Heart Failure and Related Risk-factors After Preeclampsia

Heart Failure Clinical Trial

— QoH  

Official title:

Queen of Hearts Research Program. Identifying the Risk on Heart Failure After Preeclampsia.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02347540
• Other study ID #: METC 14-02-013
• Secondary ID: 2013T084
• Status: Enrolling by invitation
• Start date: December 2014
• Est. completion date: July 2025

Study information

• Verified date: July 2022
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is a cross-sectional case-control study where classical as well as more innovative risk factors for CVD will be explored. In western countries, more women than men die of cardiovascular disease (CVD), making CVD in women an important public health issue. Misdiagnosis of CVD in women is frequently observed, posing the clinician for diagnostic and therapeutic dilemmas that can easily result in inadequate treatment and worse prognosis. Despite these challenges, CVD in women has been underexposed in scientific research. Women have gender-specific risk factors like a history of preeclampsia (PE) that contribute to their risk for CVD. PE complicates 5-10% of pregnancies, recurs in ~25% and is associated with a 2-4 fold increased risk for CVD. Moreover, pre-symptomatic heart failure (HF) stage B occurs in 40% of women with a history of PE. HF stage B is thought to precede the development of the, mortality related, clinical HF stages C and D (structural heart disease in combination with symptomatic disease). Early detection and tailored intervention of women with stage B HF decreases progression to the clinical stages and might therefore improve clinical outcome and cardiovascular related mortality. Phenotypic presentation of HF is currently split up between systolic HF also called HF with reduced ejection fraction (HFrEF) and diastolic HF or HF with preserved ejection fraction (HFpEF). Women more often have HFpEF in contrast to men. Different pathophysiology and disease progression in women compared to men seems to be an important underlying factor. The current clinical HF diagnostic tools (e.g. natriuretic hormones and high sensitivity troponins) fail to identify early changes that prelude adverse cardiac remodelling and HF, and do not discriminate between HFrEF and HFpEF. Moreover, there are sex-related differences in biomarker levels for detection of CVD. As a result, clinicians are forced to wait for the failing heart to become clinically evident before they can intervene. Therefore, there is an urgent need to assess novel biomarkers that could help select high risk women needing further follow up and intervention. Biomarkers may not only improve early diagnosis but may also unravel disease pathways of HFpEF. Especially when combined with measurements of subclinical, surrogate risk markers. Objectives - To determine the impact of PE on incidence of macro-and micro-vascular dysfunction reflected by surrogate measures for coronary artery disease (CAD) and HFpEF. - To perform a genome wide association study (GWAS) and associate novel biomarker expression levels with endothelial function, cardiac diastolic function and IMT measurement. - To identify risk factors and surrogate measures for CVD in a) former PE patients without HFpEF, b) former PE patients with HFpEF and c) healthy parous controls. Study population Cases: women with a history of PE Controls: women with uncomplicated pregnancies in the history. Measurements will be performed in clusters at postpartum intervals of: ½-2, 5-10, 10-15 and 15-30 years. Number of inclusions will be: 425, 350, 282 and 233 for each follow-up group respectively. Primary endpoints The prevalence of macro- and microvascular dysfunction in former PE patients. Novel biomarker detection in former PE patients associated with HF in general and HFpEF in particular. Secondary endpoints - Lifestyle (questionnaire) - Cognitive ability (questionnaire) - Depression score (questionnaire) - Metabolic syndrome (MetS) - Arterial endothelial function (Flow mediated dilation (FMD)) - Intima Media Thickness (IMT) - Glycocalyx thickness (by means of the Glycocheck) - Venous function (plethysmograph) - Electrocardiogram (ECG) - Ergometry

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 2580
• Est. completion date: July 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Cases

• Women aged = 18 years
• ½ till 30 years after the complicated pregnancy
• Experienced PE in any pregnancy. PE defined as hypertension (systolic BP = 140 mmHg and/or diastolic BP = 90 mmHg) developed after 20 weeks of pregnancy with the development of proteinuria (= 300 mg/ 24 hours).
• Women who had their last delivery at least 6 months ago. Controls
• Women aged = 18 years
• ½ till 30 years after the pregnancy that matches the sequence number of pregnancy of the specifically matched case.
• Experienced pregnancies that were not complicated by foetal or maternal placental syndrome (pregnancy induced hypertension, preeclampsia, HELLP-syndrome).
• Women who had their last pregnancy at least 6 months ago.
• Women with a negative family history for PE (mother and sisters did not experience PE). Exclusion Criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: Cases
• Women with auto-immune diseases prior to the complicated pregnancy.
• Chronic hypertension prior to the complicated pregnancy.
• Renal disease prior to the complicated pregnancy.
• Pregnant women
• Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results.

Control group:

• Women with auto-immune diseases
• Chronic hypertension prior to the matched pregnancy.
• Women with IUGR in the matching pregnancy (p<10)
• Solutio placentae in the matching pregnancy
• Pregnant women
• Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Eclampsia
• Heart Failure
• Pre-Eclampsia

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (6)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Amsterdam UMC, location VUmc, Dutch Heart Foundation, Leiden University Medical Center, UMC Utrecht, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The prevalence of Heart Failure (number with percentage)	Heart Failure will be assessed with the transthoracic echocardiography based on the criteria of the American Heart Association. The sub classification for Heart Failure with preserved ejection fraction (EF) will be made (EF >55%)	At time of assessment
Secondary	Structural en Functional Cardiac Measurements	The objective is to estimate structural and functional cardiac measurements with the TTE based on the ASA guidelines.	At time of assessment
Secondary	Metabolic syndrome	The objective is to assess the prevalence of constituents of the Metabolic syndrome based on the WHO criteria. The prevalence will be reported in number with percentage.	At time of assessment
Secondary	Arterial endothelial function (Flow mediated dilation (FMD))	The objective is to estimate NO mediated endothelial function of the brachial artery with ultrasound by FMD and sublingual NTG administration. FMD will be reported in relative increase in diameter (%).	At time of assessment
Secondary	Common Carotid Intima media thickness	The objective is to estimate IMT of the common carotid artery in cm using ultrasound.	At time of assessment
Secondary	Glycocalyx thickness en microvascular tortuosity	The objective is to estimate the glycocalyx dimensions using sublingual orthogonal polarization spectral (OPS) measurements. Derivative of the glycocalyx (perfused boundary region) will be reported in um. Tortuosity will be reported based on a score system.	At time of assessment
Secondary	Cognitive, Lifestyle and Depression rates	To evaluate subjective cognitive functioning and depression rates and lifestyle behavior in formerly preeclamptic women with heart failure compared to controls.	At time of assessment