Gender Difference in NET Activation in Patients With Congenital Heart Disease and Heart Failure

NCT05263843 | Unknown

• 1 other identifier: APHP211359
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

Neutrophil hyperactivation has detrimental effects on cardiac tissue after injuries, leading to fibrosis lesions and cardiac dysfunction. It is now well-established that women present with different clinical symptoms in cardiovascular disease compared to men. A cardioprotective effect in women has been suggested in some studies including patients with congenital heart disease (CHD) and heart failure. Our hypothesis is that estrogen protects the hearts of female patients aged 18-45 with CHD. There is no information available as to the involvement of neutrophils in heart failure in females compared to male patients, and therefore this study will provide important information for both the CHD and neutrophil biology fields comparing NET activation in women and men with severe CHD.

Conditions

Congenital Heart Disease; Heart Failure; Gender

Keywords

Congenital heart disease; Heart failure; Gender; Fibrosis; Inflammation

Outcome Measures

Primary Outcomes (1)

• NET activation levels and PAD4 Levels

  Measurements of MPO-DNA, citrullinated histone, Elastase, Calprotectine, MMP9, NGAL, and MPO, IL-8

  baseline

Secondary Outcomes (6)

• The association of NET / PAD4 biomarker levels will be analyzed to NYHA functional class.

  baseline

• The association of NET / PAD4 biomarker levels will be analyzed in relation to QRS width and late potentials.

  baseline

• The association of NET / PAD4 biomarker levels will be analyzed in relation to ventricular function, ventricular longitudinal strain, diastolic parameters, presence of valvular disease, change in systemic ventricular filling profile after exercise

  baseline

• The association of NET / PAD4 biomarker levels will be analyzed in relation to measurement of myocardial stiffness.

  baseline

• The association of NET / PAD4 biomarker levels will be analyzed in relation to volumes, masses and ventricular ejection fraction, late enhancement and T1 measurement

  baseline

Study Arms (2)

Patients

Patients with a complex congenital heart disease

Diagnostic Test: Biological markers of myocardial fibrosis

controls

healthy subjects

Diagnostic Test: Biological markers of myocardial fibrosis

Interventions

Biological markers of myocardial fibrosis DIAGNOSTIC_TEST

Blood sample for measurements of NET activation and collagen biomarkers

Patients; controls

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: 50 male and 50 female including half of them with a history of pregnancy
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population will therefore be represented by: * heart diseases at risk of heart failure with an equal proportion of men and women to be able to study the protective character of the female sex on the inflammatory process and the development of myocardial fibrosis. * healthy adult subjects.

You may qualify if:

• Patients:
• Male or female aged 18 to 45; having one of the following 3 complex congenital heart disease:
• Congenital heart disease with a systemic right ventricle Congenital heart disease with a single ventricle palliated by Fontan's circulation Tetralogy of Fallot repaired - Patient benefiting from a social security scheme or having rights, or CMU; obtaining informed consent from the patient
• Healthy subjects:
• Age over 18 years old, matched by sex and age +/- 5 years; Normal ECG; with a prior clinical examination; benefiting from social security; obtaining informed consent from the patient

You may not qualify if:

• Patients:
• patients with cyanosis defined as saturation ≤ 90% at rest; Usual MRI contraindications Possible confounding factors with increased NET formation unrelated to thrombosis, namely cancer, rheumatoid arthritis, lupus, antiphospholipid syndrome, history of pre-Eclampsia or hypertension; Contraindication to performing a stress test; Glomerular filtration rate \<30ml / min / 1.73m² of body surface area A physical or mental disability that does not allow for a stress test; Pregnant or lactating patient;Patient under legal protection
• \- Healthy subjects: Known or detectable history of a heart attack on the ECG; known or detectable primary or secondary cardiomyopathy on ECG; history of chest radiation therapy or chemotherapy;Possible confounding factors with increased NET formation unrelated to thrombosis, namely cancer, rheumatoid arthritis, lupus, antiphospholipid syndrome, history of pre-Eclampsia or hypertension Contraindication to performing a stress test;Glomerular filtration rate \<30ml / min;BMI\>30; Pregnant or lactating patient;Patient under legal protection

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• National Research Agency, France: collaborator
• European Commission: collaborator

Study Sites (2)

C01 - Hôpital Européen Georges Pompidou - Unité des cardiopathies congénitales de l'adulte

Paris, 75015, France

RECRUITING

C02- Hôpital Européen Georges Pompidou - CIC

Paris, 75015, France

NOT YET RECRUITING

Related Publications (11)

• Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation. 2007 Jan 16;115(2):163-72. doi: 10.1161/CIRCULATIONAHA.106.627224. Epub 2007 Jan 8.

  PMID: 17210844 BACKGROUND

• Burchill LJ, Broberg CS, Maxwell BG, McLarry J, Opotowskuy S. National Heart Failure Admissions and Associated Mortality Trends in Adults With Congenital Heart Disease in the United States, 1998-2011. J Heart Lung Transplant. 1 avr 2015;34(4):S155.

