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Evaluation of Cirrhotic Cardiomyopathy by Cardiac MRI in Patients Waiting for Liver Transplant.

Not yet recruiting
Conditions
Cirrhosis
Interventions
Diagnostic Test: MRI
Biological: Blood sampling
Registration Number
NCT06327308
Lead Sponsor
Centre Hospitalier Universitaire de Besancon
Brief Summary

The aim of this multicenter prospective observational pilot study is to describe the evolution of myocardial fibrosis in cirrhotic patients before and after liver transplantation (LT). Through multimodal analysis of myocardial function and architecture, and analysis of specific markers of inflammation, we aim to explore the following hypotheses: 1) systemic inflammation promotes myocardial fibrosis in cirrhotic patients and could be an early marker of cirrhotic cardiomyopathy; 2) LT allows resolution of myocardial fibrosis by preventing the bacterial translocation that favors the development of deleterious systemic inflammation.

Detailed Description

Cirrhotic patients with an indication for LT and undergoing pre-transplant assessment will be eligible for this study. All included patients will undergo myocardial Magnetic Resonance Imaging (MRI) at the time of inclusion, then at a second visit that will be planned as close as possible to the expected date of LT or at 9 months in the absence of LT, then 12 months after LT or 21 months after inclusion for non-transplanted patients. Markers of systemic inflammation will be analyzed at these same time points.

* Primary outcome : to describe the evolution of the percentage of myocardial fibrosis on cardiac MRI before and 12 months after LT in cirrhotic patients.

* Secondary outcomes

1. To describe the evolution of the percentage of myocardial fibrosis at 9 months and 21 months in non-transplanted patients.

2. To estimate the prevalence of cirrhotic cardiomyopathy in cirrhotic patients before and 12 months after LT.

3. To describe the relationship between plasma 3-hydroxymyristate (3-HM) concentration and the level of myocardial fibrosis estimated by myocardial extracellular volume (MECV) before and 12 months after LT

4. To describe the relationship between several markers of inflammation (CRP, procalcitonin, copeptin, IL-6) or proteins modulating the degree of inflammation (LPS-binding protein (LPB), Phospholipid Transfer Protein (PLTP), Cholesteryl Ester Transfer Protein (CETP)) and the level of myocardial fibrosis estimated by MECV, before and 12 months after LT.

5. To describe, in liver transplanted patients, the evolution of the percentage of myocardial fibrosis before and 12 months after LT according to the degree of immunosuppression.

6. To describe, in liver transplanted patients, the occurrence of cardiovascular events according to the cirrhotic cardiomyopathy status, from inclusion (i.e., placement on the transplant waiting list) to transplantation.

7. To describe the occurrence of cardiovascular events according to the cirrhotic cardiomyopathy status in the 12 months following LT.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Inclusion of cirrhotic patients when registering on the liver transplant list
  • Women who have been menopausal for at least 24 months, surgically sterilized, or, for women of childbearing age, use an effective method of contraception (oral contraceptives, contraceptive injections, intrauterine devices, double-barrier method, contraceptive patches)
  • Signature of an informed consent form indicating that the subject has understood the purpose and procedures required by the study and that he or she agrees to participate in the study and to comply with the requirements and restrictions inherent in the study
  • Patient with a social security system or beneficiary of such a system.
Exclusion Criteria
  • Minor or over 70 years old
  • Transplant Patient
  • Patient with a TIPS
  • Known cardiorespiratory disease including portopulmonary hypertension and coronary artery disease
  • Uncontrolled hypertension with interventricular septal thickness ≥ 15 mm
  • Hemodynamic instability
  • Type 1 diabetes
  • Current bacterial infection
  • HIV infection (or unknown HIV status)
  • Contraindications for MRI including pacemaker, implantable defibrillators, electrosystolic pacing probe, Swan-Ganz probe, postoperative epicardial electrodes, Starr-Ewards metal ball valves, insulin pumps, ferromagnetic vascular clips, ocular and otological implants, ocular ferromagnetic foreign bodies, renal failure with a GFR < 30 mL/min/1.73 m², contraindication to contrast media, patient unable to maintain apnea for a few seconds, claustrophobia
  • Inability to receive informed information in patients with severe encephalopathy who do not have a trusted person
  • Refusal to agree to participation by signing the information and consent form as defined
  • Patient under guardianship, curatorship, Legal incapacity or limited legal capacity
  • Patient deprived of liberty
  • Pregnant woman or breastfeeding
  • Subject unlikely to cooperate in the study and/or low cooperation anticipated by the investigator
  • Subject without health insurance
  • Subject being in the period of exclusion from another study or provided for by the "national volunteer file"

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Patient with cirrhosis requiring liver transplantationMRI-
Patient with cirrhosis requiring liver transplantationBlood sampling-
Primary Outcome Measures
NameTimeMethod
Primary outcome measuresixth month-21th month after inclusion

Difference in myocardial extracellular volume (MECV) on cardiac MRI between the pre-LT visit (visit 2) and 12 months after LT (visit 3). If patients are transplanted less than 6 months after the inclusion visit, visit 2 will not be performed and the reference visit will be visit 1.

Secondary Outcome Measures
NameTimeMethod
Analysis of the association between myocardial extracellular volume (MECV) and the concentration of markers of inflammation (CRP, procalcitonin, copeptin, IL-6) and proteins modulating the degree of inflammation (LBP, PLTP, CETP).33 months

Analysis of the association between myocardial extracellular volume (MECV) and the concentration of markers of inflammation (CRP, procalcitonin, copeptin, IL-6) and proteins modulating the degree of inflammation (LBP, PLTP, CETP) will be based on the observation of the point cloud.

Analysis of the association between the difference in MECV in transplant recipients between visit 2 and visit 3 according to the degree of immunosuppression, measured by mean residual tacrolemia in the 12 months post-LT.sixth month-21th month after inclusion
Prevalence of cirrhotic cardiomyopathy according to 2019 criteria [Izzy M, et al. Hepatology 2020;71:334-45], echocardiographic signs of left ventricular systolic and diastolic dysfunction :33 months

* Systolic dysfunction: left ventricular ejection fraction ≤ 50% and/or absolute value of left ventricular global longitudinal strain value \< 18%.

* Diastolic dysfunction if ≥ 3 criteria among the following:

* Mitral e' wave velocity \< 7 cm/s ;

* Mitral e' wave / E wave ratio ≥ 15 ;

* Indexed left atrial volume \> 34 mL/m² ;

* Tricuspid regurgitation velocity \> 2.8 m/s.

Number, type and cumulative incidence of cardiovascular events (heart failure, rhythm disorders, etc.) occurring between inclusion and LT, according to cirrhotic cardiomyopathy status.33 months
Analysis of the association between myocardial extracellular volume (MECV) (explained variable) and plasma 3-HM concentration (explanatory variable).33 months

The concentration of 3-hydroxy-myristate will be in pg/ml. Analysis of the association between myocardial extracellular volume (MECV) (explained variable) and plasma 3-HM concentration (explanatory variable) will be based on the observation of the point cloud.

Number, type and cumulative incidence of cardiovascular events (heart failure, rhythm disorders, etc.) according to cirrhotic cardiomyopathy status occurring between inclusion and LT.33 months

Trial Locations

Locations (4)

CHU Besancon - Hopital Minjoz

🇫🇷

Besançon, France

CHRU Nancy - Hôpital de Brabois

🇫🇷

Nancy, France

CHU Dijon - Hopital François Mitterrand

🇫🇷

Dijon, France

CHU Strasbourg - Hopital de HautePierre

🇫🇷

Strasbourg, France

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