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.

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.

Heart transplantation: focus on donor recovery strategies, left ventricular assist devices, and novel therapies.

Heart transplantation is advocated in selected patients with advanced heart failure in the absence of contraindications. Principal challenges in heart transplantation centre around an insufficient and underutilized donor organ pool, the need to individualize titration of immunosuppressive therapy, and to minimize late complications such as cardiac allograft vasculopathy, malignancy, and renal dysfunction. Advances have served to increase the organ donor pool by advocating the use of donors with underlying hepatitis C virus infection and by expanding the donor source to use hearts donated after circulatory death. New techniques to preserve the donor heart over prolonged ischaemic times, and enabling longer transport times in a safe manner, have been introduced. Mechanical circulatory support as a bridge to transplantation has allowed patients with advanced heart failure to avoid progressive deterioration in hepato-renal function while awaiting an optimal donor organ match. The management of the heart transplantation recipient remains a challenge despite advances in immunosuppression, which provide early gains in rejection avoidance but are associated with infections and late-outcome challenges. In this article, we review contemporary advances and challenges in this field to focus on donor recovery strategies, left ventricular assist devices, and immunosuppressive monitoring therapies with the potential to enhance outcomes. We also describe opportunities for future discovery to include a renewed focus on long-term survival, which continues to be an area that is under-studied and poorly characterized, non-human sources of organs for transplantation including xenotransplantation as well as chimeric transplantation, and technology competitive to human heart transplantation, such as tissue engineering.

Evolving Characteristics of Heart Transplantation Donors and Recipients: JACC Focus Seminar.

Although the burden of end-stage heart failure continues to increase, the number of available organs for heart transplantation (HT) remains inadequate. The HT community has been challenged to find ways to expand the number of donor hearts available. Recent advances include use of hearts from donors infected with hepatitis C virus as well as other previously underutilized donors, including those with left ventricular dysfunction, of older age, and with a history of cocaine use. Concurrently, emerging trends in HT surgery include donation after circulatory death, ex vivo normothermic heart perfusion, and controlled hypothermic preservation, which may enable procurement of organs from farther distances and prevent early allograft dysfunction. Contemporary HT recipients have also evolved in light of the 2018 revision to the U.S. heart allocation policy. This focus seminar discusses recent trends in donor and recipient phenotypes and management strategies for successful HT, as well as evolving areas and future directions.

New Approaches to Donor Selection and Preparation in Heart Transplantation.

PURPOSE OF REVIEW: With increasing survival of patients with stage D heart failure, the demand for heart transplantation has increased. The supply of donor hearts remains relatively limited. Strategies have been investigated and new technologies have been developed to expand the current donor pool. These new approaches will be discussed herein. RECENT FINDINGS: Donor hearts are often considered "marginal" due to risk factors such as older age, size mismatch with the intended recipient, prolonged ischemic time, presence of left ventricular hypertrophy, and hepatitis B/C infection. We reviewed recent data regarding the use of donor hearts with these risk factors and suggest ways to safely liberalize current donor heart acceptance criteria. New technologies such as temperature-controlled transport systems and ex vivo cardiac perfusion methods have also demonstrated promising short-term and intermediate outcomes as compared with routine cold storage, by promoting heart preservation and enabling heart procurement from remote sites with shorter cold ischemic time. Recent use of hearts from donation after circulatory death donors has demonstrated comparable outcomes to conventional donation after brain death, which can further expand the current donor pool. SUMMARY: Careful selection of "marginal" donor hearts, use of ex vivo cardiac perfusion, and acceptance of hearts after circulatory death may expand our current cardiac donor pool with comparable outcomes to conventional donor selection and preparation methods.