Details

Autor(en) / Beteiligte

• Kaizer, Alexander M
• Winbo, Annika
• Clur, Sally-Ann B
• Etheridge, Susan P
• Ackerman, Michael J
• Horigome, Hitoshi
• Herberg, Ulrike
• Dagradi, Federica
• Spazzolini, Carla
• Killen, Stacy A S
• Wacker-Gussmann, Annette
• Wilde, Arthur A M
• Sinkovskaya, Elena
• Abuhamad, Alfred
• Torchio, Margherita
• Ng, Chai-Ann
• Rydberg, Annika
• Schwartz, Peter J
• Cuneo, Bettina F

Titel

Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome

Ist Teil von

• Europace (London, England), 2023-11, Vol.25 (11)

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract 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. Graphical Abstract Graphical Abstract Summary of findings from the manuscript.