Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids)
Language English Country United States Media print
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
Grant support
FS/16/72/32270
British Heart Foundation - United Kingdom
Department of Health - United Kingdom
PubMed
31411652
PubMed Central
PMC6694401
DOI
10.1001/jamacardio.2019.2861
PII: 2747608
Knihovny.cz E-resources
- MeSH
- Child MeSH
- Risk Assessment methods MeSH
- Cardiomyopathy, Hypertrophic complications mortality MeSH
- Incidence MeSH
- Humans MeSH
- Survival Rate trends MeSH
- Adolescent MeSH
- Death, Sudden, Cardiac epidemiology etiology MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe epidemiology MeSH
IMPORTANCE: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. OBJECTIVE: To develop and validate an SCD risk prediction model that provides individualized risk estimates. DESIGN, SETTING, AND PARTICIPANTS: A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017. EXPOSURES: The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping. MAIN OUTCOMES AND MEASURES: A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise). RESULTS: Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95% CI, 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years. CONCLUSIONS AND RELEVANCE: This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.
Cardiology Unit IRCCS Ospedale Maggiore Policlinico Milan Italy
Cardiothoracovascular Department Careggi University Hospital Florence Italy
Children's Heart Centre University Hospital Motol Prague Czech Republic
Children's Heart Service Evelina Children's Hospital London United Kingdom
Children's Heart Unit University Hospital of Wales Cardiff United Kingdom
Department of Ambulatory Cardiology Favaloro Foundation University Hospital Buenos Aires Argentina
Department of Cardiology Aarhus University Hospital Aarhus Denmark
Department of Cardiology Alder Hey Children's Hospital Liverpool United Kingdom
Department of Cardiology and Geriatrics Kochi Medical School Kochi University Kochi Japan
Department of Cardiology Odense University Hospital Odense Denmark
Department of Cardiology Onassis Cardiac Surgery Center Athens Greece
Department of Cardiology S Orsola Malpighi Hospital Bologna Italy
Department of Cardiology The Children's Memorial Health Institute Warsaw Poland
Department of Cardiology The Royal Children's Hospital Melbourne Australia
Department of Cardiology University Francisco de Vitoria Pozuelo de Alarcon Spain
Department of Cardiology University Hospital La Paz Madrid Spain
Department of Cardiology University Hospital Virgen de la Arrixaca Murcia Spain
Department of Cardiology University Hospitals Parma Parma Italy
Department of Cardiothoracic Sciences Monaldi Hospital Naples Italy
Department of Clinical Sciences The Murdoch Children's Research Institute Parkville Australia
Department of Medical and Health Sciences University of Melbourne Melbourne Australia
Department of Paediatric Cardiology and Cardiac Surgery Bambino Gesu Hospital Rome Italy
Department of Paediatric Cardiology Bristol Royal Hospital for Children Bristol United Kingdom
Department of Paediatric Cardiology Ghent University Hospital Ghent Belgium
Department of Paediatric Cardiology Glenfield Hospital Leicester United Kingdom
Department of Paediatric Cardiology Hospital General Universitario Gregorio Marañón Madrid Spain
Department of Paediatric Cardiology John Radcliffe Hospital Oxford United Kingdom
Department of Paediatric Cardiology Leeds General Infirmary Leeds United Kingdom
Department of Paediatric Cardiology Leiden University Medical Center Leiden the Netherlands
