Therapeutic Approaches in Heart Failure with Preserved Ejection Fraction (HFpEF) in Children: Present and Future

Abstract

For a long time, pediatric heart failure (HF) with preserved systolic function (HFpEF) has been noted in patients with cardiomyopathies and congenital heart disease. HFpEF is infrequently reported in children and instead of using the HFpEF terminology the HF symptoms are attributed to diastolic dysfunction. Identifying HFpEF in children is challenging because of heterogeneous etiologies and unknown pathophysiological mechanisms. Advances in echocardiography and cardiac magnetic resonance imaging techniques have further increased our understanding of HFpEF in children. However, the literature does not describe the incidence, etiology, clinical features, and treatment of HFpEF in children. At present, treatment of HFpEF in children is extrapolated from clinical trials in adults. There are significant differences between pediatric and adult HF with reduced ejection fraction, supported by a lack of adequate response to adult HF therapies. Evidence-based clinical trials in children are still not available because of the difficulty of conducting trials with a limited number of pediatric patients with HF. The treatment of HFpEF in children is based upon the clinician's experience, and the majority of children receive off-level medications. There are significant differences between pediatric and adult HFpEF pharmacotherapies in many areas, including side-effect profiles, underlying pathophysiologies, the β-receptor physiology, and pharmacokinetics and pharmacodynamics. This review describes the present and future treatments for children with HFpEF compared with adults. This review also highlights the need to urgently test new therapies in children with HFpEF to demonstrate the safety and efficacy of drugs and devices with proven benefits in adults.