Perhaps a heart-brain connection remains even after the transplant, says researcher Shinobu Itagaki.
For heart transplant patients, mortality and allograft failure are higher when the organ they receive comes from a younger donor whose brain death was due to stroke rather than d other causes, according to new data. But stroke as a cause of death is not linked to additional risk when the donor is older.
Still, the researchers stress that their findings should not affect decision-making when accepting potential hearts for transplant.
“We’re not trying to say that young stroke donors should be avoided,” co-author Shinobu Itagaki, MD (Mount Sinai Medical Center, New York, NY), told TCTMD. “Young donors are always very valuable resources for the transplant community. But still, I think what we’re trying to suggest is that this study may provide opportunities for future studies to improve overall transplant outcomes.
Likewise, in an accompanying editorial, Sunit-Preet Chaudhry, MD (St. Vincent Medical Group, Indianapolis, IN), and colleagues caution against misinterpreting the results.
The findings, they write, “should in no way dissuades us from accepting and implanting these donor hearts”, the overall survival at 1 year being greater than 90%. “Instead, these results underscore the importance of further evaluating the mechanisms underlying differences in clinical outcomes so that interventions (eg, right ventricular protective strategies) can be developed that, would hopefully mitigate the adverse effects of stroke in younger donors and lead to further improved outcomes.
Worst outcome with stroke in younger donors
Today, organs for heart transplantation are usually harvested from brain-dead donors, but there has been some controversy over whether stroke as a cause of death in the donor would affect the outcome. long term of the recipient. However, having the heart from a younger patient was considered beneficial to the recipient, as the organ would have been less exposed to comorbidities.
For the study, published in the March 22, 2022 issue of Journal of the American College of CardiologyTakahisa Mikami, MD (Tufts University School of Medicine, Boston, MA), and colleagues analyzed the long-term mortality of 3,761 allograft recipients from donors with stroke as the cause of brain death and 14,677 with causes other than stroke from the United Network for Organ Sharing (UNOS) who had a transplant between 2005 and 2018. The researchers used inverse probability weighting for risk adjustment.
I think your heart is somehow connected to your brain, even after it’s gone to someone else. Shinobu Itagaki
Over a median follow-up period of 4 years, there was no change in the rate of donors having stroke as the cause of brain death. There was a relationship between the cause of brain death and the age of the donor (P for interaction = 0.008). When donors were aged 40 or younger and stroke was the cause of brain death, the recipient’s 5-year mortality risk increased (23% versus 19%; HR 1.17; 95% CI 1 .02-1.35) as did allograft failure (HR 1.30; 95% CI 1.04-1.63). Benchmark analyzes showed that these increased risks were most likely within the first 60 days. However, the cause of brain death was not associated with outcomes when donors were over 40 years old.
Hemodynamics were similar for younger donors who died of stroke or other causes. But the median time between admission and brain death was significantly longer in young donors with stroke than in donors without stroke (3.4 vs. 2.8 days), and similarly when the time between brain death and aortic clamping was included (5.0 vs 4.3 days; P
Mikami and colleagues suggest several possible explanations for the age-dependent effect they observed. First, younger patients are more likely to have hemorrhage compared to ischemic stroke, with the former causing “a more abrupt increase in intracranial pressure, which could lead to more frequent and severe myocardial damage and permanent impairment or transient allografts,” they write. .
Furthermore, stroke at an early age, “particularly when not associated with traditional risk factors such as uncontrolled hypertension, may be a surrogate marker for underlying vasculopathy. inherent,” say the authors. “This predisposition may be correlated with allograft coronary vasculopathy.”
Finally, there is the fact that younger patients generally have a larger gap between hospital presentation and brain death than older patients. During this extended period, the allograft may be exposed to “detrimental physiological insults”, write Mikami et al.
“We made a lot of assumptions about the results we got, but we don’t really know what really explains the findings we found,” Itagaki said, adding that further work on the mechanisms at play here is needed. justified. Other factors such as donor age and ejection fraction have been linked to recipient outcomes, but the association between strokes is “not very intuitive,” he said. Ultimately, Itagaki concluded, “I think your heart is somehow connected to your brain, even after it’s gone to someone else.”
Nosheen Reza, MD (University of Pennsylvania Hospital and University of Pennsylvania Perelman School of Medicine, Philadelphia), who reviewed the study for the TCTMD, agrees with the authors that he There are differences in the types of strokes occurring in younger and older patients. “Perhaps there’s just a difference in the physiological impact of these types of intracranial events when a stroke is hemorrhagic versus ischemic,” Reza said.
However, she pointed out that the cause of death can be difficult to determine. “And while there certainly is an approximate cause of death, could there be something else underlying that we’re just not aware of?” she says.
Like Itagaki and the columnists, Reza doesn’t think the results should affect a younger donor’s potential for a heart to be used for transplant. “I think this consideration, however, and future investigation of some of these points that the authors raise as possible explanatory hypotheses, provides us with an opportunity to think more about how to personalize the transplant,” she said. .
These data provide an opportunity to change the “broad set of rules and best practices” that have been applied to all heart transplant candidates for many years, regardless of underlying characteristics, Reza said. “This may represent another item on the checklist that we go through when, for example, we encounter the opportunity for a donation from a young donor who has had an intracranial event.”
Specifically, she envisions better prospective phenotyping of young donors who die of intracranial events as well as differentiation of ischemic stroke from hemorrhagic stroke, and then careful attention to monitor for any signs of primary graft dysfunction in the early post-transplant period. .
While various characteristics of the donor are known to the recipient’s care team, Reza said, “I don’t know if I can say lastingly that at day 50 post-transplant I’m still thinking about the cause of death for this donor as an impact on me. at present [when] take care of this patient in front of me.
But maybe doctors should pay more attention to this, she suggested. “Perhaps stroke as a cause of death isn’t the only area where we’re going to see associations like this.”