  BACKGROUND

• Moussa NB, Karsenty C, Pontnau F, Malekzadeh-Milani S, Boudjemline Y, Legendre A, Bonnet D, Iserin L, Ladouceur M. Characteristics and outcomes of heart failure-related hospitalization in adults with congenital heart disease. Arch Cardiovasc Dis. 2017 May;110(5):283-291. doi: 10.1016/j.acvd.2017.01.008. Epub 2017 Mar 14.

  PMID: 28314706 BACKGROUND

• Diller G-P. Incidence and Prevalence of Heart Failure in Adults with Congenital Heart Disease. In: Swan L, Frogoudaki AA, éditeurs. Heart Failure in Adult Congenital Heart Disease [Internet]. Cham: Springer International Publishing; 2018. p. 3-9. (Congenital Heart Disease in Adolescents and Adults). Disponible sur: https://doi.org/10.1007/978-3-319-77803-7_1

  BACKGROUND

• Khairy P, Fernandes SM, Mayer JE Jr, Triedman JK, Walsh EP, Lock JE, Landzberg MJ. Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation. 2008 Jan 1;117(1):85-92. doi: 10.1161/CIRCULATIONAHA.107.738559. Epub 2007 Dec 10.

  PMID: 18071068 BACKGROUND

• Engelings CC, Helm PC, Abdul-Khaliq H, Asfour B, Bauer UM, Baumgartner H, Kececioglu D, Korten MA, Diller GP, Tutarel O. Cause of death in adults with congenital heart disease - An analysis of the German National Register for Congenital Heart Defects. Int J Cardiol. 2016 May 15;211:31-6. doi: 10.1016/j.ijcard.2016.02.133. Epub 2016 Mar 2.

  PMID: 26970963 BACKGROUND

• Diller GP, Kempny A, Alonso-Gonzalez R, Swan L, Uebing A, Li W, Babu-Narayan S, Wort SJ, Dimopoulos K, Gatzoulis MA. Survival Prospects and Circumstances of Death in Contemporary Adult Congenital Heart Disease Patients Under Follow-Up at a Large Tertiary Centre. Circulation. 2015 Dec 1;132(22):2118-25. doi: 10.1161/CIRCULATIONAHA.115.017202. Epub 2015 Sep 14.

  PMID: 26369353 BACKGROUND

• Zomer AC, Vaartjes I, van der Velde ET, de Jong HM, Konings TC, Wagenaar LJ, Heesen WF, Eerens F, Baur LH, Grobbee DE, Mulder BJ. Heart failure admissions in adults with congenital heart disease; risk factors and prognosis. Int J Cardiol. 2013 Oct 3;168(3):2487-93. doi: 10.1016/j.ijcard.2013.03.003. Epub 2013 Apr 18.

  PMID: 23602867 BACKGROUND

• Wang F, Liu A, Brophy JM, Cohen S, Abrahamowicz M, Paradis G, Marelli A. Determinants of Survival in Older Adults With Congenital Heart Disease Newly Hospitalized for Heart Failure. Circ Heart Fail. 2020 Aug;13(8):e006490. doi: 10.1161/CIRCHEARTFAILURE.119.006490. Epub 2020 Jul 16.

  PMID: 32673500 BACKGROUND

• Ghali JK, Krause-Steinrauf HJ, Adams KF, Khan SS, Rosenberg YD, Yancy CW, Young JB, Goldman S, Peberdy MA, Lindenfeld J. Gender differences in advanced heart failure: insights from the BEST study. J Am Coll Cardiol. 2003 Dec 17;42(12):2128-34. doi: 10.1016/j.jacc.2003.05.012.

  PMID: 14680739 BACKGROUND

• Zomer AC, Ionescu-Ittu R, Vaartjes I, Pilote L, Mackie AS, Therrien J, Langemeijer MM, Grobbee DE, Mulder BJ, Marelli AJ. Sex differences in hospital mortality in adults with congenital heart disease: the impact of reproductive health. J Am Coll Cardiol. 2013 Jul 2;62(1):58-67. doi: 10.1016/j.jacc.2013.03.056. Epub 2013 May 1.

  PMID: 23644083 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

At the end of the study, the samples may be used for further analysis not described in the initial protocol but which may be useful for investigation of congenital cardiopathy in light of advances in scientific knowledge, provided the participant is informed and does not oppose this, as stated in the information note/consent form.

MeSH Terms

Conditions

Heart Defects, Congenital; Heart Failure; Coitus; Fibrosis; Inflammation

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sexual Behavior; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Magalie Ladouceur, Pr

  Hôpital Européen Georges-Pompidou

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Magalie Ladouceur, Pr

CONTACT

0033608260618; magalie.ladouceur@aphp.fr

Liliane HAMMANI-BERKANI, Msc

CONTACT

0033156093762; liliane.berkani@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 3, 2022
• Study Start: February 22, 2022
• Primary Completion: February 23, 2025
• Study Completion: February 23, 2025
• Last Updated: January 9, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Two years after the last publication
• Access Criteria: Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).

Locations

FR (2)