MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)

Juan Francisco Delgado Jimenez

Status: Active, not recruiting

Conditions: Antibody-mediated Rejection; Heart Transplant Rejection; Transplant Failure

Treatments: Diagnostic Test: Coronary angiography; Diagnostic Test: Endomyocardial biopsy; Diagnostic Test: Echocardiogram; Diagnostic Test: Cardiac magnetic resonance

Study type: Observational

Funder types: Other

Identifiers

NCT05184426

LEONE-HT

Details and patient eligibility

About

Cross-sectional evaluation of antibody mediated injury in heart transplantation patients through a multimodal approach: electron microscopy, optic microscopy, immunohistochemistry techniques, transthoracic echocardiography, cardiac magnetic resonance, pressure guide wire, intravascular ultrasound

Full description

Heart transplant survival has barely improved in the last decades and unsatisfactory for a large proportion of heart transplant recipients. The development of leukocyte antigen antibodies (anti-HLA) in the post-transplant patient is associated to the main causes of graft dysfunction. The mechanisms of this damage are unclear and there's no effective treatment.

The investigators aim is to identify early markers of graft injury through a complete morphological and functional evaluation with histological analysis, immunological assays, advanced imaging techniques and invasive evaluation of coronary vasculature in patients with anti-HLA compared to matching controls.

The investigators propose a cross-sectional study within a large heart transplant cohort. This is a multicentric observational multimodal study. The investigators aim is to establish early characteristics of antibody mediated damage and set the bases for future studies looking for new treatment targets.

Enrollment: 90 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Exposed:

   • Heart transplant recipients

   • "De novo" antiHLA detection (after heart transplant):

     • Mean fluorescence intensity (MFI)) > 2000 for donor-specific antibodies
     • Standard fluorescence intensity (SFI) > 150 000 for non-donor specific antibodies

   • Detailed immunological history:

     • Determination of anti-HLA antibodies before heart transplant.
     • Serial determination of anti-HLA antibodies during heart transplantation follow-up

   • Known HLA typing of the donor.

2. Non-exposed: Heart transplant procedure contemporary to the index case with negative anti-HLA antibodies.

Exclusion criteria

• Recipient of a second HT
• Multiple organ transplantation
• Unknown immunological history
• Recipients sensitized with anti-HLA antibodies against donor's HLA before the transplant
• CMR contrast will not be administered in patients with glomerular filtration rate < 30 ml/kg/1.73m2
• Patients with implanted cardiac devices or any other magnetic resonance non-compatible metallic prosthetic material will not undergo CMR.

Trial design

90 participants in 2 patient groups

Exposed: Positive anti-HLA antibodies

Description:

Heart transplant patients who have developed antiHLA antibodies after transplant

Treatment:

Diagnostic Test: Coronary angiography

Diagnostic Test: Endomyocardial biopsy

Diagnostic Test: Echocardiogram

Diagnostic Test: Cardiac magnetic resonance

Non-exposed: Negative anti-HLA antibodies

Description:

Heart transplant patients without antiHLA antibodies with similar transplant date to its correspondent case.

Treatment:

Diagnostic Test: Coronary angiography

Diagnostic Test: Endomyocardial biopsy

Diagnostic Test: Echocardiogram

Diagnostic Test: Cardiac magnetic resonance