Long QT Syndrome, Pregnancy
Conditions
Keywords
Postpartum period, ventricular repolarization, QT interval, QTcF, Fridericia correction, QTcB, Bazett correction, sex hormones, cLQTS, calcium, potassium, SHBG
Brief summary
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.
Detailed description
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.
Interventions
OTHEREvaluation of QT interval duration
ECG to evaluation of QT interval duration
OTHERCirculating sex hormones levels sample
Association between circulating sex hormones levels (progesterone, estradiol, testosterone, FSH) and QTcF duration (univariate and multivariate analysis).
Sponsors
French Cardiology Society
Clinical Investigation Center Paris-Est (CIC-2503), AP-HP / INSERM
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fridericia-Corrected QT Interval (QTcF) From Late Pregnancy to Postpartum | Third-trimester visit and postpartum follow-up visit. Planned window: 30-38 weeks' gestation and 2 weeks-12 months after delivery. | Within-participant postpartum minus third-trimester QTcF, in milliseconds, measured from standardized triplicate 12-lead ECGs using a semi-automated computer-assisted method with expert review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association Between Circulating Sex Hormone Concentrations and QTcF | Third-trimester visit and postpartum follow-up visit. | Univariable and multivariable associations of progesterone, estradiol, testosterone, and follicle-stimulating hormone concentrations with QTcF at the pregnancy and postpartum visits. |
| Association Between Within-Participant Changes in Sex Hormones and Change in QTcF | From the third-trimester visit to the postpartum follow-up visit. | Association between pregnancy-to-postpartum changes in progesterone, estradiol, testosterone, and follicle-stimulating hormone concentrations and the within-participant change in QTcF. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORJoe-Elie SALEM, MD PHD
Centre d'investigation Clinique - Paris est
Outcome results
None listed