BACKGROUND: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. METHODS: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). RESULTS: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. CONCLUSIONS: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Aalborg University Hospital Denmark

Aarhus University Hospital Denmark

Alder Hey Children's Hospital Liverpool United Kingdom

Bambino Gesu Hospital Rome Italy

Birmingham Children's Hospital United Kingdom

Bristol Royal Hospital for Children United Kingdom

Cardiology Unit S Orsola Malpighi Hospital IRCCS Azienda Ospedalierao Universitaria di Bologna Italy

Careggi University Hopsital Florence Italy

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

Complexo Hospitalario Universitario A Coruna INIBIC CIBERCV Spain

Department of Pediatric Cardiology Charite Universitatsmedizin Berlin Germany

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

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

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

Department of Statistical Science University College London United Kingdom

Evelina Children's Hospital London United Kingdom

Experimental and Clinical Research Center a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine Charite Universitatsmedizin Berlin Germany

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Dept di Medicina Interna UOC Cardiologica Milano Italy

Fondazione Toscana G Monasterio Massa Pisa Italy

Fundación Favaloro University Hospital Buenos Aires Argentina

German Centre for Cardiovascular Research Partner Site Berlin Germany

Ghent University Hospital Belgium

Glenfield Hospital Leicester

Heart Muscle Disease Registry Trieste University of Trieste Italy

Hospital General Universitario Gregorio Marañón Madrid Spain

Hospital Saint Joseph Marseille France

Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

Institute of Cardiovascular Sciences University College London United Kingdom

John Radcliffe Hospital Oxford

Kochi Medical School Hospital Japan

Leeds General Infirmary United Kingdom

Leiden University Medical Center the Netherlands

Mater Dei Hospital Malta

Monaldi Hospital Naples Italy

Necker Enfants Malades Hospital Paris France

Niguarda Hospital Milan Italy

Onassis Cardiac Surgery Center Athens Greece

Our Lady's Children's Hospital Dublin Ireland

Papa Giovanni XXIII Hospital Bergamo

Rio Hortega University Hospital Valladolid Spain

Royal Brompton and Harefield NHS Trust London United Kingdom

Royal Children's Hospital Melbourne Australia

Royal Hospital for Children Glasgow United Kingdom

Sant Joan de Deu Barcelona Spain

Southampton General Hospital Southampton United Kingdom

St Bartholomew's Centre for Inherited Cardiovascular Diseases St Bartholomew's Hospital West Smithfield London United Kingdom

The Children's Memorial Health Institute Warsaw Poland

The Freeman Hospital Newcastle United Kingdom

University Hospital La Paz Madrid Spain

University Hospital Motol Prague Czech Republic

University Hospital of Wales Cardiff

University Hospital Virgen de la Arrixaca Murcia Spain

Val d'Hebron University Hospital Barcelona Spain

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Circ Arrhythm Electrophysiol. 2022 May;15(5):e011033. doi: 10.1161/CIRCEP.122.011033. PubMed

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