Risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy

Sudden cardiac death (SCD) is the most common cause of mortality in childhood onset hypertrophic cardiomyopathy (HCM). Despite this, our understanding of risk factors and ability to identify those at highest risk is limited. The aims of this thesis were to perform the first systematic investigation of SCD in childhood HCM and develop a novel paediatric-specific risk model. Using a large, retrospective, international multi-centre cohort of children with HCM this thesis firstly describes the natural history of childhood onset disease. The second part of the thesis presents the results of the first systematic review and metaanalysis of clinical risk factors for SCD in childhood HCM identifying four major clinical risk factors; previous malignant arrhythmic event, unexplained syncope, nonsustained ventricular tachycardia (NSVT) and extreme left ventricular hypertrophy. In the third part of this thesis, the current risk stratification guidelines are shown to have only moderate discriminatory ability (C statistic 0.62 (95% CI 0.55-0.70)) with a corresponding 5-year positive and negative predictive value of 9.0% and 94.5%. Thus, a novel paediatric model is developed using pre-selected clinical variables from the meta-analysis (unexplained syncope, NSVT, left atrial diameter, maximal wall thickness and left ventricular outflow tract gradient). The model's ability to predict risk at 5 years was validated; C statistic 0.69 (95% CI, 0.66-0.72) and calibration slope 0.98 (95% CI, 0.59-1.38). In the final part of this thesis the role of additional novel risk factors, including 12-lead electrocardiograph and genotype, are explored. In summary, this thesis is the first systematic and comprehensive investigation of risk factors for SCD in childhood HCM. Important differences between adult and childhood disease are described and the first validated risk model for use in paediatric clinical care is presented

Track 5: Cardiology and the imaging revolution - Part I

Cardiology and the imaging revolution