Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism (COEURALDO)

Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism Noninvasive Comparative Study in Humans of the Respective Cardiovascular Effects of Hyperaldosteronism and Hypertension by Magnetic Resonance Imaging

Animal models have demonstrated the role of aldosterone in left ventricular remodeling involving fibrosis, apoptosis and hypertrophy. Myocardial fibrosis is a risk factor for serious arrhythmia and sudden death in ischemic and idiopathic hypertrophic heart disease. It is accepted that patients with primary aldosteronism have a higher prevalence of LV hypertrophy , arterial involvement and increased cardiovascular risk. In humans, a link has been demonstrated between aldosterone and heart failure as well as the benefit of the administration of an anti -aldosterone drug to lower mortality in this population , regardless of blood pressure level . The administration of spironolactone ( aldosterone ) in hypertensive rats has prevented the occurrence of aortic fibrosis . Plasma aldosteronism in humans has been associated with inflammation, fibrosis and aortic stiffness . However, primary aldosteronism is generally associated with so-called secondary hypertension . Chronic hypertension alone is a recognized etiological factor of myocardial hypertrophy ( myocardial fibrosis very advanced ) . The purpose of this study is to investigate the effects of MRI hyperaldosteronism on the heart.

Study Overview

• Status: Completed
• Conditions: Healthy; Essential Hypertension; Primary Hyperaldosteronism; Secondary Hyperaldosteronism
• Intervention / Treatment: Other: non interventional study

Detailed Description

Cross-sectional study with double analysis (A and B) with 2 x 2 sub-groups (ratio control/case 1/1)

• clinical situation: subjects are hypertensive. 20 subjects with primary aldosteronism will be compared to 20 patients with essential arterial hypertension
• clinical situation are normotensive subjects, 20 subjects with secondary aldosteronism loss in congenital salt (Bartter's syndrome / Gitelman) will be compared to 20 healthy volunteers. Controls (essential hypertension and healthy volunteers) are matched for age, sex and body size in two experimental groups (HAP and Gitelman). All subjects were recruited by the CIC of the European Georges Pompidou Hospital (Paris).

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Centre d\'investigation Clinique, hopital Europeen George Pompidou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with primary or secondary hyperaldosteronism compared to hypertensive or normotensive controls

Description

• Patients with primary hyperaldosteronism:

  • Aldosterone / renin plasma ratio SUP 64 pmol / mU
  • aldosterone in a semi-sitting position SUP 500pmol / l or an aldosteronuria> 63nmol/24h,
  • Both under neutral treatment for at least 15 days (alpha-blocker, calcium channel blockers, central inhibitors). BMI = 35 kg / m².

• For patients with secondary hyperaldosteronism :

  • Documented diagnosis by the detection of mutation (s) homozygous or compound heterozygous for the gene SLC12A3 encoding CLCNKB chloride channel, or the gene encoding the HTSC Na-Cl cotransport thiazide sensitive.
  • Normal blood pressure (mean of three consecutive measurements of SBP INF 140 mmHg and DBP INF 90 mmHg measured in a semi-sitting position after 5 minutes of rest).

• For hypertensive patients :

  • Hypertension diagnosed on an average of three consecutive BP measurements = 140 and / or = 90 mmHg in the supine position after 5 minutes of rest or average daytime PA SUP 135/85 mmHg in ambulatory blood pressure monitoring (ABPM) in self-measurement , the presence of one or more antihypertensive medications regardless of the BP level.
  • No argument for secondary hypertension (renal artery stenosis, hypermineralocorticoidism, pheochromocytoma, iatrogenic ...) or negative balance of secondary hypertension.
  • BMI < 35 kg/m2.

• For healthy subjects :

  • Normal blood pressure (mean of three consecutive measurements of SBP INF 140 mmHg and DBP INF 90 mmHg measured in a semi-sitting position after 5 minutes of rest).
  • Absence of HA known or detected on determinations carried out during the study (see criteria for PAHs).
  • BMI <35 kg / m²
  • Laboratory tests (hematological and biochemical blood tests, urinalysis, serology and Research toxic) within normal limits or clinically acceptable for age and sex.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers; Healthy volunteers with normal blood pressure	Other: non interventional study; Non invasive imaging study without interventional procedures
Primary Hyperaldosteronism; Subjects with hypertension and high levels of seric aldosterone.	Other: non interventional study; Non invasive imaging study without interventional procedures
Secondary Hyperaldosteronism; Patient with Gitelman syndrome, with normal blood pressure and high level of aldosterone	Other: non interventional study; Non invasive imaging study without interventional procedures
Essential Hypertension; Patient with hypertension without secondary cause of hypertension	Other: non interventional study; Non invasive imaging study without interventional procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interstitial fibrosis assessed by MRI	Quantitative interstitial fibrosis indices (intra- and extra-cellular LV mass) derived from myocardial relaxation time T1 MRI will be estimated in 4 populations with and without hypertension (patients with essential hypertension or with primary hyperaldosteronism versus healthy volunteers or patients with Gitelman syndrome), and with and without high level of aldosterone (patients with primary hyperaldosteronism or Gitelman syndrome versus patients with essential hypertension or healthy volunteers)	One visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of myocardial remodeling by MRI	Quantitative left ventricular remodeling (LV Mass and LV mass/end diastolic volume) will be estimated in 4 populations with and without hypertension (patients with essential hypertension or with primary hyperaldosteronism versus healthy volunteers or patients with Gitelman syndrome), and with and without high level of aldosterone (patients with primary hyperaldosteronism or Gitelman syndrome versus patients with essential hypertension or healthy volunteers)	One visit
Effect of hypertension on myocardial fibrosis assessed by MRI	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of myocardial fibrosis	One visit
Effect of aldosteronism on myocardial fibrosis assessed by MRI	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of myocardial fibrosis	One visit
Effect of hypertension on LV diastolic dysfunction	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of LV diastolic dysfunction	One visit
Effect of aldosteronism on LV diastolic dysfunction	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of LV diastolic dysfunction	One visit
Effect of hypertension on the relationship between circulating biomarkers of fibrosis	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between circulating biomarkers of fibrosis	One visit
Effect of aldosteronism on the relationship between circulating biomarkers of fibrosis	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between circulating biomarkers of fibrosis	One visit

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Elie MOUSSEAUX, MD, PhD, Assistance Publique des Hopitaux de Paris; Study Director: Alban REDHEUIL, MD,PhD, Assistance Publique des Hopitaux de Paris

Publications and helpful links

General Publications

• Redheuil A, Blanchard A, Pereira H, Raissouni Z, Lorthioir A, Soulat G, Vargas-Poussou R, Amar L, Paul JL, Helley D, Azizi M, Kachenoura N, Mousseaux E. Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance. JACC Cardiovasc Imaging. 2020 Oct;13(10):2149-2159. doi: 10.1016/j.jcmg.2020.06.026. Epub 2020 Sep 16.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: October 17, 2016
• First Posted (ESTIMATE): October 19, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 19, 2016
• Last Update Submitted That Met QC Criteria: October 17, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; Cardiac fibrosis; Primary hyperaldosteronism; Secondary hyperaldosteronism
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Fibrosis; Hypertension; Essential Hypertension; Hyperaldosteronism
• Other Study ID Numbers: P110912