Assistant Professor of Pediatrics Baylor College of Medicine Houston, Texas, United States
Abstract: Heart failure (HF) is a major cause of morbidity and mortality in children and adults. To bridge end-stage HF patients to heart transplantation, mechanical circulatory support devices called Ventricular Assist Devices (VADs) have been developed. Approximately 5-20% of failing adult hearts exhibited recovery of ventricular function after VAD placement. The underlying molecular mechanisms behind such recovery is an area of active investigation. Furthermore, it is unclear whether similar recovery is possible in pediatric patients with heart failure, including patients with Hypoplastic Left Heart Syndrome (HLHS).
Dilated Cardiomyopathy (DCM) and HLHS are two major causes of progressive HF in children. We collected ventricular tissues from patients at the time of placement of a VAD (pre-VAD) and at the time of heart transplantation (post-VAD). Tissue was collected from 5 pediatric patients with DCM and 2 patients with HLHS. The age of the DCM patients ranged from 3 months to 16 years and duration of VAD support ranged from 25 days to 533 days. The two patients with HLHS were of ages 13 mo and 16 years and length of VAD support was 97 days and 209 days respectively. Single-cell RNA sequencing (scRNA-seq) was performed on the DCM and HLHS pre-VAD/post-VAD tissue pairs. A total of >200,000 single-cell transcriptomes were analyzed. We present data on changes in cell composition and gene expression profiles after ventricular unloading in DCM and HLHS tissue pairs.
This study represents the first scRNA-seq analysis of pre- and post- VAD myocardium from pediatric patients with DCM and HLHS. Our analyses will elucidate critical pathways involved in myocardial remodeling after ventricular unloading in failing pediatric hearts.
