Clinical trial NCT02938910: Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Primary Hyperaldosteronism
Secondary Hyperaldosteronism
Essential Hypertension
Healthy
Keywords: Primary hyperaldosteronism
Secondary hyperaldosteronism
Cardiac fibrosis
magnetic resonance imaging
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2016-10-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with primary or secondary hyperaldosteronism compared to hypertensive or normotensive controls

Brief summary: 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.

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).

Eligibility criteria: * 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.

Primary outcomes:
measure: Interstitial fibrosis assessed by MRI
timeFrame: One visit
Secondary outcomes:
measure: Evaluation of myocardial remodeling by MRI
timeFrame: One visit
measure: Effect of hypertension on myocardial fibrosis assessed by MRI
timeFrame: One visit
measure: Effect of aldosteronism on myocardial fibrosis assessed by MRI
timeFrame: One visit
measure: Effect of hypertension on LV diastolic dysfunction
timeFrame: One visit
measure: Effect of aldosteronism on LV diastolic dysfunction
timeFrame: One visit
measure: Effect of hypertension on the relationship between circulating biomarkers of fibrosis
timeFrame: One visit
measure: Effect of aldosteronism on the relationship between circulating biomarkers of fibrosis
timeFrame: One visit
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre d\'investigation Clinique, hopital Europeen George Pompidou
Study officials:
affiliation: Assistance publique des hopitaux de Paris
name: Elie MOUSSEAUX, MD, PhD
role: STUDY_DIRECTOR
affiliation: Assistance publique des hopitaux de Paris
name: Alban REDHEUIL, MD,PhD
role: STUDY_DIRECTOR
References:
citation: 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.