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

Cirrhosis Clinical Trial

— CARDIOFIBROCIR  

Official title:

Evaluation of Cirrhotic Cardiomyopathy by Cardiac MRI in Patients Waiting for Liver Transplant. A Multicenter Prospective Pilot Study. (CARDIO-FIBROCIR)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06327308
• Other study ID #: 2023/803
• Status: Not yet recruiting
• Start date: March 31, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: September 2023
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: Delphine WEIL, MD, PHD
• Phone: +33381669457
• Email: dweil[@]chu-besancon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2027
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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"

Related Conditions & MeSH terms

• Cardiomyopathies
• Cirrhosis
• Fibrosis

Intervention

Diagnostic Test:
• 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.

Biological:
• 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.

Locations

Country	Name	City	State
France	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

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome measure	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.	sixth month-21th month after inclusion
Secondary	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 :	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.	33 months
Secondary	Analysis of the association between myocardial extracellular volume (MECV) (explained variable) and plasma 3-HM concentration (explanatory variable).	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.	33 months
Secondary	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).	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.	33 months
Secondary	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
Secondary	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
Secondary	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