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

Study Overview

• Status: Completed
• Conditions: Pregnancy; Long QT Syndrome
• Intervention / Treatment: Other: Evaluation of QT interval duration; Other: Circulating sex hormones levels sample

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.

• Study Type: Observational
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Clinical Investigation Center Paris-Est, Pitié-Salpêtrière University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consisted of women recruited in collaboration with the Department of Obstetrics and Gynecology. Eligible participants were prospectively included in the study and underwent the clinical investigations planned as part of the research at the Clinical Investigation Center (CIC) Paris Est, Pitié-Salpêtrière Hospital.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy pregnant women; Adult pregnant women without cLQTS. Seventy-eight were enrolled; two were excluded at the first visit, leaving 76 eligible for analysis; 62 completed the postpartum assessment.	Other: Evaluation of QT interval duration; ECG to evaluation of QT interval duration; Other: Circulating sex hormones levels sample; Association between circulating sex hormones levels (progesterone, estradiol, testosterone, FSH) and QTcF duration (univariate and multivariate analysis).
Pregnant women with cLQTS; Adult pregnant women with congenital long QT syndrome. Twelve were enrolled and included at the first visit; 10 completed the postpartum assessment. Clinically indicated antiarrhythmic/beta-blocker therapy was permitted.	Other: Evaluation of QT interval duration; ECG to evaluation of QT interval duration; Other: Circulating sex hormones levels sample; Association between circulating sex hormones levels (progesterone, estradiol, testosterone, FSH) and QTcF duration (univariate and multivariate analysis).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fridericia-Corrected QT Interval (QTcF) From Late Pregnancy to Postpartum	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.	Third-trimester visit and postpartum follow-up visit. Planned window: 30-38 weeks' gestation and 2 weeks-12 months after delivery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between Circulating Sex Hormone Concentrations and QTcF	Univariable and multivariable associations of progesterone, estradiol, testosterone, and follicle-stimulating hormone concentrations with QTcF at the pregnancy and postpartum visits.	Third-trimester visit and postpartum follow-up visit.
Association Between Within-Participant Changes in Sex Hormones and Change in QTcF	Association between pregnancy-to-postpartum changes in progesterone, estradiol, testosterone, and follicle-stimulating hormone concentrations and the within-participant change in QTcF.	From the third-trimester visit to the postpartum follow-up visit.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Residual Heart-Rate Dependence of Bazett and Fridericia QT Corrections	Pearson correlations between within-participant change in RR interval and the corresponding changes in QTcB and QTcF.	From the third-trimester visit to the postpartum follow-up visit.
Longitudinal and Visit-Specific Associations Between QTcF and an Expanded Biochemical and Endocrine Biomarker Panel	Exploratory adjusted longitudinal and visit-specific associations between standardized biomarkers and QTcF, with analytical censoring rules, collinearity screening, and BIC-based candidate-model comparison.	Third-trimester and postpartum visits.

Collaborators and Investigators

• Sponsor: French Cardiology Society
• Collaborators: Clinical Investigation Center Paris-Est (CIC-2503), AP-HP / INSERM
• Investigators: Principal Investigator: Joe-Elie SALEM, MD PHD, Centre d'investigation Clinique - Paris est

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Actual): October 19, 2021
• Study Completion (Actual): February 3, 2026

Study Registration Dates

• First Submitted: September 15, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimated): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: potassium; QT interval; calcium; Postpartum period; ventricular repolarization; sex hormones; QTcF; SHBG; Fridericia correction; QTcB; Bazett correction; cLQTS
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Long QT Syndrome; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2016-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No