Department of Paediatric Cardiology Mater Dei Hospital Msida Malta
Department of Paediatric Cardiology Papa Giovanni XXIII Hospital Bergamo Italy
Department of Paediatric Cardiology Royal Brompton and Harefield NHS Trust London United Kingdom
Department of Paediatric Cardiology Royal Hospital for Children Glasgow United Kingdom
Department of Paediatric Cardiology Southampton General Hospital Southampton United Kingdom
Department of Paediatric Cardiology The Freeman Hospital Newcastle United Kingdom
Department of Statistical Science University College London London United Kingdom
European Reference Network for Rare and Complex Diseases of the Heart Amsterdam the Netherlands
Institute of Cardiovascular Sciences University College London London United Kingdom
Medical Sciences Department School of Medicine University of Girona Girona Spain
Paediatric Cardiology Department Val d'Hebron University Hospital Barcelona Spain
Paediatric Cardiology Unit Niguarda Hospital Milan Italy
The Children's Heart Centre Our Lady's Children's Hospital Dublin Ireland
The Heart Unit Birmingham Children's Hospital Birmingham United Kingdom
See more in PubMed
Colan SD, Lipshultz SE, Lowe AM, et al. . Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation. 2007;115(6):773-781. doi:10.1161/CIRCULATIONAHA.106.621185 PubMed DOI
Alexander PMA, Nugent AW, Daubeney PEF, et al. ; National Australian Childhood Cardiomyopathy Study . Long-term outcomes of hypertrophic cardiomyopathy diagnosed during childhood: results from a national population-based study. Circulation. 2018;138(1):29-36. doi:10.1161/CIRCULATIONAHA.117.028895 PubMed DOI
Norrish G, Field E, Mcleod K, et al. . Clinical presentation and survival of childhood hypertrophic cardiomyopathy: a retrospective study in United Kingdom. Eur Heart J. 2019;40(12):986-993. doi:10.1093/eurheartj/ehy798 PubMed DOI PMC
Gersh BJ, Maron BJ, Bonow RO, et al. ; American College of Cardiology Foundation/American Heart Association Task Force on Practice; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons . 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg. 2011;142(6):e153-e203. doi:10.1016/j.jtcvs.2011.10.020 PubMed DOI
Elliott PM, Anastasakis A, Borger MA, et al. ; Authors/Task Force Members . 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733-2779. doi:10.1093/eurheartj/ehu284 PubMed DOI
Norrish G, Ding T, Field E, et al. . A validation study of the European Society of Cardiology guidelines for risk stratification of sudden cardiac death in childhood hypertrophic cardiomyopathy. [published online June 1, 2019]. Europace. 2019;euz118. doi:10.1093/europace/euz118 PubMed DOI PMC
O’Mahony C, Tome-Esteban M, Lambiase PD, et al. . A validation study of the 2003 American College of Cardiology/European Society of Cardiology and 2011 American College of Cardiology Foundation/American Heart Association risk stratification and treatment algorithms for sudden cardiac death in patients with hypertrophic cardiomyopathy. Heart. 2013;99(8):534-541. doi:10.1136/heartjnl-2012-303271 PubMed DOI
O’Mahony C, Jichi F, Pavlou M, et al. ; Hypertrophic Cardiomyopathy Outcomes Investigators . A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD). Eur Heart J. 2014;35(30):2010-2020. doi:10.1093/eurheartj/eht439 PubMed DOI
Fernández A, Quiroga A, Ochoa JP, et al. . Validation of the 2014 European Society of Cardiology sudden cardiac death risk prediction model in hypertrophic cardiomyopathy in a reference center in South America. Am J Cardiol. 2016;118(1):121-126. doi:10.1016/j.amjcard.2016.04.021 PubMed DOI
