Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy
Background: Sex differences have been described in adults with hypertrophic cardiomyopathy (HCM), but it is unknown if similar differences exist in childhood-onset disease. Objectives: This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of chi...
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2025-08-01
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| Series: | JACC: Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772963X25003278 |
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| author | Gabrielle Norrish, PhD Kimberley Hall, BSc Ella Field, MSc Elena Cervi, MD Olga Boleti, MD Lidia Ziółkowska, MD Iacopo Olivotto, MD Sylvia Passantino, MD Diala Khraiche, MD Giuseppe Limongelli, MD Robert G. Weintraub, MD Aris Anastasakis, MD Elena Biagini, MD Luca Ragni, MD Georgia Sarquella-Brugada, MD Sergi Cesar, MD Terrence Prendiville, MD Karen McLeod, MD Maria Ilina, MD Anwar Baban, MD Tiina H. Ojala, MD Georgia Spentzou, MD Vinay Bhole, MD Feran Gran, MD Elspeth Brown, MD Grazia Delle Donne, MD Bernadette Khodaghalian, MD Adrian Fernandez, MD Piers E.F. Daubeney, MD Katie Linter, MD Peter Kubus, MD Orhan Uzun, MD Regina Bökenkamp, MD Francesca Raimondi, MD Chiara Marrone, MD Constantio Medrano, MD Esther Gonzalez-Lopez, MD Ana Siles, MD Katarzyna Luczak-Wozniak, MD Tara Bharucha, MD Satish Adwani, MD Sabine Klaassen, MD Fernando J. Castro, MD Luis Guereta, MD Hirokuni Yamazawa, MD Gianfranco Sinagra, MD Anca Popoiu, MD Francesca Perin, MD B. Chana, MD Hans De Wilde, MD Torsten.B. Rasmussen, MD Jens Mogensen, MD Sujeev Mathur, MD Fernando Centeno, MD Zdenka Reinhardt, MD Roberto Barriales-Villa, MD Toru Kubo, MD Tiziana Felice, MD Cristina Radulescu, MD Sylvie Schouvey, MD Melissa Chaker, MD Juan Pablo Kaski, MD |
| author_facet | Gabrielle Norrish, PhD Kimberley Hall, BSc Ella Field, MSc Elena Cervi, MD Olga Boleti, MD Lidia Ziółkowska, MD Iacopo Olivotto, MD Sylvia Passantino, MD Diala Khraiche, MD Giuseppe Limongelli, MD Robert G. Weintraub, MD Aris Anastasakis, MD Elena Biagini, MD Luca Ragni, MD Georgia Sarquella-Brugada, MD Sergi Cesar, MD Terrence Prendiville, MD Karen McLeod, MD Maria Ilina, MD Anwar Baban, MD Tiina H. Ojala, MD Georgia Spentzou, MD Vinay Bhole, MD Feran Gran, MD Elspeth Brown, MD Grazia Delle Donne, MD Bernadette Khodaghalian, MD Adrian Fernandez, MD Piers E.F. Daubeney, MD Katie Linter, MD Peter Kubus, MD Orhan Uzun, MD Regina Bökenkamp, MD Francesca Raimondi, MD Chiara Marrone, MD Constantio Medrano, MD Esther Gonzalez-Lopez, MD Ana Siles, MD Katarzyna Luczak-Wozniak, MD Tara Bharucha, MD Satish Adwani, MD Sabine Klaassen, MD Fernando J. Castro, MD Luis Guereta, MD Hirokuni Yamazawa, MD Gianfranco Sinagra, MD Anca Popoiu, MD Francesca Perin, MD B. Chana, MD Hans De Wilde, MD Torsten.B. Rasmussen, MD Jens Mogensen, MD Sujeev Mathur, MD Fernando Centeno, MD Zdenka Reinhardt, MD Roberto Barriales-Villa, MD Toru Kubo, MD Tiziana Felice, MD Cristina Radulescu, MD Sylvie Schouvey, MD Melissa Chaker, MD Juan Pablo Kaski, MD |
| author_sort | Gabrielle Norrish, PhD |
| collection | DOAJ |
| description | Background: Sex differences have been described in adults with hypertrophic cardiomyopathy (HCM), but it is unknown if similar differences exist in childhood-onset disease. Objectives: This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods: An international retrospective cohort of patients diagnosed with nonsyndromic HCM ≤16 years was formed. Sex differences in baseline characteristics and clinical outcomes were investigated. Primary outcome was all-cause mortality or cardiac transplantation. Secondary outcomes include major arrhythmic cardiac event and heart failure event. Results: Of 1,433 patients diagnosed at a median age of 11 years (IQR: 6-14), 471 (33.0%) were female. Although there were no sex differences in phenotype in preadolescent patients (<12 years), adolescent female patients were more likely to have heart failure symptoms (n = 53 [31.9%] vs n = 86 [22.5%]; P = 0.019). Adolescent female patients had larger left atrial size (1.4 z-score [±2.3] vs 2.1 z-score [±2.5]; P = 0.0056) but there was no difference in degree of hypertrophy or proportion with obstructive disease. Over a median follow-up of 5.3 years (IQR: 2.9, 8.0) annual incidence of all-cause mortality or cardiac transplantation, major arrhythmic cardiac event or heart failure events did not vary by sex. Conclusions: Young female patients with HCM are more likely to experience heart failure symptoms and have echocardiographic features of diastolic impairment. Despite differences in phenotype, outcomes during childhood and young adulthood are not different. Further studies are required to explore the underlying mechanisms for these observed differences. |
| format | Article |
| id | doaj-art-cdfce74917ae4473aea683debe12fd37 |
| institution | DOAJ |
| issn | 2772-963X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Advances |
| spelling | doaj-art-cdfce74917ae4473aea683debe12fd372025-08-20T03:15:22ZengElsevierJACC: Advances2772-963X2025-08-014810190710.1016/j.jacadv.2025.101907Sex Differences in Children and Adolescents With Hypertrophic CardiomyopathyGabrielle Norrish, PhD0Kimberley Hall, BSc1Ella Field, MSc2Elena Cervi, MD3Olga Boleti, MD4Lidia Ziółkowska, MD5Iacopo Olivotto, MD6Sylvia Passantino, MD7Diala Khraiche, MD8Giuseppe Limongelli, MD9Robert G. Weintraub, MD10Aris Anastasakis, MD11Elena Biagini, MD12Luca Ragni, MD13Georgia Sarquella-Brugada, MD14Sergi Cesar, MD15Terrence Prendiville, MD16Karen McLeod, MD17Maria Ilina, MD18Anwar Baban, MD19Tiina H. Ojala, MD20Georgia Spentzou, MD21Vinay Bhole, MD22Feran Gran, MD23Elspeth Brown, MD24Grazia Delle Donne, MD25Bernadette Khodaghalian, MD26Adrian Fernandez, MD27Piers E.F. Daubeney, MD28Katie Linter, MD29Peter Kubus, MD30Orhan Uzun, MD31Regina Bökenkamp, MD32Francesca Raimondi, MD33Chiara Marrone, MD34Constantio Medrano, MD35Esther Gonzalez-Lopez, MD36Ana Siles, MD37Katarzyna Luczak-Wozniak, MD38Tara Bharucha, MD39Satish Adwani, MD40Sabine Klaassen, MD41Fernando J. Castro, MD42Luis Guereta, MD43Hirokuni Yamazawa, MD44Gianfranco Sinagra, MD45Anca Popoiu, MD46Francesca Perin, MD47B. Chana, MD48Hans De Wilde, MD49Torsten.B. Rasmussen, MD50Jens Mogensen, MD51Sujeev Mathur, MD52Fernando Centeno, MD53Zdenka Reinhardt, MD54Roberto Barriales-Villa, MD55Toru Kubo, MD56Tiziana Felice, MD57Cristina Radulescu, MD58Sylvie Schouvey, MD59Melissa Chaker, MD60Juan Pablo Kaski, MD61Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom; Department of Cardiology, Institute of Cardiovascular Sciences University College London, London, United KingdomCentre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom; Department of Cardiology, University of Exeter, Exeter, United KingdomCentre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United KingdomCentre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United KingdomDepartment of Cardiology, Institute of Cardiovascular Sciences University College London, London, United KingdomDepartment of Cardiology, The Children’s Memorial Health Institute, Warsaw, PolandDepartment of Cardiology, Meyer Children’s Hospital IRCSS, Florence, ItalyDepartment of Cardiology, Meyer Children’s Hospital IRCSS, Florence, ItalyDepartment of Cardiology, Necker –Enfants Malades Hospital, Paris, FranceDepartment of Cardiology, Monaldi Hospital, Naples, ItalyDepartment of Cardiology, The Royal Children’s Hospital, Melbourne, Australia; Department of Cardiology, University of Melbourne, Melbourne, Australia; Department of Cardiology, Murdoch Children’s Research Institute, Parkville, AustraliaDepartment of Cardiology, Onassis Cardiac Surgery Center, Athens, GreeceCardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Amsterdam, the NetherlandsCardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyEuropean Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Amsterdam, the Netherlands; Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Barcelona, Spain; Medical Science Department, School of Medicine, Universitat de Girona, Girona, Spain; Pediatrics Department, School of Medicine, Universitat de