BACKGROUND: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. OBJECTIVES: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. METHODS: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. RESULTS: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. CONCLUSIONS: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

Aalborg University Hospital Aalborg Denmark

Aarhus University Hospital Aarhus Denmark

Alder Hey Children's Hospital Liverpool United Kingdom

Bambino Gesu Hospital Rome Italy

Birmingham Children's Hospital Birmingham United Kingdom

Bristol Royal Hospital for Children Bristol United Kingdom

Cardiology Unit St Orsola Hospital IRCCS Azienda Ospedalierao Universitaria di Bologna Bologna Italy

Cardiothoracovascular Department University of Trieste Trieste Italy

Careggi University Hospital Florence Italy

Centre for Inherited Cardiovascular Diseases Great Ormond Street Hospital London United Kingdom

Centre for Inherited Cardiovascular Diseases Great Ormond Street Hospital London United Kingdom; Institute of Cardiovascular Sciences University College London London United Kingdom

Complexo Hospitalario Universitario A Coruña INIBIC CIBERCV La Coruña Spain

Department of Pediatric Cardiology Charite Universitatsmedizin Berlin Berlin Germany; Experimental and Clinical Research Center a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine Charite Universitatsmedizin Berlin Berlin Germany; DZHK partner site Berlin Berlin Germany

Department of Pediatric Cardiology Pediatric Research Center New Children's Hospital University of Helsinki and Helsinki University Hospital Helsinki Finland

Department of Pediatrics Faculty of Medicine and Graduate School of Medicine Hokkaido University Hospital Sapporo Japan

Evelina Children's Hospital London United Kingdom

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico Milano Department di Medicina Interna UOC Cardiologica Milan Italy

Fundación Favaloro University Hospital Buenos Aires Argentina

Ghent University Hospital Ghent Belgium

Glenfield Hospital Leicester United Kingdom

Hospital General Universitario Gregorio Marañón Madrid Spain

Hospital Saint Joseph Marseille France

Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

Inherited and Rare Cardiovascular Disease Unit AO dei Colli Monaldi Hospital Universita della Campania Luigi Vanvitelli Naples Italy

Institute of Cardiovascular Sciences University College London London United Kingdom

Institute of Cardiovascular Sciences University College London London United Kingdom; St Bartholomew's Centre for Inherited Cardiovascular Diseases St Bartholomew's Hospital West Smithfield London United Kingdom

John Radcliffe Hospital Oxford United Kingdom

Kochi Medical School Hospital Kochi Japan

Leeds General Infirmary Leeds United Kingdom

Leiden University Medical Center Leiden the Netherlands

Mater Dei Hospital Msida Malta

Necker Enfants Malades Hospital Paris France

Onassis Cardiac surgery Center Athens Greece

Our Lady's Children's Hospital Dublin Ireland

Papa Giovanni XXIII Hospital Bergamo Italy; Fondazione Toscana G Monasterio Massa Pisa Italy

Rio Hortega University Hospital Valladolid Spain

Royal Brompton and Harefield NHS Trust London United Kingdom

Royal Hospital for Children Glasgow United Kingdom

Sant Joan de Deu Barcelona Spain

Southampton General Hospital Southampton United Kingdom

The Children's Memorial Health Institute Warsaw Poland

The Freeman Hospital Newcastle United Kingdom

The Royal Children's Hospital Melbourne Victoria Australia

University Hospital La Paz Madrid Spain

University Hospital Motol Prague Czech Republic

University Hospital of Wales Cardiff United Kingdom

University Hospital Virgen de la Arrixaca Murcia Spain

University of Medicine and Pharmacy Victor Babes Timisoara Department of Pediatrics Children's Hospital Louis Turcanu Timisoara Romania

Vall d'Hebron University Hospital Barcelona Spain

J Am Coll Cardiol. 2022 May 24;79(20):1998-2000. doi: 10.1016/j.jacc.2022.03.356. PubMed

See more in PubMed

Kaski J.P., Syrris P., Esteban M.T., et al. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2009;2(5):436–441. PubMed

Morita H., Rehm H.L., Menesses A., et al. Shared genetic causes of cardiac hypertrophy in children and adults. N Engl J Med. 2008;358(18):1899–1908. PubMed PMC

Maron B.J., Spirito P., Wesley Y., Arce J. Development and progression of left ventricular hypertrophy in children with hypertrophic cardiomyopathy. N Engl J Med. 1986;315(10):610–614. PubMed

Norrish G., Field E., McLeod K., et al. Clinical presentation and survival of childhood hypertrophic cardiomyopathy: a retrospective study in United Kingdom. Eur Heart J. 2019;40(12):986–993. PubMed PMC

Marston N.A., Han L., Olivotto I., et al. Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy. Eur Heart J. 2021;42(20):1988–1996. PubMed PMC

Alexander P.M.A., Nugent A.W., Daubeney P.E.F., et al. Long-term outcomes of hypertrophic cardiomyopathy diagnosed during childhood: results from a national population-based study. Circulation. 2018;138(1):29–36. PubMed

Lipshultz S.E., Orav E.J., Wilkinson J.D., et al. Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry. Lancet. 2013;382(9908):1889–1897. PubMed PMC

Ostman-Smith I., Wettrell G., Keeton B., et al. Age- and gender-specific mortality rates in childhood hypertrophic cardiomyopathy. Eur Heart J. 2008;29(9):1160–1167. PubMed

