Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids)

Gabrielle Norrish, Tao Ding, Ella Field, Lidia Ziólkowska, Iacopo Olivotto, Giuseppe Limongelli, Aristides Anastasakis, Robert Weintraub, Elena Biagini, Luca Ragni, Terence Prendiville, Sophie Duignan, Karen McLeod, Maria Ilina, Adrián Fernández, Regina Bökenkamp, Anwar Baban, Peter Kubuš, Piers E F Daubeney, Georgia Sarquella-Brugada & 29 others Sergi Cesar, Chiara Marrone, Vinay Bhole, Constancio Medrano, Orhan Uzun, Elspeth Brown, Ferran Gran, Francisco J Castro, Graham Stuart, Gabriele Vignati, Roberto Barriales-Villa, Luis G Guereta, Satish Adwani, Katie Linter, Tara Bharucha, Pablo Garcia-Pavia, Torsten B Rasmussen, Margherita M Calcagnino, Caroline B Jones, Hans De Wilde, J Toru-Kubo, Tiziana Felice, Jens Mogensen, Sujeev Mathur, Zdenka Reinhardt, Constantinos O'Mahony, Perry M Elliott, Rumana Z Omar, Juan P Kaski

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJAMA Cardiology
DOIs
Publication statusE-pub ahead of print - Aug 14 2019

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Hypertrophic Cardiomyopathy
Sudden Cardiac Death
Implantable Defibrillators
Ventricular Tachycardia
Validation Studies
Syncope
Heart Arrest
Calibration
Longitudinal Studies
Cohort Studies
Hemodynamics
Outcome Assessment (Health Care)
Pediatrics
Population

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Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids). / Norrish, Gabrielle; Ding, Tao; Field, Ella; Ziólkowska, Lidia; Olivotto, Iacopo; Limongelli, Giuseppe; Anastasakis, Aristides; Weintraub, Robert; Biagini, Elena; Ragni, Luca; Prendiville, Terence; Duignan, Sophie; McLeod, Karen; Ilina, Maria; Fernández, Adrián; Bökenkamp, Regina; Baban, Anwar; Kubuš, Peter; Daubeney, Piers E F; Sarquella-Brugada, Georgia; Cesar, Sergi; Marrone, Chiara; Bhole, Vinay; Medrano, Constancio; Uzun, Orhan; Brown, Elspeth; Gran, Ferran; Castro, Francisco J; Stuart, Graham; Vignati, Gabriele; Barriales-Villa, Roberto; Guereta, Luis G; Adwani, Satish; Linter, Katie; Bharucha, Tara; Garcia-Pavia, Pablo; Rasmussen, Torsten B; Calcagnino, Margherita M; Jones, Caroline B; De Wilde, Hans; Toru-Kubo, J; Felice, Tiziana; Mogensen, Jens; Mathur, Sujeev; Reinhardt, Zdenka; O'Mahony, Constantinos; Elliott, Perry M; Omar, Rumana Z; Kaski, Juan P.

In: JAMA Cardiology, 14.08.2019.