Barcelona, Barcelona, SpainArrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Barcelona, Spain; Medical Science Department, School of Medicine, Universitat de Girona, Girona, SpainDepartment of Cardiology, Our Lady’s Children’s Hospital, Dublin, IrelandDepartment of Cardiology, Royal Hospital for Children, Glasgow, United KingdomDepartment of Cardiology, Royal Hospital for Children, Glasgow, United KingdomDepartment of Cardiology, Bambino Gesu Hospital, Rome, Italy; Department Clinical Molecular Genetics and Precision Medicine, Mediclinic City Hospital, Dubai, UAEDepartment of Pediatric Cardiology, New Children’s Hospital, University of Helsinki, Helsinki, FinlandDepartment of Cardiology, Bristol Royal Hospital for Children, Bristol, United KingdomDepartment of Cardiology, Birmingham Children’s Hospital, Birmingham, United KingdomDepartment of Cardiology, Val D’Hebron University Hospital, Barcelona, SpainDepartment of Cardiology, Val D’Hebron University Hospital, Barcelona, SpainDepartment of Cardiology, Leeds General Infirmary, Leeds, United KingdomDepartment of Cardiology, Alder Hey Children’s Hospital, Liverpool, United KingdomDepartment of Cardiology, Fundación Favaloro University Hospital, Buenos Aires, ArgentinaDepartment of Cardiology, Royal Brompton and Harefield NHS Trust, London, United KingdomDepartment of Cardiology, Glenfield Hospital, Leicester, United KingdomDepartment of Cardiology, University Hospital Motol, Prague, Czech RepublicDepartment of Cardiology, University Hospital of Wales, Cardiff, United KingdomDepartment of Cardiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Cardiology, Fondazione Toscana G Monasterio, Massa-Pisa, Pisa, ItalyDepartment of Cardiology, Papa Giovanni XXIII Hospital, Bergamo, ItalyDepartment of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, Madrid, SpainHeart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, Madrid, SpainDepartment of Pediatrics, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, SpainDepartment of Pediatric Cardiology and General Pediatrics, Medical University of Warsaw, Warsaw, PolandDepartment of Cardiology, Southampton General Hospital, Southampton, United KingdomDepartment of Cardiology, John Radcliffe Hospital, Oxford, United Kingdom; Department of Pediatric Cardiology, Deutsches Herzzentrum der Charité, Berlin, Germany; Experimental and Clinical Research Center (ECRC), a Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine (MDC), Charite – Universitatsmedizin Berlin, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, GermanyDepartment of Cardiology, University Hospital Virgen de la Arrixaca, Murcia, SpainDepartment of Cardiology, University Hospital La Paz, Madrid, SpainDepartment of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Hospital, Sapporo, JapanHeart Muscle Disease Registry Trieste, University of Trieste, Trieste, ItalyUniversity of Medicine and Pharmacy ''Victor Babes'' Timisoara, Department of Pediatrics, Children’s Hospital ‘Louis Turcanu’, Timisoara, RomaniaDepartment of Cardiology, Hospital Universitario Virgen de las Nieves, Granada, SpainDepartment of Cardiology, Ospedaliero Universitaria di Parma, Parma, ItalyDepartment of Cardiology, Ghent University Hospital, Ghent, BelgiumDepartment of Cardiology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Cardiology, Odense University Hospital, Odense, DenmarkDepartment of Cardiology, Evelina Children’s Hospital, London, United KingdomDepartment of Cardiology, Rio Hortega University Hospital, Valladolid, SpainDepartment of Cardiology, The Freeman Hospital, Newcastle, United KingdomComplexo Hospitalario Universitario A Coruna, INIBIC, CIBERCV, Coruna, SpainDepartment of Cardiology, Kochi Medical School Hospital, Kochi, JapanDepartment of Cardiology, Mater Dei Hospital, Msida, MaltaDepartment of Cardiology, UMPCD Bucharest, Bucharest, RomaniaDepartment of Cardiology, Hospital Saint Joseph, Marseille, FranceDepartment of Cardiology, Hospital Garrahan, Buenos Aires, ArgentinaCentre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom; Department of Cardiology, Institute of Cardiovascular