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Higher mortality in heart transplants from Covid donors, analysis finds

Adult heart transplant recipients from donors with active Covid-19 infection had higher mortality at six and 12 months than those with transplants from donors who had either a recently resolved Covid case or did not have Covid, a retrospective analysis found.

For heart transplant recipients in propensity-matched cohort analyses, post-transplant mortality at six months was 4.9% for recipients with non-Covid hearts compared to 13.8% for recipients with active Covid heart transplants, reports MedPage Today.

Mortality at one year was 9.2% for recipients with non-Covid heart transplants, compared with 23.2% for recipients with active Covid heart transplants, according to Dr Shivank Madan of the Montefiore Medical Centre and Albert Einstein College of Medicine in New York and co-authors in the Journal of the American College of Cardiology.

However, heart transplants from recently resolved Covid donors had similar post-transplant mortality to non-Covid donors, with 8.7% and 8.5% mortality at six months, respectively, and 13.7% vs 12.6% mortality at one year, respectively.

“We need to realise that Covid-19 infection can have a wide spectrum of disease severity including extra-pulmonary manifestations in potential donors, and our understanding of the virus in the presence of immunosuppression continues to evolve,” Madan told MedPage Today.

“Our study highlights a need for continued evaluation, risk-stratification, and a more nuanced approach in evaluating potential heart donors with Covid-19 infection.”

Compared with heart transplant recipients from non-Covid donors, unadjusted analyses showed those who received a transplant from an active Covid donor had increased mortality at six months (HR 1.74, 95% CI 1.02-2.96, P=0.043), and at one year (HR 1.98 95% CI 1.22-3.22, P=0.006). Adjusted analyses showed similar trends.

“HT (heart transplant) centres have had to continuously modify recipient and donor management practices during the pandemic as our understanding of the virus has evolved,” Madan and colleagues wrote. “Our early analysis suggests that while HTs from recently resolved Covid donors appears to be safe, HTs from active Covid donors may be associated with increased mortality.”

From May 2020 to June 2022, the authors found the use of Covid heart donors – both active and recently resolved Covid – increased significantly and was highest when Delta and Omicron were dominant.

Covid heart donors were younger (30 vs 32-years-old), mostly male (80% vs 72%), and were more likely to have died from head trauma (44.77 vs 39%) compared with non-Covid donors.

Autopsy studies have suggested that while viable transmissible virus was limited to the respiratory tract, Covid-19 proteins could still be found outside it, according to Madan and co-authors.

A small number of studies have sought to evaluate potential risks of transplantation from donors with a history of Covid-19 infection, and though early outcomes suggested “acceptable short-term outcomes”, short follow-up times, the authors noted for one study, were “too short to detect any significant difference”.

“This issue directly affects our patients with advanced heart failure on the transplant waiting list; and given the ongoing shortage of donors, we … are forced to make a clinical judgment of whether to use potential donors with Covid-19 infection for a heart transplant or not on a routine basis,” Madan said. “This becomes especially challenging due to lack of clear outcomes data.”

Dr Josef Stehlik of the University of Utah School of Medicine, who was not involved with the analysis, said the study provided “important insights”.

“Outcome of patients transplanted using donors with recently recovered Covid-19 infection was similar to donors without Covid infection,” Stehlik said, “suggesting that at least in the short term, there is no signal for increased risk which is quite reassuring”.

Stehlik also said the higher risk of mortality in recipients of organs from donors with active infections ‘is concerning… we need more data to determine the reason”.

“Transmission of Covid from the donor to the recipient has not been reported in heart transplantation, so if there is an increased risk, it is possibly through a different mechanism,” he added.

Researchers used United Network for Organ Sharing (UNOS) data from May 2020 to June 2022 to identify Covid donors and subdivided this group into active Covid (who had a positive test within two days of organ procurement) and recently resolved Covid.

After excluding multi-organ transplants, retransplants, paediatric recipients, and patients with missing follow-up, heart transplants from 150 active Covid and 89 recently resolved Covid donors were included in the study, along with 5 641 heart transplants from non-Covid donors.

