Beyond donation to organ utilization in the USA.

PURPOSE OF REVIEW: The deceased donor organ pool has broadened beyond young, otherwise healthy head trauma victims. But an abundance of donated organs only benefits patients if they are accepted, expeditiously transported and actually transplanted. This review focuses on postdonation challenges and opportunities to increase the number of transplants through improved organ utilization. RECENT FINDINGS: We build upon recently proposed changes in terminology for measuring organ utilization. Among organs recovered for transplant, the nonuse rate (NUR REC ) has risen above 25% for kidneys and pancreata. Among donors, the nonuse rate (NUR DON ) has risen to 40% for livers and exceeds 70% for thoracic organs. Programme-level variation in offer acceptance rates vastly exceeds variation in the traditional, 1-year survival benchmark. Key opportunities to boost utilization include donation after circulatory death and hepatitis C virus (HCV)+ organs; acute kidney injury and suboptimal biopsy kidneys; older and steatotic livers. SUMMARY: Underutilization of less-than-ideal, yet transplant-worthy organs remains an obstacle to maximizing the impact of the U.S. transplant system. The increased risk of inferior posttransplant outcomes must always be weighed against the risks of remaining on the waitlist. Advanced perfusion technologies; tuning allocation systems for placement efficiency; and data-driven clinical decision support have the potential to increase utilization of medically complex organs.

Early Outcomes of Adult Heart Transplantation From COVID-19 Infected Donors.

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 hospitalization. These donors were subclassified as "active COVID-19" (aCOV) donors if they were NAT positive within 2 days of organ procurement, or "recently resolved COVID-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 6 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.

OPTN/SRTR 2021 Annual Data Report: Heart.

The past 5 years have posed challenges to the field of heart transplantation. The 2018 heart allocation policy revision was accompanied by anticipated practice adjustments and increased use of short-term circulatory support, changes that may ultimately serve to advance the field. The COVID-19 pandemic also had an impact on heart transplantation. While the number of heart transplants in the United States continued to increase, the number of new candidates decreased slightly during the pandemic. There were slightly more deaths following removal from the waiting list for reasons other than transplant during 2020, and a decline in transplants among candidates listed as status 1, 2, or 3 compared with the other statuses. Heart transplant rates decreased among pediatric candidates, most notably among those younger than 1 year. Despite this, pretransplant mortality has declined for both pediatric and adult candidates, particularly candidates younger than 1 year. Transplant rates have increased in adults. The prevalence of ventricular assist device use has increased among pediatric heart transplant recipients, while the prevalence of short-term mechanical circulatory support, particularly intra-aortic balloon pump and extracorporeal membrane oxygenation, has increased among adult recipients.

Retrospective Evaluation of COVID-19 Infection and COVID-19 Vaccines in Heart Transplant Patients.

BACKGROUND: Patients who have performed solid organ transplantation in terms of COVID-19 infection are included in the high-risk group. In this study, it was aimed to evaluate the relationship between vaccination and retrospective evaluation of 32 patients who underwent a heart transplant in the clinic and tested positive for SARS-CoV-2 polymerase chain reaction. METHODS: In this study, demographic characteristics of the cases, comorbidities, timing of heart transplantation, immunosuppressive treatments, symptoms of COVID-19 infection, lung imaging findings, follow-up (outpatient/inpatient), treatments, 1-month mortality, and vaccination histories against COVID-19 infection were evaluated. The data obtained from the study were analyzed with SPSS version 25.0. RESULTS: The 3 most common symptoms are cough (37.5%), myalgia (28.1%), and fever (21.8%). COVID-19 infection was severe in 6.2% of the patients, moderate in 37.5%, and mild in 56.2%. Hospitalization was required in 5 patients (15.6%, 1 in the intensive care unit), and the other patients were followed up as an outpatient. Severe COVID-19 infection was seen more in 33% of unvaccinated patients; 93.5% were vaccinated. Nineteen patients (68%) were vaccinated before COVID-19 infection. Our patients received the CoronoVac (Sinovac, China) vaccine. CONCLUSION: COVID-19 infection is more likely to be severe and mortal in patients with heart transplant recipients. It is also crucial to comply with preventive measures other than immunization in this group of patients. This study is the largest series investigating COVID-19 infection in heart transplant recipient patients in our country.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States.

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology.

