Clinical trial NCT06327308: Evaluation of Cirrhotic Cardiomyopathy by Cardiac MRI in Patients Waiting for Liver Transplant.
Official title: Evaluation of Cirrhotic Cardiomyopathy by Cardiac MRI in Patients Waiting for Liver Transplant. A Multicenter Prospective Pilot Study. (CARDIO-FIBROCIR)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cirrhosis
Keywords: Cirrhosis
cirrhotic cardiomyopathy
Liver Transplantation
MRI
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2024-03-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any patient with cirrhosis requiring LT and eligible for LT according to a pre-liver transplant assessment that does not contraindicate LT. Patients listed for fulminant hepatitis or early re-transplantation will be excluded.

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.

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"

Primary outcomes:
measure: Primary outcome measure
timeFrame: sixth month-21th month after inclusion
Secondary outcomes:
measure: 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 :
timeFrame: 33 months
measure: Analysis of the association between myocardial extracellular volume (MECV) (explained variable) and plasma 3-HM concentration (explanatory variable).
timeFrame: 33 months
measure: 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).
timeFrame: 33 months
measure: 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.
timeFrame: sixth month-21th month after inclusion
measure: Number, type and cumulative incidence of cardiovascular events (heart failure, rhythm disorders, etc.) according to cirrhotic cardiomyopathy status occurring between inclusion and LT.
timeFrame: 33 months
measure: Number, type and cumulative incidence of cardiovascular events (heart failure, rhythm disorders, etc.) occurring between inclusion and LT, according to cirrhotic cardiomyopathy status.
timeFrame: 33 months
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU Besancon - Hopital Minjoz
city: Dijon
country: France
facility: CHU Dijon - Hopital François Mitterrand
city: Nancy
country: France
facility: CHRU Nancy - Hôpital de Brabois
city: Strasbourg
country: France
facility: CHU Strasbourg - Hopital de HautePierre
Study officials:
affiliation: Centre Hospitalier Universitaire de Besancon
name: Thierry THEVENOT, MD, PHD
role: STUDY_DIRECTOR
affiliation: Centre Hospitalier Universitaire de Besancon
name: Delphine WEIL, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Strasbourg
name: Camille BESCH, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU Nancy
name: Mouni BENSENANE -OUSSALAH, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Dijon
name: Marianne LATOURNERIE, MD
role: PRINCIPAL_INVESTIGATOR
References: