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.
Study Type
OBSERVATIONAL
Enrollment
90
Ultrasound study to assess cardiac anatomy and function
MR to assess cardiac anatomy, function and tissue damage
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, Spain
Hospital General Universitario Gregorio Marañon
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Histology findings with transmission electron microscopy (TEM)
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Time frame: 14 days
Histology findings with optic microscopy (OM)
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Time frame: 14 days
Histology findings with immunohistochemistry (IHQ) techniques.
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Time frame: 14 days
Microvascular function (pressure guidewire)
Index of microcirculatory resistance
Time frame: 14 days
Microvascular function (pressure guidewire 2)
Coronary flow reserve
Time frame: 14 days
Microvascular function (cardiac magnetic resonance)
Quantitative perfusion evaluation
Time frame: 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
Time frame: 14 days
Myocardial fibrosis (cardiac magnetic resonance)
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Optic microscopy, immunofluorescence, transmission electron microscopy
T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage
Time frame: 14 days
Myocardial fibrosis (cardiac magnetic resonance 2)
Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage
Time frame: 14 days
Myocardial fibrosis (echocardiography)
Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage
Time frame: 14 days
Serum markers of fibrosis
FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling
Time frame: 14 days
Coronary allograft vasculopathy (CAV)
Fractional flow reserve (coronary physiology) as early marker of CAV
Time frame: 14 days
Coronary allograft vasculopathy (CAV 2)
Intimal thickness (intravascular ultrasound) as early marker of CAV
Time frame: 14 days