Cardiomyopathies in children and adolescents: aetiology, management, and outcomes in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Registry.
Kaski, Juan Pablo; Norrish, Gabrielle; Gimeno Blanes, Juan Ramonet al.
[en] BACKGROUND AND AIMS: Childhood-onset cardiomyopathies are rare and poorly characterized. This study examined the baseline characteristics and 1-year follow-up of children with cardiomyopathy in the first European Cardiomyopathy Registry. METHODS: Prospective data were collected on individuals aged 1-<18 years enrolled in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis long-term registry (June 2014-December 2016). RESULTS: A total of 633 individuals aged ≤18 years with hypertrophic [HCM; n = 388 (61.3%)], dilated [DCM; n = 206 (32.5%)], restrictive [RCM; n = 28 (4.4%)], and arrhythmogenic right ventricular cardiomyopathy [ARVC; n = 11 (1.7%)] were enrolled by 23 referral centres in 14 countries. Median age at diagnosis was 4.0 [interquartile range (IQR) 0-10] years, and there was a male predominance [n = 372 (58.8%)] across all subtypes, with the exception of DCM diagnosed <10 years of age; 621 (98.1%) patients were receiving cardiac medication and 80 (12.6%) had an implantable cardioverter-defibrillator. A total of 253 patients (253/535, 47.3%) had familial disease. Genetic testing was performed in 414 (67.8%) patients with a pathogenic or likely pathogenic variant reported in 250 (60.4%). Rare disease phenocopies were reported in 177 patients (28.0%) and were most frequent in patients under 10 years [142 (30.9%) vs. 35 (19.6%); P = .003]. Over a median follow-up of 12.5 months (IQR 11.3-15.3 months), 18 patients (3.3%) died [HCM n = 9 (2.6%), DCM n = 5 (3.0%), RCM n = 4 (16.0%)]. Heart failure events were most frequent in RCM patients (36.0%). CONCLUSIONS: The findings confirm the heterogeneous aetiology of childhood cardiomyopathies and show a high frequency of familial disease. Outcomes differed by cardiomyopathy subtype, highlighting a need for disease-specific evaluation and treatment.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Kaski, Juan Pablo ; Centre for Paediatric Inherited and Rare Cardiovascular Disease, University College London Institute of Cardiovascular Science and Great Ormond Street Hospital NHS Foundation Trust, 20 Guilford Street, WC1N 1DZ London, United Kingdom.
Norrish, Gabrielle ; Centre for Paediatric Inherited and Rare Cardiovascular Disease, University College London Institute of Cardiovascular Science and Great Ormond Street Hospital NHS Foundation Trust, 20 Guilford Street, WC1N 1DZ London, United Kingdom.
Gimeno Blanes, Juan Ramon ; Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
Charron, Philippe ; Assistance Publique-Hôpitaux de Paris, ICAN, Inserm UMR1166, Sorbonne Université, Centre de Référence des Maladies Cardiaques Héréditaires ou Rares, Hôpital Pitié-Salpêtrière, Paris, France.
Elliott, Perry ; Centre for Inherited Cardiovascular Diseases, University College London and St. Bartholomew's Hospital, London, United Kingdom.
Tavazzi, Luigi ; Department of Cardiology, Maria Cecilia Hospital, GVM Care&Research, Cotignola, Italy.
Tendera, Michal ; Department of Cardiology and Structural Heart Disease, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Laroche, Cécile; EURObservational Research Programme, European Society of Cardiology, Sophia-Antipolis, France.
Maggioni, Aldo P ; EURObservational Research Programme, European Society of Cardiology, Sophia-Antipolis, France. ; Department of Cardiology, ANMCO Research Center, Florence, Italy.
Baban, Anwar ; Cardiogenetic Centre, Medical and Surgical Department of Pediatric Cardiology, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy.
Khraiche, Diala; Pediatric and Congenital Cardiology Unit, Hôpital Necker Enfants Malades, M3C-Necker, Paris, France.
Ziolkowska, Lidia ; Pediatric Cardiology, The Children's Memorial Health Institute, Warsaw, Poland.
Limongelli, Giuseppe ; Inherited and Heart Disease Unit, Monaldi Hospital, A.O. Colli (University of Campania 'Luigi Vanvitelli'), Naples, Italy.
Ojala, Tiina ; Pediatric Cardiology, University of Helsinki and Helsinki University Hospital, Hospital for Children and Adolescents, Helsinki, Finland.
Gorenflo, Matthias ; Pediatric Cardiology and Congenital Heart Diseases, University of Heidelberg, Heidelberg, Germany.
Anastasakis, Aris ; Unit of Rare and Inherited CVD-Department of Cardiology, Kappa Unit, Onassis Cardiac Surgery Centre, Athens, Greece.
Cardiomyopathies in children and adolescents: aetiology, management, and outcomes in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Registry.
