Pathophysiology and molecular signalling in pediatric heart failure and VAD therapy

Changes in adiponectin system after ventricular assist device in pediatric heart failure

“…Pediatric heart failure (HF) is a clinical syndrome resulting from a broad spectrum of genetic, structural, and neurohormonal abnormalities, characterized by ventricular dysfunction and, as a consequence, impaired oxygenation of organs and tissues. 1 , 2 , 3 It was estimated that each year 11,000 to 14,000 children are hospitalized for HF in the United States. 4 Congenital heart disease (CHD) and dilated cardiomyopathy (DCM) are indicated as the most common etiologies underlying pediatric HF and the main causes of heart transplants in children.…”

Epigenetic Regulation of Cardiac Troponin Genes in Pediatric Patients with Heart Failure Supported by Ventricular Assist Device

“…A dedicated trial aimed to verify the best medical treatments for HF children has not been performed yet, and drugs used in pediatric patients are Biomedicines 2021, 9, 1409 2 of 15 mainly derived from adult studies, although the underlying etiologies of HF are very different. Accordingly, beta-blockers and anticoagulation medication were included as medical treatment also in pediatric patients in the attempt to reduce the HF progress, minimizing morbidity and mortality and improving the quality of life [5,6]. The application of ventricular assist device (VAD) therapy, as bridge to heart transplant, is now considered as a part of standard care also for end-stage HF children unresponsive to medical management [5,6].…”

“…Accordingly, beta-blockers and anticoagulation medication were included as medical treatment also in pediatric patients in the attempt to reduce the HF progress, minimizing morbidity and mortality and improving the quality of life [5,6]. The application of ventricular assist device (VAD) therapy, as bridge to heart transplant, is now considered as a part of standard care also for end-stage HF children unresponsive to medical management [5,6].…”

“…In recent years, molecular mechanisms underlying HF in children have been studied and cardiac fetal genes re-expression (genes of sarcomere components) or epigenetic modifications (DNA methylation, ATP-dependent chromatin remodeling, histone modifications, and microRNA-related mechanisms) have emerged as factors inducing left ventricle (LV) remodeling and HF progression [5,7]. Among them, microRNA (miRNA), small noncoding RNAs (~22 nucleotides) with a role in regulating gene/protein expression [5,7], are expressed during normal growth from embryonic, postnatal to adult hearts and their aberrant expression or genetic deletion is associated with abnormal cardiac cell differentiation, cardiac dysfunction [8], hypertrophy and fibrosis [9,10].…”

“…In recent years, molecular mechanisms underlying HF in children have been studied and cardiac fetal genes re-expression (genes of sarcomere components) or epigenetic modifications (DNA methylation, ATP-dependent chromatin remodeling, histone modifications, and microRNA-related mechanisms) have emerged as factors inducing left ventricle (LV) remodeling and HF progression [5,7]. Among them, microRNA (miRNA), small noncoding RNAs (~22 nucleotides) with a role in regulating gene/protein expression [5,7], are expressed during normal growth from embryonic, postnatal to adult hearts and their aberrant expression or genetic deletion is associated with abnormal cardiac cell differentiation, cardiac dysfunction [8], hypertrophy and fibrosis [9,10]. In human, the cardiac expression levels of some miRNAs were impaired in end-stage HF adult patients compared to healthy subjects [11], and cardiac miRNA profile of adult HF patients supported by VAD, as bridge to transplant, was different from that of HF patients directly submitted to transplantation, suggesting a potential effect of mechanical heart unloading on molecular mechanisms underlying ventricular remodeling [12].…”