MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Exposed: Positive anti-HLA antibodies Heart transplant patients who have developed antiHLA antibodies after transplant |
Diagnostic Test: Echocardiogram
Ultrasound study to assess cardiac anatomy and function
Diagnostic Test: Cardiac magnetic resonance
MR to assess cardiac anatomy, function and tissue damage
Diagnostic Test: Coronary angiography
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Diagnostic Test: Endomyocardial biopsy
Optic microscopy, immunofluorescence, transmission electron microscopy
|
| Non-exposed: Negative anti-HLA antibodies Heart transplant patients without antiHLA antibodies with similar transplant date to its correspondent case. |
Diagnostic Test: Echocardiogram
Ultrasound study to assess cardiac anatomy and function
Diagnostic Test: Cardiac magnetic resonance
MR to assess cardiac anatomy, function and tissue damage
Diagnostic Test: Coronary angiography
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Diagnostic Test: Endomyocardial biopsy
Optic microscopy, immunofluorescence, transmission electron microscopy
|
Outcome Measures
Primary Outcome Measures
- Histology findings with transmission electron microscopy (TEM) [14 days]
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
- Histology findings with optic microscopy (OM) [14 days]
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
- Histology findings with immunohistochemistry (IHQ) techniques. [14 days]
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Secondary Outcome Measures
- Microvascular function (pressure guidewire) [14 days]
Index of microcirculatory resistance
- Microvascular function (pressure guidewire 2) [14 days]
Coronary flow reserve
- Microvascular function (cardiac magnetic resonance) [14 days]
Quantitative perfusion evaluation
- Increased water content (intracellular edema) [14 days]
T2 recovery times mapping (cardiac magnetic resonance) to detect intracellular edema (endothelial vacuolization) as an early sign of microvascular damage
- Myocardial fibrosis (cardiac magnetic resonance) [14 days]
T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage
- Myocardial fibrosis (cardiac magnetic resonance 2) [14 days]
Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage
- Myocardial fibrosis (echocardiography) [14 days]
Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage
- Serum markers of fibrosis [14 days]
FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling
- Coronary allograft vasculopathy (CAV) [14 days]
Fractional flow reserve (coronary physiology) as early marker of CAV
- Coronary allograft vasculopathy (CAV 2) [14 days]
Intimal thickness (intravascular ultrasound) as early marker of CAV
Other Outcome Measures
- Adverse events [5 years]
Heart failure, re-transplant, death
Eligibility Criteria
Criteria
Inclusion Criteria:
- 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.
- 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitario Puerta de Hierro Majadahonda | Majadahonda | Madrid | Spain | 28222 |
| 2 | Hospital General Universitario Gregorio Marañon | Madrid | Spain | 28007 | |
| 3 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 |
Sponsors and Collaborators
- Juan Francisco Delgado Jimenez
- Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Investigators
- Study Chair: Juan F Delgado, MD PhD, University Hospital 12 de Octubre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LEONE-HT