For propensity-matched analyses, heart transplants from 150 active Covid donors were matched with 300 non-Covid donors. Heart transplants from 87 recently resolved Covid donors were matched with 174 non-Covid donors.

Recipient mortality was compared using Cox proportional hazards regression models and Kaplan-Meier analysis. All recipients were censored at one year of post-transplant follow-up.

Overall median follow-up time for the outcomes analysis cohort was 11.2 months, but only 5.7 months for Covid donor heart transplants.

“Despite adjusting, there remains a possibility that the results are confounded by factors not taken into account in the analysis, or due to the fact that not all patients in the study group completed six- and 12-month follow-up after transplant,” Stehlik noted.

Limitations included a wide range of timing and frequency for Covid-19 testing among potential donors despite recommendations to test as close as possible to the time of organ procurement, and a lack of detailed information about Covid disease activity or specific SARS-CoV-2 strain. Vaccination status of donors and recipients was unknown.

The study was not powered sufficiently to directly compare active Covid and recently resolved Covid subgroups, Madan and colleagues said. They also did not have information on anti-retroviral therapies that may have been administered around the time of the transplants.

Study details

Early Outcomes of Adult Heart Transplantation From COVID-19 Infected Donors
Shivank Madan, Marvyn Chan, Omar Saeed, et al.

Published in the Journal of the American College of Cardiology on 17 May 2023.

Abstract

Background
There is a paucity of data on heart transplantation (HT) using Covid-19 donors.

Objectives
This study investigated Covid-19 donor use, donor and recipient characteristics, and early post-HT outcomes.

Methods
Between May 2020 and June 2022, study investigators identified 27,862 donors in the United Network for Organ Sharing, with 60,699 COVID-19 nucleic acid amplification testing (NAT) performed before procurement and with available organ disposition. Donors were considered “Covid-19 donors” if they were NAT positive at any time during terminal hospitalisation. These donors were subclassified as “active Covid-19” (aCOV) donors if they were NAT positive within 2 days of organ procurement, or “recently resolved Covi-19” (rrCOV) donors if they were NAT positive initially but became NAT negative before procurement. Donors with NAT-positive status >2 days before procurement were considered aCOV unless there was evidence of a subsequent NAT-negative result ≥48 hours after the last NAT-positive result. HT outcomes were compared.

Results
During the study period, 1 445 “Covid-19 donors” (Covid-19 NAT positive) were identified; 1 017 of these were aCOV, and 428 were rrCOV. Overall, 309 HTs used Covid-19 donors, and 239 adult HTs from Covid-19 donors (150 aCOV, 89 rrCOV) met study criteria. Compared with non-COV, Covid-19 donors used for adult HT were younger and mostly male (∼80%). Compared with HTs from non-COV donors, recipients of HTs from aCOV donors had increased mortality at 6 months (Cox HR: 1.74; 95% CI: 1.02-2.96; P = 0.043) and 1 year (Cox HR: 1.98; 95% CI: 1.22-3.22; P = 0.006). Recipients of HTs from rrCOV and non-COV donors had similar 6-month and 1-year mortality. Results were similar in propensity-matched cohorts.

Conclusions
In this early analysis, although HTs from aCOV donors had increased mortality at six months and 1 year, HTs from rrCOV donors had survival similar to that seen in recipients of HTs from non-COV donors. Continued evaluation and a more nuanced approach to this donor pool are needed.

 

JACC article – Early Outcomes of Adult Heart Transplantation From COVID-19 Infected Donors (Open access)

 

MedPage Today article – Heart Transplants From Active Covid Donors Linked With Higher Mortality (Open access)

 

See more from MedicalBrief archives:

 

COVID-19 causes SA's heart transplant programmes to skip a beat

 

Donor to recipient transmission of SARS‐CoV‐2 by lung transplant

 

Unvaccinated heart failure patients three times likelier to die from COVID – US studyhttps://www.medicalbrief.co.za/unvaccinated-heart-failure-patients-three-times-likelier-to-die-from-covid-us-study/

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