Clinical trial NCT03690076: Human Cardiac Mitochondria in Acute Endocarditis and Obesity
Official title: Development of the Purification of Human Cardiac Mitochondria, Characterization of These Organelles and Validation of the Model in Acute Endocarditis and Obesity
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Obesity
Endocarditis
Keywords: Heart
Mitochondria
Obesity
Endocarditis
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
name: Université d'Auvergne
name: Auvergne/Rhône-Alpes area
name: Heart and Research Foundation
First posted: 2018-10-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: adult patients

Brief summary: Data about human cardiac mitochondria are cruelly lacking in the literature. However, damages of the activity of these organelles are often the source of abnormal cardiac function in several pathologies. The purpose of this study is to develop a model of purified human cardiac mitochondria, to verify the purity of these organelles and to validate the authenticity of their function in acute endocarditis and obesity, two situations known to alter their activity. Animal studies have shown that microbial infection reduced mitochondrial metabolism whereas obesity increases it. The investigator's hypotheses are the following: 1) acute endocarditis, a form of cardiac microbial infection, reduces the function of human cardiac mitochondria; 2) obesity (body mass index \> 30) activates the metabolism of human cardiac mitochondria.

Detailed description: 3 groups of patients:

* Controls: patients with normal weight (23 \< BMI \< 27) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis
* Endocarditis: patients with normal weight (23 \< BMI \< 27) carriers of endocarditis with surgery indication
* Obese: obese patients (BMI \> 30) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis

Comparisons studied:

* Controls vs. endocarditis
* Controls vs. obese patients

Eligibility criteria: Inclusion Criteria:

* For the controls : adult patients with normal body weight (23 \< BMI \< 27) necessitating a cardiac surgery with sternotomy and extracorporeal circulation for myocardial revascularization or valve replacement
* For endocarditis : adult patients with normal body weight (23 \< BMI \< 27) and endocarditis of bacterial origin necessitating a cardiac surgery with sternotomy and extracorporeal circulation in order to cure a major valve regurgitation or vegetation with higher size than 15 mm with embolic risk
* For obese patients: adult patients with high body weight (BMI \> 30 and waist to hip ration \> or = 1 for men and 0.85 for women) necessitating a cardiac surgery with sternotomy and extracorporeal circulation for myocardial revascularization or valve replacement

For all the patients:

* Ability to furnish an enlightened agreement
* Menbership of the French social security insurance

Exclusion Criteria:

* Criteria linked to the surgery:
* Surgery of pressing emergency
* Aortic dissection
* Redux surgery

Criteria linked to the patient:

* Protocol refusal
* Protected adult patients
* Previous psychiatric pathology including known addiction states
* Physical or intellectual inability
* Preexisting pathologies such as respiratory failure
* Cardiac failure (ejection fraction \< 30% pulmonary hypertenstion \> 80 mmHg); aortic counterpulsation; pre-operatory cardiogenic shock
* Severe acute or chronic renal failure with creatinine clearance \< 40 ml/min
* Inherited dyslipidemia
* Previous cardiac or thoracic surgery with pericardium opening
* Severe hepatic failure and severe chronic hepatic pathologies
* Evolving neoplasia
* Patients with long course corticoid treatment and with inflammatory diseases
* Patients with double anti-platelet treatment not stopped 48h before the surgery
* Protected people not involved in the study: pregnant women, nursing women, guardianship, deprived of liberty,

Primary outcomes:
measure: Mitochondrial function
timeFrame: at day 1 (Moment of the surgery)
Secondary outcomes:
measure: walk test
timeFrame: at the moment of inclusion in the study (day (-10-5)) and of the end of hospitalization (day +7+10)
measure: body composition
timeFrame: 1 day before the surgery
measure: Electrocardiogram : Detections of the rates in events per min of arrhythmias
timeFrame: at days (-10-5), (+7+10), (+30) and (+90)
measure: Membrane lipid composition
timeFrame: at day 1 (at the day of surgery)
measure: Markers of oxidative stress in the plasma
timeFrame: at days (0) and (+30) for the plasma and day (0) for the myocardium
measure: Concentrations of inflammation cytokines in the plasma
timeFrame: at days (-10-5), (0), (+1), (+2), (+7) and (+90)
measure: Semi-quantitative analysis of the amounts of approximatively 6000 molecules in the plasma by metabolomic and lipidomic techniques
timeFrame: at days (0) and (+30)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: at day (+30)
measure: Patient follow-up during the hospital stay
timeFrame: morbi-mortality at day (+90)
measure: Morbi-mortality
timeFrame: measurement during the post-operative 90 days
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Chu Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Kasra AZARNOUSH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mourmoura E, Rigaudiere JP, Couturier K, Hininger I, Laillet B, Malpuech-Brugere C, Azarnoush K, Demaison L. Long-term abdominal adiposity activates several parameters of cardiac energy function. J Physiol Biochem. 2016 Sep;72(3):525-37. doi: 10.1007/s13105-015-0427-7. Epub 2015 Aug 10.