Publication date :
01 March 2024
Journal title :
European Heart Journal
ISSN :
0195-668X
eISSN :
1522-9645
Publisher :
Oxford University Press, Oxford, Gb
Volume :
45
Pages :
1443
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
Abbott Vascular Int/; Amgen Cardiovascular/; AstraZeneca/; Bayer AG/; Boehringer Ingelheim/; Boston Scientific/; Bristol Myers Squibb/; Pfizer Alliance/; Daiichi Sankyo Europe GmbH/; Alliance Daiichi Sankyo Europe GmbH/; Eli Lilly and Company/; Edwards/; Gedeon Richter Plc/; Menarini Int. Op/; MSD-Merck & Co/; Novartis Pharma AG/; ResMed/; Sanofi/; SERVIER/; Vifor/
Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: A position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008;29:270-6. https://doi.org/10.1093/eurheartj/ehm342
Burch M, Siddiqi SA, Celermajer DS, Scott C, Bull C, Deanfield JE. Dilated cardiomyopathy in children: determinants of outcome. Br Heart J 1994;72:246-50. https://doi.org/ 10.1136/hrt.72.3.246
Denfield SW, Rosenthal G, Gajarski RJ, Bricker JT, Schowengerdt KO, Price JK, et al. Restrictive cardiomyopathies in childhood. Etiologies and natural history. Tex Heart Inst J 1997;24:38-44.
Maurizi N, Passantino S, Spaziani G, Girolami F, Arretini A, Targetti M, et al. Long-Term outcomes of pediatric-onset hypertrophic cardiomyopathy and age-specific risk factors for lethal arrhythmic events. JAMA Cardiol 2018;3:520-5. https://doi.org/10.1001/ jamacardio.2018.0789
Yetman AT, Hamilton RM, Benson LN, McCrindle BW. Long-Term outcome and prognostic determinants in children with hypertrophic cardiomyopathy. J Am Coll Cardiol 1998;32:1943-50. https://doi.org/10.1016/S0735-1097(98)00493-8
Lipshultz SE, Sleeper LA, Towbin JA, Lowe AM, Orav EJ, Cox GF, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 2003;348: 1647-55. https://doi.org/10.1056/NEJMoa021715
Nugent AW, Daubeney PEF, Chondros P, Carlin JB, Cheung M, Wilkinson LC, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 2003;348: 1639-46. https://doi.org/10.1056/NEJMoa021737
Norrish G, Field E, McLeod K, Ilina M, Stuart G, Bhole V, et al. Clinical presentation and survival of childhood hypertrophic cardiomyopathy: A retrospective study in United Kingdom. Eur Heart J 2019;40:986-93. https://doi.org/10.1093/eurheartj/ehy798
Charron P, Elliott PM, Gimeno JR, Caforio ALP, Kaski JP, Tavazzi L, et al. The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies. Eur Heart J 2018;39:1784-93. https://doi.org/10.1093/ eurheartj/ehx819
Elliott P, Charron P, Blanes JRG, Tavazzi L, Tendera M, Konte M, et al. European Cardiomyopathy Pilot Registry: EURObservational Research Programme of the European Society of Cardiology. Eur Heart J 2016;37:164-73. https://doi.org/10.1093/ eurheartj/ehv497
Norrish G, Kolt G, Cervi E, Field E, Dady K, Ziółkowska L, et al. Clinical presentation and long-Term outcomes of infantile hypertrophic cardiomyopathy: A European multicentre study. ESC Heart Fail 2021;8:5057-67. https://doi.org/10.1002/ehf2.13573
Colan SD, Lipshultz SE, Lowe AM, Sleeper LA, Messere J, Cox GF, et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation 2007;115:773-81. https://doi.org/10. 1161/CIRCULATIONAHA.106.621185
Singh RK, Canter CE, Shi L, Colan SD, Dodd DA, Everitt MD, et al. Survival without cardiac transplantation among children with dilated cardiomyopathy. J Am Coll Cardiol 2017; 70:2663-73. https://doi.org/10.1016/j.jacc.2017.09.1089
Andrews RE, Fenton MJ, Ridout DA, Burch M; British Congenital Cardiac Association. New-onset heart failure due to heart muscle disease in childhood: A prospective study in the United Kingdom and Ireland. Circulation 2008;117:79-84. https://doi.org/10.1161/ CIRCULATIONAHA.106.671735
Kaski JP, Syrris P, Esteban MT, Jenkins S, Pantazis A, Deanfield JE, et al. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet 2009;2:436-41. https://doi.org/10.1161/ CIRCGENETICS.108.821314
Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, et al. Shared genetic causes of cardiac hypertrophy in children and adults. N Engl J Med 2008;358:1899-908. https://doi.org/10.1056/NEJMoa075463
Ouellette AC, Mathew J, Manickaraj AK, Manase G, Zahavich L, Wilson J, et al. Clinical genetic testing in pediatric cardiomyopathy: is bigger better? Clin Genet 2018;93:33-40. https://doi.org/10.1111/cge.13024
