Transplant Docs Are Sticking With Invasive Biopsies After Heart Transplants
Endomyocardial biopsies (EMBs) may be losing favor as non-invasive alternatives improve, but the gold standard for routine surveillance of heart transplant rejection isn’t going away anytime soon, transplant cardiologists agreed.
For any screening to be effective, it has to be safe and the prevalence of the disease must be high enough to justify the screening, said G. Michael Felker, MD, MHS, of the Duke Clinical Research Institute in Durham, North Carolina, during a debate at the Heart Failure Society of America (HFSA) meeting, held both virtually and in Denver.
In transplant recipients without any signs or symptoms of graft dysfunction or heart failure, EMB doesn’t meet these criteria, he argued, citing the possibility of life-threatening complications such as tamponade and cardiac perforation, as well as low diagnostic yield given the “extraordinarily low” prevalence of asymptomatic rejection after heart transplantation (1-3% in contemporary practice).
“We’re doing a lot of biopsies to try to find a needle in a haystack in a small number of people,” Felker told the audience. “Routine EMB surveillance is not supported by science, logic, patient preferences, or randomized trial data.”
EMB entails using a bioptome, a catheter with jaws on the tip, to scrape away small pieces of tissue from the heart. Patients currently undergo multiple routine EMBs after receiving a heart transplant, with each center determining its preferred frequency of biopsy.
Aside from the major safety concerns, EMB causes a lot of patient anxiety and discomfort, uses up a lot of resources, and leads to common chronic complications like tricuspid regurgitation that can be highly morbid, Felker explained.
The information that can be gleaned from EMB isn’t even that good, he added, noting that even expert pathologists only agree about 50-70% of the time during histological interpretation of EMB samples.
He suggested that progress in donor-derived cell-free DNA (dd-cfDNA) and other non-invasive techniques means patients may have better alternatives to EMB.
“Is it time to hang up the bioptome? Almost but not yet,” said JoAnn Lindenfeld, MD, of Vanderbilt University Medical Center in Nashville, who took the opposing side of the debate. “Most of us have cut back on our biopsies. At Vanderbilt, we’re down to six protocol biopsies, and we’re getting down to five. But we still think [EMBs are] valuable.”
Lindenfeld agreed that acute rejection is not common, but it is clinically significant given that rejection within 1 year is the greatest hazard for 5-year survival in adult heart transplant recipients.
dd-cfDNA is “very promising,” but any technique that diagnoses heart transplant rejection has to work early given its early occurrence, Lindenfeld said. A preliminary study recently found dd-cfDNA to reliably detect acute rejection — its accuracy wasn’t very good until day 28, however, “so we’ve already missed a lot of rejection by then,” she said during the HFSA session.
“We’ll agree that noninvasive tests are unproven, and clearly there are clinical scenarios for biopsy,” Felker said.
“I don’t think anyone thinks biopsies are going away totally. I just think we need a more sensible approach like we do in so many other things,” he urged, citing the example of non-invasive testing for ischemia before proceeding to catheterization.
In any case, Felker said that people who are sick after heart transplantation are sick not because of rejection, but rather to the consequences of too much immunosuppression. “There’s never been a randomized trial to say that treating asymptomatic rejection is a good thing to do,” he said.
Felker disclosed grant support from the NHLBI, American Heart Association (AHA), Novartis, Amgen, Merck, Bayer, and Myokardia; and personal ties to Novartis, Amgen, Medtronic, Bristol Myers Squibb, Cytokinetics, Abbott, Cardionomic, Reprieve, Boehringer Ingelheim, AstraZeneca, Sequana, Merck, EBR Systems, V-Wave, LifaNova, Rocket Pharma, and Siemens.
Lindenfeld reported consulting to Abbott Alleviant, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Merck, and V-Wave; and receiving grants from AstraZeneca, Sensible Medical, VoluMetrix, AHA, and NIH.
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