Variant R94C in TNNT2‐encoded troponin T predisposes to pediatric restrictive dardiomyopathy and sudden death through impaired thin filament relaxation resulting in myocardial diastolic dysfunction

Background Pediatric-onset restrictive cardiomyopathy (RCM) is associated with high mortality, but underlying mechanisms of disease are under investigated. RCM-associated diastolic dysfunction secondary to variants i

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

ObjectivesThis study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation.BackgroundViral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival.MethodsBetween June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17).ResultsViral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06).ConclusionsViral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation

Management of Advanced Heart Failure in Children with Cancer Therapy-Related Cardiac Dysfunction

The evolution of cancer therapies has led to marked improvement in survival of those affected by childhood malignancies, while also increasing the recognition of early and late toxicities associated with cancer therapies. Cardiotoxicity can include cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction as a result of exposure to chemotherapy and/or radiation. Anthracyclines remain the most common cause of chemotherapy-induced cardiomyopathy (CCM) with varying clinical presentations including: acute, early onset, and late-onset. Many individuals develop cardiac dysfunction over the long-term, ranging from subclinical cardiac dysfunction to end-stage symptomatic heart failure. The focus of this review is on characterization of symptomatic heart failure in children with cancer therapy-related cardiac dysfunction (CTRCD) primarily due to CCM and utilization of advanced heart failure therapies, including ventricular assist device (VAD) support and heart transplantation, with consideration of unique patient-related factors