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

NCT ID: NCT06327308

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2027-06-01

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.

Conditions

Cirrhosis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patient with cirrhosis requiring liver transplantation

MRI

Intervention Type: DIAGNOSTIC_TEST

The examination lasts between 45 minutes and one hour. The patient lies down in the MRI tube. He is fitted with headphones that muffle the noise produced by the machine and enable him to receive instructions from the technician. Four electrodes are applied to his chest to continuously record his heartbeat. Finally, his chest is covered with a plastic plate, which receives the MRI signals needed to form the image. Acquiring an MRI image takes between 2 and 20 seconds. To ensure that image quality is not impaired by respiratory movements, images are acquired in apnea. The technician will ask the patient to hold his or her breath repeatedly throughout the examination.

Blood sampling

Intervention Type: BIOLOGICAL

Additional blood will be drawn for dosing acylcarnitines, copeptin, interleukin-6 (IL-6), LPS-Binding Protein (LBP), Phospholipid TransferProtein (PLTP)/Cholesteryl Ester Tranfer Protein (CETP) activity, and for plasma banking. The volume of blood will be 20 ml in total (5 ml for each assay) at each visit. Patients participating in this study will have 3 visits. Total blood volume will therefore be 20 x 3, or 60 ml for the 3 visits.

Interventions

MRI

The examination lasts between 45 minutes and one hour. The patient lies down in the MRI tube. He is fitted with headphones that muffle the noise produced by the machine and enable him to receive instructions from the technician. Four electrodes are applied to his chest to continuously record his heartbeat. Finally, his chest is covered with a plastic plate, which receives the MRI signals needed to form the image. Acquiring an MRI image takes between 2 and 20 seconds. To ensure that image quality is not impaired by respiratory movements, images are acquired in apnea. The technician will ask the patient to hold his or her breath repeatedly throughout the examination.

Intervention Type: DIAGNOSTIC_TEST

Blood sampling

Additional blood will be drawn for dosing acylcarnitines, copeptin, interleukin-6 (IL-6), LPS-Binding Protein (LBP), Phospholipid TransferProtein (PLTP)/Cholesteryl Ester Tranfer Protein (CETP) activity, and for plasma banking. The volume of blood will be 20 ml in total (5 ml for each assay) at each visit. Patients participating in this study will have 3 visits. Total blood volume will therefore be 20 x 3, or 60 ml for the 3 visits.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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"

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thierry THEVENOT, MD, PHD

Role: STUDY_DIRECTOR

Centre Hospitalier Universitaire de Besancon

Delphine WEIL, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Besancon

Camille BESCH, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Strasbourg

Mouni BENSENANE -OUSSALAH, MD

Role: PRINCIPAL_INVESTIGATOR

CHRU Nancy

Marianne LATOURNERIE, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Dijon

Locations

CHU Besancon - Hopital Minjoz

Besançon, , France

CHU Dijon - Hopital François Mitterrand

Dijon, , France

CHRU Nancy - Hôpital de Brabois

Nancy, , France

CHU Strasbourg - Hopital de HautePierre

Strasbourg, , France

Countries

France

Central Contacts

Delphine WEIL, MD, PHD

Role: CONTACT

dweil@chu-besancon.fr

+33381669457

Facility Contacts

Delphine WEIL, MD, PHD

Role: primary

Marianne LATOURNERIE, MD

Role: primary

Mouni BENSENANE -OUSSALAH, MD

Role: primary

Camille BESCH, MD

Role: primary

Other Identifiers

2023/803

Identifier Type: -

Identifier Source: org_study_id