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Natural history and outcomes in paediatric RASopathy-associated hypertrophic cardiomyopathy

Lookup NU author(s): Nicola Boyd, Dr Zdenka Reinhardt


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© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.Aims: This study aimed to describe the natural history and predictors of all-cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). Methods and results: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS-LAH)]. One hundred forty-nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan-like syndrome, and 3 (2%) NS-LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36–80) mmHg, P = 0.004]. Over a median follow-up of 197.5 [inter-quartile range (IQR) 93.58–370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6–175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69–98.51], 90.42% (95% CI 84.04–94.33), and 84.12% (95% CI 75.42–89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non-sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all-cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. Conclusions: These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy-related HCM.

Publication metadata

Author(s): Boleti O, Norrish G, Field E, Dady K, Summers K, Nepali G, Bhole V, Uzun O, Wong A, Daubeney PEF, Stuart G, Fernandes P, McLeod K, Ilina M, Ali MNL, Bharucha T, Donne GD, Brown E, Linter K, Jones CB, Searle J, Regan W, Mathur S, Boyd N, Reinhardt Z, Duignan S, Prendiville T, Adwani S, Kaski JP

Publication type: Article

Publication status: Published

Journal: ESC Heart Failure

Year: 2024

Pages: epub ahead of print

Online publication date: 13/01/2024

Acceptance date: 23/11/2023

ISSN (electronic): 2055-5822

Publisher: John Wiley and Sons Inc


DOI: 10.1002/ehf2.14637

PubMed id: 38217456


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