Selection of Patients for the Initial Clinical Trials of Cardiac Xenotransplantation
Here, we offer our opinion regarding patient characteristics that should be considered to identify potential candidates for “first-in-man” heart xenotransplantation trials. For an initial attempt at cardiac xenotransplantation to be ethically justified, t
- PDF / 218,439 Bytes
- 12 Pages / 439.37 x 666.142 pts Page_size
- 70 Downloads / 160 Views
Richard N. Pierson III, Lars Burdorf, and David A. D’Alessandro
Abbreviations MCSD PRA TAH VA ECMO VAD
Mechanical circulatory support device Panel-reactive antibodies Total artificial heart Venoarterial extracorporeal membrane oxygenator Ventricular assist device
Introduction A major limiting factor constraining the demonstrated efficacy of cardiac allotransplantation remains the availability of organs from human donors. Each year, over 150 of the ~4000 patients on the United Network for Organ Sharing (UNOS) waiting list die resulting from the unavailability of a suitable human donor heart [1, 2]. Many additional patients are removed from consideration because of clinical deterioration while waiting. More than half of the 3500 North American patients fortunate enough to receive a heart transplant each year have previously required “bridging” with a mechanical circulatory support device (MCSD) to stabilize them until a suitable donor can be identified. In addition to the substantial added costs associated with MCSD, many device-treated patients experience major morbidities that complicate or prevent
R. N. Pierson III (*) · L. Burdorf Division of Cardiac Surgery and Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital and Harvard University, Boston, MA, USA e-mail: [email protected] D. A. D’Alessandro Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital and Harvard University, Boston, MA, USA © Springer Nature Switzerland AG 2020 D. K. C. Cooper, G. Byrne (eds.), Clinical Xenotransplantation, https://doi.org/10.1007/978-3-030-49127-7_15
221
222
R. N. Pierson III et al.
subsequent transplantation. Use of hearts from “expanded criteria” donors or resuscitated after “donation after cardiac death” is being investigated in clinical trials but appears unlikely to fill the gap between supply and demand [3]. If predictably healthy organs were dependably available when needed, many patients who are currently not offered heart transplantation might also benefit if cardiac xenotransplantation is proven effective. These considerations justify efforts to develop pig cardiac xenotransplantation as a readily available alternative source of hearts for patients with life-threatening cardiac diseases [1]. Survival of nonhuman primate recipients of life-supporting porcine heart grafts for 6 months strongly suggests that clinical application of heart xenografts is likely to be successful [4]. For the purposes of argument, we presume that a combination of pig phenotype and clinically acceptable drug regimen will be defined that is successful in the preclinical life-supporting orthotopic heart xenograft model [5–8]. If renal xenograft clinical trials advance more rapidly to the clinic, successful approaches and lessons learned will be useful to the implementation of the first heart efforts.
Background The use of pigs as a source of hearts for use as “xenografts” in humans (cardiac xenotransplantation) could potentially address the current donor heart s
Data Loading...
