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| Name | Class |
|---|---|
| Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III | OTHER |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exposed: Positive anti-HLA antibodies | Heart transplant patients who have developed antiHLA antibodies after transplant |
| |
| Non-exposed: Negative anti-HLA antibodies | Heart transplant patients without antiHLA antibodies with similar transplant date to its correspondent case. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Echocardiogram | Diagnostic Test | Ultrasound study to assess cardiac anatomy and function |
|
| Measure | Description | Time Frame |
|---|---|---|
| Histology findings with transmission electron microscopy (TEM) | Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation | 14 days |
| Histology findings with optic microscopy (OM) | Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation | 14 days |
| Histology findings with immunohistochemistry (IHQ) techniques. | Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Microvascular function (pressure guidewire) | Index of microcirculatory resistance | 14 days |
| Microvascular function (pressure guidewire 2) | Coronary flow reserve |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | Heart failure, re-transplant, death | 5 years |
Inclusion Criteria:
Exposed:
Heart transplant recipients
"De novo" antiHLA detection (after heart transplant):
Detailed immunological history:
Known HLA typing of the donor.
Non-exposed: Heart transplant procedure contemporary to the index case with negative anti-HLA antibodies.
Exclusion Criteria:
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The study population will be conformed of heart transplant patients who are under follow-up at 3 hospitals of the Autonomous Region of Madrid (Spain). All the three hospitals are national referral center for heart transplantation.
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| Name | Affiliation | Role |
|---|---|---|
| Juan F Delgado, MD PhD | University Hospital 12 de Octubre | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Puerta de Hierro Majadahonda | Majadahonda | Madrid | 28222 | Spain | ||
| Hospital General Universitario Gregorio Marañon |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36287047 | Derived | Nuche J, de la Cruz Bertolo J, Marco Clement I, Sanchez VS, Sarnago Cebada F, Mancebo E, Enguita AB, Alonso-Riano M, Ruiz-Hurtado G, Lopez-Azor JC, Hernandez-Perez FJ, Castrodeza J, Sanchez Gonzalez J, Arribas Ynsaurriaga F, Garcia-Cosio Carmena MD, Delgado JF. Rationale and Protocol of the Multimodality Evaluation of Antibody-Mediated Injury in Heart Transplantation (LEONE-HT) Observational Cross-Sectional Study. Methods Protoc. 2022 Sep 25;5(5):75. doi: 10.3390/mps5050075. |
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Endomyocardial biopsy samples Blood samples (leukocytes)
| Cardiac magnetic resonance | Diagnostic Test | MR to assess cardiac anatomy, function and tissue damage |
|
| Coronary angiography | Diagnostic Test | Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation |
|
| Endomyocardial biopsy | Diagnostic Test | Optic microscopy, immunofluorescence, transmission electron microscopy |
|
| 14 days |
| Microvascular function (cardiac magnetic resonance) | Quantitative perfusion evaluation | 14 days |
| Increased water content (intracellular edema) | T2 recovery times mapping (cardiac magnetic resonance) to detect intracellular edema (endothelial vacuolization) as an early sign of microvascular damage | 14 days |
| Myocardial fibrosis (cardiac magnetic resonance) | T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage | 14 days |
| Myocardial fibrosis (cardiac magnetic resonance 2) | Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage | 14 days |
| Myocardial fibrosis (echocardiography) | Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage | 14 days |
| Serum markers of fibrosis | FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling | 14 days |
| Coronary allograft vasculopathy (CAV) | Fractional flow reserve (coronary physiology) as early marker of CAV | 14 days |
| Coronary allograft vasculopathy (CAV 2) | Intimal thickness (intravascular ultrasound) as early marker of CAV | 14 days |
| Madrid |
| 28007 |
| Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| ID | Term |
|---|---|
| D004452 | Echocardiography |
| D017023 | Coronary Angiography |
| ID | Term |
|---|---|
| D057791 | Cardiac Imaging Techniques |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D014463 | Ultrasonography |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D000792 | Angiography |
| D011859 | Radiography |
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