Maron BJ, Casey SA, Chan RH, Garberich RF, Rowin EJ, Maron MS. Independent assessment of the European Society of Cardiology sudden death risk model for hypertrophic cardiomyopathy. Am J Cardiol. 2015;116(5):757-764. doi:10.1016/j.amjcard.2015.05.047 PubMed DOI
O’Mahony C, Jichi F, Ommen SR, et al. . International external validation study of the 2014 European Society of Cardiology guidelines on sudden cardiac death prevention in hypertrophic cardiomyopathy (EVIDENCE-HCM). Circulation. 2018;137(10):1015-1023. doi:10.1161/CIRCULATIONAHA.117.030437 PubMed DOI
Vriesendorp PA, Schinkel AF, Liebregts M, et al. . Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol. 2015;8(4):829-835. doi:10.1161/CIRCEP.114.002553 PubMed DOI
Ross RD. The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision. Pediatr Cardiol. 2012;33(8):1295-1300. doi:10.1007/s00246-012-0306-8 PubMed DOI
Moak JP, Leifer ES, Tripodi D, Mohiddin SA, Fananapazir L. Long-term follow-up of children and adolescents diagnosed with hypertrophic cardiomyopathy: risk factors for adverse arrhythmic events. Pediatr Cardiol. 2011;32(8):1096-1105. doi:10.1007/s00246-011-9967-y PubMed DOI
Ziółkowska L, Turska-Kmieć A, Petryka J, Kawalec W. Predictors of long-term outcome in children with hypertrophic cardiomyopathy. Pediatr Cardiol. 2016;37(3):448-458. doi:10.1007/s00246-015-1298-y PubMed DOI PMC
Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna WJ. Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. J Am Coll Cardiol. 2003;42(5):873-879. doi:10.1016/S0735-1097(03)00827-1 PubMed DOI
Maron MS, Olivotto I, Betocchi S, et al. . Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003;348(4):295-303. doi:10.1056/NEJMoa021332 PubMed DOI
Elliott PM, Poloniecki J, Dickie S, et al. . Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol. 2000;36(7):2212-2218. doi:10.1016/S0735-1097(00)01003-2 PubMed DOI
Norrish G, Cantarutti N, Pissaridou E, et al. . Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: a systematic review and meta-analysis. Eur J Prev Cardiol. 2017;24(11):1220-1230. doi:10.1177/2047487317702519 PubMed DOI
Criteria Committee of the New York Heart Association; New York Heart Association . Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed New York, NY: Little Brown; 1994.
Maron BJ, Spirito P, Ackerman MJ, et al. . Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013;61(14):1527-1535. doi:10.1016/j.jacc.2013.01.037 PubMed DOI
Lopez L, Colan S, Stylianou M, et al. ; Pediatric Heart Network Investigators . Relationship of echocardiographic z scores adjusted for body surface area to age, sex, race, and ethnicity: the Pediatric Heart Network Normal Echocardiogram Database. Circ Cardiovasc Imaging. 2017;10(11):e006979. doi:10.1161/CIRCIMAGING.117.006979 PubMed DOI PMC
Neilan TG, Pradhan AD, King ME, Weyman AE. Derivation of a size-independent variable for scaling of cardiac dimensions in a normal paediatric population. Eur J Echocardiogr. 2009;10(1):50-55. doi:10.1093/ejechocard/jen110 PubMed DOI PMC
Bailey BJ, Briars GL. Estimating the surface area of the human body. Stat Med. 1996;15(13):1325-1332. doi:10.1002/(SICI)1097-0258(19960715)15:13<1325::AID-SIM233>3.0.CO;2-K PubMed DOI
van Buuren S, Boshuizen HC, Knook DL. Multiple imputation of missing blood pressure covariates in survival analysis. Stat Med. 1999;18(6):681-694. doi:10.1002/(SICI)1097-0258(19990330)18:6<681::AID-SIM71>3.0.CO;2-R PubMed DOI
White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30(4):377-399. doi:10.1002/sim.4067 PubMed DOI
Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York, NY: Wiley Classics Library; 2004.
Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis; II: accuracy and precision of regression estimates. J Clin Epidemiol. 1995;48(12):1503-1510. doi:10.1016/0895-4356(95)00048-8 PubMed DOI
Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69(1):239-241. doi:10.1093/biomet/69.1.239 DOI
White H. A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity. Econometrica. 1980;48(4):817-838. doi:10.2307/1912934 DOI
Harrell F. Regression Modeling Strategies. New York, NY: Springer; 2001. doi:10.1007/978-1-4757-3462-1 DOI
Steyerberg EW. Clinical Prediction Modes: A Practical Approach to Development, Validation, and Updating. New York, NY: Springer; 2009. doi:10.1007/978-0-387-77244-8 DOI
Uno H, Cai T, Pencina MJ, D’Agostino RB, Wei LJ. On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med. 2011;30(10):1105-1117. doi:10.1002/sim.4154 PubMed DOI PMC
Rahman MS, Ambler G, Choodari-Oskooei B, Omar RZ. Review and evaluation of performance measures for survival prediction models in external validation settings. BMC Med Res Methodol. 2017;17(1):60. doi:10.1186/s12874-017-0336-2 PubMed DOI PMC
Nugent AW, Daubeney PE, Chondros P, et al. ; National Australian Childhood Cardiomyopathy Study . The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med. 2003;348(17):1639-1646. doi:10.1056/NEJMoa021737 PubMed DOI
Kaski JP, Syrris P, Esteban MT, et al. . Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2009;2(5):436-441. doi:10.1161/CIRCGENETICS.108.821314 PubMed DOI
Morita H, Rehm HL, Menesses A, et al. . Shared genetic causes of cardiac hypertrophy in children and adults. N Engl J Med. 2008;358(18):1899-1908. doi:10.1056/NEJMoa075463 PubMed DOI PMC
Bharucha T, Lee KJ, Daubeney PE, et al. ; NACCS (National Australian Childhood Cardiomyopathy Study) Investigators . Sudden death in childhood cardiomyopathy: results from a long-term national population-based study. J Am Coll Cardiol. 2015;65(21):2302-2310. doi:10.1016/j.jacc.2015.03.552 PubMed DOI
Ho CY, Day SM, Ashley EA, et al. . Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation. 2018;138(14):1387-1398. doi:10.1161/CIRCULATIONAHA.117.033200 PubMed DOI PMC
Lipshultz SE, Orav EJ, Wilkinson JD, et al. ; Pediatric Cardiomyopathy Registry Study Group . Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry. Lancet. 2013;382(9908):1889-1897. doi:10.1016/S0140-6736(13)61685-2 PubMed DOI PMC
Maurizi N, Passantino S, Spaziani G, et al. . Long-term outcomes of pediatric-onset hypertrophic cardiomyopathy and age-specific risk factors for lethal arrhythmic events. JAMA Cardiol. 2018;3(6):520-525. doi:10.1001/jamacardio.2018.0789 PubMed DOI PMC
Balaji S, DiLorenzo MP, Fish FA, et al. . Risk factors for lethal arrhythmic events in children and adolescents with hypertrophic cardiomyopathy and an implantable defibrillator: an international multicenter study [published online April 23, 2019]. Heart Rhythm. 2019;S1547-5271(19)30369-8. doi:10.1016/j.hrthm.2019.04.040 PubMed DOI
Kaski JP, Tomé Esteban MT, Lowe M, et al. . Outcomes after implantable cardioverter-defibrillator treatment in children with hypertrophic cardiomyopathy. Heart. 2007;93(3):372-374. doi:10.1136/hrt.2006.094730 PubMed DOI PMC
Axelsson Raja A, Farhad H, Valente AM, et al. . Prevalence and progression of late gadolinium enhancement in children and adolescents with hypertrophic cardiomyopathy. Circulation. 2018;138(8):782-792. doi:10.1161/CIRCULATIONAHA.117.032966 PubMed DOI PMC
Ostman-Smith I, Wisten A, Nylander E, et al. . Electrocardiographic amplitudes: a new risk factor for sudden death in hypertrophic cardiomyopathy. Eur Heart J. 2010;31(4):439-449. doi:10.1093/eurheartj/ehp443 PubMed DOI PMC
von Gunten S, Schaer BA, Yap SC, et al. . Longevity of implantable cardioverter defibrillators: a comparison among manufacturers and over time. Europace. 2016;18(5):710-717. doi:10.1093/europace/euv296 PubMed DOI PMC
Atallah J, Erickson CC, Cecchin F, et al. ; Pediatric and Congenital Electrophysiology Society (PACES) . Multi-institutional study of implantable defibrillator lead performance in children and young adults: results of the Pediatric Lead Extractability and Survival Evaluation (PLEASE) study. Circulation. 2013;127(24):2393-2402. doi:10.1161/CIRCULATIONAHA.112.001120 PubMed DOI
Nugent AW, Daubeney PE, Chondros P, et al. ; National Australian Childhood Cardiomyopathy Study . Clinical features and outcomes of childhood hypertrophic cardiomyopathy: results from a national population-based study. Circulation. 2005;112(9):1332-1338. doi:10.1161/CIRCULATIONAHA.104.530303 PubMed DOI
Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy