio cordis' prognosis depends on the availability of cardiac defibrillation.

Orthotopic heart transplantation in a child with histiocytoid cardiomyopathy.

We report a case of histiocytoid cardiomyopathy in a 30-month-old child. This rare disorder has been identified in <100 patients worldwide and no previous reports of cardiac transplantation with this condition have been identified. We reviewed the clinical and pathologic findings and compared them to previous studies.