TY - JOUR
T1 - Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome
AU - Kaizer, Alexander M.
AU - Winbo, Annika
AU - Clur, Sally Ann B.
AU - Etheridge, Susan P.
AU - Ackerman, Michael J.
AU - Horigome, Hitoshi
AU - Herberg, Ulrike
AU - Dagradi, Federica
AU - Spazzolini, Carla
AU - Killen, Stacy A.S.
AU - Wacker-Gussmann, Annette
AU - Wilde, Arthur A.M.
AU - Sinkovskaya, Elena
AU - Abuhamad, Alfred
AU - Torchio, Margherita
AU - Ng, Chai Ann
AU - Rydberg, Annika
AU - Schwartz, Peter J.
AU - Cuneo, Bettina F.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Aims: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS. Methods and results: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-Adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity. Conclusion: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.
AB - Aims: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS. Methods and results: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-Adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity. Conclusion: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.
KW - Bradycardia
KW - Channelopathy
KW - Foetal arrhythmia
KW - Foetus
KW - Inherited arrhythmias
KW - Long QT syndrome
KW - Potassium currents
KW - Stillbirth
KW - Sudden death
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U2 - 10.1093/europace/euad319
DO - 10.1093/europace/euad319
M3 - Article
C2 - 37975542
AN - SCOPUS:85177987474
SN - 1099-5129
VL - 25
JO - Europace
JF - Europace
IS - 11
M1 - euad319
ER -