Heart Transplant Donor Recovery and Novel Therapies

Crespo-Leiro MG, Costanzo MR, Gustafsson F, et al.
Heart Transplantation: Focus on Donor Recovery Strategies, Left Ventricular Assist Devices, and Novel Therapies. Eur Heart J 2022;43:2237-2246.

The following are key points to remember from this review on heart transplant donor recovery strategies, left ventricular assist devices, and transplant recipient management:

  1. Advances in donor selection include use of hepatitis C–positive donors. Therapy for hepatitis C can be initiated periprocedurally, which permits low levels of viremia and shorter duration of treatment, but payer coverage is challenging. Alternatively, therapy can be initiated after viremia is established. Short-term outcomes from hepatitis C virus (HCV) donors are no different but longer-term outcomes remain unknown.
  2. For organ preservation, historically, cold preservation has been used. More recently, normothermic machine perfusion has been tested and may lead to increase in use of donor hearts. Other techniques for donor organ preservation such as use of continuous perfusion with a cold oxygenated cardioplegic and nutrition hormone solution containing erythrocytes has also been tested with successful results.
  3. Use of donation after circulation death (DCD) hearts has also emerged as a new venue to expand the donor pool and studies suggest similar 4-to-5-year outcome comparing DCD to donation after brain death donors. An echocardiogram demonstrating normal biventricular function prior to withdrawal of life support is needed. Due to differences in legislation permitting interventions before and after death, protocols vary across centers.
  4. Since some patients with end-stage heart failure may not survive the wait to a heart transplant, mechanical circulatory support (MCS) devices are used as a bridge. The use of temporary MCS has increased in the United States after the new 2018 transplant allocation rules. Currently, evidence suggests that post-transplant outcomes may be worse for patients supported with temporary MCS but this may improve with time.
  5. Durable MCS with left ventricular assist devices can support patients for years until a transplant is possible. Outcomes with HeartMate 3 devices have the lowest risk of pump thrombosis and stroke.
  6. Since newer antiviral agents for hepatitis C have an efficacy of >95%, there has been an increased use of HCV-infected donors. Studies have shown shorter waiting time with HCV donors and comparable 1-year survival. Longer-term outcomes are not yet reported.
  7. Post-transplant surveillance of rejection now includes use of gene expression profiling (AlloMap assay) that evaluates 11 genes expressed differently in the setting of acute cellular rejection. Another noninvasive test for rejection surveillance includes use of donor-derived cell free DNA (ddcfDNA). Elevated ddcfDNA levels are found in acute cellular and antibody-mediated rejection.
  8. Other emerging tests include use of anellovirus assay to monitor strength of immune response in transplant recipients and use of molecular microscope assays to refine biopsy-based diagnosis of acute rejection and minimize errors made by pathologists in reading biopsies.
  9. Newer agents are now available to treat and minimize rejections in sensitized patients. This includes monoclonal antibodies against complement system (eculizumab), CD 52 (alemtuzumab), CD 38 (daratumumab), and interleukin-6 (clazakizumab).
  10. Simultaneous heart-kidney transplant is preferred in patients with glomerular filtration rate <30 mL/min. Multiorgan transplant is protective of the cardiac allograft in patients with simultaneous heart-lung, heart-liver, and heart-kidney transplant.
  11. COVID-19–associated death rates in transplant recipients are 10-fold higher than in the general population. Transplant recipients also have a weaker immune response to COVID-19 vaccination. Accordingly, many centers mandate vaccination for patients waitlisted for cardiac transplant.
  12. In January 2022, the first successful xenotransplantation was performed with a genetically edited porcine to human heart transplant with a 60-day patient survival. Tissue engineering may provide new options for heart failure patients in the future.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support

Keywords: Allografts, COVID-19, COVID-19 Vaccines, Diagnostic Techniques and Procedures, Donor Selection, Heart Failure, Heart Transplantation, Heart-Assist Devices, Hepatitis C, Kidney Transplantation, Organ Preservation, Perfusion, Stroke, Thrombosis, Tissue Donors, Transplant Recipients, Viremia

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