Sciences University College London, London, United Kingdom; Address for correspondence: Dr Juan Pablo Kaski, Centre for Paediatric Inherited and Rare Cardiovascular Disease, UCL Institute of Cardiovascular Science, London WC1N 1DZ, United Kingdom.Background: Sex differences have been described in adults with hypertrophic cardiomyopathy (HCM), but it is unknown if similar differences exist in childhood-onset disease. Objectives: This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods: An international retrospective cohort of patients diagnosed with nonsyndromic HCM ≤16 years was formed. Sex differences in baseline characteristics and clinical outcomes were investigated. Primary outcome was all-cause mortality or cardiac transplantation. Secondary outcomes include major arrhythmic cardiac event and heart failure event. Results: Of 1,433 patients diagnosed at a median age of 11 years (IQR: 6-14), 471 (33.0%) were female. Although there were no sex differences in phenotype in preadolescent patients (<12 years), adolescent female patients were more likely to have heart failure symptoms (n = 53 [31.9%] vs n = 86 [22.5%]; P = 0.019). Adolescent female patients had larger left atrial size (1.4 z-score [±2.3] vs 2.1 z-score [±2.5]; P = 0.0056) but there was no difference in degree of hypertrophy or proportion with obstructive disease. Over a median follow-up of 5.3 years (IQR: 2.9, 8.0) annual incidence of all-cause mortality or cardiac transplantation, major arrhythmic cardiac event or heart failure events did not vary by sex. Conclusions: Young female patients with HCM are more likely to experience heart failure symptoms and have echocardiographic features of diastolic impairment. Despite differences in phenotype, outcomes during childhood and young adulthood are not different. Further studies are required to explore the underlying mechanisms for these observed differences.http://www.sciencedirect.com/science/article/pii/S2772963X25003278adolescenthypertrophic cardiomyopathyphenotypesex differences |
| spellingShingle | Gabrielle Norrish, PhD Kimberley Hall, BSc Ella Field, MSc Elena Cervi, MD Olga Boleti, MD Lidia Ziółkowska, MD Iacopo Olivotto, MD Sylvia Passantino, MD Diala Khraiche, MD Giuseppe Limongelli, MD Robert G. Weintraub, MD Aris Anastasakis, MD Elena Biagini, MD Luca Ragni, MD Georgia Sarquella-Brugada, MD Sergi Cesar, MD Terrence Prendiville, MD Karen McLeod, MD Maria Ilina, MD Anwar Baban, MD Tiina H. Ojala, MD Georgia Spentzou, MD Vinay Bhole, MD Feran Gran, MD Elspeth Brown, MD Grazia Delle Donne, MD Bernadette Khodaghalian, MD Adrian Fernandez, MD Piers E.F. Daubeney, MD Katie Linter, MD Peter Kubus, MD Orhan Uzun, MD Regina Bökenkamp, MD Francesca Raimondi, MD Chiara Marrone, MD Constantio Medrano, MD Esther Gonzalez-Lopez, MD Ana Siles, MD Katarzyna Luczak-Wozniak, MD Tara Bharucha, MD Satish Adwani, MD Sabine Klaassen, MD Fernando J. Castro, MD Luis Guereta, MD Hirokuni Yamazawa, MD Gianfranco Sinagra, MD Anca Popoiu, MD Francesca Perin, MD B. Chana, MD Hans De Wilde, MD Torsten.B. Rasmussen, MD Jens Mogensen, MD Sujeev Mathur, MD Fernando Centeno, MD Zdenka Reinhardt, MD Roberto Barriales-Villa, MD Toru Kubo, MD Tiziana Felice, MD Cristina Radulescu, MD Sylvie Schouvey, MD Melissa Chaker, MD Juan Pablo Kaski, MD Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy JACC: Advances adolescent hypertrophic cardiomyopathy phenotype sex differences |
| title | Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy |
| title_full | Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy |
| title_fullStr | Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy |
| title_full_unstemmed | Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy |
| title_short | Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy |
| title_sort | sex differences in children and adolescents with hypertrophic cardiomyopathy |
| topic | adolescent hypertrophic cardiomyopathy phenotype sex differences |
| url | http://www.sciencedirect.com/science/article/pii/S2772963X25003278 |
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