Heart transplantation remains the treatment of choice for many patients with end-stage heart failure. Heart transplant volume in the United States had remained relatively stable from the early 1990s until 2012, falling in the 2,100-2,200 transplants per year range. Since that time, there has been consistent annual growth, including throughout the COVID-19 pandemic. In 2022, 4,111 heart transplants were performed in the U.S. and over 6,000 worldwide, including 491 pediatric (<18 years) patients in the U.S. (asamonitor.pub/37XeH3A; J Heart Lung Transplant 2021;40:1035-49). However, despite the increase in heart transplants, there continues to be a shortage, with over 3,300 patients remaining on the waitlist in the U.S. alone.

Heart transplantation is a complex undertaking involving much more than just the transplant itself. From the initial patient selection and the entirety of their perioperative care, it requires multidisciplinary collaboration, with anesthesiologists playing a crucial role throughout the process. Once patients are approved and listed, donor hearts are allocated based on geographic location as well as urgency status. For adults, there are six statuses, with status 1 being the most urgent and status 6 being the least urgent. For children, there are 3 statuses, 1A, 1B, and 2.

Because medical and surgical management of patients with heart failure has continued to improve, the characteristics of patients who receive a heart transplant have continually evolved as well. Patients are now older, have a higher BMI, higher incidences of diabetes and previous cardiac surgery, and are more likely to be allosensitized (J Heart Lung Transplant 2021;40:1035-49). Interestingly, patients have lower serum creatinine and lower preoperative inotrope use; however, this may be explained by increasing prevalence of some form of mechanical circulatory support (MCS) before transplant. The most common form of MCS in patients receiving a transplant was a durable ventricular assist device (VAD), which was seen in 40% of transplant recipients in the period from 2010-2018 (J Heart Lung Transplant 2021;40:1035-49). However, as discussed below, the modification in the United Network for Organ Sharing (UNOS) listing in 2018 has significantly altered this rate again.

“Despite the improvements in medical management and VAD therapies, heart transplantation remains the best long-term treatment option, with median survival greater than 14 years. The 38th International Society for Heart and Lung Transplantation heart transplantation report shows improved one-year survival to >90% for the first time in heart transplants performed in North America in the 2012-2017 period.”

Despite the improvements in medical management and VAD therapies, heart transplantation remains the best long-term treatment option, with median survival greater than 14 years. The 38th International Society for Heart and Lung Transplantation heart transplantation report shows improved one-year survival to >90% for the first time in heart transplants performed in North America in the 2012-2017 period. Five-year survival conditional on one-year survival was 86.9%. Cardiac allograft vasculopathy (CAV) remains the leading cause of both long-term graft dysfunction and graft loss (Cardiovasc Res 2021;117:2624-38). While the advent of statins and proliferation of signal inhibitors were a significant improvement in the prevention of CAV, no other significant advancements have occurred since their release, making CAV a significant concern for any patient requiring an anesthetic after they have received a heart transplant.

UNOS revised their donor heart allocation system in October 2018 (asamonitor.pub/3PVkucp). This revision abolished the previous three-tiered recipient status system and replaced it with a new six-tier system. This change was made in response to data suggesting outcomes were similar in patients without MCS when compared to those with both stable long-term and temporary MCS. The goal of this new allocation system was to prioritize patients with temporary MCS, given their increased acuity. The change has resulted in a decreased average wait time to transplant after listing, but has also had several unintended consequences. Given the prioritization for patients with temporary MCS, patients are now less often receiving durable VADs as a bridge until transplant. Instead, they are more frequently supported with temporary MCS support. Heart transplants with a durable VAD have decreased from 41.8% to 21.2%, and the rate of transplant recipients on temporary MCS has increased from 11.3% to 22.9% (JACC Heart Fail 2020;8:548-56). The downstream effects of the prioritization of temporary MCS have also altered VAD placement. The 2022 INTERMACS (Society of Thoracic Surgeons (STS)-Interagency Registry for Mechanically Assisted Circulatory Support) Annual Report now shows 81.1% of VAD implants are now placed for destination therapy, up from 49.3% in 2017 (Ann Thorac Surg 2023;115:311-27). Placement as bridge to transplant is now 3.3%, down from 23.7% in 2017.

