by Elise Wachspress
Imagine you need a new heart to survive.
First, there is the drama of waiting for a donor heart that is a good match—knowing that your chance at life depends on someone else losing theirs.
Then, there is the actual surgery—having your chest opened and an entire team implanting this new organ, followed by both the euphoria of success—one year survival rates are now over 85 percent—and the realization that rehabilitation will require strength of body, mind, and will.
Next comes an intense drug regimen to protect your new heart from being rejected by your body’s immune system. The early danger is that your body’s specialized T-cells will attack the new heart itself. Over the past few decades, transplant specialists have developed a number of strategies to tamp down these cellular incursions, balanced with vigorous antibiotic management to address opportunistic infections. So your chances of thriving through this early stage are strong.
Yet even with a carefully calibrated drug regimen, a significant number of patients still fall prey to serious problems later, especially later during the first five years after surgery. Most common is a condition known as cardiac allograft vasculopathy (CAV). In CAV—known as the Achilles heel of heart transplantation—fibers grow down the inside of the cardiac artery wall, thickening the vessels, not dissimilar to how old galvanized pipes in a home’s plumbing eventually corrode and slow the flow of water to a trickle. Though this kind of thickening can happen in other types of cardiac disease, it progresses much more quickly in patients with heart transplants and often leads to failure of the graft.
Transplant specialists like Ann Nguyen, MD, have suspected for a while that CAV results from an attack not by the body’s immune cells, but by immune proteins—antibodies—circulating in the blood. Growing evidence suggests that certain sensitizing events, like a blood transfusion or pregnancy, can cause the body to create new donor-specific antibodies. Fewer than 10% or so of patients have these antibodies before transplant, but up to three times that many develop these antibodies afterward, and their presence can increase the odds of a failed heart graft fivefold.
Nguyen and her fellow, Mark Dela Cruz, MD, have been following the work of Duchossois Family Institute Director Eric Pamer, MD. His research has shown that certain gut microbes can protect against infections in patients receiving a bone marrow transplant and that bacterial diversity in the gut decreases mortality after the transplant. Nguyen and Dela Cruz are interested in understanding how a patient’s individual microbiome might affect the production of donor-specific antibodies and the outcomes patients experience after heart transplants.
To do so, they have designed an observational clinical study, with one fairly simple change in each patient’s regimen: the addition of one more type of sample—stool—to the blood and urine samples normally collected to monitor patients before and for months after heart transplant. The stool samples will allow Pamer and the DFI team to assess the patient’s microbiome before surgery and track any changes after transplant. They will then correlate what they learn about each patient’s microbiome with the progress of their cardiac transplant for at least the first two years after each patient’s transplant.
UChicago is extremely well-positioned to conduct this study. Not only does the University of Chicago Medicine perform 40 heart transplants per year—with the best survival rates in the state—but the DFI provides facilities for microbial characterization and study matched by few other research centers. Nguyen and Dela Cruz aim to enroll as many patients as possible within one year.
With what they learn about the microbiome’s effects on long-term success after cardiac transplant, they hope they can keep transplanted hearts beating healthily for many more years.
Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office