Change in Protocol? Heart Transplants for Amyloidosis Patients
By Adrienne Mueller, PhD
August 28, 2020
If you need a new heart, becoming a transplant recipient is a daunting prospect. In the US, at any point in time, there are about 4,000 people on the waiting list to receive donor hearts. Because of this incredibly high demand and the life-or-death nature of the need, when a heart becomes available, the procedure for allocating it is an extremely thorough one. Clinicians want to identify patients who will benefit most from receiving a new heart. And because the tissue is so precious, the number of reasons that can disqualify someone from receiving a donor heart is a very long list. For most medical centers, having a condition called cardiac amyloidosis is one of those reasons.
Amyloidosis occurs when misfolded proteins accumulate in our tissue. These accumulated proteins, called amyloid deposits, are toxic and eventually cause organ dysfunction. There are about 30 different types of amyloidosis, each related to the misfolding of a specific protein. The two most common forms of amyloidosis that affect the heart are light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). AL amyloidosis arises as a consequence of a cancerous transformation in the bone marrow, whereas ATTR amyloidosis can be a consequence of aging or of an inherited genetic susceptibility. In the US, it is estimated that there are at least 4,000 new cases of AL every year, and ATTR amyloidosis is now increasingly recognized as one of the more common forms of heart failure in older patients. Both forms of cardiac amyloidosis cause significant morbidity and mortality.
Because amyloidosis is a chronic disorder and clinicians are concerned that if you give a person with amyloidosis a healthy heart it will become damaged by amyloid deposits again over time, individuals with amyloidosis are typically rejected as candidates for new hearts. Not so at Stanford University and the Stanford Amyloid Center. Because of advances in treatments for amyloidosis, in very specific circumstances clinicians have been able to make exceptions to the criteria that normally prevents amyloidosis patients from receiving hearts and have had excellent overall outcomes. Between 2004 and 2017, 31 patients—13 with AL and 18 with ATTR—received heart transplants at Stanford. These surgeries provided data for a group of researchers, led by first author Christopher Barrett, MD and Stanford Cardiovascular Institute-affiliated senior author Ronald Witteles, MD, to perform one of the largest single-center studies reported to date to determine whether individuals with amyloidosis do in fact have worse outcomes than other heart transplant recipients.
In their paper, recently published in the Journal of the American College of Cardiology: Heart Failure, the researchers examined the outcomes of individuals with both AL amyloidosis and ATTR amyloidosis after receiving a heart transplant. Immediately after the transplant, there were no differences between either group of amyloidosis patients and patients with other heart conditions in terms of their post-operative bleeding, renal failure, rates of infection, or tissue rejection. And eight years later there was also no difference in mortality. Not only that, but of the four amyloidosis patient who died, their deaths were not due to amyloidosis or amyloidosis therapy-related complications (two died of pneumonia, and two died of unrelated cancers).
What this study from the Stanford Amyloid Center shows is that we have come a long way in the treatment of amyloidosis and that, if you are careful about the patients you select to receive a heart transplant, you can have outcomes that are every bit as successful as patients with other causes of heart failure. With better diagnostic options, better therapies, and in select cases heart transplantation, the world of amyloidosis has been changing dramatically for the better over the last decade, with the Stanford Amyloid Center helping to lead the way.