Enduring Hearts Blog

RESEARCH FOCUS: PREVENT, EARLY DIAGNOSE AND TREAT CAV

Jun 4, 2020 11:12:35 AM / by Carolyn Salvador

cav

Heart transplantation can be a lifesaving procedure for children with inoperable heart diseases. Cardiac Allograft Vasculopathy (CAV) is a leading cause for these transplanted hearts to fail.

What is CAV?

Cardiac Allograft Vasculopathy ( CAV) is a disease affecting coronary arteries of some transplanted hearts. The coronary arteries supply blood to the heart muscle so it can then pump blood that is carrying oxygen to our body. In adults with “hardening of the arteries”, the coronary arteries can become blocked causing a life-threatening heart attack. CAV also blocks blood flow thru the coronary arteries causing the transplanted heart to lose function over time. Like a heart attack the narrowing of the CAV can cause the progressive loss of function in the transplanted heart.

CAV leads to progressive narrowing of the coronary arteries. The injury begins even before the heart is transplanted (Pre-HT) and continues after the transplant (HT; early post-HT). Current evidence suggests that CAV is caused by direct injuries to the coronary arteries of the donor heart (allograft injuries).The transplant recipient’s inflammatory and immune cell responses cause further injury to the coronary arteries (“response to injury”) later post-HT. If we were able to diagnose CAV early post-transplant, we could begin to treat CAV early and prevent its progression. In research supported by Enduring Hearts and published in 2015, we now know in children that CAV likely begins in the smallest coronary arteries, or “microvessels” (Feingold et al, 2015).

Enduring Hearts has funded eight (8) different research teams across the country to investigate novel strategies to prevent, diagnose early and prevent the onset of CAV in children who have received new hearts:

The projected outcomes of these research initiatives by Enduring Hearts are as follows:

  1. Targeted Ex vivo Nanotherapy for use in Cardiac Transplantation.
    1. This unique “drug”, nanotherapy, infused into the coronary arteries of the donor heart, could reduce the pre-transplant-related allograft coronary artery injury and, in turn, reduce CAV.
  2. Functional consequences of antigen specificity in CMV-responsive T cells.
    1. CM Virus infections can occur due to immune suppression following heart transplantation, causing severe coronary artery damage to a transplanted heart. This study will try to reduce CMV-mediated coronary artery injury and, in turn, CAV.
  3. The Causal Role of Axl in the Acceleration of Cardiac Allograft Vasculopathy.
    1. This experimental study will determine if a molecular signaling pathway contributes to CAV.
  4. MicroRNA Biomarkers of Allograft Rejection in Cardiac Transplantation.
    1. Damage to the coronary arteries releases signaling molecules into the blood. If unique to CAV-related injury, these biomarkers could contribute to the development of a diagnostic test for early detection of CAV.
  5. Predictive Modeling.
    1. A unique approach for the detection of early (<6 months post-transplant) microvascular injury is the goal of this project and could lead to early diagnosis of the onset of CAV.
  6. Developing a Comprehensive Biomedical Imaging Informatics Tool for Precision Care of Pediatric Heart Transplant Patients.
    1. This pilot project will develop a clinical decision support system to assist in quantifying the analyses of the heart biopsy. Such a system will improve the detection and treatment of rejection, resulting in injury which is a likely contributor to CAV.
  7. Integrating Multi-parametric Echocardiography with Computer-Assisted Analyses in Detection for Early Allograft Rejection in Pediatric Heart Transplant Recipients: A Pilot Prospective Multi-center Trial.
    1. Optimizing and standardization of echocardiogram to provide more accurate screening/detection of early rejection and reduce injury-related CAV, in pediatric heart recipients
  8. Leukotriene B4: A Potential Mediator and Biomarker for Cardiac Allograft Vasculopathy.
    1. One of the heart’s responses to injury is inflammation that can lead to CAV. CAV causes the release of a newly found signaling substance that can become a biomarker for early CAV detection. That signaling pathway will be studied as an important target for novel drugs that could prevent and/or treat CAV

Tags: HEART TRANSPLANT, CONGENITAL HEART DEFECT, TRANSPLANTATION, HEART TRANSPLANTATION, DONATION, ENDURING HEARTS, PEDIATRIC HEART TRANSPLANT, CHD, CHARITY, NONPROFIT, NEW HEART, ORGAN REJECTION, TRANSPLANT ORGAN REJECTION, cav, Cardiac Allograft Vasculopathy

Carolyn Salvador

Written by Carolyn Salvador