Genotype predicts outcomes in fetuses and neonates with severe congenital long QT syndrome

Jeremy P Moore; Roberto G Gallotti; Kevin M Shannon; J Martijn Bos; Elham Sadeghi; Janette F Strasburger; Ronald T Wakai; Hitoshi Horigome; Sally-Ann Clur; Allison C Hill; Maully J Shah; Shashank Behere; Georgia Sarquella-Brugada; Richard Czosek; Susan P Etheridge; Peter Fischbach; Prince J Kannankeril; Kara Motonaga; Andrew P Landstrom; Matthew Williams; Akash Patel; Federica Dagradi; Reina B Tan; Elizabeth Stephenson; Mani Ram Krishna; Christina Y Miyake; Michelle E Lee; Shubhayan Sanatani; Seshadri Balaji; Ming-Lon Young; Saad Siddiqui; Peter J Schwartz; Kalyanam Shivkumar; Michael J Ackerman

doi:10.1016/j.jacep.2020.06.001

Genotype predicts outcomes in fetuses and neonates with severe congenital long QT syndrome

Jeremy P Moore, Roberto G Gallotti, Kevin M Shannon, J Martijn Bos, Elham Sadeghi, Janette F Strasburger, Ronald T Wakai, Hitoshi Horigome, Sally-Ann Clur, Allison C Hill, Maully J Shah, Shashank Behere, Georgia Sarquella-Brugada, Richard Czosek, Susan P Etheridge, Peter Fischbach, Prince J Kannankeril, Kara Motonaga, Andrew P Landstrom, Matthew WilliamsAkash Patel, Federica Dagradi, Reina B Tan, Elizabeth Stephenson, Mani Ram Krishna, Christina Y Miyake, Michelle E Lee, Shubhayan Sanatani, Seshadri Balaji, Ming-Lon Young, Saad Siddiqui, Peter J Schwartz, Kalyanam Shivkumar, Michael J Ackerman

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Research output: Contribution to journal › Article

Abstract

OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs).

BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown.

METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death.

RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001).

CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

Original language	American English
Journal	JACC Clinical Electrophysiology
DOIs	https://doi.org/10.1016/j.jacep.2020.06.001
Status	Published - Nov 1 2020

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Moore, J. P., Gallotti, R. G., Shannon, K. M., Bos, J. M., Sadeghi, E., Strasburger, J. F., Wakai, R. T., Horigome, H., Clur, S.-A., Hill, A. C., Shah, M. J., Behere, S., Sarquella-Brugada, G., Czosek, R., Etheridge, S. P., Fischbach, P., Kannankeril, P. J., Motonaga, K., Landstrom, A. P., ... Ackerman, M. J. (2020). Genotype predicts outcomes in fetuses and neonates with severe congenital long QT syndrome. JACC Clinical Electrophysiology. https://doi.org/10.1016/j.jacep.2020.06.001

Moore, JP, Gallotti, RG, Shannon, KM, Bos, JM, Sadeghi, E, Strasburger, JF, Wakai, RT, Horigome, H, Clur, S-A, Hill, AC, Shah, MJ, Behere, S, Sarquella-Brugada, G, Czosek, R, Etheridge, SP, Fischbach, P, Kannankeril, PJ, Motonaga, K, Landstrom, AP, Williams, M, Patel, A, Dagradi, F, Tan, RB, Stephenson, E, Krishna, MR, Miyake, CY, Lee, ME, Sanatani, S, Balaji, S, Young, M-L, Siddiqui, S, Schwartz, PJ, Shivkumar, K & Ackerman, MJ 2020, 'Genotype predicts outcomes in fetuses and neonates with severe congenital long QT syndrome', JACC Clinical Electrophysiology. https://doi.org/10.1016/j.jacep.2020.06.001

@article{55bb054425d048369931a8e8fa9059e4,

title = "Genotype predicts outcomes in fetuses and neonates with severe congenital long QT syndrome",

abstract = "OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.",

author = "Moore, {Jeremy P} and Gallotti, {Roberto G} and Shannon, {Kevin M} and Bos, {J Martijn} and Elham Sadeghi and Strasburger, {Janette F} and Wakai, {Ronald T} and Hitoshi Horigome and Sally-Ann Clur and Hill, {Allison C} and Shah, {Maully J} and Shashank Behere and Georgia Sarquella-Brugada and Richard Czosek and Etheridge, {Susan P} and Peter Fischbach and Kannankeril, {Prince J} and Kara Motonaga and Landstrom, {Andrew P} and Matthew Williams and Akash Patel and Federica Dagradi and Tan, {Reina B} and Elizabeth Stephenson and Krishna, {Mani Ram} and Miyake, {Christina Y} and Lee, {Michelle E} and Shubhayan Sanatani and Seshadri Balaji and Ming-Lon Young and Saad Siddiqui and Schwartz, {Peter J} and Kalyanam Shivkumar and Ackerman, {Michael J}",

year = "2020",

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doi = "10.1016/j.jacep.2020.06.001",

language = "American English",

journal = "JACC Clinical Electrophysiology",

}

TY - JOUR

T1 - Genotype predicts outcomes in fetuses and neonates with severe congenital long QT syndrome

AU - Moore, Jeremy P

AU - Gallotti, Roberto G

AU - Shannon, Kevin M

AU - Bos, J Martijn

AU - Sadeghi, Elham

AU - Strasburger, Janette F

AU - Wakai, Ronald T

AU - Horigome, Hitoshi

AU - Clur, Sally-Ann

AU - Hill, Allison C

AU - Shah, Maully J

AU - Behere, Shashank

AU - Sarquella-Brugada, Georgia

AU - Czosek, Richard

AU - Etheridge, Susan P

AU - Fischbach, Peter

AU - Kannankeril, Prince J

AU - Motonaga, Kara

AU - Landstrom, Andrew P

AU - Williams, Matthew

AU - Patel, Akash

AU - Dagradi, Federica

AU - Tan, Reina B

AU - Stephenson, Elizabeth

AU - Krishna, Mani Ram

AU - Miyake, Christina Y

AU - Lee, Michelle E

AU - Sanatani, Shubhayan

AU - Balaji, Seshadri

AU - Young, Ming-Lon

AU - Siddiqui, Saad

AU - Schwartz, Peter J

AU - Shivkumar, Kalyanam

AU - Ackerman, Michael J

PY - 2020/11/1

Y1 - 2020/11/1

N2 - OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

AB - OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

U2 - 10.1016/j.jacep.2020.06.001

DO - 10.1016/j.jacep.2020.06.001

M3 - Article

JO - JACC Clinical Electrophysiology

JF - JACC Clinical Electrophysiology

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