Impact of Donor Specific Anti-HLA Antibody on Cardiac Hemodynamics and Graft Function 3 years after Pediatric Heart Transplantation: First Results from the CTOTC-09 Multi-Institutional Study.

2023

08/2023

1600-6143

The aim of this study (CTOTC-09) was to assess the impact of 'preformed' (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly-detected DSA (ndDSA) on allograft function at 3-years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary endpoint was pulmonary capillary wedge pressure (PCWP) at 3-years post-transplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age 7.7 years, 57% male). Pre-PHTx sensitization status was: non-sensitized (n=163, 44%), sensitized/no DSA (n=115, 31%), sensitized/DSA (n=87, 24%) and 5 (1%) insufficient DSA data; 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the two groups for: other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide. However, in the multivariable analysis, persistent first year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first year DSA was a risk factor for late graft dysfunction.

10.1016/j.ajt.2023.08.006

Am J Transplant

37579817

Pediatric Cardiomyopathies.

2017

855-873

2017 Sep 15

1524-4571

<p>Pediatric cardiomyopathies are rare diseases with an annual incidence of 1.1 to 1.5 per 100 000. Dilated and hypertrophic cardiomyopathies are the most common; restrictive, noncompaction, and mixed cardiomyopathies occur infrequently; and arrhythmogenic right ventricular cardiomyopathy is rare. Pediatric cardiomyopathies can result from coronary artery abnormalities, tachyarrhythmias, exposure to infection or toxins, or secondary to other underlying disorders. Increasingly, the importance of genetic mutations in the pathogenesis of isolated or syndromic pediatric cardiomyopathies is becoming apparent. Pediatric cardiomyopathies often occur in the absence of comorbidities, such as atherosclerosis, hypertension, renal dysfunction, and diabetes mellitus; as a result, they offer insights into the primary pathogenesis of myocardial dysfunction. Large international registries have characterized the epidemiology, cause, and outcomes of pediatric cardiomyopathies. Although adult and pediatric cardiomyopathies have similar morphological and clinical manifestations, their outcomes differ significantly. Within 2 years of presentation, normalization of function occurs in 20% of children with dilated cardiomyopathy, and 40% die or undergo transplantation. Infants with hypertrophic cardiomyopathy have a 2-year mortality of 30%, whereas death is rare in older children. Sudden death is rare. Molecular evidence indicates that gene expression differs between adult and pediatric cardiomyopathies, suggesting that treatment response may differ as well. Clinical trials to support evidence-based treatments and the development of disease-specific therapies for pediatric cardiomyopathies are in their infancy. This compendium summarizes current knowledge of the genetic and molecular origins, clinical course, and outcomes of the most common phenotypic presentations of pediatric cardiomyopathies and highlights key areas where additional research is required.</p>

<p><strong>CLINICAL TRIAL REGISTRATION: </strong>URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02549664 and NCT01912534.</p>

10.1161/CIRCRESAHA.116.309386

Circ. Res.

28912187