Fewer biopsies, happier patients: Why molecular blood testing is a game-changer for managing heart transplant recipients
Follow-up care after a successful heart transplant can be challenging—both for providers and their patients.
Consider, for example, the fact that so many patients who develop complications never actually present with symptoms. After undergoing a heart transplant, patients typically have to endure biopsies, sometimes as many as 14 in the first year alone, to monitor for early evidence of rejection. However, the vast majority of those biopsies are negative, making it easy to wonder if they are even necessary.
Biopsies also come with risks. The heart could be perforated, for example, or there may be bleeding or an infection. While these incidents are increasingly rare, they still happen.
“Whenever you take a catheter to a patient, you are creating that small possibility of something going wrong,” explains Jeffrey John Teuteberg, MD, a veteran heart failure cardiologist and CareDx’s chief medical officer.
On top of that, he adds, the very idea behind a biopsy—that one small sample represents what is happening across an entire muscle—is false.
“You are only sampling maybe a dime-sized area of the heart with a biopsy,” he says. “And we know from pathologic studies that rejection isn’t an all-or-nothing thing. It’s possible that one part of the muscle may show signs of subclinical rejection and another may not.”
A new approach, however, is changing the post-transplant care path. It involves two molecular blood tests designed to limit unnecessary biopsies. One of the tests, AlloMap, looks for gene expression patterns that suggest a high likelihood of rejection. The other, AlloSure Heart, uses donor-derived cell-free DNA to detect signs of graft injury. Both tests are available as part of the CareDx HeartCare testing platform.
By using this pair of molecular tests in tandem, clinicians can significantly improve their understanding of a patient’s immediate risk of rejection. If both test results are negative, there is a very low risk of rejection, and an invasive biopsy can be safely skipped. When both are positive, the patient is at the highest risk and physicians will then consider a biopsy.
“In cardiology, we combine tests to improve our diagnostic prowess all the time,” says Jeremy Kobulnik, MD, CareDx’s medical director of heart transplantation and a former heart failure cardiologist. “We pair electrocardiograms (ECGs) with troponins, for example, and we pair echocardiograms with B-type natriuretic peptide blood tests. This is the same basic concept—performing complementary tests to guide decision-making.”
Kobulnik emphasizes that AlloMap and AlloSure Heart are as different from each other as ECGs are from troponins. They’re both molecular blood tests, yes, but they provide different information about the patient’s health.
“Just like you wouldn’t get rid of ECGs because you can run troponin tests, you wouldn’t get rid of AlloMap because you have AlloSure Heart. Using them together is how you achieve the best possible performance.”
— Jeremy Kobulnik, MD, Heart Failure Cardiologist and CareDx Medical Director of Heart Transplantation
The strategy doesn’t look to replace biopsies altogether, Kobulnik notes. Instead, CareDx believes the early use of HeartCare tests can inform the timing of biopsies by minimizing low-yield procedures and ensuring patients only undergo procedures that are clinically necessary.
Clinical data highlight the value of HeartCare
The company’s confidence comes from its data. The Surveillance HeartCare Outcomes Registry (SHORE) is a large-scale, prospective, observational clinical trial focused on the long-term impact of monitoring heart transplant recipients with AlloMap and AlloSure Heart. More than 2,700 patients were enrolled across 67 U.S. facilities in the CareDx-funded trial.
The results were significant. Overall, researchers found that using AlloMap and AlloSure Heart to surveil heart transplant recipients was an effective way to identify patients who face a heightened risk of acute cellular rejection (ACR) or require a follow-up biopsy.1 The ACR rates were 1.5% for patients with two negative test results and 9.2% for patients with two positive results. Follow-up biopsies, meanwhile, were performed on only 8.8% of patients with two negative test results and 35.4% of patients with two positive results.
In addition, 94.9% of patients surveilled with HeartCare were alive after two years, and 97.3% of those patients had normal graft function.
In addition, the latest SHORE manuscript confirms the substantial impact these noninvasive tests can make on patient care beyond the decision of whether or not to perform a biopsy.2 It included nearly 2,000 patients treated across 59 U.S. facilities, following them for up to five years. Overall, the study’s authors found that simultaneously positive results for both tests in the first six months post-transplant were linked to a nearly twofold increase in the cumulative incidence of graft dysfunction and cardiovascular death over the following year. This was even true when testing patients with no history of ACR during the first 6 months.
“These tests can clearly reduce the amount of biopsies you end up performing,” Kobulnik says. “And then the biopsies you do end up being much more meaningful. This is all particularly relevant for patients who live far away from their doctors.”
Cutting down on low-yield biopsies seen as a major victory for patients
Perhaps it goes without saying, but heart transplant recipients universally like the idea of undergoing fewer biopsies.
“Biopsies are invasive and patients don’t like them,” Teuteberg says. “In fact, most patients say they hate the biopsies more than the actual transplant procedure.”
Limiting low-yield biopsies has a positive impact on the mental health of heart transplant recipients as well. Kobulnik says he always felt bad asking patients to come back to the hospital again and again for invasive testing, especially when they feel so much better and want to move on.
“We’ve taken this person crippled by heart failure and essentially cured them—but they still perceive themself as a patient, because they’re still being treated that way,” he says. “We want them living life to the fullest and doing all the things they love to do. You do that by keeping their post-transplant care comfortable and non-invasive whenever possible.”
Blood tests lead to more personalized care
Teuteberg, who spent many years using these CareDx tests before joining the company, says he has seen firsthand how helpful these tests are when it comes to improving patient care.
“Anything that makes it easier for you and your team to take care of your patients is important,” he says.
“This technology can decongest clinics and cath labs, and it helps clinicians spend less time worrying about biopsies and more time performing life-saving procedures like transcatheter aortic valve replacement or percutaneous coronary intervention.”
— Jeffrey John Teuteberg, MD, Heart Failure Cardiologist and CareDx Chief Medical Officer
Another significant benefit of these tests is the way clinicians regain the ability to provide personalized care. At many hospitals and health systems, post-transplant protocols require a cascade of biopsies, including an added procedure anytime a change is being considered to the patient’s drug intake. With these molecular tests, however, monitoring the body’s response to medication changes can be handled without the use of additional biopsies.
For example, transplant recipients are typically prescribed a lifetime of multiple immunosuppression medications designed to help the body fight off rejection. Physicians like to get patients on as low a dose as possible when they can, but they also don’t want to order a new biopsy just to consider a medication change. AlloMap and AlloSure Heart make that easier than ever.
“Clinicians know they are probably over-immunosuppressing patients right now,” Kobulnik explains. “Historically, they’ve really had no choice. But now they can provide that more personalized care based on the specific needs of each patient. There’s a tremendous opportunity here to removes the handcuffs and allow clinicians to address each patient's needs in terms of exactly what they need—no more and no less.”
References:
Michael has more than 19 years of experience as a professional writer and editor. He has written at length about cardiology, radiology, artificial intelligence and other key healthcare topics.