External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy

Gabrielle Norrish; Chen Qu; Ella Field; Elena Cervi; Diala Khraiche; Sabine Klaassen; Tiina H Ojala; Gianfranco Sinagra; Hirokuni Yamazawa; Chiara Marrone; Anca Popoiu; Fernando Centeno; Sylvie Schouvey; Iacopo Olivotto; Sharlene M Day; Steve Colan; Joseph Rossano; Samuel G Wittekind; Sara Saberi; Mark Russell; Adam Helms; Jodie Ingles; Christopher Semsarian; Perry M Elliott; Carolyn Y Ho; Rumana Z Omar; Juan P Kaski

doi:10.1093/eurjpc/zwab181

External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy

Eur J Prev Cardiol. 2022 Mar 30;29(4):678-686. doi: 10.1093/eurjpc/zwab181.

Authors

Gabrielle Norrish^{1

2}, Chen Qu³, Ella Field^{1

2}, Elena Cervi¹, Diala Khraiche⁴, Sabine Klaassen^{5

6

7}, Tiina H Ojala⁸, Gianfranco Sinagra⁹, Hirokuni Yamazawa¹⁰, Chiara Marrone¹¹, Anca Popoiu¹², Fernando Centeno¹³, Sylvie Schouvey¹⁴, Iacopo Olivotto¹⁵, Sharlene M Day¹⁶, Steve Colan¹⁷, Joseph Rossano¹⁸, Samuel G Wittekind¹⁹, Sara Saberi²⁰, Mark Russell²⁰, Adam Helms²⁰, Jodie Ingles²¹, Christopher Semsarian²², Perry M Elliott^{2

23}, Carolyn Y Ho²⁴, Rumana Z Omar³, Juan P Kaski^{1

2}

Affiliations

¹ Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London WC1N 3JH, UK.
² Institute of Cardiovascular Sciences, University College London, London, UK.
³ Department of Statistical Science, University College London, London, UK.
⁴ Necker - Enfants Malades hospital, Paris, France.
⁵ Department of Paediatric Cardiology, Charite - Universitatsmedizin Berlin, Berlin, Germany.
⁶ Experimental and Clinical Research Centre (ECRC), a joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Centre for Molecular Medicine (MDC), Charite - Universitatsmedizin Berlin, Berlin, Germany.
⁷ DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
⁸ Department of Paediatric Cardiology, New Children's Hospital, University of Helsinki, Helsinki, Finland.
⁹ Heart Muscle Disease Registry Trieste, University of Trieste, Trieste, Italy.
¹⁰ Department of Paediatrics, Faculty of Medicine and Graduate school of Medicine, Hokkaido University Hospital, Sapporo, Japan.
¹¹ Fondazione Toscana G Monasterio, Massa-Pisa, Italy.
¹² Department of Paediatrics, Children's Hospital 'Louis Turcanu', University of Medicine and Pharmacy "Victor Babes" Timisoara, Timisoara, Romania.
¹³ Rio Hortega University Hospital, Valladolid, Spain.
¹⁴ Hospital Saint Joseph, Marseille, France.
¹⁵ Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
¹⁶ Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁷ Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁸ Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁹ Cincinnati Children's Hospital Medical Center, Heart Institute, Cincinnati, OH, USA.
²⁰ Department of Internal Medicine-Cardiology, University of Michigan, Ann Arbor, MI, USA.
²¹ Cardio Genomics Program at Centenary Institute, The University of Sydney, Sydney, Australia.
²² Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, The University of Sydney, Sydney, Australia.
²³ St Bartholomew's Centre for Inherited Cardiovascular Diseases, St Bartholomew's Hospital, West Smithfield, London, UK.
²⁴ Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Abstract

Aims: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort.

Methods and results: A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1-16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48-2.78]. Model validation showed a Harrell's C-index of 0.745 (95% CI 0.52-0.97) and Uno's C-index 0.714 (95% 0.58-0.85) with a calibration slope of 1.15 (95% 0.51-1.80). A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60-0.81).

Conclusions: This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM.

Keywords: Hypertrophic cardiomyopathy; Paediatric; Risk stratification; Sudden death.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Cardiomyopathy, Hypertrophic* / complications
Cardiomyopathy, Hypertrophic* / diagnosis
Cardiomyopathy, Hypertrophic* / epidemiology
Child
Child, Preschool
Cohort Studies
Death, Sudden, Cardiac* / epidemiology
Death, Sudden, Cardiac* / etiology
Humans
Incidence
Infant
Retrospective Studies
Risk Assessment / methods
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding