Ventricular Repolarization During the Pregnancy-to-Postpartum Transition (QuTe)

Overview

Pregnancy and the postpartum period are accompanied by marked changes in heart rate, circulating hormones, and electrolyte balance that may influence ventricular repolarization. This prospective longitudinal study evaluated adult women during the third trimester of pregnancy and again after delivery, including healthy participants and a prespecified subgroup with congenital long QT syndrome (cLQTS). Standardized triplicate 12-lead electrocardiograms and concomitant blood samples were obtained at both visits. The prespecified primary objective was to quantify the within-participant change in the Fridericia-corrected QT interval (QTcF) from late pregnancy to postpartum. Secondary objectives were to examine associations between QTcF and circulating sex hormones. Additional exploratory analyses compared Bazett and Fridericia heart-rate correction methods and evaluated longitudinal and visit-specific associations between QTcF and biochemical and endocrine biomarkers.

This single-center prospective longitudinal cohort enrolled pregnant adult women during the third trimester, including healthy participants and women with cLQTS. Participants underwent a third-trimester visit (V1) and a postpartum follow-up visit (V2). No therapeutic intervention was assigned by the study. At each visit, three consecutive 10-second standard 12-lead electrocardiograms were recorded under standardized resting conditions. QT measurements were obtained using a semi-automated computer-assisted triplicate concatenation method with expert review of fiducial points. QT was corrected for heart rate using both Bazett (QTcB) and Fridericia (QTcF) formulas. The ECG outcome assessment was performed without knowledge of whether the recording was obtained during pregnancy or postpartum. Blood sampling was performed concomitantly with ECG acquisition. The biochemical and endocrine assessment included routine electrolytes and a broad panel of reproductive, thyroid, pituitary, placental, and adrenal biomarkers, including an LC-MS/MS steroid profile. The prespecified primary endpoint was the within-participant change in QTcF between V1 and V2. Prespecified secondary analyses evaluated associations between QTcF and progesterone, estradiol, testosterone, and follicle-stimulating hormone, including associations between within-participant hormone changes and QTcF changes. Exploratory analyses evaluated residual heart-rate dependence of QTcB and QTcF and screened an expanded biomarker panel using longitudinal and physiological-state-specific models.