The first heart transplant performed in 1967 was a DCD transplant. However, these donors quickly fell out of favor as they were felt to be inferior to donation after brain death (DBD) organs. Currently, the majority of heart transplant organs are from DBD. The donor pool has always been the limiting factor. While abdominal DCD transplantation has been performed for almost 30 years, cardiac DCD has seen a reappearance, initially in Australia and Europe, and now in the U.S., where the first DCD cardiac transplant was performed in 2019 (Surgery 2011;150:692-702; J Am Soc Nephrol 2017;28:3647-57; Curr Transplant Rep 2020;7:194-204). In the U.S., 17% of abdominal organ transplants and 3% of heart transplants are from DCD (asamonitor.pub/37XeH3A).

Heart transplant after DCD is accomplished using one of four different pathways for organ procurement. Direct procurement of the organ is performed immediately after declaration of death and a five-minute standby period. The organ is then placed either into cold storage or into an ex-vivo organ perfusion machine. Ex-vivo perfusion involves taking a donated organ and placing it on a machine pump that maintains normothermia while also providing perfusion with oxygenated blood. The other two pathways utilize normothermic regional perfusion of the organ prior to procurement. Normothermic regional perfusion of the heart involves either extracorporeal membrane oxygenation or cardiopulmonary bypass, while excluding perfusion to the brain. Following perfusion of the heart, it is then placed in cold storage or into an ex-vivo perfusion machine during transport to the recipient (J Cardiothorac Vasc Anesth 2022;36:3867-76). The use of an ex-vivo perfusion machine or normothermic regional perfusion maintains organ perfusion and reduces metabolites prior to transplantation, thereby allowing organs that may otherwise not be considered for transplant to be further assessed and utilized.

The use of DCD organs is projected to increase the number of heart transplants by 15%-25% (Curr Opin Organ Transplant 2020;25:241-7). Short-term results have indicated that survival is very similar to DBD heart transplants. In the United Kingdom, 30-day survival is 97% for DCD and 99% for DBD heart transplants, and one-year survival is 91% for DCD and 89% for DBD heart transplants (J Heart Lung Transplant 2020;39:1463-75). In Australia, the DCD one-, three-, and five-year survival rates are 96%, 94%, and 94%, respectively (J Am Coll Cardiol 2019;73:1447-59).

Xenotransplantation involves the transplantation of tissue or organs from nonhuman animal donors into human recipients. In 1984, Baby Fae was the first human recipient of a cardiac xenotransplant. She received her new heart from a baboon and survived for two weeks. Posthumous examination revealed rejection of the xenoheart and renal failure (West J Med 1985;142:401-2). The most recent xenoheart transplant was for David Bennet Sr. from a pig at the University of Maryland in January 2022. The donor pig had been genetically modified to prevent hyperacute rejection by inactivating the gene GGTA1, which encodes the alph1,3-galactosyltransferase enzyme. Porcine endogenous retroviruses were also a concern, and now genetic engineering can generate pigs with inactive endogenous retroviruses (Transgenic Res 2022;31:391-8). David Bennet Sr. lived for almost two months after the xenoheart transplant (JAMA 2022;328:1999-2001). Postmortem examination of his heart was not consistent with signs of rejection, as seen with Baby Fae. However, there were concerns that his passing may have been attributable to infection with porcine cytomegalovirus, since he tested positive. He also had severe diastolic dysfunction, as the left and right ventricular walls had increased in thickness to 1.7 and 1.4 cm, respectively. His heart nearly doubled in size and mass from 328 gm to 600 gm (N Engl J Med 2022;387:35-44).

More research continues with cardiac xenotransplantation. NYU has transplanted xenopig hearts into brain dead donors to study transmissibility of porcine viruses (asamonitor.pub/3ZROlH6). Areas of concern for xenotransplantation include immunological organ rejection, appropriate physiologic organ performance, and prevention of transmission of infectious agents.

Currently, heart transplantation is the best option for patients with heart failure who have failed medical therapy. The UNOS organ allocation system was revised in 2018 to decrease wait time and mortality while on the wait list. The use of donor organs from high-risk patients, DCD, and preservation and optimization methods may increase the number of viable donor organs. Methods to increase the number of heart transplants will help many more patients.