Beating heart transplantation – Heart in the box technology

Beating heart transplantation – Heart in the box technology

Beating heart transplantation – Heart in the box technology: Beating heart transplantation is a new technology being perfected by UCLA (University of California, Los Angeles) Health System which keeps the donor heart beating in a near physiologic state during transportation till implantation in the recipient. This enables preservation of the donor heart and could potentially facilitate long distance transport to achieve better tissue matching to reduce the chance of graft rejection. Conventionally the donor hearts have been transported in ice boxes, which would limit the time for which they would remain viable, which is currently at a cut off of six hours. The new technology known as Organ Care System (OCS) has been developed by Transmedics, perfused the heart with oxygen and nutrient rich blood and is maintained at a controlled optimal temperature. Cardiac function during transport is monitored and displayed as well.

The PROCEED II trial conducted by Abbas Ardehali, Fardad Esmailian, Mario Deng, Edward Soltesz, Eileen Hsich, Yoshifumi Naka, Donna Mancini, Margarita Camacho, Mark Zucker, Pascal Leprince, Robert Padera and Jon Kobashigawa, the PROCEED II trial investigators randomly assigned 130 patients to the Organ Care System (n=67) or standard cold group (n=63). The enrolled was between 29th June 2010 and 16th September 2013 [1].

Primary endpoint was the thirty day patient and graft survival. Eight patients in the Organ Care System group and nine patients in the standard cold storage group had serious heart related adverse events. The investigators concluded that both types of care yielded similar short term results.

INSPIRE was a phase 3 trial which was open label, randomized and of non-inferiority design [2]. It used Organ Care System Lung device for bilateral lung transplantation. The trial reached its primary effectiveness and safety endpoints. No survival benefit was reported. The intermediate follow up at 2 years also reported similar results [3]. It may be noted that the study group had significantly longer total ischemic time (361 min vs 207 min; p < 0.001) and shorter cold ischemia time (134 min vs 207 min; p < 0.001) compared to the cold storage group.

Results of the EXPAND Trial lead by Jacob Schroder was presented at the 39th annual meeting of the International Society for Heart and Lung Transplantation in Orlando, Florida. GlobalNewswire website quoted Dr. Schroder’s presentation with  successful transplantation of 81% of donor hearts that may not be used routinely with cold storage, with patient survival of 95% at 30 days after transplantation. International EXPAND Heart Pivotal Trial (EXPANDHeart) at ClinicalTrials.gov.

Reference

1. Abbas Ardehali, Fardad Esmailian, Mario Deng, Edward Soltesz, Eileen Hsich, Yoshifumi Naka, Donna Mancini, Margarita Camacho, Mark Zucker, Pascal Leprince, Robert Padera, Jon Kobashigawa, PROCEED II trial investigators. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet. 2015 Jun 27;385(9987):2577-84.
2. Gregor Warnecke, Dirk Van Raemdonck, Michael A Smith, Gilbert Massard, Jasleen Kukreja, Federico Rea, Gabriel Loor, Fabio De Robertis, Jayan Nagendran, Kumud K Dhital, Francisco Javier Moradiellos Díez, Christoph Knosalla, Christian A Bermudez, Steven Tsui, Kenneth McCurry, I-Wen Wang, Tobias Deuse, Guy Lesèche, Pascal Thomas, Igor Tudorache, Christian Kühn, Murat Avsar, Bettina Wiegmann, Wiebke Sommer, Arne Neyrinck, Marco Schiavon, Fiorella Calabrese, Nichola Santelmo, Anne Olland, Pierre-Emanuel Falcoz, Andre R Simon, Andres Varela, Joren C Madsen, Marshall Hertz, Axel Haverich, Abbas Ardehali. Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study. Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study. Lancet Respir Med. 2018 May;6(5):357-367.
3. Joshua L Chan, Jon A Kobashigawa, Heidi J Reich, Danny Ramzy, Maria M Thottam, Zhe Yu, Tamar L Aintablian, Frank Liou, Jignesh K Patel, Michelle M Kittleson, Lawrence S Czer, Alfredo Trento, Fardad Esmailian. Intermediate outcomes with ex-vivo allograft perfusion for heart transplantation. J Heart Lung Transplant. 2017 Mar;36(3):258-263.