The End of Endomyocardial Biopsy?: A Practical Guide for Noninvasive Heart Transplant Rejection Surveillance.

Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.

Severity of SARS-CoV-2 Omicron variant infection in heart transplant recipients.

SARS-CoV-2 Omicron variant was first detected in France mid-November 2021 in wastewater treatment plants while cases started to increase at the beginning of December. The maximum incidence occurred in mid-January 2022. The Omicron wave spread rapidly throughout France in general population with lower case-fatality rate compared with previous waves. Little is known about infection with Omicron variant in heart transplant (HT) recipients. In this study, we examined incidence and mortality rate of COVID-19 in the general population and among 1,263 HT recipients during the period from June, 2021 to February, 2022, described characteristics of HT recipients infected with SARS-CoV-2 during Omicron (December 1st, 2021-February 7, 2022) and Delta (June 1st- November 30, 2021) periods, and compared hospital course of HT recipients with Omicron and Delta variant infection. Our findings contrast with the reported lower severity for Omicron variant infection compared with Delta variant infection in immunocompetent individuals.

Heart transplantation for pediatric foreign nationals in the United States.

BACKGROUND: This study aimed to clarify survival outcomes, waitlist mortality, and waitlist days of heart transplantation of pediatric foreign nationals compared to pediatric United States (US) citizens. METHODS: We retrieved data from March 2012 to June 2021 in the United Network Organ Sharing (UNOS) registry. RESULTS: Of 5857 pediatric patients newly waitlisted, 133 (2.27%) patients were non-US citizen/non-US residents (non-citizen non-resident [NCNR]). Patients with congenital heart disease were higher in the US citizen group than in the NCNR group (51.9% vs. 22.6%, p < .001); 76.7% of patients in the NCNR group (102/133) had cardiomyopathy. Of the 133 NCNRs, 111 patients (83.5%) underwent heart transplantation, which was significantly higher than that in the US citizen group (68.6%, p < .001). The median waitlist time was 71 days (IQR, 22-172 days) in the NCNR group and 74 days (29-184 days) in the US citizen group (p = .48). Survival after heart transplant was significantly better in the NCNR group than in the US citizen group (n = 3982; logrank test p = .015). CONCLUSIONS: Heart transplantation for pediatric foreign nationals was mostly indicated for cardiomyopathy, and their transplant rate was significantly higher than that in the US citizen group, with better survival outcomes. The better survival outcomes in the NCNR group compared to the US citizen group can likely be attributed to the differing diagnoses for which transplantation was performed.

ST-segment elevation myocardial infarction as a COVID-19 manifestation in a recent heart transplant recipient.

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Accelerated Cardiac Allograft Vasculopathy in an Orthotopic Heart Transplant Recipient with Prior COVID-19.

BACKGROUND Cardiac allograft vasculopathy (CAV) is a post-orthotopic heart transplant (OHT) complication driven by intimal smooth muscle proliferation and immune hyperactivity to donor heart tissue. Accelerated CAV leads to allograft failure within 1 year after receiving a normal angiogram result. Viruses can contribute to CAV development, but CAV after SARS-CoV-2 infection has not been reported to date. CASE REPORT A 48-year-old man, 5 years after OHT for non-ischemic cardiomyopathy, was admitted to the Cardiac Care Unit with 3 days of abdominal pain, dyspnea, and palpitations. His medical history included hyperlipidemia and insulin-dependent diabetes. He was compliant with all medications. Two months prior, he had a mild COVID-19 case. An echocardiogram and coronary angiogram 6 and 9 months prior, respectively, were unremarkable. Right and left heart catheterization demonstrated increased filling pressures, a cardiac index of 1.7 L/ml/m², and diffuse vasculopathy most severe in the LAD artery. Flow could not be restored despite repeated ballooning and intra-catheter adenosine. Empiric ionotropic support, daily high-dose methylprednisolone, and plasmapheresis were started. A few days later, the patient had cardiac arrest requiring venoarterial extracorporeal membranous oxygenation. Given CAV's irreversibility, re-transplantation was considered, but the patient had an episode of large-volume hemoptysis and remained clinically unstable for transplant. The patient died while on palliative care. CONCLUSIONS Our patient developed accelerated CAV 2 months after having COVID-19. While CAV has known associations with certain viruses, its incidence after SARS-CoV-2 infection is unknown. Further research is needed to determine if prior SARS-CoV-2 infection is a risk factor for development of CAV in OHT recipients.

Attitudes of patients with renal disease on xenotransplantation: A systematic review.

BACKGROUND: Recent years have seen major advancements in xenotransplantation: the first pig-to-human heart transplant, the development of a brain-dead recipient model for kidney xenotransplantation, and the registration of the first xenokidney clinical trial. The attitudes of patients with kidney disease or transplants on xenotransplantation and an assessment of their reservations and considerations regarding the technology are crucial to successful clinical translation and eventual widespread implementation. METHODS: This systematic review was registered through PROSPERO (CRD42022344581) prior to initiation of the study and reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. We included studies that evaluated attitudes towards and willingness to undergo xenotransplantation in patients with end-stage renal disease (ESRD), including those who had already undergone transplantation. MEDLINE (via Ovid), Embase (via Elsevier), and Web of Science (via Clarivate) were searched from database inception to July 15, 2022 by an experienced medical librarian for studies on xenotransplantation and attitudes. Abstracts and full text were screened using Covidence software and data items regarding study methodology, patient demographics, and attitudes regarding xenotransplantation were extracted using Microsoft Excel. Risk of bias assessments were performed using the Critical Appraisal Skills Programmed and National Institute of Health study quality assessment tools. RESULTS: Of 1992 studies identified, 14 studies met the inclusion criteria. These studies were conducted across eight countries, four in the United States, for a total of 3114 patients on the kidney waitlist or with a kidney transplant. All patients were over 17 years old and 58% were male. Acceptance of a xenotransplant was assessed using surveys in 12 studies. Sixty-three percent (n = 1354) of kidney patients reported that they would accept a xenotransplant with function comparable to that of an allotransplant. Acceptance of xenografts with inferior function to allografts (15%) or as bridge organs (35%) to allotransplantation was lower. Specific concerns expressed by patients included graft function, infection, social stigma, and animal rights. Subgroup analyses showed higher acceptance in already transplanted compared to waitlist patients and white compared to Black Americans. CONCLUSION: An understanding of patient attitudes and reservations is key to the successful execution of the first xenotransplantation clinical trials. This study compiles important factors to consider, such as patient concerns, attitudes regarding practical clinical scenarios for the use of xenotransplantation, and the impact of demographic factors on acceptance of this emerging technology.

Utilization of COVID-19 positive donors for Heart transplantation and associated short-term outcomes.

BACKGROUND: The safety and efficacy of using COVID-19 positive donors in heart transplantation (HT) are increasingly relevant, but not well established. The present study evaluated the characteristics and utilization of such donors and associated post-HT outcomes. METHODS: All adult (≥18 years old) potential donors and HT recipients in the United States from April 21, 2020 to March 31, 2022 were included. Donor COVID-19 status was defined by the presence (or absence) of any positive test within 21 days of organ recovery. Donor and recipient characteristics and post-HT outcomes, including a primary composite of death, graft failure, and re-transplantation, were compared by donor COVID-19 status. RESULTS: Of 967 COVID-19(+) potential donors, 19.3% (n = 187) were used for HT compared to 26.7% (n = 6277) of COVID-19(-) donors (p < 0.001). Transplanted COVID-19(+) vs COVID-19(-) donors were younger, but otherwise were similar. Recipients of hearts from COVID-19+ vs COVID-19(-) donors less frequently received pre-HT inotropes (24.1% vs 31.7%, p = 0.023) and ventricular assist device therapy (29.7% vs 36.8%, p = 0.040). There were no significant differences in any post-HT outcome by donor COVID-19 status, including the primary composite outcome at 90 days (5.4% vs 5.6%, p = 0.91). Among COVID-19(+) donors, the presence of a subsequent negative test prior to transplant was not associated with posttransplant outcomes. CONCLUSIONS: Our results suggest that carefully selected COVID-19 positive donors may be used for HT with no difference in short-term post-transplant outcomes. Additional data regarding donor and recipient treatments and impact of vaccination should be collected to better inform our use of organs from COVID(+) donors.

The COVID-19 Pandemic and Adult Cardiac Transplantation: Impact, Interventions, and Implications.

