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

Ventricular Repolarization During the Pregnancy-to-Postpartum Transition: A Longitudinal Comparison of QT Correction Methods and Hormonal Correlates

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.

Inclusion Criteria:

• Female participant aged 18 years or older.
• Pregnant at the third-trimester inclusion visit (protocol window: 30-38 weeks of gestation).
• Affiliated with the French social security system.
• Able to understand French and provide written informed consent.
• Healthy pregnant women and pregnant women with congenital long QT syndrome were eligible.

Exclusion Criteria:

• Treatment known to modify QT duration, except beta-blockers clinically indicated antiarrhythmic treatment for congenital long QT syndrome.
• History of cardiac disease, except hypertension or congenital long QT syndrome (whether treated or untreated).
• History of endocrine disease, except non-insulin-requiring diabetes.
• Bundle branch block or QRS duration greater than 120 milliseconds.

Post-Inclusion Exclusion Criteria:

• Ventricular repolarization not interpretable on the ECG.
• Hormonal treatment or QT-modifying treatment initiated after inclusion and still active at the postpartum visit.
• Cardiovascular complication occurring after inclusion and still active at the postpartum visit.

Exclusion Criteria:

• Uninterpretable ventricular repolarization.
• Hormonal or QT-modifying treatment still active at V2.
• Cardiovascular complication that occurred after V1 and was still ongoing at V2.