Treatment Strategies for Cardiomyopathy in Children: A Scientific Statement From the American Heart Association

Abstract

This scientific statement from the American Heart Association focuses on treatment strategies and modalities for cardiomyopathy (heart muscle disease) in children and serves as a companion scientific statement for the recent statement on the classification and diagnosis of cardiomyopathy in children. We propose that the foundation of treatment of pediatric cardiomyopathies is based on these principles applied as personalized therapy for children with cardiomyopathy: (1) identification of the specific cardiac pathophysiology; (2) determination of the root cause of the cardiomyopathy so that, if applicable, cause-specific treatment can occur (precision medicine); and (3) application of therapies based on the associated clinical milieu of the patient. These clinical milieus include patients at risk for developing cardiomyopathy (cardiomyopathy phenotype negative), asymptomatic patients with cardiomyopathy (phenotype positive), patients with symptomatic cardiomyopathy, and patients with end-stage cardiomyopathy. This scientific statement focuses primarily on the most frequent phenotypes, dilated and hypertrophic, that occur in children. Other less frequent cardiomyopathies, including left ventricular noncompaction, restrictive cardiomyopathy, and arrhythmogenic cardiomyopathy, are discussed in less detail. Suggestions are based on previous clinical and investigational experience, extrapolating therapies for cardiomyopathies in adults to children and noting the problems and challenges that have arisen in this experience. These likely underscore the increasingly apparent differences in pathogenesis and even pathophysiology in childhood cardiomyopathies compared with adult disease. These differences will likely affect the utility of some adult therapy strategies. Therefore, special emphasis has been placed on cause-specific therapies in children for prevention and attenuation of their cardiomyopathy in addition to symptomatic treatments. Current investigational strategies and treatments not in wide clinical practice, including future direction for investigational management strategies, trial designs, and collaborative networks, are also discussed because they have the potential to further refine and improve the health and outcomes of children with cardiomyopathy in the future.

Natural history and outcomes in paediatric RASopathy‐associated hypertrophic cardiomyopathy

“…This is in keeping with previous studies that have shown particularly severe cardiac phenotypes in children with NSML 15 and has implications for consideration of novel treatments such as MEK inhibitors, which have shown some promise in the treatment of severe HCM in infants with NS and NSML, 42,43 as recognized by recent guidance. 40,44 A novel finding in this study is the identification of a distinct group of patients with a clinical diagnosis of Noonan-like syndrome, 50% of whom had a variant in a RASopathy gene that was either a VUS or did not fit the clinical syndrome described in the literature, whose features did not fit into one of the other RASopathy syndrome categories. Although their demographics and baseline clinical characteristics were similar to those of the other RASopathy syndromes, they did have a significantly higher prevalence of extra-cardiac manifestations.…”

“…This is in keeping with previous studies that have shown particularly severe cardiac phenotypes in children with NSML 15 and has implications for consideration of novel treatments such as MEK inhibitors, which have shown some promise in the treatment of severe HCM in infants with NS and NSML, 42 , 43 as recognized by recent guidance. 40 , 44 …”

Focus on Paediatric Restrictive Cardiomyopathy: Frequently Asked Questions

“…In few cases, RCM coexists with systemic arterial hypertension. In these patients, angiotensin converting enzyme inhibitors or non-dihydropyridine calcium channel blockers may be considered [96].…”

The clinical profile, genetic basis and survival of childhood cardiomyopathy: a single-center retrospective study

“…In recent decades, emerging studies have assessed the clinical progression of CM, Nevertheless, there remains a scarcity of data on Asian populations [ 3 , 4 ]. The clinical features and profile of CM in the Chinese population may differ from those in other ethnic groups.…”