Research output: Contribution to journalArticle

Norrish, G, Ding, T, Field, E, Ziólkowska, L, Olivotto, I, Limongelli, G, Anastasakis, A, Weintraub, R, Biagini, E, Ragni, L, Prendiville, T, Duignan, S, McLeod, K, Ilina, M, Fernández, A, Bökenkamp, R, Baban, A, Kubuš, P, Daubeney, PEF, Sarquella-Brugada, G, Cesar, S, Marrone, C, Bhole, V, Medrano, C, Uzun, O, Brown, E, Gran, F, Castro, FJ, Stuart, G, Vignati, G, Barriales-Villa, R, Guereta, LG, Adwani, S, Linter, K, Bharucha, T, Garcia-Pavia, P, Rasmussen, TB, Calcagnino, MM, Jones, CB, De Wilde, H, Toru-Kubo, J, Felice, T, Mogensen, J, Mathur, S, Reinhardt, Z, O'Mahony, C, Elliott, PM, Omar, RZ & Kaski, JP 2019, 'Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids)', JAMA Cardiology. https://doi.org/10.1001/jamacardio.2019.2861
Norrish, Gabrielle ; Ding, Tao ; Field, Ella ; Ziólkowska, Lidia ; Olivotto, Iacopo ; Limongelli, Giuseppe ; Anastasakis, Aristides ; Weintraub, Robert ; Biagini, Elena ; Ragni, Luca ; Prendiville, Terence ; Duignan, Sophie ; McLeod, Karen ; Ilina, Maria ; Fernández, Adrián ; Bökenkamp, Regina ; Baban, Anwar ; Kubuš, Peter ; Daubeney, Piers E F ; Sarquella-Brugada, Georgia ; Cesar, Sergi ; Marrone, Chiara ; Bhole, Vinay ; Medrano, Constancio ; Uzun, Orhan ; Brown, Elspeth ; Gran, Ferran ; Castro, Francisco J ; Stuart, Graham ; Vignati, Gabriele ; Barriales-Villa, Roberto ; Guereta, Luis G ; Adwani, Satish ; Linter, Katie ; Bharucha, Tara ; Garcia-Pavia, Pablo ; Rasmussen, Torsten B ; Calcagnino, Margherita M ; Jones, Caroline B ; De Wilde, Hans ; Toru-Kubo, J ; Felice, Tiziana ; Mogensen, Jens ; Mathur, Sujeev ; Reinhardt, Zdenka ; O'Mahony, Constantinos ; Elliott, Perry M ; Omar, Rumana Z ; Kaski, Juan P. / Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids). In: JAMA Cardiology. 2019.
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abstract = "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.",
author = "Gabrielle Norrish and Tao Ding and Ella Field and Lidia Zi{\'o}lkowska and Iacopo Olivotto and Giuseppe Limongelli and Aristides Anastasakis and Robert Weintraub and Elena Biagini and Luca Ragni and Terence Prendiville and Sophie Duignan and Karen McLeod and Maria Ilina and Adri{\'a}n Fern{\'a}ndez and Regina B{\"o}kenkamp and Anwar Baban and Peter Kubuš and Daubeney, {Piers E F} and Georgia Sarquella-Brugada and Sergi Cesar and Chiara Marrone and Vinay Bhole and Constancio Medrano and Orhan Uzun and Elspeth Brown and Ferran Gran and Castro, {Francisco J} and Graham Stuart and Gabriele Vignati and Roberto Barriales-Villa and Guereta, {Luis G} and Satish Adwani and Katie Linter and Tara Bharucha and Pablo Garcia-Pavia and Rasmussen, {Torsten B} and Calcagnino, {Margherita M} and Jones, {Caroline B} and {De Wilde}, Hans and J Toru-Kubo and Tiziana Felice and Jens Mogensen and Sujeev Mathur and Zdenka Reinhardt and Constantinos O'Mahony and Elliott, {Perry M} and Omar, {Rumana Z} and Kaski, {Juan P}",
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TY - JOUR

T1 - Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids)

AU - Norrish, Gabrielle

AU - Ding, Tao

AU - Field, Ella

AU - Ziólkowska, Lidia

AU - Olivotto, Iacopo

AU - Limongelli, Giuseppe

AU - Anastasakis, Aristides

AU - Weintraub, Robert

AU - Biagini, Elena

AU - Ragni, Luca

AU - Prendiville, Terence

AU - Duignan, Sophie

AU - McLeod, Karen

AU - Ilina, Maria

AU - Fernández, Adrián

AU - Bökenkamp, Regina

AU - Baban, Anwar

AU - Kubuš, Peter

AU - Daubeney, Piers E F

AU - Sarquella-Brugada, Georgia

AU - Cesar, Sergi

AU - Marrone, Chiara

AU - Bhole, Vinay

AU - Medrano, Constancio

AU - Uzun, Orhan

AU - Brown, Elspeth

AU - Gran, Ferran

AU - Castro, Francisco J

AU - Stuart, Graham

AU - Vignati, Gabriele

AU - Barriales-Villa, Roberto

AU - Guereta, Luis G

AU - Adwani, Satish

AU - Linter, Katie

AU - Bharucha, Tara

AU - Garcia-Pavia, Pablo

AU - Rasmussen, Torsten B

AU - Calcagnino, Margherita M

AU - Jones, Caroline B

AU - De Wilde, Hans

AU - Toru-Kubo, J

AU - Felice, Tiziana

AU - Mogensen, Jens

AU - Mathur, Sujeev

AU - Reinhardt, Zdenka

AU - O'Mahony, Constantinos

AU - Elliott, Perry M

AU - Omar, Rumana Z

AU - Kaski, Juan P

PY - 2019/8/14

Y1 - 2019/8/14

N2 - 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.

AB - 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.

U2 - 10.1001/jamacardio.2019.2861

DO - 10.1001/jamacardio.2019.2861

M3 - Article

JO - JAMA Cardiology

JF - JAMA Cardiology

SN - 2380-6583

ER -