Meyer S, van der Meer P, van Tintelen JP, van den Berg MP. Sex differences in cardiomyopathies. Eur J Heart Fail 2014;16:238-47. https://doi.org/10.1002/ejhf.15
van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, et al. Birth prevalence of congenital heart disease worldwide: A systematic review and meta-Analysis. J Am Coll Cardiol 2011;58:2241-7. https://doi.org/10.1016/j.jacc.2011.08. 025
Marston NA, Han L, Olivotto I, Day SM, Ashley EA, Michels M, et al. Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy. Eur Heart J 2021; 42:1988-96. https://doi.org/10.1093/eurheartj/ehab148
Ware SM, Wilkinson JD, Tariq M, Schubert JA, Sridhar A, Colan SD, et al. Genetic causes of cardiomyopathy in children: first results from the pediatric cardiomyopathy genes study. J Am Heart Assoc 2021;10:e017731. https://doi.org/10.1161/JAHA.120.017731
Bagnall RD, Singer ES, Wacker J, Nowak N, Ingles J, King I, et al. Genetic basis of childhood cardiomyopathy. Circ Genom Precis Med 2022;15:e003686. https://doi.org/10. 1161/CIRCGEN.121.003686
Ware SM, Bhatnagar S, Dexheimer PJ, Wilkinson JD, Sridhar A, Fan X, et al. The genetic architecture of pediatric cardiomyopathy. Am J Hum Genet 2022;109:282-98. https:// doi.org/10.1016/j.ajhg.2021.12.006
Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, et al. Evidence-based assessment of genes in dilated cardiomyopathy. Circulation 2021;144:7-19. https://doi.org/10. 1161/CIRCULATIONAHA.120.053033
Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 2006;296:1867-76. https:// doi.org/10.1001/jama.296.15.1867
Levine JC, Kishnani PS, Chen YT, Herlong JR, Li JS. Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. Pediatr Cardiol 2008;29:1033-42. https://doi.org/10.1007/s00246-008-9267-3
Andelfinger G, Marquis C, Raboisson MJ, Theoret Y, Waldmöller S, Wiegand G, et al. Hypertrophic cardiomyopathy in Noonan syndrome treated by MEK-inhibition. J Am Coll Cardiol 2019;73:2237-9. https://doi.org/10.1016/j.jacc.2019.01.066
El Refaey M, Xu L, Gao Y, Canan BD, Adesanya TMA, Warner SC, et al. In vivo genome editing restores dystrophin expression and cardiac function in dystrophic mice. Circ Res 2017;121:923-9. https://doi.org/10.1161/CIRCRESAHA.117.310996
Norrish G, Cantarutti N, Pissaridou E, Ridout DA, Limongelli G, Elliott PM, et al. Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: A systematic review and meta-Analysis. Eur J Prev Cardiol 2017;24:1220-30. https://doi.org/10. 1177/2047487317702519
Norrish G, Ding T, Field E, Ziólkowska L, Olivotto I, Limongelli G, et al. Development of a novel risk prediction model for sudden cardiac death in childhood hypertrophic cardiomyopathy (HCM Risk-Kids). JAMA Cardiol 2019;4:918-27. https://doi.org/10.1001/ jamacardio.2019.2861
Maron BJ, Spirito P, Ackerman MJ, Casey SA, Semsarian C, Estes NA III, et al. Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 2013;61:1527-35. https:// doi.org/10.1016/j.jacc.2013.01.037
Wilkinson JD, Lowe AM, Salbert BA, Sleeper LA, Colan SD, Cox GF, et al. Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: A study from the Pediatric Cardiomyopathy Registry. Am Heart J 2012;164:442-8. https://doi.org/10. 1016/j.ahj.2012.04.018
Alexander PMA, Nugent AW, Daubeney PEF, Lee KJ, Sleeper LA, Schuster T, et al. Long-Term outcomes of hypertrophic cardiomyopathy diagnosed during childhood: results from a national population-based study. Circulation 2018;138:29-36. https://doi. org/10.1161/CIRCULATIONAHA.117.028895
Nugent AW, Daubeney PE, Chondros P, Carlin JB, Colan SD, Cheung M, et al. Clinical features and outcomes of childhood hypertrophic cardiomyopathy: results from a national population-based study. Circulation 2005;112:1332-8. https://doi.org/10. 1161/CIRCULATIONAHA.104.530303
Webber SA, Lipshultz SE, Sleeper LA, Lu M, Wilkinson JD, Addonizio LJ, et al. Outcomes of restrictive cardiomyopathy in childhood and the influence of phenotype: A report from the Pediatric Cardiomyopathy Registry. Circulation 2012;126:1237-44. https:// doi.org/10.1161/CIRCULATIONAHA.112.104638
Wang H, Liu S, Zhang X, Zheng J, Lu F, Lip GYH, et al. Prevalence and impact of arrhythmia on outcomes in restrictive cardiomyopathy-A report from the Beijing Municipal Health Commission Information Center (BMHCIC) database. J Clin Med 2023;12: 1236. https://doi.org/10.3390/jcm12031236