In this review, we provide a comprehensive overview of the impact of the COVID-19 pandemic on adult heart transplantation. We highlight the decline in the number of adult transplantations performed throughout the pandemic as a consequence of restrictions imposed on individual programs and hospitals. There were challenges to maintaining cardiac transplant activity at multiple levels, including organ donation in intensive care units, logistical difficulties with organ procurement, and rapidly changing resource considerations at health system and jurisdictional levels. We also review the impact of COVID-19 on cardiac transplant recipients. Despite the high rates of morbidity and mortality observed during the initial phases of the pandemic among heart transplant patients infected with COVID-19, the availability of effective vaccines, pre-exposure prophylaxis, and specific antiviral therapies have drastically improved outcomes over time. Vaccines have proven to be safe and effective in reducing infections and illness severity, but specific considerations in the immunocompromised solid organ transplant population apply, including the need for additional booster doses to achieve sufficient immunisation. We further outline the strong rationale for vaccination before transplantation wherever possible. Finally, the COVID-19 response created a number of barriers to safe and efficient post-transplantation care. Given the need for frequent evaluation and monitoring, especially in the first several months after cardiac transplantation, the pandemic provided the impetus to improve virtual care delivery and explore noninvasive rejection surveillance through gene expression profiling. We hope that lessons learned will allow us to prepare and pivot effectively during future pandemics and health care emergencies.

SARS-CoV-2 Vaccination-Induced Immunogenicity in Heart Transplant Recipients.

Among heart transplant (HT) recipients, a reduced immunological response to SARS-CoV-2 vaccination has been reported. We aimed to assess the humoral and T-cell response to SARS-CoV-2 vaccination in HT recipients to understand determinants of immunogenicity. HT recipients were prospectively enrolled from January 2021 until March 2022. Anti-SARS-CoV-2-Spike IgG levels were quantified after two and three doses of a SARS-CoV-2 vaccine (BNT162b2, mRNA1273, or AZD1222). Spike-specific T-cell responses were assessed using flow cytometry. Ninety-one patients were included in the study (69% male, median age 55 years, median time from HT to first vaccination 6.1 years). Seroconversion rates were 34% after two and 63% after three doses. Older patient age (p = 0.003) and shorter time since HT (p = 0.001) were associated with lower antibody concentrations after three vaccinations. There were no associations between vaccine types or immunosuppressive regimens and humoral response, except for prednisolone, which was predictive of a reduced response after two (p = 0.001), but not after three doses (p = 0.434). A T-cell response was observed in 50% after two and in 74% after three doses. Despite three vaccine doses, a large proportion of HT recipients exhibits a reduced immune response. Additional strategies are desirable to improve vaccine immunogenicity in this vulnerable group of patients.

Real-world experience of tixagevimab-cilgavimab pre-exposure prophylaxis in orthotopic heart transplant recipients.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab (tix-cil) may be associated with cardiovascular adverse events. Also, in vitro studies have reported a reduced activity of tix-cil against emerging SARS-CoV-2 Omicron subvariants. Our study aimed to report the real-world outcomes of tix-cil prophylaxis in orthotopic heart transplant (OHT) recipients METHODS: We retrospectively studied all OHT recipients who received one dose of tix-cil (150-150 mg or 300-300 mg) at Mayo Clinic in Arizona, Florida, and Minnesota, between February 5, 2022 and September 8, 2022. We collected data on cardiovascular adverse events and breakthrough COVID-19 following tix-cil administration. RESULTS: One hundred sixty-three OHT recipients were included. The majority were male (65.6%), and the median age was 61 years (IQR 48, 69). During the median follow-up of 164 days (IQR 123, 190), one patient presented an episode of asymptomatic hypertensive urgency that was managed with outpatient antihypertensive treatment optimization. Twenty-four patients (14.7%) experienced breakthrough COVID-19 at the median of 63.5 days (IQR 28.3, 101.3) after tix-cil administration. The majority (70.8%) completed the primary vaccine series and received at least one booster dose (70.8%). Only one patient with breakthrough COVID-19 required hospitalization. All patients survived. CONCLUSIONS: In this cohort of OHT recipients, no patients developed severe cardiovascular events related to tix-cil. The high incidence of breakthrough COVID-19 could be due to the reduced activity of tix-cil against current circulating SARS-CoV-2 Omicron variants. These results emphasize the need for a multimodal prevention strategy against SARS-CoV-2 in these high-risk patients.