Olivotto I., Oreziak A., Barriales-Villa R., et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759–769. PubMed

Prondzynski M., Mearini G., Carrier L. Gene therapy strategies in the treatment of hypertrophic cardiomyopathy. Pflugers Arch. 2019;471(5):807–815. PubMed

Norrish G., Ding T., Field E., et al. Development of a novel risk prediction model for sudden cardiac death in childhood hypertrophic cardiomyopathy (HCM Risk-Kids) JAMA Cardiol. 2019;4(9):918–927. PubMed PMC

Elliott P.M., Anastasakis A., Borger M.A., et al. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC) Eur Heart J. 2014;35(39):2733–2779. PubMed

Norrish G., Kolt G., Cervi E., et al. Clinical presentation and long-term outcomes of infantile hypertrophic cardiomyopathy: a European multicentre study. ESC Heart Fail. 2021;8(6):5057–5067. PubMed PMC

Ross R.D. The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision. Pediatr Cardiol. 2012;33(8):1295–1300. PubMed

Lopez L., Colan S., Stylianou M., et al. Relationship of echocardiographic z scores adjusted for body surface area to age, sex, race, and ethnicity: the Pediatric Heart Network Normal Echocardiogram Database. Circ Cardiovasc Imaging. 2017;10(11) PubMed PMC

Ommen S.R., Mital S., Burke M.A., et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25):e533–e557. PubMed

Priori S.G., Blomström-Lundqvist C., Mazzanti A., et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC) Eur Heart J. 2015;36(41):2793–2867. PubMed

Al-Khatib S.M., Stevenson W.G., Ackerman M.J., et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2018;72(14):e91–e220. PubMed

Richards S., Aziz N., Bale S., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424. PubMed PMC

Lorenzini M., Norrish G., Field E., et al. Penetrance of hypertrophic cardiomyopathy in sarcomere protein mutation carriers. J Am Coll Cardiol. 2020;76(5):550–559. PubMed PMC

Norrish G., Jager J., Field E., et al. Yield of clinical screening for hypertrophic cardiomyopathy in child first-degree relatives. Circulation. 2019;140(3):184–192. PubMed PMC

Lafreniere-Roula M., Bolkier Y., Zahavich L., et al. Family screening for hypertrophic cardiomyopathy: is it time to change practice guidelines? Eur Heart J. 2019;40(45):3672–3681. PubMed PMC

Arola A., Jokinen E., Ruuskanen O., et al. Epidemiology of idiopathic cardiomyopathies in children and adolescents. A nationwide study in Finland. Am J Epidemiol. 1997;146(5):385–393. PubMed

Lipshultz S.E., Sleeper L.A., Towbin J.A., et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med. 2003;348(17):1647–1655. PubMed

Nugent A.W., Daubeney P.E., Chondros P., et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med. 2003;348(17):1639–1646. PubMed

Colan S.D., Lipshultz S.E., Lowe A.M., et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation. 2007;115(6):773–781. PubMed

Miron A., Lafreniere-Roula M., Fan C.S., et al. A validated model for sudden cardiac death risk prediction in pediatric hypertrophic cardiomyopathy. Circulation. 2020;142(3):217–229. PubMed PMC

Ziolkowska L., Turska-Kmiec A., Petryka J., Kawalec W. Predictors of long-term outcome in children with hypertrophic cardiomyopathy. Pediatr Cardiol. 2016;37(3):448–458. PubMed PMC

Calcagni G., Limongelli G., D’Ambrosio A., et al. Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results. Int J Cardiol. 2017;245:92–98. PubMed

Kühnisch J., Herbst C., Al-Wakeel-Marquard N., et al. Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3. Clin Genet. 2019;96(6):549–559. PubMed

Mathew J., Zahavich L., Lafreniere-Roula M., et al. Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy. Clin Genet. 2018;93(2):310–319. PubMed

Gruner C., Ivanov J., Care M., et al. Toronto hypertrophic cardiomyopathy genotype score for prediction of a positive genotype in hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2013;6(1):19–26. PubMed

Robyns T., Breckpot J., Nuyens D., et al. Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy. Eur J Med Genet. 2020;63(3):103754. PubMed

Kaski J.P., Syrris P., Shaw A., et al. Prevalence of sequence variants in the RAS-mitogen activated protein kinase signaling pathway in pre-adolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2012;5(3):317–326. PubMed

Nugent A.W., Daubeney P.E., Chondros P., et al. Clinical features and outcomes of childhood hypertrophic cardiomyopathy: results from a national population-based study. Circulation. 2005;112(9):1332–1338. PubMed

O’Mahony C., Jichi F., Ommen S.R., et al. International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM) Circulation. 2018;137(10):1015–1023. PubMed

Ostman-Smith I., Wettrell G., Keeton B., Riesenfeld T., Holmgren D., Ergander U. Echocardiographic and electrocardiographic identification of those children with hypertrophic cardiomyopathy who should be considered at high-risk of dying suddenly. Cardiol Young. 2005;15(6):632–642. PubMed

Norrish G., Chubb H., Field E., et al. Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study. Europace. 2020;23(3):400–408. PubMed PMC

Norrish G., Qu C., Field E., et al. External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy. Eur J Prev Cardiol. 2022;29(4):678–686. PubMed PMC

Analysis of risk stratification and prevention of sudden death in pediatric patients with hypertrophic cardiomyopathy: Dilemmas and clarity