Heart Transplantation Insights with David Baran, MD

Transplant cardiologist David A. Baran, MD, FACC, FSCAI, FHFSA, serves as Section Head of Advanced Heart Failure, Transplant and Mechanical Circulatory Support (MCS) at Cleveland Clinic Weston Hospital. Throughout his career, spanning more than 20 years, Dr. Baran has personally cared for more than 1,000 heart transplant patients. He is also a prolific clinical researcher, whose work has made important contributions in the areas of transplant immunosuppression and the management of cardiogenic shock.

In addition to being an active member of the International Society of Heart Lung Transplantation (ISHLT), having previously served as co-chair of both the ISHLT Donor Heart Selection Task Force and the Cardiogenic Shock Task Force, Dr. Baran recently completed a three-year term (2020-2023) on the Organ Procurement and Transplantation Network (OPTN) Heart Transplantation Committee.

Consult QD had the opportunity to talk with Dr. Baran about the latest developments in the field of heart transplantation. Here are some highlights from that conversation.

Q. It’s been five years since the revamp of the U.S. heart allocation system. In your experience, what has been the biggest effect?

The heart transplant allocation schema has shifted over the years from a 2-tier system, then a 3-tier system (1A/1B/2), and now to our current 6-tiered system. The first three tiers (1-3) are the most urgent cases, with patients on ECMO (extracorporeal membrane oxygenation) and other temporary assist devices, while tiers 4-6 include more stable patients. The goal with these changes has been to prioritize the sickest patients, reduce wait list mortality, and address disparities.

An early study, published in 2020, found that the policy change is having its desired effect with a reduction in risk of death or clinical deterioration for patients on the wait list. Unfortunately, the researchers also noted a 4% decline in post-transplant survival at one year. Other single-center reports confirm that their sickest patients are getting rapid access to the highest quality hearts, while the most stable patients are experiencing longer wait times or receiving extended criteria donor (ECD) organs.

Here at Weston Hospital we are very aggressive at how we look at donor hearts so that our status 4 and 5 patients aren’t left behind. According to data from the Scientific Registry of Transplant Recipients (SRTR), we have a higher organ offer acceptance ratio (2.31) and a shorter time-to-transplant. Approximately 35% of our patients are transplanted in their first 30 days on the wait list versus 21% nationally. Likewise, at three years, 83% of our patients have received a transplant versus 68% nationally.

Q. Another major shift in the heart allocation system was to extend competition for donor hearts to 500 miles from donor hospitals. What has that meant for patients?

The policy goal was to foster broader geographic sharing of donor organs. What we see is that there are always a large and ever-changing number of recipients at high status who have priority, which means more stable patients are having to wait longer. It is important to note, patients in Florida continue to benefit from living in a state that ranks third in the nation for donor registry enrollment and from the generosity of our donor families.

Responding quickly to donor offers and having access to rapid transport is another way the Heart Transplant Program at Cleveland Clinic Florida has adjusted to the change. As a result, we have a higher offer acceptance ratio (1.93) for donor hearts more than 500 miles away.

Last year I joined a team of researchers to look at travel distances under the new allocation system. What we found is that while the distances between donors and recipients have increased, survival outcomes remain largely unchanged. However, because greater distance can result in longer ischemic time during organ transport, we agreed it merits further studies to determine impacts on recipient survival.

Q. You’ve done considerable research in transplant immunosuppression. How has the approach changed in recent years?

Advancements in immunosuppressive therapy post-transplantation have contributed significantly to prolonging recipient survival. Today adult heart transplant recipients enjoy a median survival of 12 to 13 years. But balancing the risk of rejection with the risk of infection continues to evolve. While heart transplant rejection rates in the first-year post-transplant have fallen to about 24%, there is still room for improvement.

Earlier this year my former colleagues at Newark Beth Israel Medical Center and I reported the 15-year outcomes of the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus (TAC) monotherapy to TAC and mycophenolate mofetil (MMF) without long-term steroids. This follow-up study demonstrated that rapid steroid weaning is not associated with long-term negative impacts and that we can safely tailor immunosuppression by using TAC monotherapy for select patients while achieving similar outcomes to the conventional TAC/MMF regimen.

This past February, our team at Weston Hospital adopted a new, leaner immunosuppression protocol that includes discontinuation of steroids after two months. A steroid-free approach protects patients from some of the known side effects of corticosteroids, including weight gain, delayed wound healing, diabetes and hypertension, among others.

Q. You also recently published a commentary on alternatives to percutaneous endomyocardial biopsy (EMB). What is your hope for the future?

Heart transplant recipients often undergo multiple EMB procedures in the first year following transplantation as way to calibrate the intensity of immunosuppression. In addition to being an invasive procedure, EMB is not without risks. Plus, the pathological finding of an EMB is a relatively late indicator of immune activation seen prior to graft infiltration and allograft dysfunction. Newer approaches have been identified that can recognize low baseline immune activation, including gene expression markers and donor-derived cell-free DNA (ddCF-DNA). As I shared in my commentary, there also has been some exciting developments in the use of blood-based miRNA biomarkers to detect cardiac acute cellular rejection. This could lead to a more sensitive, noninvasive diagnostic tool for identifying rejection at an earlier stage. I am hopeful others will pursue this approach and further develop this promising technique.