Genomic Revolution in Heart Transplant Medicine

Heart transplants are an extremely high-risk medical procedure. The main reason for a patient to undergo a heart transplant is to increase survivability, but an inherent contradiction arises due to the myriad postoperative risks. Among these is the risk of transplant rejection. Cardiac transplant recipients have an average of one to three rejection episodes in the first year following the procedure, while 18% of all deaths within the first year are due to acute rejection. The current procedure for detecting rejection is quite invasive: a piece of the new heart is cut through a biopsy and examined for cell-death. Researchers have found a promising method of using genetic sequencing to predict instances of cardiac transplant rejection, preventing a need for additional surgery.

Image courtesy  of cooldesign via
Image courtesy of cooldesign via

During a rejection episode, the donor’s immune system attacks and may eventually destroy the new organ. A research team based out of Stanford University discovered that dying cells within the heart release snippets of DNA, called cell-free, donor-derived DNA (cfdDNA). Before transplant surgery is performed, the recipient and their donor both undergo genome sequencing, and a genotypic profile is built which describes the thousands of single-nucleotide polymorphism variations between donor and recipient. This genotypic profile is used to determine the difference between both parties DNA.

Once the DNA profile is complete and the surgery is performed, the patient’s blood is closely monitored for cfdDNA. The team of researchers established a threshold for normalcy in cfdDNA levels following a transplant in their study, finding that approximately 6% of total circulating blood belongs to the donor during the first day. After a week, however, levels drop to around 2%. They found that rejection events can be accurately predicted by a marked increase in these baseline levels of cfdDNA. The researchers tested this accuracy by also performing the invasive biopsy mentioned earlier alongside cfdDNA monitoring, and found that levels were low in biopsies that reported no rejection compared with those diagnosed with mild rejection. Not only that, but cfdDNA levels increased with the class of rejection (low, mild, severe), meaning cfdDNA monitoring offers a quantitative approach. All this five months before a rejection event could be predicted by biopsy.

The science surrounding transplant surgery isn’t exactly the pinnacle of preventative medicine. Transplants generally only occur in dire medical circumstances, after a major trauma has already occurred. While this blog has focused on the truly personalized, preventative care genomics can provide, it’s important to understand that there are uses beyond those areas. Genomics is applicable in nearly all fields of medicine, and each use has a stake in improving patient care and clinical outcomes. New Amsterdam Genomics is excited about a future where genomics is applied in as many ways as is practical and effective.



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