Rise in Overdose-related Donor Hearts in US

Debra L Beck

February 06, 2019

The number of hearts recovered for transplant from drug-intoxication deaths is up, which might be what is driving a downward trend in the length of the heart transplant waiting list, new research suggests.

The proportion of deaths from drug abuse rose from 6.8 per 100,000 people in 1999 to 20.8 per 100,00 people in 2016. During a similar period of time (1999-–2017), the percentage of adult organ donors who died from drug intoxication from whom hearts were recovered for transplantation increased from 1.5% to 17.6%.

"We saw a threefold increase in drug intoxication-related deaths in the general population in the United States, and during approximately the same period, there was an elevenfold increase in the proportion of hearts taken from people who died from this particular organ source," reported senior author Mandeep R. Mehra, MD, MSc, Brigham and Women's Hospital and Harvard Medical School, Boston.

"Put another way, before 2009, we were basically recovering two lives for every 1000 lives lost through the medium of heart transplantation from these lives tragically lost to the drug-abuse epidemic. But starting around 2009, the trend started to linearly increase such that by 2016, we estimate that 6.24 adult organ donors were recovered per 1000 lives lost to drug intoxication."

Their findings are published online February 6 as a letter to the editor in the New England Journal of Medicine.

This new analysis, by cofirst authors Muthiah Vaduganathan, MD, MPH, Brigham and Women's Hospital, and Sara R. Machado, PhD, London School of Economics and Political Science, combines data from multiple sources to demonstrate that these trends show considerable regional variation, which appears consistent with the varying impact of the opioid crisis across the United States.

"This is a regionally heterogeneous epidemic," said Mehra in an interview. "It's very concentrated in the northeast and midwest of the United States, and we see regional increases over time in Pennsylvania, Ohio, Michigan, Massachusetts, Connecticut, on the northeast sector, and sporadic increases in California, Florida, and Texas, which represent the border states. Looked at carefully, it tells a tale of the socioeconomic implications of this epidemic."

Perhaps more intriguing, the data also hint that this increase in the donor pool might actually be serving to decrease the numbers of people waiting for heart transplants.

Machado, who is also the Harvey Chair Scholar at Brigham and Women's, Harvard Medical School, clarified the waiting list findings for theheart.org | Medscape Cardiology:

"Since 2009, the heart transplant waiting list had been increasing in size. In 2014 and 2015, we still saw a net increase, although the increase was smaller," Machado said. "But in 2016 and 2017, the wait-list size actually decreased, not because there were fewer people being added, but as a result of an increase in the number of people being removed from the list."

The researchers used data from the Organ Procurement and Transplantation Network (1999–2017) to examine state-specific patterns in the use of donor organs from drug-related deaths and to determine net annual changes in the size of the heart transplant wait list (the number of new registrations minus the total number of removals).

The data on age-adjusted annual rates of drug-intoxication-related deaths were obtained from the Centers for Disease Control and Prevention's WONDER online database, a comprehensive online source of public health information.

Heart transplantation remains the best treatment option for selected patients with advanced heart failure, with median survival now exceeding 10 years in adults.

Mehra and colleagues first reported the increase in the recovery of organs from brain-dead donors in the United States last May in a letter to the editor published in the New England Journal of Medicine.

They showed then that the opioid epidemic has been associated with a sharp increase in the recovery of organs from brain-dead donors in the United States, a trend not seen in Europe, but also that those who received hearts from those who died from drug overdoses had 1-year survival rates similar to those receiving hearts from donors who died from other causes.

This new analysis extends those findings to include information on regional variations in hearts recovered from drug-related deaths and the association between these data points and the waiting list size.

Higher-Risk Donor Hearts

"As a community, we've become more comfortable with using organs from drug-intoxicated donors because we see the organs generally function well over time and are not shown to increase post-transplant adverse effects," said Kiran K. Khush, MD, MAS, Stanford University Medical Center, California.

Khush explained that in the United States, and especially in Europe, the availability of donor organs had been steadily decreasing over the past 2 decades, for a variety of reasons, including improved seatbelt and traffic laws and better medical therapies.

"Most of the donor organs we were getting were from older donors, who have a lot of other medical problems, so it's not just the quantity but also the quality that has decreased over time," said Khush.

"Now with this tragic drug epidemic, we're seeing a surge in deaths in young people who really don't have a lot of other medical problems, which has resulted in an increase in very good quality donor organs."

Khush noted that about 22% of organ donors who die from drug overdose are hepatitis C positive. Accepting a higher-risk heart has been shown to offer better outcomes for patients, if only because it limits time on the waiting list.

Her group at Stanford just published a study showing that among the increased numbers of hepatitis C–positive donor hearts transplanted in recent years, risk-adjusted survival did not differ from hepatitis C–negative donor hearts.

"Now that we have incredibly effective antiviral drugs to treat and eradicate hepatitis C, there are four or five centers across the United States that now accept organs from hep C–positive donors, and then they treat the recipients after transplantation."

"With the right processes in place, we feel quite comfortable using these organs," said Khush, who added that there has been documentation of reduced waiting times for heart transplantation with this new practice.

"We've only been doing this for maybe 2 or 3 years, so we don't yet have any good long-term data on these patients, but it's an area of real interest in our community."

She is also interested in seeing more research into long-term function in hearts from donors who died from amphetamines, as opposed to opioids.

"I think in California we see slightly more drug overdoses from amphetamines, whereas on the east coast, I think it's more opioids. Amphetamines can definitely affect heart function, especially over time, making us a bit more leery about accepting hearts from folks who've had longstanding amphetamine use," she said.

If every cloud has a silver lining, it's this increased acceptance of higher-risk organs that is the silver lining of the opioid epidemic, said Mehra.

"We want to see this cause of accidental death disappear, but if these deaths do occur, for us in the transplant community, it is critical that we don't leave behind this opportunity to actually heal patients by making sure we recover these hearts, and other organs," said Mehra.

Mehra is a consultant for Abbott, Medtronic, Janssen (a division of Johnson & Johnson) Stealth Biotherapeutics Teva (now Mesoblast), NupulseCV Inc., and Portola. Machado reported having no conflicts of interest. Khush is the principal investigator of an NIH-funded study on donor heart utilization (R01 HL 125303).

N Engl J Med. 2019;380:597-599. Abstract

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